Pravastatin modulates macrophage functions of Leishmania (L.) amazonensis-infected BALB/c mice.

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.

[Schistosoma-associated chronic septicemic salmonellosis: evolution of knowledge and immunopathogenic mechanisms]. / Salmonelose septicêmica prolongada associada à esquistossomose: evolução do conhecimento e mecanismos imunopatogênicos.

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.

Salmonelose septicêmica prolongada associada à esquistossomose: evolução do conhecimento e mecanismos imunopatogênicos: [revisão] / Schistosoma-associated chronic septicemic salmonellosis: evolution of knowledge and immunopathogenic mechanisms: [review]

A salmonelose septicêmica prolongada é uma entidade clinicamente individualizada caracterizada por febre prolongada com hepatoesplenomegalia que ocorre em indivíduos esquistossomóticos coinfectados com salmonelas. Os mecanismos imunopatogênicos são vários e dependem das peculiaridades das interações entre as salmonelas e várias espécies do gênero Schistosoma. As modificações ocasionadas no sistema imunitário pela infecção parasitária são responsáveis pela evolução do quadro da doença. Nesta revisão, analisamos a evolução do conhecimento sobre a entidade e discutimos os possíveis mecanismos imunofisiopatogênicos que concorrem para seu desenvolvimento.

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.

Stages of in vitro phagocytosis of Plasmodium falciparum-infected erythrocytes by human monocytes.

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.

Stages of in vitro phagocytosis of Plasmodium falciparum-infected erythrocytes by human monocytes / Estágios da fagocitose in vitro por monócitos humanos de eritrócitos infectados por Plasmodium falciparum

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.

Monócitos/macrófagos desempenham uma função crítica nos mecanismos de defesa antiplasmódio e constituem as principais células responsáveis pela eliminação das formas eritrocitárias do plasmódio da circulação sangüínea. Realizamos uma avaliação microscópica dos estágios da fagocitose in vitro de eritrócitos infectados por Plasmodium falciparum por monócitos humanos. Essas células foram obtidas de indivíduos adultos sadios por centrifugação em Percoll e incubadas com eritrócitos infectados por Plasmodium falciparum previamente incubados com um pool de soro imune contra plasmódio. Descrevemos os estágios da fagocitose, desde a aderência dos eritrócitos infectados até sua destruição nos fagolisossomas dos monócitos. Observou-se que eritrócitos infectados por todos os diferentes estágios assexuados do parasito foram ingeridos pelos monócitos e que o processo de fagocitose pode se completar em cerca de 30 minutos. Além disso, mostramos que a fagocitose pode ocorrer de uma forma contínua, de tal maneira que diferentes fases do processo foram observadas no mesmo fagócito.

Coadaptation and malaria control.

Malaria emerges from a disequilibrium of the system 'human-plasmodium-mosquito' (HPM). If the equilibrium is maintained, malaria does not ensue and the result is asymptomatic plasmodium infection. The relationships among the components of the system involve coadaptive linkages that lead to equilibrium. A vast body of evidence supports this assumption, including the strategies involved in the relationships between plasmodium and human and mosquito immune systems, and the emergence of resistance of plasmodia to antimalarial drugs and of mosquitoes to insecticides. Coadaptive strategies for malaria control are based on the following principles: (1) the system HPM is composed of three highly complex and dynamic components, whose interplay involves coadaptive linkages that tend to maintain the equilibrium of the system; (2) human and mosquito immune systems play a central role in the coadaptive interplay with plasmodium, and hence, in the maintenance of the system's equilibrium; the under- or overfunction of human immune system may result in malaria and influence its severity; (3) coadaptation depends on genetic and epigenetic phenomena occurring at the interfaces of the components of the system, and may involve exchange of infectrons (genes or gene fragments) between the partners; (4) plasmodia and mosquitoes have been submitted to selective pressures, leading to adaptation, for an extremely long while and are, therefore, endowed with the capacity to circumvent both natural (immunity) and artificial (drugs, insecticides, vaccines) measures aiming at destroying them; (5) since malaria represents disequilibrium of the system HPM, its control should aim at maintaining or restoring this equilibrium; (6) the disequilibrium of integrated systems involves the disequilibrium of their components, therefore the maintenance or restoration of the system's equilibrium depend on the adoption of integrated and coordinated measures acting on all components, that means, panadaptive strategies. Coadaptive strategies for malaria control should consider that: (1) host immune response has to be induced, since without it, no coadaptation is attained; (2) the immune response has to be sustained and efficient enough to avoid plasmodium overgrowth; (3) the immune response should not destroy all parasites; (4) the immune response has to be well controlled in order to not harm the host. These conditions are mostly influenced by antimalarial drugs, and should also be taken into account for the development of coadaptive malaria vaccines.

Coadaptation and malaria control

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

Dynamics and kinetics of natural killer cell cytotoxicity in human malaria as evaluated by a novel stepwise cytotoxicity assay.

Malaria causes important functional alterations of the immune system, but several of them are poorly defined. To evaluate thoroughly the natural killer cell cytotoxicity in patients with malaria, we developed a technique capable to assess both the dynamics and the kinetics of the process. For the kinetics assay, human peripheral blood mononuclear cells were previously incubated with K562 cells and kept in agarose medium, while for the dynamics assay both cells were maintained in suspension. NK activity from patients with vivax malaria presented a kinetics profile faster than those with falciparum malaria. NK cytotoxicity positively correlated with parasitemia in falciparum malaria. The dynamics of NK cytotoxicity of healthy individuals was elevated at the beginning of the process and then significantly decreased. In contrast, malaria patients presented successive peaks of NK activity. Our results confirmed the occurrence of alteration in NK cell function during malaria, and added new data about the NK cytotoxicity process.

O coração em portadores do vírus da hepatite C: avaliação Dopplerecocardiográfica / Cardiac morphofunctional injuries in patients with hepatitis C virus: doppler echocardiographic evaluation

OBJETIVO: Avaliar possíveis alterações morfofuncionais cardíacas em portadores crônicos do vírus da hepatite C pela Dopplerecocardiografia. MÉTODOS: Estudo observacional caso-controle com análise de parâmetros Dopplerecocardiográficos de 31 pacientes portadores crônicos do vírus da hepatite C numa fase não avançada da doença, diagnosticados por biópsia (sem cirrose, carcinoma hepatocelular ou disfunção hepática) e 20 casos-controle. RESULTADOS: Não houve diferenças estatisticamente significantes da espessura parietal, diâmetros cavitários, fração de ejeção, encurtamento circunferencial e nas velocidades de fluxo mitral e teciduais sistólica e diastólica do anel mitral entre os dois grupos estudados. CONCLUSÃO: Nas fases não avançadas, portadores do vírus da hepatite C não apresentaram alterações morfo-funcionais cardíacas, sob análise do ventrículo esquerdo.

OBJECTIVE: To evaluate the possible morphological and functional heart injuries in hepatitis C virus patients. METHODS: Control-case study analyzing Doppler echocardiographic aspects in 31 hepatitis C virus patients and 20 controls. RESULTS: There were no significant difference in relation to the myocardial thickening, left ventricular diameters, circumferential shortening, ejection fraction, mitral valve flow velocities, tissue sistolic and diastolic mitral annular ones. CONCLUSION: Individuals with hepatitis C virus in the initial phases of the disease did not show morpho-functional abnormalities of the heart when evaluated by doppler echocardiography.

Dynamics and kinetics of natural killer cell cytotoxicity in human malaria as evaluated by a novel stepwise cytotoxicity assay

Malaria causes important functional alterations of the immune system, but several of them are poorly defined. To evaluate thoroughly the natural killer cell cytotoxicity in patients with malaria, we developed a technique capable to assess both the dynamics and the kinetics of the process. For the kinetics assay, human peripheral blood mononuclear cells were previously incubated with K562 cells and kept in agarose medium, while for the dynamics assay both cells were maintained in suspension. NK activity from patients with vivax malaria presented a kinetics profile faster than those with falciparum malaria. NK cytotoxicity positively correlated with parasitemia in falciparum malaria. The dynamics of NK cytotoxicity of healthy individuals was elevated at the beginning of the process and then significantly decreased. In contrast, malaria patients presented successive peaks of NK activity. Our results confirmed the occurrence of alteration in NK cell function during malaria, and added new data about the NK cytotoxicity process.

A malária causa importantes alterações do sistema imunitário, muitas ainda mal definidas. Para permitir uma avaliação abrangente da atividade citotóxica das células natural killer em pacientes com malária, desenvolvemos um teste capaz de avaliar concomitantemente a dinâmica e a cinética do processo. Para a avaliação da cinética, células mononucleares do sangue periférico interagiram com células K562 e foram mantidas em agarose, enquanto para avaliar a dinâmica as células eram mantidas em suspensão. A cinética da atividade citotóxica das células NK foi mais rápida em pacientes com Plasmodium vivax, do que naqueles infectados com P. falciparum. Nestes, houve correlação positiva entre a atividade citotóxica das células NK e a parasitemia. O padrão da dinâmica da atividade citotóxica nos pacientes com malária foi bem diferente daquele apresentado pelos indivíduos sadios. Enquanto nestes, a atividade estava muito aumentada no início da incubação das células, sofrendo posteriormente uma redução, nos indivíduos infectados foram detectados sucessivos picos de atividade citotóxica. Nossos resultados confirmam a ocorrência de alteração funcional das células NK na malária humana e acrescentam novos dados sobre a dinâmica e a cinética da atividade citotóxica.

Inhibition of nitric oxide production by macrophages in chromoblastomycosis: a role for Fonsecaea pedrosoi melanin.

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 IFNgamma 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.

[Coinfection between hepatitis B virus and malaria: clinical, serologic and immunologic aspects]. / Co-infecção humana pelo plasmódio e o vírus da hepatite B: aspectos clínicos, sorológicos e imunológicos.

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.

Co-infeccão humana pelo plasmódio e o vírus da hepatite B: aspectos clínicos, sorológicos e imunológicos / Coinfection between hepatitis B virus and malaria: clinical, serologic and immunologic aspects

A Amazônia é conhecida pela elevada prevalência de infeccão pelo vírus da hepatite B, contribui também com mais de 90 por cento dos casos de malária do país. É proposto que a ocorrência de co-infeccões seja importante e que na associacão ocorram alteracões na história natural dessas enfermidades. O estudo avalia 545 pacientes com malária, em Coari, AM: 333 (61,1 por cento) pelo Plasmodium vivax, 193 (35,4 por cento) pelo Plasmodium falciparum e 19 (3,5 por cento) com infeccão mista. A prevalência do AgHBs foi 4,2 por cento e a do anti-HBc total 49,7 por cento. Os pacientes sororreativos para o VHB, não apresentaram diferencas clínicas dos outros pacientes com malária, nem associacão a sinais clássicos de comprometimento hepático. Apesar de não ter sido detectada associacão estatisticamente significativa, os indivíduos AgHBs reativos apresentaram baixas parasitemias e índices de reatividade de anticorpos mais elevados, sugerindo a possibilidade da resposta imune em um indivíduo co-infectado ser diferenciada e favorecer variacões em relacão à parasitemia e producão de anticorpos.

Cardiac morphofunctional injuries in patients with hepatitis C virus: doppler echocardiographic evaluation.

OBJECTIVE: To evaluate the possible morphological and functional heart injuries in hepatitis C virus patients. METHODS: Control-case study analyzing Doppler echocardiographic aspects in 31 hepatitis C virus patients and 20 controls. RESULTS: There were no significant difference in relation to the myocardial thickening, left ventricular diameters, circumferential shortening, ejection fraction, mitral valve flow velocities, tissue sistolic and diastolic mitral annular ones. CONCLUSION: Individuals with hepatitis C virus in the initial phases of the disease did not show morpho-functional abnormalities of the heart when evaluated by Doppler echocardiography.

Soroprevalência da infecção pelo vírus da hepatite B e pelo plasmódio em Lábrea, Amazonas: estimativa da ocorrência de prováveis coinfecções / Seroprevalence of hepatitis B and malaria infection in Lábrea, Brazilian western Amazon: estimates of coinfection rates

A Amazônia é conhecida pela elevada ocorrência de hepatite B e suas seqüelas. Contribui também com mais de 98 por cento 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 por cento (IC 95 por cento 2,1 por cento a 5,1 por cento,), e a do anti-HBc total 49,9 por cento (IC 95 por cento 45,9 por cento a 53,8 por cento). A prevalência de anticorpos contra antígenos do Plasmodium vivax e Plasmodium falciparum foi de 51,4 por cento (311/605) (IC 95 por cento 47,3 por cento a 55,4 por cento). Em relação à presença simultânea de anticorpos contra antígenos do Plasmodium vivax e Plasmodium falciparum com marcadores do VHB, 1,8 por cento (11/605), (IC95 por cento 1,0 por cento a 3,3 por cento), apresentavam também o AgHBs, tendo estes em média 26 anos de idade (p<0,001). Este estudo aponta semelhanças na distribuição dessas enfermidades como, a ocorrência preferencialmente entre adulto jovens. Os eventos provavelmente ocorrem em momentos distintos. Mostra também diferenças como, o baixo risco de malária entre menores de quinze anos, onde o VHB circula com moderada intensidade. As taxas de coinfecções são provavelmente menores que as de portadores do AgHBs, apresentando padrão heterogêneo em relação ao espectro clínico da infecção pelo VHB.

[Seroprevalence of hepatitis B and malaria infection in Lábrea, Brazilian western Amazon: estimates of coinfection rates]. / Soroprevalência da infecção pelo vírus da hepatite B e pelo plasmódio em Lábrea, Amazonas: estimativa da ocorrência de prováveis coinfecções.

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 (p <0.001). 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.

Thalidomide influences the function of macrophages and increases the survival of Plasmodium berghei-infected CBA mice.

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.

Cross-sectional study defines difference in malaria morbidity in two Yanomami communities on Amazonian boundary between Brazil and Venezuela.

It is well established that immunity to malaria is short-lived and is maintained by the continuous contact with the parasite. We now show that the stable transmission of malaria in Yanomami Amerindian communities maintains a degree of immunity in the exposed population capable to reduce prevalence and morbidity of malaria. We examined 508 Yanomami Amerindians living along Orinoco (407) and Mucajaí (101) rivers, on the Venezuelan and Brazilian Amazon region, respectively. At Orinoco villages, malaria was hyperendemic and presented stable transmission, while at Mucajaí villages it was mesoendemic and showed unstable transmission. The frequency of Plasmodium vivax and P. falciparum was roughly comparable in Venezuelan and Brazilian communities. Malaria presented different profiles at Orinoco and Mucajaí villages. In the former communities, malaria showed a lower prevalence (16% x 40.6%), particularly among those over 10 years old (5.2% x 34.8%), a higher frequency of asymptomatic cases (38.5% x 4.9%), and a lower frequency of cases of severe malaria (9.2% x 36.5%). Orinoco villagers also showed a higher reactivity of the immune system, measured by the frequency of splenomegaly (72.4% x 29.7%) and by the splenic index (71.4% over level 1 x 28.6), and higher prevalence (91.1% x 72.1%) and mean titer (1243 x 62) of antiplasmodial IgG antibodies, as well as a higher prevalence (77.4% x 24.7%) and mean titer (120 x 35) of antiplasmodial IgM antibodies. Our findings show that in isolated Yanomami communities the stability of malaria transmission, and the consequent continuous activation of the immune system of the exposed population, leads to the reduction of malaria prevalence and morbidity.