RESUMEN
Background: Patients with active visceral leishmaniasis are important reservoirs in the anthroponotic transmission cycle of Leishmania donovani. The role of the blood or skin as a source of infection to sand flies remains unclear, and the possible effect of multiple exposures to fly bites on transmissibility has not been addressed. Methods: L. donovani-infected hamsters underwent xenodiagnoses with Lutzomyia longipalpis on the same or different sites on the abdomen on 2 consecutive days or by artificial feeding on the skin or blood. Results: The transmission of L. donovani from sick hamsters to flies was surprisingly low (mean, 24% of fed flies). New flies fed on the same site acquired significantly more infections (mean, 61%; P < .0001). By artificial feeding, flies could acquire infection from blood and skin. However, only artificial feeding on blood produced infections that correlated with the natural feeding (R = 0.792; P < .0001). Infections acquired from blood increased dramatically for blood obtained after exposure to bites, as did the parasitemia level and the number of monocytes in the circulation. Conclusions: The bites of uninfected sand flies favor the transmissibility of L. donovani by infected hosts, owing to a systemic effect that exposure to bites has on the parasitemia. Patients with active visceral leishmaniasis are important reservoirs in the anthroponotic transmission cycle of Leishmania donovani. Using the hamster model of visceral disease, we demonstrate that prior exposure to bites of uninfected sand flies potentiates their ability to transmit infection to the vector.
Asunto(s)
Mordeduras y Picaduras de Insectos/parasitología , Leishmaniasis Visceral/transmisión , Psychodidae/parasitología , Piel/parasitología , Animales , Cricetinae/parasitología , Femenino , Insectos Vectores/parasitología , Leishmania donovani , Recuento de Leucocitos , Masculino , Carga de Parásitos , Saliva/parasitologíaRESUMEN
BACKGROUND: A falsely high cerebrospinal fluid (CSF) total protein (TP) result measured by pyrogallol red (PGR) method was suspected to be caused by preparation of the collection site with povidone-iodine (PVP-iodine) solution. METHODS: CSF TP was evaluated for interference in samples with different final concentrations of PVP-iodine (up to 0.25% PVP and 0.025% iodine) or iodine alone (up to 0.025% iodine) using three methods: PGR, modified biuret and benzethonium chloride (BZTC). Interference exceeding ±20% of the baseline value is considered clinically significant according to the criterion defined by the College of American Pathologists. RESULTS: There were positive interference with the PGR method and negative inference for the BZTC method in CSF samples spiked with PVP-iodine. The PVP-iodine (up to 0.25% PVP and 0.025% iodine) did not cause a clinically significant interference with the modified biuret method. PVP alone without iodine caused a positive interference with the PGR method but did not interfere with the modified biuret or the BZTC method. When the samples were spiked with iodine alone, none of the three methods was affected (change<20%) by iodine concentration up to 0.025%. CONCLUSIONS: Contamination of CSF specimens with PVP-iodine can lead to interference with CSF TP measurements using PGR or BZTC methods.
Asunto(s)
Proteínas del Líquido Cefalorraquídeo/análisis , Química Clínica/métodos , Povidona Yodada , Manejo de Especímenes/métodos , Artefactos , Bencetonio , Pruebas de Química Clínica/métodos , Humanos , Pirogalol/análogos & derivados , Espectrofotometría/métodosRESUMEN
Despite decades of research and multiple initiatives, malaria continues to be one of the world's most debilitating infectious diseases. New insights for malaria control and vaccine development will be essential to thwart the staggering worldwide impact of this disease (A. Bjorkman and A. Bhattarai, Acta Trop. 94:163-169, 2005); ultimately successful vaccine strategies will undoubtedly be multifactorial, incorporating multiple antigens and targeting diverse aspects of the malaria parasites' biology (M. F. Good et al., Immunol. Rev. 201:254-267, 2004). Using a murine model of malaria infection, we show here that exposure to bites from uninfected mosquitoes prior to Plasmodium yoelii infection influences the local and systemic immune responses and limits parasite development within the host. In hosts preexposed to bites from uninfected mosquitoes, reduced parasite burdens in the livers were detected early, and during the blood-stage of the life cycle, these burdens remained lower than those in hosts that received mosquito bites only at the time of infection. Repeated exposure to bites from uninfected mosquitoes skewed the immune response towards a T-helper 1 (Th1) phenotype as indicated by increased levels of interleukin-12, gamma interferon, and inducible nitric oxide synthase. These data suggest that the addition of mosquito salivary components to antimalaria vaccines may be a viable strategy for creating a Th1-biased environment known to be effective against malaria infection. Furthermore, this strategy may be important for the development of vaccines to combat other mosquito-transmitted pathogens.
Asunto(s)
Anopheles/inmunología , Mordeduras y Picaduras de Insectos/inmunología , Malaria/inmunología , Plasmodium yoelii/patogenicidad , Saliva/inmunología , Animales , Hígado/inmunología , Hígado/parasitología , Malaria/parasitología , Malaria/prevención & control , Ratones , Ratones Endogámicos BALB C , Saliva/química , Bazo/inmunología , Bazo/parasitología , Células TH1/inmunologíaRESUMEN
Ischemia-reperfusion injury (IRI) represents a major determinant of liver transplantation. IRI-induced graft dysfunction is related to biliary damage, partly due to a loss of bile canaliculi (BC) integrity associated with a dramatic remodeling of actin cytoskeleton. However, the molecular mechanisms associated with these events remain poorly characterized. Using liver biopsies collected during the early phases of organ procurement (ischemia) and transplantation (reperfusion), we characterized the global patterns of expression and phosphorylation of cytoskeleton-related proteins during hepatic IRI. This targeted functional proteomic approach, which combined protein expression pattern profiling and phosphoprotein enrichment followed by mass spectrometry analysis, allowed us to identify IQGAP1, a Cdc42/Rac1 effector, as a potential regulator of actin cytoskeleton remodeling and maintenance of BC integrity. Cell fractionation and immunohistochemistry revealed that IQGAP1 expression and localization were affected upon IRI and related to actin reorganization. Furthermore using an IRI model in human hepatoma cells, we demonstrated that IQGAP1 silencing decreased the basal level of actin polymerization at BC periphery, reflecting a defect in BC structure coincident with reduced cellular resistance to IRI. In summary, this study uncovered new mechanistic insights into the global regulation of IRI-induced cytoskeleton remodeling and led to the identification of IQGAP1 as a regulator of BC structure. IQGAP1 therefore represents a potential target for the design of new organ preservation strategies to improve transplantation outcome.