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Sent on Thursday, 2009 Aug 27Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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| PubMed Results |
- 1: Arch Dermatol Res. 2009 Aug 26. [Epub ahead of print]
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Lymphocyte subsets in peripheral blood of patients with psoriasis before and after treatment with leishmania antigens.
Astralis LTD., 75 Passaic Ave., Fairfield, NJ, 07004, USA, joseodaly@aol.com.
Peripheral blood mononuclear cells (PBMC) collected from subjects prior to treatment and post-treatment with a vaccine composed of leishmania antigens were analyzed by flow cytometry. Upon analysis, it was noticed that lymphocyte subsets (LS) varied with psoriasis area and severity index (PASI) range (1-10, 11-20 and 21-72). Pre-treatment absolute values of gated LS were as follows. CD4+CD8-, CD3+CD8-, CD8+CD3+, CD8+CD4- and CD8+HLA- decreased in PBMC as PASI increased, suggesting migration from the blood to the skin. Contrary to the previous finding, the following LS, CD8+HLA+ and HLA+CD8-, and membrane surface immunoglobulin IgA+, IgD+ and IgM+ increased in PBMC as PASI increased, suggesting activation and proliferation by unknown antigens. After treatment with seven doses of AS100, the following LS, CD3+CD8-, CD8+CD3-, HLA+CD8-, CD8+HLA+ and CD4+CD8-, increased, while CD8+CD3+, CD8+HLA-, CD19 and CD8+CD4+ decreased in PBMC.
PMID: 19707779 [PubMed - as supplied by publisher]
- 2: PLoS Negl Trop Dis. 2009 Aug 25;3(8):e412.
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Neglected tropical diseases in sub-saharan Africa: review of their prevalence, distribution, and disease burden.
Department of Microbiology, Immunology, and Tropical Medicine, The George Washington University, Washington, D.C., United States of America.
The neglected tropical diseases (NTDs) are the most common conditions affecting the poorest 500 million people living in sub-Saharan Africa (SSA), and together produce a burden of disease that may be equivalent to up to one-half of SSA's malaria disease burden and more than double that caused by tuberculosis. Approximately 85% of the NTD disease burden results from helminth infections. Hookworm infection occurs in almost half of SSA's poorest people, including 40-50 million school-aged children and 7 million pregnant women in whom it is a leading cause of anemia. Schistosomiasis is the second most prevalent NTD after hookworm (192 million cases), accounting for 93% of the world's number of cases and possibly associated with increased horizontal transmission of HIV/AIDS. Lymphatic filariasis (46-51 million cases) and onchocerciasis (37 million cases) are also widespread in SSA, each disease representing a significant cause of disability and reduction in the region's agricultural productivity. There is a dearth of information on Africa's non-helminth NTDs. The protozoan infections, human African trypanosomiasis and visceral leishmaniasis, affect almost 100,000 people, primarily in areas of conflict in SSA where they cause high mortality, and where trachoma is the most prevalent bacterial NTD (30 million cases). However, there are little or no data on some very important protozoan infections, e.g., amebiasis and toxoplasmosis; bacterial infections, e.g., typhoid fever and non-typhoidal salmonellosis, the tick-borne bacterial zoonoses, and non-tuberculosis mycobaterial infections; and arboviral infections. Thus, the overall burden of Africa's NTDs may be severely underestimated. A full assessment is an important step for disease control priorities, particularly in Nigeria and the Democratic Republic of Congo, where the greatest number of NTDs may occur.
PMID: 19707588 [PubMed - in process]
- 3: PLoS Negl Trop Dis. 2009 Aug 25;3(8):e506.
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Adenosine Kinase of T. b. rhodesiense Identified as the Putative Target of 4-[5-(4-phenoxyphenyl)-2H-pyrazol-3-yl]morpholine Using Chemical Proteomics.
Pharmaceutical Biochemistry Group, School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva, Switzerland.
BACKGROUND: Human African trypanosomiasis (HAT), a major parasitic disease spread in Africa, urgently needs novel targets and new efficacious chemotherapeutic agents. Recently, we discovered that 4-[5-(4-phenoxyphenyl)-2H-pyrazol-3-yl]morpholine (compound 1) exhibits specific antitrypanosomal activity with an IC(50) of 1.0 microM on Trypanosoma brucei rhodesiense (T. b. rhodesiense), the causative agent of the acute form of HAT. METHODOLOGY/PRINCIPAL FINDINGS: In this work we show adenosine kinase of T. b. rhodesiense (TbrAK), a key enzyme of the parasite purine salvage pathway which is vital for parasite survival, to be the putative intracellular target of compound 1 using a chemical proteomics approach. This finding was confirmed by RNA interference experiments showing that down-regulation of adenosine kinase counteracts compound 1 activity. Further chemical validation demonstrated that compound 1 interacts specifically and tightly with TbrAK with nanomolar affinity, and in vitro activity measurements showed that compound 1 is an enhancer of TbrAK activity. The subsequent kinetic analysis provided strong evidence that the observed hyperactivation of TbrAK is due to the abolishment of the intrinsic substrate-inhibition. CONCLUSIONS/SIGNIFICANCE: The results suggest that TbrAK is the putative target of this compound, and that hyperactivation of TbrAK may represent a novel therapeutic strategy for the development of trypanocides.
PMID: 19707572 [PubMed - in process]
- 4: Interdiscip Perspect Infect Dis. 2009;2009:195040. Epub 2009 Aug 20.
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Chemotherapy of human african trypanosomiasis.
Department of Biological and Health Sciences, Haskins Laboratory, Pace University, New York, NY 10038, USA.
Human Africa trypanosomiasis is a centuries-old disease which has disrupted sub-Saharan Africa in both physical suffering and economic loss. This article presents an update of classic chemotherapeutic agents, in use for >50 years and the recent development of promising non-toxic combination chemotherapy suitable for use in rural clinics.
PMID: 19707529 [PubMed - in process]
- 5: Am J Trop Med Hyg. 2009 Sep;81(3):407-15.
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Immunolocalization and challenge studies using a recombinant Vibrio cholerae ghost expressing Trypanosoma brucei Ca(2+) ATPase (TBCA2) antigen.
Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, Georgia 30310, USA. kramey@msm.edu
Human African trypanosomiasis is a neglected disease caused by Trypanosoma brucei spp. A parasite cation pump (Ca(2+) ATPase; TBCA2) essential for survival and cation homeostasis was identified and characterized. It was hypothesized that targeting this pump using a Vibrio cholerae ghost (VCG)-based vaccine could protect against murine T. brucei infection. mRNA and protein expression of TBCA2 was differentially expressed in blood and insect stages of parasites and immunolocalized in the pericellular membrane and the flagellar pocket of bloodstream forms. Antigen-specific antibodies and Th1 cytokines, interleukin-2, interferon-gamma, and tumor necrosis factor-alpha were induced in rVCG-TBCA2-immunized mice and in vitro on antigen stimulation of splenic immune T cells, but the corresponding Th2-type response was unremarkable. Despite an increased median survival of 6 days in vaccinated mice, the mice were not protected against infection. Thus, immunization of mice produced robust parasite-specific antibodies but failed to protect mice against parasite challenge.
PMID: 19706905 [PubMed - in process]
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Patient Drug Information
- Glatiramer Acetate (Copaxone, Avonex, Rebif, ...)
How effective are disease-modifying drugs in the treatment of multiple sclerosis?
- Glatiramer Acetate (Copaxone, Avonex, Rebif, ...)
- 6: Am J Trop Med Hyg. 2009 Sep;81(3):387-9.
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Efficacy of extended (six weeks) treatment with miltefosine for mucosal leishmaniasis in Bolivia.
Centro de Investigaciones Bioclínicas de la Fundación FADER, Bogotá, Colombia. jaime.soto@prodderma.com
We investigated whether increasing the period of follow-up or increasing the duration of therapy would markedly alter the 71% cure rate of mucosal leishmaniasis in Bolivia consequent to treatment with miltefosine for 4 weeks. Increasing the follow-up from 12 months to 24 months demonstrated additional relapse in only 2 of 41 patients. Increasing the period of therapy from 4 weeks to 6 weeks only increased the cure rate to 75%. The cure rate of mucosal leishmaniasis in Bolivia, whether 4 or 6 weeks of therapy is used and whether 12 month or 24 months follow up is conducted, is approximately 70%.
PMID: 19706901 [PubMed - in process]
- 7: Am J Trop Med Hyg. 2009 Sep;81(3):384-6.
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The value of the otorhinolaryngologic exam in correct mucocutaneous leishmaniasis diagnosis.
Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Salvador, Brazil. voliveira@aluno.bahia.fiocruz.br
An increase in mucocutaneous leishmaniasis (ML) cases in northern (Brazil) motivated this study. In 44 ML patients with clinical diagnosis, only 13 parasitologically confirmed cases exhibited mucosal lesion suggestive of ML. Other conditions involving nasal manifestations are frequently confounded with ML. Therefore, otorhinolaryngologic examination is important in the clinical management of ML.
PMID: 19706900 [PubMed - in process]
- 8: Am J Trop Med Hyg. 2009 Sep;81(3):378-83.
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Increase of NK cells and proinflammatory monocytes are associated with the clinical improvement of diffuse cutaneous leishmaniasis after immunochemotherapy with BCG/Leishmania antigens.
Instituto de Patologia Tropical e Saúde Pública, Federal University of Goiás, Goiás Hospital de Doenças Tropicais Anuar Auad, Goiás, Brazil. ledicepereira@gmail.com
Diffuse cutaneous leishmaniasis (DCL) is characterized by disseminated lesions and the absence of a specific cellular immune response. Here, the immunochemotherapy outcome of a patient with DCL from Amazonian Brazil infected with Leishmania (Leishmania) amazonensis is presented. After several unsuccessful chemotherapy treatment regimens and many relapses, a monthly immunotherapy scheme of L. amazonensis PH8 plus L. (Viannia) braziliensis M2903 monovalent vaccines associated with Bacillus Calmette-Guerin (BCG) was established, one round of which also included an M2903 vaccine associated with intermittent antimonial treatment. Temporary healing of all lesions was achieved, although Leishmania skin tests were negative and interferon gamma was not detected in mononuclear cell cultures stimulated with Leishmania antigens. The frequencies of CD16 (+)CD56(+) NK cells (approximately 2x) and CD14 (+)CD16(+) proinflammatory monocytes (approximately 8x) increased in peripheral blood, and CD56 (+) lymphocytes were found infiltrating the lesions. An association between the increase of the frequency of innate immune system cells and the healing of lesions is shown, suggesting that this protocol of immunotherapy reduced the parasite load and activated NK cells and monocytes.
PMID: 19706899 [PubMed - in process]
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Patient Drug Information
- Glatiramer Acetate (Copaxone, Avonex, Rebif, ...)
How effective are disease-modifying drugs in the treatment of multiple sclerosis?
- Bacillus Calmette-Guerin (BCG) Vaccine (TheraCys® BCG, TICE® BCG)
BCG vaccine provides immunity or protection against tuberculosis (TB). The vaccine may be given to persons at high risk of developing TB. It is also used to treat bladder tumors or bladder cancer.
- Glatiramer Acetate (Copaxone, Avonex, Rebif, ...)
- 9: Am J Trop Med Hyg. 2009 Sep;81(3):373-7.
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Natural history of a visceral leishmaniasis outbreak in highland Ethiopia.
Disease Prevention and Control Programmes, World Health Organization, Addis Ababa, Ethiopia.
In May 2005, visceral leishmaniasis (VL) was recognized for the first time in Libo Kemken, Ethiopia, a highland region where only few cases had been reported before. We analyzed records of VL patients treated from May 25, 2005 to December 13, 2007 by the only VL treatment center in the area, maintained by Médecins Sans Frontières-Ethiopia, Operational Center Barcelona-Athens. The median age was 18 years; 77.6% were male. The overall case fatality rate was 4%, but adults 45 years or older were five times as likely to die as 5-29 year olds. Other factors associated with increased mortality included HIV infection, edema, severe malnutrition, pneumonia, tuberculosis, and vomiting. The VL epidemic expanded rapidly over a several-year period, culminating in an epidemic peak in the last third of 2005, spread over two districts, and transformed into a sustained endemic situation by 2007.
PMID: 19706898 [PubMed - in process]
- 10: PLoS Pathog. 2009 May;5(5):e1000410. Epub 2009 May 1.
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Genome-scale multilocus microsatellite typing of Trypanosoma cruzi discrete typing unit I reveals phylogeographic structure and specific genotypes linked to human infection.
London School of Hygiene and Tropical Medicine, London, UK. martin.llewellyn@lshtm.ac.uk
Trypanosoma cruzi is the most important parasitic infection in Latin America and is also genetically highly diverse, with at least six discrete typing units (DTUs) reported: Tc I, IIa, IIb, IIc, IId, and IIe. However, the current six-genotype classification is likely to be a poor reflection of the total genetic diversity present in this undeniably ancient parasite. To determine whether epidemiologically important information is "hidden" at the sub-DTU level, we developed a 48-marker panel of polymorphic microsatellite loci to investigate population structure among 135 samples from across the geographic distribution of TcI. This DTU is the major cause of resurgent human disease in northern South America but also occurs in silvatic triatomine vectors and mammalian reservoir hosts throughout the continent. Based on a total dataset of 12,329 alleles, we demonstrate that silvatic TcI populations are extraordinarily genetically diverse, show spatial structuring on a continental scale, and have undergone recent biogeographic expansion into the southern United States of America. Conversely, the majority of human strains sampled are restricted to two distinct groups characterised by a considerable reduction in genetic diversity with respect to isolates from silvatic sources. In Venezuela, most human isolates showed little identity with known local silvatic strains, despite frequent invasion of the domestic setting by infected adult vectors. Multilocus linkage indices indicate predominantly clonal parasite propagation among all populations. However, excess homozygosity among silvatic strains and raised heterozygosity among domestic populations suggest that some level of genetic recombination cannot be ruled out. The epidemiological significance of these findings is discussed.
PMID: 19412340 [PubMed - indexed for MEDLINE]
PMCID: PMC2669174
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