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Sent on Wednesday, 2012 January 11Search: kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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| 1. | Proc Natl Acad Sci U S A. 2012 Jan 9. [Epub ahead of print]Critical role for phosphoinositide 3-kinase gamma in parasite invasion and disease progression of cutaneous leishmaniasis.Cummings HE, Barbi J, Reville P, Oghumu S, Zorko N, Sarkar A, Keiser TL, Lu B, Rückle T, Varikuti S, Lezama-Davila C, Wewers MD, Whitacre C, Radzioch D, Rommel C, Seveau S, Satoskar AR.SourceDepartment of Microbiology, Davis Heart and Lung Research Institute, and Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, Columbus, OH 43210. AbstractObligate intracellular pathogens such as Leishmania specifically target host phagocytes for survival and replication. Phosphoinositide 3-kinase γ (PI3Kγ), a member of the class I PI3Ks that is highly expressed by leukocytes, controls cell migration by initiating actin polymerization and cytoskeletal reorganization, which are processes also critical for phagocytosis. In this study, we demonstrate that class IB PI3K, PI3Kγ, plays a critical role in pathogenesis of chronic cutaneous leishmaniasis caused by L. mexicana. Using the isoform-selective PI3Kγ inhibitor, AS-605240 and PI3Kγ gene-deficient mice, we show that selective blockade or deficiency of PI3Kγ significantly enhances resistance against L. mexicana that is associated with a significant suppression of parasite entry into phagocytes and reduction in recruitment of host phagocytes as well as regulatory T cells to the site of infection. Furthermore, we demonstrate that AS-605240 is as effective as the standard antileishmanial drug sodium stibogluconate in treatment of cutaneous leishmaniasis caused by L. mexicana. These findings reveal a unique role for PI3Kγ in Leishmania invasion and establishment of chronic infection, and demonstrate that therapeutic targeting of host pathways involved in establishment of infection may be a viable strategy for treating infections caused by obligate intracellular pathogens such as Leishmania. |
| 2. | Am J Trop Med Hyg. 2012 Jan;86(1):119-21.Evaluation of serum procalcitonin levels for diagnosis of secondary bacterial infections in visceral leishmaniasis patients.Pasyar N, Alborzi A, Pouladfar GR.SourceProfessor Alborzi Clinical Microbiology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. AbstractAbstract. Secondary bacterial infections are a major complication and cause of death in children with visceral Leishmaniasis (VL). Thus, early diagnosis of bacterial infections is an important step in the treatment of patients with VL. The goal of this study was to determine if serum procalcitonin (PCT) could be used as a diagnostic marker of secondary bacterial infections in VL patients. Serum PCT was measured in 35 hospitalized patients with VL before treatment and after defervescence. The level was higher than normal (> 0.5 ng/mL) in 72% (25) of the patients. Twelve (34%) of 35 patients had secondary bacterial infections with PCT levels ranging from 0.1 to 12.29 ng/mL, and those without secondary bacterial infections (23) had PCT levels ranging from 0.1 to 14.58 ng/mL. The results suggest that PCT levels increase significantly in most VL patients but are not correlated with the presence of secondary bacterial infections. |
| 3. | Am J Trop Med Hyg. 2012 Jan;86(1):115-8.Epidemiology of imported cutaneous leishmaniasis at the hospital for tropical diseases, london, United kingdom: use of polymerase chain reaction to identify the species.Wall EC, Watson J, Armstrong M, Chiodini PL, Lockwood DN.SourceDepartment of Clinical Parasitology, Hospital for Tropical Diseases, London, United Kingdom; London School of Hygiene and Tropical Medicine, London, United Kingdom. AbstractAbstract. This study reviewed all patients diagnosed with imported cutaneous leishmaniasis (CL) at the Hospital for Tropical Diseases in London, United Kingdom, over an 11-year period. Diagnostic and epidemiologic information was collected prospectively for all patients with imported CL to this hospital during 1998-2009. A total of 223 patients were given a diagnosis of CL. Ninety patients were diagnosed with Old World CL, which was caused most commonly by Leishmania donovani complex (n = 20). A total of 71% were tourists to the Mediterranean region, 36% were migrants or visiting friends and relatives, and 17% were soldiers. One hundred thirty-three patients were given a diagnosis of New World CL. The Leishmania subgenus Viannia caused 97 of these cases; 44% of these were in backpackers and 29% were in soldiers. Polymerase chain reaction was more sensitive and faster for detecting Leishmania DNA (86% for Old World CL and 96% for New World CL) than culture. This is the largest study of imported leishmaniasis, and demonstrates that tourists to the Mediterranean and backpackers in Central and South America are at risk for this disease. |
| 4. | Am J Trop Med Hyg. 2012 Jan;86(1):108-14.American visceral leishmaniasis in chiapas, Mexico.Pastor-Santiago JA, Chávez-López S, Guzmán-Bracho C, Flisser A, Olivo-Díaz A.SourceDepartamento de Prevención y Control de Enfermedades Transmitidas por Vector, Tuxtla Gutiérrez, Chiapas, México; Departamento de Parasitología, Instituto de Diagnóstico y Referencia Epidemiológicos, México City, México; Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México, México City, México; Departamento de Biología Molecular e Histocompatibilidad, Hospital General Dr. Manuel Gea González, México City, México. AbstractAbstract. We report the results of a study conducted during 1990-2006 with 89 cases of American visceral leishmaniasis in Chiapas State in southeastern Mexico and a seroprevalence study performed with 726 persons and 224 dogs that lived near cases of American visceral leishmaniasis. Clinical aspects, epidemiologic profiles, and risk factors are described. Most cases were in children ≤ 5 years of age, the prevalence of seropositive persons was 77%. The main risk factors associated with this disease were having 1-3 rooms in a house compared with ≥ 4 rooms, having a roof that was not made of cement, and having domestic animals. In contrast, only 19% of dogs were seropositive, suggesting that this species is not important in the transmission cycle of Leishmania. These data indicate that active transmission is taking place in the central valley of Chiapas State, Mexico, in communities located < 1,000 meters above sea level near the Grijalva River. |
| 5. | Am J Trop Med Hyg. 2012 Jan;86(1):99-107.Leishmania infantum chagasi in Northeastern Brazil: Asymptomatic Infection at the Urban Perimeter.Lima ID, Queiroz JW, Lacerda HG, Queiroz PV, Pontes NN, Barbosa JD, Martins DR, Weirather JL, Pearson RD, Wilson ME, Jeronimo SM.SourceHealth Post-Graduate Program, Department of Infectious Diseases, Health Sciences Center, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil; Department of Biochemistry and Department of Biology and Genetics, Biosciences Center, Universidade Federal do Rio Grande do Norte Natal, RN, Brazil; Fundação Nacional de Saúde, Natal, RN, Brazil; Departments of Medicine and Pathology, University of Virginia, Charlottesville, Virginia; Interdisciplinary Graduate Program in Genetics, Departments of Internal Medicine, Microbiology, and Epidemiology, University of Iowa, Iowa City, Iowa; Veteran's Affairs Medical Center, Iowa City, Iowa; Instituto Nacional de Ciência e Tecnologia de Doenças Tropicais (INCT-DT/CNPQ/MCT), Brazil. AbstractAbstract. Visceral leishmaniasis (VL) is endemic in large cities in Brazil, including Natal. We determined the prevalence of asymptomatic human infection with Leishmania infantum chagasi and associated environmental risks around Natal. Infection was detected by Leishmania skin test (LST) and anti-leishmanial antibodies in humans and anti-leishmanial antibodies in dogs. Amongst 345 humans, 24.6% were seropositive, and 38.6% were LST-positive. Prevalence of positive serology was similar in both sexes and across all ages. However, positive LST responses increased with age, suggesting that LST is long-lasting and cumulative. Multinomial logistic analysis showed that LST response varied with location (P = 0.007) and that males were more frequently LST-positive (P = 0.027). Indicators of lower socioeconomic status associated significantly with human infection. Furthermore, there was geographic coincidence of seropositive humans and dogs (r = 0.7926, P = 0.011). These data suggest that dog and human L. i. chagasi infection are intimately interrelated in environmental conditions associated with low income. |
| 6. | Parasitol Res. 2012 Jan 10. [Epub ahead of print]Epidemiological implications of the use of various methods for the diagnosis of canine leishmaniasis in dogs with different characteristics and in differing prevalence scenarios.Morales-Yuste M, Morillas-Márquez F, Díaz-Sáez V, Barón-López S, Acedo-Sánchez C, Martín-Sánchez J.SourceDepartment of Parasitology, Faculty of Pharmacy, University of Granada, Granada, Spain. AbstractOur aim was to establish the influence on the prevalence of canine leishmaniasis (CanL) of the following: (1) the use of different diagnostic techniques; (2) different positivity thresholds; (3) selection of animals either at random from a population or focused on symptomatic individuals, (4) the function which the dog performs; and (5) scenarios with differing epidemiological characteristic. Three groups of dogs were analysed (416 sampled at random from an endemic area, 71 with symptomatology compatible with CanL and 15 from a non-endemic area) using three serological techniques (indirect fluorescence antibody test (IFAT), Kalazar Detect(TM) and Q Letitest ELISA) and a PCR-ELISA. The diagnostic technique had a considerable influence on the CanL prevalence value obtained. Uncertain antibody titres were more representative in dogs sampled at random and with the IFAT technique. Although employing different capture antigens, correlation of results was higher between the two commercial techniques in the group of dogs with symptomatology compatible with CanL. The sensitivity and specificity values of the different diagnostic techniques were affected by the epidemiological characteristic of the area under study, the presence of clinical signs and the function which the dog performs. This must be taken into account when comparing endemicity in different geographical areas, such as in studies carried out for the construction of risk maps. Using more than one technique, and adopting the criterion of considering an animal to be positive only when it has been diagnosed as such by more than one technique, considerably raises the prevalence values but maintains the differences between areas with different characteristics. |
| 7. | Rev Soc Bras Med Trop. 2011 Dec;44(6):771-3.Characterization of Leishmania infantum species in dogs from the urban area of Cuiabá, State of Mato Grosso, Brazil.Santis BD, Santos EG, Cupolillo E, Porrozzi R, Cavalcanti Ados S, Santos BN, Moura ST, Malhado K, Chaves SA.SourceLaboratório de Zoonoses, Escola Nacional de Saúde Pública Sérgio Arouca, Fundação Oswaldo Cruz, Rio de Janeiro, RJ. AbstractINTRODUCTION:Visceral leishmaniasis presents urban behavior in some Brazilian cities, with domestic dogs as the main infection source. In Cuiabá, MT, canine visceral leishmaniasis was diagnosed and characterized as recommended by the Ministry of Health. METHODS:Biological samples from suspected canine carriers were analyzed by the isoenzyme electrophoresis technique. The 6PGDH enzyme and reference strain IOC/L0566 (MHOM/BR/1975/M2903) of Leishmania (Leishmania) infantum was used as one of the controls. RESULTS:Electrophoresis analysis revealed that the canine isolates belonged to the species L. (L.) infantum. CONCLUSIONS:The authors emphasize the importance of species characterization, particularly in areas of mixed infection like Cuiabá. |
| 8. | Rev Soc Bras Med Trop. 2011 Dec;44(6):722-4.Relationship between rainfall and temperature: observations on the cases of visceral leishmaniasis in São Luis Island, State of Maranhão, Brazil.Viana GM, Nascimento Mdo D, Rabelo EM, Diniz Neto JA, Binda Júnior JR, Galvão Cde S, Santos AC, Santos Júnior OM, Oliveira RA, Guimarães RS.SourceDepartamento de Patologia, Universidade Federal do Maranhão, São Luis, MA. AbstractINTRODUCTION:Visceral leishmaniasis is a serious public health problem that requires global control strategies, especially with respect to factors that may intervene in reducing the incidence of endemicity. In this work, rainfall density and temperature were correlated with the incidence of human cases in an area endemic for leishmaniasis in São Luis do Maranhão, Northeastern Brazil. METHODS:Notification of human cases by the National Health Foundation/Regional Coordination of Maranhão (FUNASA/COREMA) from 2002 to 2010 was used. Ecological data (mean temperature and rainfall density) were provided by the Meteorological Office of State. RESULTS:A significant association was verified between the number of VL cases and rainfall rate but not in the analysis concerning mean temperatures. CONCLUSIONS:These data suggest that the control actions in visceral leishmaniasis should be performed during rainy season in the State of Maranhão, which is in the first half of the year. |
| 9. | Braz J Infect Dis. 2011 Oct;15(5):442-8.Miltefosine induces metacaspase and PARP genes expression in Leishmania infantum.Khademvatan S, Gharavi MJ, Saki J.SourceDepartment of Medical Parasitology, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. AbstractOBJECTIVES:Apoptosis is the process of programmed cell death (PCD) that occurs in both animal and plant cells. Protozoan parasites possess metacaspase and these caspase-related proteases could be involved in the PCD pathways in these organisms. Therefore we analyzed the activities of metacaspase and PARP genes in Leishmania infantum (MCAN/IR/96/LON49) treated with miltefosine. MATERIALS AND METHODS:Anti-leishmania activity of miltefosine was studied by treatment of cultured promastigotes with various concentration of miltefosine. MTT assay and Annexin-V FLUOS staining by using FACS flow cytometry methods were used. Cytotoxic potential of HePC on the amastigots of L.infantum was evaluated in J774 cell line. In addition, metacaspase and PARP genes expression of treated L. infantum were studied. RESULTS:Miltefosine led to dose-dependent death of L. infantumwith features compatible with apoptosis. Over expression of metacaspase and PARP was seen 6 hr after treatment. CONCLUSIONS:Our study showed that miltefosine exerts cytotoxic effect on L. infantum via an apoptotic-related mechanism. |
| 10. | J Biomed Sci. 2012 Jan 9;19(1):5. [Epub ahead of print]The Role of Indoleamine 2, 3 Dioxygenase in Regulating Host Immunity to Leishmania Infection.Makala LH.AbstractABSTRACT: Pathogen persistence in immune-competent hosts represents an immunological paradox. Increasing evidence suggests that some pathogens, such as, Leishmania major (L. major) have evolved strategies and mechanisms that actively suppress host adaptive immunity. If this notion is correct conventional vaccination therapies may be ineffective in enhancing host immunity, unless natural processes that suppress host immunity are also targeted therapeutically. The key problem is that the basis of pathogen persistence in immune-competent individuals is unknown, despite decades of intense research. This fact, coupled with poor health care and a dearth of effective treatments means that these diseases will remain a scourge on humans unless a better understanding of why the immune system tolerates such infections emerges from research. Indoleamine 2,3-dioxygenase (IDO) has been shown to act as a molecular switch regulating host responses, and IDO inhibitor drugs shown to possess potential in enhancing host immunity to established leishmania infections. It is hoped that this review will help stimulate and help generate critical new knowledge pertaining to the IDO mechanism and how to exploit it to suppress T cell mediated immunity, thus offer an innovative approach to studying the basis of chronic leishmania infection in mice. |
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