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Resume Objectifs L’objectif de cette etude est d’analyser les bases potentielles de l’immunotherapie du paludisme. Cette maladie est en effet une cause majeure de souffrances et de deces dans le monde, notamment dans les formes severes dues a Plasmodium falciparum. Epidemiologie Selon l’Organisation Mondiale de la Sante (OMS), l’estimation du nombre annuel de cas serait de 350 a 500 millions de cas cliniques, avec environ 1,1 a 1,3 millions de morts chaque annee. L’hyperactivation du systeme immun s’accompagne d’une production accrue de cytokines, principalement le TNF, ce qui joue un role important dans la pathogenie complexe de cette maladie. Pathogenie La sequestration accrue des erythrocytes, parasites a l’interieur des petits vaisseaux des principaux organes, est le facteur central de l’infection a P. falciparum . La production augmentee de cytokines pro-inflammatoires et d’oxide nitrique est suivie de regulation accrue des molecules d’adhesion aux cellules endotheliales ; ce processus influence la progression des lesions cerebrales. Immunomodulation Plusieurs approches ont tente une approche immunomodulatrice en diminuant l’hyperactivite du systeme immun dans le paludisme : l’administration de cytokines ou d’anticorps anti-cytokines, d’anticorps anti-molecules d’adherence, de medicaments qui reduisent la synthese excessive d’oxygene reactif de cette espece, et enfin des drogues avec une action pleiotrope sur le systeme immunitaire sont les principaux axes de recherche. L’impact de ces therapeutiques immunomodulatrices au cours du paludisme a atteint des resultats variables. Applications Nous avons soumis ces donnees a une evaluation critique et d’autres voies d’utilisation des moyens de l’immunomodulation associees aux therapeutiques anti-amariles pourront reduire la morbi-mortalite du paludisme.

The growing resistance of microorganisms to antibiotics has been considered as a global public health problem. Therefore, the search for novel antimicrobial drugs, chemically unrelated to the presently used antibiotics, is urgently needed. Our group has recently characterized a new family of antimicrobial peptides – phylloseptins – isolated from the skin secretion of the South American amphibian Phyllomedusa hypochondrialis, which showed a strong antimicrobial effect against Gram-positive and Gram-negative bacteria. We now investigate the in vivo toxicity of synthetic phylloseptin-1 (PS-1) toward bone marrow, liver, spleen, kidney and lung after endovenous administration to Swiss mice of a bolus dose of 4 mg/kg. Genotoxicity was evaluated by quantifying erythrocyte micronuclei. PS-1-treated mice showed no alteration in the histology of liver, spleen, kidney and lung, as well as of blood biochemistry, as compared to normal controls. Cytotoxicity tests, evaluated either by blood cytometry or bone marrow polychromatophilic erythrocyte index, revealed no deleterious effect of PS-1. Moreover, the peptide showed no toxicity towards bone marrow erythrocytes. We concluded that, in a concentration ten times over that providing antimicrobial effect, synthetic PS-1 showed no in vivo toxicity.

A Amazônia é conhecida pela elevada ocorrência de hepatite B e suas seqüelas. Contribui também com mais de 98% dos casos de malária do país. Apesar de controvérsias, é proposto que quando associadas ocorram alterações na história natural das duas patologias. Este estudo estima a prevalência de prováveis coinfecções em população geral de área endêmica de ambas infecções na Amazônia Brasileira. A taxa de portadores do AgHBs encontrada foi de 3,3% (IC 95% 2,1% a 5,1%,), e a do anti-HBc total 49,9% (IC 95% 45,9% a 53,8%). A prevalência de anticorpos contra antígenos do Plasmodium vivax e Plasmodium falciparum foi de 51,4% (311/605) (IC 95% 47,3% a 55,4%). Em relação à presença simultânea de anticorpos contra antígenos do Plasmodium vivax e Plasmodium falciparum com marcadores do VHB, 1,8% (11/605), (IC95% 1,0% a 3,3%), apresentavam também o AgHBs, tendo estes em média 26 anos de idade (p

Em 1992 foi feita uma investigação sobre o efeito protetor do uso de mosquiteiros impregnados com deltametrina, em uma população do município de Costa Marques, Rondônia, sujeita à transmissão malárica. Os mosquiteiros impregnados se comportaram de modo semelhante aos não impregnados, sem modificar os índices de infecção na época de baixa transmissão. A análise multivariada, por idade e títulos de anticorpos, mostrou uma proteção significante para o grupo com mosquiteiros impregnados contra o risco de infecção, apenas na estação de alta transmissão, quando os mosquiteiros foram usados mais regularmente. Não houve diferença no efeito de ambos os tipos de mosquiteiros na prevenção de elevadas parasitemias. Ao fim do estudo, ocorreu diminuição da prevalência de esplenomegalia em ambos os grupos, porém houve uma aparente recuperação da taxa normal de hematócrito em menores de 15 anos de idade em uso de mosquiteiros impregnados.

Antibody response to Salmonella typhi O and H antigens was evaluated in 24 individuals with either hepatointestinal or hepatosplenic schistosomiasis mansoni before and after typhoid vaccination, and compared with that of non-infected controls. Before vaccination, Schistosoma-infected patients showed a higher frequency of positive antibody to O antigen and the same frequency to H antigen when compared with that of healthy individuals. However, those with hepatosplenic schistosomiasis showed higher titres of antibody to H antigen than those with hepatointestinal disease or healthy individuals. Infected subjects, particularly those with hepatointestinal disease, showed a decreased response after typhoid vaccine. Tins diminished ability to mount an immune response towards typhoid antigens dining schistosomiasis may interfere ivith the clearance of the bacteria from blood stream and, therefore, play a role in the prolonged survival of salmonella as obsewed in some patients with chronic salmonellosis associated with schistosomiasis.A resposta de anticorpos para os antígenos O e H da Salmonella typhi foi avaliada em 24 indivíduos com esquistossomose hepatointestinal ou hepatoesplênica antes e apôs vacinação antitifoídica, e comparada com a resposta de indivíduos controles normais. Antes da vacinação, pacientes esquistossomóticos mostraram uma maior frequência de anticoipos positivos para o antígeno O e a mesma frequência de anticoipos positivos para o antígeno H quando comparada com aquela de indivíduos controles normais. Porém, aqueles com esquistossomose hepatoesplênica mostraram títulos maiores de anticoipos para o antígeno H do que aqueles com a forma hepatointestinal da doença ou os indivíduos controles normais. Pacientes esquistossomóticos, particularmente aqueles com a forma hepatointestinal, mostraram uma menor resposta após a vacinação antitifoídica. Esta menor capacidade para apresentar uma resposta imune para antígenos de salmonela pode interferir com a retirada da bactéria da corrente sanguínea e, portanto, contribuir como um dos determinantes de sua prolongada sobrevivência como obsewada em pacientes com salmonelose septicêmica prolongada associada â esquistossomose.

The control of leishmaniases poses an important challenge due to the scarcity and toxicity of the pharmacological options available. We have previously shown that pravastatin significantly improves the course of the disease in Leishmania (L.) amazonensis-infected BALB/c mice. Since the drug caused no direct effect on the parasite, we decided to evaluate its immunomodulatory action in this experimental model. To evaluate the impact of pravastatin treatment, BALB/c mice infected or not with L. (L.) amazonensis were treated with pravastatin (20 mg/kg daily) or saline during 30 or 90 days and phagocytosis, hydrogen peroxide, nitric oxide and the tumor necrosis factor production by peritoneal macrophages were assessed. We showed that pravastatin increased the phagocytosis mediated by complement and immunoglobulin receptors (63.5 to 130.3; p=0.03, t test), but not that occurring via pattern recognition receptors, induced a rise of nitric oxide production by macrophages (2.1 μM to 12.9 μM; p=0.04, Mann-Whitney test), endowing these cells to better kill ingested leishmania organisms, caused no modification of the otherwise increased production of hydrogen peroxide by macrophages, and reduced the overproduction of tumor necrosis factor (166.6 pg/mL to 3.9 pg/mL; p=0.016, Mann-Whitney test), a major component of the exacerbated inflammation associated to leishmaniases. Our findings point to the potential usefulness of pravastatin as an adjunct to the treatment of leishmaniases, based on its powerful immunomodulatory effects and low toxicity.

Com uma incidência de 3 a 10% dos casos e letalidade próxima a 70%, o comprometimento pulmonar constitui uma das manifestações mais graves da malária por Plasmodium falciparum. Embora sua patogênese não esteja perfeitamente esclarecida, reconhece-se que a hiperativação do sistema imune por antígenos liberados pelo Plasmodium falciparum desempenhe um importante papel no desencadeamento e agravamento das lesões. A estrutura alvo parece ser o endotélio capilar, responsável pelo fluxo de líquidos para o espaço intersticial. Essas células são ativadas por ação de citocinas, produzidas por linfócitos e macrófagos durante a resposta imune, e passam a expressar em sua membrana celular receptores e moléculas de aderência que facilitam a sequestração de eritrócitos parasitados e também a aderência de células capazes de produzir mediadores inflamatórios. A reação inflamatória e a lesão endotelial que se seguem, juntamente com as alterações hemodinâmicas induzidas pelo bloqueio capilar devido ao acúmulo local de eritrócitos e células inflamatórias causam alterações de permeabilidade vascular e, consequentemente, acúmulo de líquido nos espaços intersticiais e alvéolos. Nos casos mais graves, as manifestações clínicas assemelham-se às do quadro da Síndrome do desconforto respiratório do adulto. Comprometimento pulmonar grave pode se instalar rapidamente em qualquer estágio da evolução clínica da malária, mesmo após a cura parasitológica, desconhecendo-se os fatores desencadeantes. Hiperparasitismo, insuficiência renal e gravidez constituem fatores predisponentes. O prognóstico dependerá da rapidez com que o diagnóstico for estabelecido e o correto tratamento instituído. Além do tratamento instituído contra o parasita, especial atenção deverá ser dispensada à monitorização hemodinâmica, se possível através de cateter de Swan-Ganz, à manutenção de adequada oxigenação e balanço hídrico, e ao controle de outras complicações, frequentemente associadas ao comprometimento pulmonar. O esclarecimento da patogenia do comprometimento pulmonar associado à malária deverá concorrer para a racionalização da conduta terapêutica e, consequentemente, melhorar o prognóstico dos indivíduos acometidos por esta complicação. Pulmonary involvement occurs in 3 to 10% of the cases of Plasmodium falciparum malaria and represents the most serious complication of this infection, with a lethality of about 70%. The understanding of its pathogenesis is still very fragmentary, however it is recognized that activation of the immune system by antigens released by the parasite plays an important role in the induction and worsening of lung damage. Capillary endothelial cells, which control the flux of fluids to the interstitial space, appear to be the most involved structure. These cells are activated by cytokines, produced by lymphocytes and macrophages during the immune response, and express receptors and molecules of adhesion, allowing for sequestration of parasitized erythrocytes and adherence of cells, which will produce locally inflammatory mediators. The inflammatory reaction and lesion of endothelial cells that ensue, together with the hemodynamic alterations induced by the capillary blockade due to the sequestration of parasitized erythrocytes and leukocytes, cause alterations of the vascular permeability and transfer of liquid to intertitial space and alveoles. Severe cases are clinically expressed by a picture of Adult Respiratory Distress Syndrome. The clinical manifestations of pulmonary involvement may start suddenly at any time during the course of malaria, even after desappearance of circulating parasites. The inducing factors are unknown. Hyperparasite-mia, renal failure and pregnancy are predisposing factors. The prognosis will depend on how fast the diagnosis is established and convenient treatment initiated. If parasites are present they shall be treated with schizonticidal drugs, hemodynamic parameters continuously evaluated, preferably through a Swam-Ganz catheter. Appropriate oxygen supply and fluid balance have to be warranted. Other complications of malaria, frequently associated to the pulmonary involvement, need special attention and proper treatment. A better understanding of the pathogenesis of lung damage associated to malaria will certainly help to improve treatment and reduce morbidity and mortality.

Patients infected with schistosomes may develop a clinical picture of chronic salmonellosis. We have investigated the altered function of macrophages capable of playing a role in the development of chronic salmonellosis associated with Schistosoma mansoni in an experimental model. The capacity of mouse peritoneal macrophages to ingest and kill Salmonella was assessed in mice infected with S. mansoni with or without concurrent Salmonella typhimurium infection. Schistosomiasis was associated with a significant decrease in the phagocytic index of macrophages, due to the reduced number of cells engaged in phagocytosis. However, the number of bacteria ingested by these cells was comparable to that of the control group. The bactericidal capacity of macrophages from S. mansoni-infected mice was also significantly lower than that of cells from normal mice. Macrophages from animals infected only with Salmonella typhimurium showed an increased phagocytic capacity. It was concluded that S. mansoni infection alters phagocytosis and intracellular destruction of salmonellae. This demonstration of a novel mechanism of survival of salmonellae represents a step forward in understanding the pathogenesis and management of chronic septicemic salmonellosis.

Chronic septicemic salmonellosis is an individualized clinical entity characterized by prolonged fever with enlargement of the liver and spleen that occurs in Schistosoma-infected individuals who are coinfected with Salmonella. Several immunopathogenic mechanisms are involved, and they depend on the peculiarities of the interactions between Salmonella and various species of the genus Schistosoma. The modifications to the immune system that are caused by parasite infection are responsible for the evolution of the disease. In this review, we analyze the evolution of the knowledge on this entity and discuss the possible immuno-physiopathogenic mechanisms that contribute towards its development.

Monocytes/macrophages play a critical role in the defense mechanisms against malaria parasites, and are the main cells responsible for the elimination of malaria parasites from the blood circulation. We carried out a microscope-aided evaluation of the stages of in vitro phagocytosis of Plasmodium falciparum-infected erythrocytes, by human monocytes. These cells were obtained from healthy adult individuals by means of centrifugation through a cushion of Percoll density medium and were incubated with erythrocytes infected with Plasmodium falciparum that had previously been incubated with a pool of anti-plasmodial immune serum. We described the stages of phagocytosis, starting from adherence of infected erythrocytes to the phagocyte membrane and ending with their destruction within the phagolisosomes of the monocytes. We observed that the different erythrocytic forms of the parasite were ingested by monocytes, and that the process of phagocytosis may be completed in around 30 minutes. Furthermore, we showed that phagocytosis may occur continuously, such that different phases of the process were observed in the same phagocyte.

The Amazon region is known for a high prevalence of hepatitis B infection, and accounts for more than 90% of malaria cases in Brazil. It has been suggested that the occurrence of coinfections may be important, and may influence the natural history of both diseases. This study evaluated 545 patients with acute malaria, in Coari, Western Brazilian Amazon. 333 (61.1%) presented Plasmodium vivax malaria, 193 (35.4%) Plasmodium falciparum and 19 (3.5%) mixed infections. The HBsAg prevalence was 4.2% and total anti-HBc 49.7%. Patients with HBV serological markers presented no clinical differences than those with malaria only, nor showed any association with classic signs of hepatic disorder. Although showing no statistical significance, HBsAg reactive subjects presented lower parasitic load and higher antibody titers, suggesting the possibility that the immune response in a coinfected individual is differentiated and leads to a variation in the parasite load and antibody production.

Made available in DSpace on 2016-10-10T03:53:04Z (GMT). No. of bitstreams: 5 Inhibition of nitric oxide production by macrophages in chromoblastomycosis_ a role for Fonsecaea pedrosoi melanin.pdf: 358906 bytes, checksum: 733f49bffbe71e638ac4e7010aac38ca (MD5) license_url: 52 bytes, checksum: 2f32edb9c19a57e928372a33fd08dba5 (MD5) license_text: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) license_rdf: 24623 bytes, checksum: 378d22d8fe50e084ee2f354be78cbe62 (MD5) license.txt: 1887 bytes, checksum: 445d1980f282ec865917de35a4c622f6 (MD5) Previous issue date: 2006 Chromoblastomycosis is a chronic and progressive deep mycosis that is usually found in tropical and subtropical areas. Fonsecaea pedrosoi is considered its most frequent etiologic agent and causes a typical granulomatous inflammatory response, whose degree reflects the immune status of the host. Since macrophages play a fundamental role in the control of the infection, this study aimed at investigating the production of oxygen reactive specimens, the phagocytic capacity and the production of nitric oxide (NO) by macrophages employing in vitro assays and an in vivo model of chromoblastomycosis. Our results demonstrated that, during the infection, peritoneal macrophages show an increased phagocytic capacity and H2O2 production, but also a reduced ability to produce NO. Moreover, F. pedrosoi stimulated H2O2 production in vitro but not the synthesis of NO. The incubation of IFNc and LPS-stimulated macrophages with melanin, obtained from the fungus, inhibited NO production. Examination of the liver and spleen of infected animals, at day 30 or 60 following inoculation, showed a progressive increase in the number and size of granulomas, indicating that macrophages are properly mobilized and activated. Our data suggest that the inability of the host to clear F. pedrosoi, leading to a chronic disease, is due, at least in part, to the inhibition of NO synthesis by macrophages by fungus-produced melanin. Sim Publicado

The Amazon region is known for the high occurrence of hepatitis B virus (HBV) infection, and accounts for more than 98% of malaria cases in Brazil. Despite the controversy, it has been proposed that when associated they may lead to important effects in the natural history of both infections. This study estimates the prevalence of coinfection within general population of an endemic region of HBV and malaria in the Brazilian Amazon. The prevalence of HBsAg was 3.3% (95% CI 2.1%-5.1%,) and total anti-HBc 49.9% (95% CI 45.9%-53.8%). The prevalence of antibodies against Plasmodium vivax and Plasmodium falciparum antigens was 51.4% (311/605) (95% CI 47.3%-55.4%). Related to the simultaneous presence of malaria antibodies and HBV serological markers, in 1.8% (11/605), (95% CI 1.0%-3.3%), the presence of HBsAg was also demonstrated, mean age 26 years (p0.001). This study points to similarities in the distribution of these diseases, such as the occurrence mainly among young adults. The events may occur in different times. Also shown differences such as the low risk of malaria in the group up to fifteen years, where HBV circulates with moderate intensity. The prevalence of HBV and malaria coinfection is in fact less than the rates of HBsAg carriage, showing a heterogeneous pattern related to the clinical spectrum of HBV infection.

Malaria remains a major cause of morbidity and mortality in vast areas of the world, mainly due to the severe forms of Plasmodium falciparum infection. The exacerbated immune response, with increased production of TNF and reactive nitrogen and oxygen intermediates, plays a role in the complex pathogenesis of the disease. It is recognised that thalidomide decreases TNF production and may modulate several functions of the immune system. This work evaluated the influence of thalidomide on macrophage functions, and its ability to protect against severe disease. Plasmodium berghei ANKA-infected mice were (n = 11) or were not (n = 10) intra-gastric treated with thalidomide (150 mg/kg per day), and two other control groups not infected with the parasite were (n = 8) or were not (n = 10) treated with the drug, and macrophage production of hydrogen peroxide and nitric oxide, and phagocytosis were assessed on the eighth day post-infection. Thalidomide increased the survival time of infected mice, in parallel with a 26.5% increase of the mean of macrophage phagocytic index, and augmented in 13% the mean of the production of hydrogen peroxide and in 45% the mean of nitric oxide production by macrophages related to the non-treated P. berghei-infected mice. Our data indicate that thalidomide improves the outcome of P. berghei ANKA-infected CBA mice and suggest that this drug could represent a new alternative to be associated to antimalarial drugs to decrease the morbidity and mortality of severe malaria in non-pregnant individuals.

It has been shown that administration of TNF-alpha causes an increase of survival of plasmodium-infected mice. However, this anti-parasitic effect cannot be reproduced in vitro upon direct incubation of the cytokine with the parasite. This suggests that TNF-alpha may act through modulation of some plasmodicidal mechanism not yet clarified. We evaluated the effect of exogenous TNF-alpha on the phagocytosis of Plasmodium falciparum-infected erythrocytes by monocytes and its influence on the ability of monocytes and lymphocytes to inhibit parasite growth. The capacity of endogenous TNF-alpha to influence the ability of monocytes to inhibit the parasite was also verified. We found that addition of 33 ng TNF-alpha/mL to cultures of human monocytes and P. falciparum-infected erythrocytes increased the phagocytic index from 3.8 to 7.8 in the presence of serum containing P. falciparum antibody. TNF-alpha increased the capacity of monocyte plus lymphocyte to inhibit parasite growth by about 3 times at 0.5 and 5 ng/mL. Sera from severely ill P. falciparum-infected individuals inhibited the parasite growth, but addition of anti-TNF-alpha antibody was unable to modify this inhibition. These data show that TNF-alpha can increase the phagocytic capacity. This was probably due to an increased expression of Fc receptors on monocytes or to the modulation of Fc receptor signaling pathways by signals originating from the binding of TNF-alpha to its receptors. TNF-alpha also acted on lymphocytes plus monocytes by increasing the inhibition of P. falciparum by a mechanism not related to phagocytosis. These findings suggest that TNF-alpha has a pleiotropic anti-malaria effect and that this protective effect depends on the interplay of different factors, such as monocytes/macrophages, lymphocytes, and antibodies, in addition to other cells and molecules.

In this study we show that antigen-specific lymphocyte proliferation and interleukin (IL)-2 production by peripheral blood lymphocytes from patients under thiopental anesthesia are significantly depressed. In contrast, mitogen-induced lymphocyte proliferation and IL-2 secretion are not depressed. We have also shown that tetanus toxoid (TT) specific CD4+ T cell clones, with a known cytokine production profile, were sensitive to the inhibitory effects of thiopental and exhibited decreased proliferation to TT as well as decreased secretion of IL-2. We observed no difference regarding IL-4 production by these clones. The data suggest that the immunosuppressive effect of thiopental is confined to antigen-specific responses. In addition, we have shown that whereas IL-2 and interferon-γ production is dramatically impaired by the drug, IL-4 production is not significantly altered. This last finding has important implications regarding the type of immune response that is most affected by this anesthetic agent. In spite of the transient decrease in antigen-driven IL-2 synthesis, no clinical evidence of infection was noted in any healthy patient.

O presente artigo descreve a população de estudo e o desenho do ensaio de campo de fase III da vacina sintética SPf66 no Brasil. São avaliados os princípios básicos de validade e precisão, essenciais para a estimação adequada da eficácia vacinal. Os resultados da análise exploratória de dados são discutidos assim como, a abordagem analítica para a estimação da eficácia vacinal. Este trabalho fornece o marco conceitual para futuras publicações. ___________________________________________________________________________________________________________ ABSTRACT This paper describes the study population and the study design of the phase III field trial of the SPf66 vaccine in Brazil. Assessment of validity and precision principles necessary for the appropriate evaluation of the protective effect of the vaccine are discussed, as well as the results of the preliminary analyses of the gathered data. The analytical approach for the estimation of the protective effect of the vaccine is presented. This paper provides the conceptual framework for future publications.

Source Citation Croft AM, Garner P. Mefloquine for preventing malaria in non-immune adult travellers. Cochrane Database Syst Rev. 2001;(1):CD000138 (latest version 28 Aug 2000). 11034675

Fazendo determinações dos níveis de transamino.se sérica (T-GP e T-GO) em Cebus apella, antes e após inoculação de Schistosoma manroni e após terapêutica pelo aminonitrotiazol, os autores puderam observar, antes da inoculação, os seguinces valores: T-GP = 28.3, T-GO = 24,7. Os desvios padrões foram respectivamente de 11,2 e 11,3 e os valores extremos variaram para T-GO 10 e 60 µF e entre 15 e 57 µF para T-GP. Após inoculação, em apenas 1 caso puderam observar, 81 dias após, um valor para T-GP de 70 µF que pode ser considerado como discretamente aumentado. Não encontraram alterações após terapêutica pelo Cl 32.644 Ba (Aminonitrotiazol). The authors studied transaminase leveis (G-OT and G-PT) in the serum of 25 monkeys (Cebus apella) before and after variable periods of infections with S. mansoni and after treatment with aminonitrotiazol (Ambilhar). The average leveis in non infected monkeys were 28.3 units (Reitman & Frankel method) to G-PT and 24,7 units to G-OT with standard deviation of 11,2 and 11,3 respectively. The extreme values were 10 and 60 to G-OT and 15 and 57 to G-PT in this qroup. In the infected group only one monkey had an abnormal levei of transaminase (70 units to G-PT) which appeared 81 days after inoculation with cercariae of S mansoni. No change was found in the transaminase leveis of treated animais.

This paper reports the efficacy results of the randomized, placebo-controlled, field trial of SPf66 malaria vaccine in Costa Marques, Rondonia, Brazil. This region is characterized by the seasonal distribution of Plasmodium falciparum and P. vivax infections, and the recent occupation by migrants from nonendemic areas. A total of 800 individuals of both sexes, ranging in age from seven to 60 years, were included in the study. Of the initial cohort, 572 participants completed the vaccination schedule. Clinical and parasitologic evaluations were obtained by active and passive searches on a periodic basis. The overall protective efficacy against P. falciparum infections was -1.6% (-32.9% to 22.4%), and 14.1% (-17.0% to 36.9%) for the first episode. The overall protective efficacy for P. vivax infections was -19.7% (-44.8% to 1.03%), and -10.8% (-41.1% to 12.8%) for the first episode. No statistical evidence of an overall significant protective effect of SPf66 malaria vaccine against P. falciparum and P. vivax malaria was obtained in this trial.The efficacy of the SPf66 malaria vaccine was evaluated in a randomized, placebo-controlled, field trial in Costa Marques, Rondonia, Brazil; a region characterized by seasonal Plasmodium falciparum and P. vivax infections and a recent influx of migrants from nonendemic areas. This vaccine is composed of sequences of 3 peptides from P. falciparum merozoite, erythrocytic stages, and a peptide from the circumsporozoite protein. Enrolled were 800 predominantly migrant men and women, 7-60 years of age, 572 of whom completed the vaccination schedule. Clinical and parasitologic evaluations were obtained by periodic active and passive searches up to Day 720. After the third dose, 5684 blood samples were collected and 967 (520 in the vaccine group and 447 in the placebo group) were positive. 212 P. falciparum infections (107 episodes in 76 participants in the vaccine group and 105 in 85 members of the placebo group) were confirmed after exclusion of relapses and treatment failures. A total of 427 P. vivax infections were detected (233 in 138 participants in the vaccine group and 194 in 127 participants in the placebo group). The overall protective efficacy against P. falciparum infections was -1.6% (95% confidence interval (CI), -32.9-22.4%) and 14.1% (95% CI, -17.0-36.9%) for the first episode. The overall protective efficacy for P. vivax infections was -19.7% (95% CI, -44.8-1.03%) and -10.8% (95% CI, -41.1-12.8%) for the first episode. These findings fail to provide evidence of an overall significant protective effect of the SPf66 malaria vaccine in this population.