RESUMEN
BACKGROUND: Severe outcomes have been described for both Plasmodium falciparum and P. vivax infections. The identification of sensitive and reliable markers of disease severity is fundamental to improving patient care. An intense pro-inflammatory response with oxidative stress and production of reactive oxygen species is present in malaria. Inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and antioxidant agents such as superoxide dismutase-1 (SOD-1) are likely candidate biomarkers for disease severity. Here we tested whether plasma levels of SOD-1 could serve as a biomarker of severe vivax malaria. METHODOLOGY/PRINCIPAL FINDINGS: Plasma samples were obtained from residents of the Brazilian Amazon with a high risk for P. vivax transmission. Malaria diagnosis was made by both microscopy and nested PCR. A total of 219 individuals were enrolled: non-infected volunteers (n = 90) and individuals with vivax malaria: asymptomatic (n = 60), mild (n = 50) and severe infection (n = 19). SOD-1 was directly associated with parasitaemia, plasma creatinine and alanine amino-transaminase levels, while TNF-alpha correlated only with the later enzyme. The predictive power of SOD-1 and TNF-alpha levels was compared. SOD-1 protein levels were more effective at predicting vivax malaria severity than TNF-alpha. For discrimination of mild infection, elevated SOD-1 levels showed greater sensitivity than TNF-alpha (76% vs. 30% respectively; p<0.0001), with higher specificity (100% vs. 97%; p<0.0001). In predicting severe vivax malaria, SOD-1 levels exhibited higher sensitivity than TNF-alpha (80% vs. 56%, respectively; p<0.0001; likelihood ratio: 7.45 vs. 3.14; p<0.0001). Neither SOD-1 nor TNF-alpha could discriminate P. vivax infections from those caused by P. falciparum. CONCLUSION: SOD-1 is a powerful predictor of disease severity in individuals with different clinical presentations of vivax malaria.
Asunto(s)
Malaria Vivax/diagnóstico , Malaria Vivax/patología , Superóxido Dismutasa/sangre , Adolescente , Adulto , Animales , Biomarcadores , Brasil , Femenino , Humanos , Masculino , Microscopía , Persona de Mediana Edad , Parasitemia , Plasma/química , Plasmodium vivax/inmunología , Plasmodium vivax/aislamiento & purificación , Reacción en Cadena de la Polimerasa , Valor Predictivo de las Pruebas , Pronóstico , Superóxido Dismutasa-1 , Adulto JovenRESUMEN
Resistance to infection by Leishmania major has been associated with the development of a Th1 type response that is dependent on the presence of interleukin 12 (IL-12). In this work the involvement of this cytokine in the response to infection by L. braziliensis, a less virulent species in the mouse model, was evaluated. Our results show that while interferon (IFN-gamma) deficient (-/-) mice inoculated L. braziliensis develop severe uncontrolled lesions, chronic lesions that remained under control up to 12 weeks of infection were observed in IL-12p40 -/- mice. IL 12p40 -/- mice had fewer parasites in their lesions than IFN-gamma (-/-) mice. Lymph node cells from IL-12p40 -/- were capable of producing low but consistent levels of IFN-gamma suggestive of its involvement in parasite control. Furthermore, as opposed to previous reports on L. major-infected animals, no switch to a Th2 response was observed in IL-12p40 -/- infected with L. braziliensis.
Asunto(s)
Interferón gamma/inmunología , Interleucina-12/deficiencia , Leishmania braziliensis/inmunología , Leishmaniasis Cutánea/inmunología , Subunidades de Proteína/deficiencia , Animales , Modelos Animales de Enfermedad , Femenino , Interferón gamma/biosíntesis , Interleucina-12/biosíntesis , Interleucina-12/inmunología , Subunidad p40 de la Interleucina-12 , Masculino , Ratones , Ratones Endogámicos C57BL , Subunidades de Proteína/biosíntesis , Subunidades de Proteína/inmunología , Factores de TiempoRESUMEN
Resistance to infection by Leishmania major has been associated with the development of a Th1 type response that is dependent on the presence of interleukin 12 (IL-12). In this work the involvement of this cytokine in the response to infection by L. braziliensis, a less virulent species in the mouse model, was evaluated. Our results show that while interferon (IFN-gamma) deficient (-/-) mice inoculated L. braziliensis develop severe uncontrolled lesions, chronic lesions that remained under control up to 12 weeks of infection were observed in IL-12p40 -/- mice. IL 12p40 -/- mice had fewer parasites in their lesions than IFN-gamma-/- mice. Lymph node cells from IL-12p40 -/- were capable of producing low but consistent levels of IFN-gamma suggestive of its involvement in parasite control. Furthermore, as opposed to previous reports on L. major-infected animals, no switch to a Th2 response was observed in IL-12p40 -/- infected with L. braziliensis.