Wednesday, March 31, 2010

What's new for 'Trypanosomatids' in PubMed

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Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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PubMed Results
Items 1 - 6 of 6

1. Parasitol Res. 2010 Mar 30. [Epub ahead of print]

Furazolidone is a selective in vitro candidate against Leishmania (L.) chagasi: an ultrastructural study.

Quero Reimão J, Nosomi Taniwaki N, Gustavo Tempone A.

Laboratory of Applied Toxinology on Antiparasitic Drugs, Department of Parasitology, Instituto Adolfo Lutz, Av. Dr. Arnaldo, 355, 8 degrees andar, Cerqueira César, CEP 01246-000, São Paulo, São Paulo, Brazil.

The current treatment for leishmaniasis is unsatisfactory due to toxic side effects, high cost, and problems with drug resistance. Various approaches have been used to identify novel drug candidates to treat Leishmania sp. parasites including the use of re-purposed drugs. Furazolidone is a nitrofuran derivative with antiprotozoal and antibacterial activity and is used for the treatment of giardiasis. In the present work, we determined the in vitro antileishmanial activity of furazolidone and its ability to induce ultrastructural alterations of parasites. Promastigotes of Leishmania (L.) chagasi, Leishmania (V.) braziliensis, Leishmania (L.) major, and Leishmania (L.) amazonensis were highly susceptible to furazolidone, with IC(50) values ranging between 0.47 and 0.73 microg/mL. Furazolidone was also very effective against L. chagasi intracellular amastigotes, and despite mammalian cytotoxicity, the selectivity index was 8.0 in human monocytes. The drug also had limited toxicity in mice erythrocytes. Furazolidone demonstrated specific activity against Leishmania, a potential consequence of the lack of macrophage nitric oxide activation. As determined by electron transmission microscopy, drug treatment induced severe damage to the parasite mitochondria and nucleus. This older oral drug is an effective agent for the treatment of L. (L.) chagasi in vitro and is a novel candidate for further experimental studies.

PMID: 20352451 [PubMed - as supplied by publisher]
2. PLoS Negl Trop Dis. 2010 Mar 23;4(3):e639.

Risk factors for anthroponotic cutaneous leishmaniasis at the household level in kabul, afghanistan.

Reithinger R, Mohsen M, Leslie T.

HealthNet TPO, Kabul, Afghanistan.

BACKGROUND: Kabul, Afghanistan, is the largest focus of anthroponotic cutaneous leishmaniasis (ACL) in the world. ACL is a protozoan disease transmitted to humans by the bite of phlebotomine sand flies. Although not fatal, ACL can lead to considerable stigmatization of affected populations. METHODS: Using data from a standardized survey of 872 households in 4 wards of Kabul, Afghanistan, univariate and multivariate logistic regression analyses tested associations between presence of active ACL and ACL scars with 15 household-level variables. FINDINGS: Univariate analyses showed that active ACL was positively associated with household member's age, ACL prevalence, and brick wall type, but negatively associated with household number of rooms, bednet use, and proportion of windows with screens. Multivariate analysis showed a positive association between active ACL and household member's age, ACL prevalence, and brick wall type, and a negative association with household proportion of windows with screens. CONCLUSION: Household-level charateristics were shown to be risk factors for ACL. Monitoring a selected number of household characteristics could assist in rapid assessments of household-level variation in risk of ACL. ACL prevention and control programs should consider improving house construction, including smoothing of walls and screening of windows.

PMID: 20351787 [PubMed - in process]
3. PLoS Negl Trop Dis. 2010 Mar 23;4(3):e638.

Discovery of Markers of Exposure Specific to Bites of Lutzomyia longipalpis, the Vector of Leishmania infantum chagasi in Latin America.

Teixeira C, Gomes R, Collin N, Reynoso D, Jochim R, Oliveira F, Seitz A, Elnaiem DE, Caldas A, de Souza AP, Brodskyn CI, de Oliveira CI, Mendonca I, Costa CH, Volf P, Barral A, Kamhawi S, Valenzuela JG.

Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America.

BACKGROUND: Sand flies deliver Leishmania parasites to a host alongside salivary molecules that affect infection outcomes. Though some proteins are immunogenic and have potential as markers of vector exposure, their identity and vector specificity remain elusive. METHODOLOGY/PRINCIPAL FINDINGS: We screened human, dog, and fox sera from endemic areas of visceral leishmaniasis to identify potential markers of specific exposure to saliva of Lutzomyia longipalpis. Human and dog sera were further tested against additional sand fly species. Recombinant proteins of nine transcripts encoding secreted salivary molecules of Lu. longipalpis were produced, purified, and tested for antigenicity and specificity. Use of recombinant proteins corresponding to immunogenic molecules in Lu. longipalpis saliva identified LJM17 and LJM11 as potential markers of exposure. LJM17 was recognized by human, dog, and fox sera; LJM11 by humans and dogs. Notably, LJM17 and LJM11 were specifically recognized by humans exposed to Lu. longipalpis but not by individuals exposed to Lu. intermedia. CONCLUSIONS/SIGNIFICANCE: Salivary recombinant proteins are of value as markers of vector exposure. In humans, LJM17 and LJM11 emerged as potential markers of specific exposure to Lu. longipalpis, the vector of Leishmania infantum chagasi in Latin America. In dogs, LJM17, LJM11, LJL13, LJL23, and LJL143 emerged as potential markers of sand fly exposure. Testing these recombinant proteins in large scale studies will validate their usefulness as specific markers of Lu. longipalpis exposure in humans and of sand fly exposure in dogs.

PMID: 20351786 [PubMed - in process]
4. PLoS Negl Trop Dis. 2010 Mar 23;4(3):e649.

Using Recombinant Proteins from Lutzomyia longipalpis Saliva to Estimate Human Vector Exposure in Visceral Leishmaniasis Endemic Areas.

Souza AP, Andrade BB, Aquino D, Entringer P, Miranda JC, Alcantara R, Ruiz D, Soto M, Teixeira CR, Valenzuela JG, de Oliveira CI, Brodskyn CI, Barral-Netto M, Barral A.

Centro de Pesquisas Gonçalo Moniz (Fundação Oswaldo Cruz - FIOCRUZ), Salvador, Brazil.

BACKGROUND: Leishmania is transmitted by female sand flies and deposited together with saliva, which contains a vast repertoire of pharmacologically active molecules that contribute to the establishment of the infection. The exposure to vector saliva induces an immune response against its components that can be used as a marker of exposure to the vector. Performing large-scale serological studies to detect vector exposure has been limited by the difficulty in obtaining sand fly saliva. Here, we validate the use of two sand fly salivary recombinant proteins as markers for vector exposure. METHODOLOGY/PRINCIPAL FINDINGS: ELISA was used to screen human sera, collected in an area endemic for visceral leishmaniasis, against the salivary gland sonicate (SGS) or two recombinant proteins (rLJM11 and rLJM17) from Lutzomyia longipalpis saliva. Antibody levels before and after SGS seroconversion (n = 26) were compared using the Wilcoxon signed rank paired test. Human sera from an area endemic for VL which recognize Lu. longipalpis saliva in ELISA also recognize a combination of rLJM17 and rLJM11. We then extended the analysis to include 40 sera from individuals who were seropositive and 40 seronegative to Lu. longipalpis SGS. Each recombinant protein was able to detect anti-saliva seroconversion, whereas the two proteins combined increased the detection significantly. Additionally, we evaluated the specificity of the anti-Lu. longipalpis response by testing 40 sera positive to Lutzomyia intermedia SGS, and very limited (2/40) cross-reactivity was observed. Receiver-operator characteristics (ROC) curve analysis was used to identify the effectiveness of these proteins for the prediction of anti-SGS positivity. These ROC curves evidenced the superior performance of rLJM17+rLJM11. Predicted threshold levels were confirmed for rLJM17+rLJM11 using a large panel of 1,077 serum samples. CONCLUSION: Our results show the possibility of substituting Lu. longipalpis SGS for two recombinant proteins, LJM17 and LJM11, in order to probe for vector exposure in individuals residing in endemic areas.

PMID: 20351785 [PubMed - in process]
5. Trans R Soc Trop Med Hyg. 2009 Nov;103(11):1085-6. Epub 2009 Mar 19.

Molecular markers for Phlebotomus papatasi (Diptera: Psychodidae) and their usefulness for population genetic analysis.

Hamarsheh O, Presber W, Al-Jawabreh A, Abdeen Z, Amro A, Schönian G.

Department of Biological Sciences, Al-Quds University, P.O. Box 51000, Jerusalem, Palestine. ohamarsheh@science.alquds.edu

Three molecular typing tools: multilocus microsatellite typing, cytochrome b sequence analysis and internal transcribed spacer 2 (ITS2) sequence analysis, were evaluated for their usefulness in inferring the population structure of Phlebotomus papatasi sand flies. ITS2 sequence analysis did not prove suitable for inferring phylogenetic and population genetic relationships across P. papatasi sand flies. Microsatellite markers showed high resolution in differentiating globally distributed P. papatasi populations, whereas cytochrome b sequence analysis provided insight into the relationships between closely related populations from the Mediterranean. Population structure, differentiation and demographic history among P. papatasi are important for understanding patterns of dispersal in this species and for planning appropriate control measures.

PMID: 19303124 [PubMed - indexed for MEDLINE]
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Publication Types:

  • Research Support, Non-U.S. Gov't
  • Review

MeSH Terms:

  • Animals
  • DNA, Mitochondrial/genetics*
  • DNA, Ribosomal/genetics*
  • Female
  • Genetic Markers
  • Genetic Variation
  • Leishmaniasis, Cutaneous/parasitology
  • Microsatellite Repeats/genetics
  • Phlebotomus/classification
  • Phlebotomus/genetics*
  • Sequence Analysis, DNA

Substances:

  • DNA, Mitochondrial
  • DNA, Ribosomal
  • Genetic Markers
6. US Army Med Dep J. 2007 Apr-Jun:56-64.

Preventive medicine support in Afghanistan during Operation Enduring Freedom VI.

Gellasch CA, Calix LC.

Environmental Health Engineering Division, US Army Center for Health Promotion and Preventive Medicine-West, Fort Lewis, Washington, USA.

PMID: 20084698 [PubMed - indexed for MEDLINE]
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MeSH Terms:

  • Afghan Campaign 2001-*
  • Afghanistan
  • Food Supply/standards
  • Humans
  • Insect Control
  • Leishmaniasis/prevention & control
  • Malaria/prevention & control
  • Military Medicine/organization & administration*
  • Military Personnel*
  • Population Surveillance
  • Preventive Medicine/organization & administration*
  • Program Evaluation
  • Public Health
  • Public Health Practice
  • United States
  • Waste Management/methods
  • Waste Management/standards
  • Water Supply/standards

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