[leish-l] Fwd: Articles found by RefScout 27/04/2004 - 17/2005

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Thu Apr 28 11:48:45 BRT 2005

    Date: Wed, 27 Apr 2005 12:22:01
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This is RefScout-Newsletter 17/2005

REQUEST: [ leishmaniasis ]

(20 articles match this request)

PMID: 15842398

TITLE: Cutaneous leishmaniasis in Afghani refugees.

AUTHORS: Emma Storer, Jeffrey Wayte

AFFILIATION: Department of Dermatology, The Women's and Children's Hospital,
North Adelaide, South Australia, Australia.

REFERENCE: Australas J Dermatol 2005 May 46(2):80-3

SUMMARY Four Afghani refugees with cutaneous leishmaniasis presented to 
the dermatology clinic at the Women's and Children's Hospital in 
Adelaide. Three of the patients had biopsy-proven cutaneous 
leishmaniasis that was treated initially with topical and then oral 
ketoconazole, without success. Intralesional sodium stibogluconate was 
then used for these patients with good results. The fourth patient had 
several plaques of biopsy-proven cutaneous leishmaniasis, for which 
cryotherapy was used. This was quite efficacious; however, a small area 
of recurrence required re-treatment. Leishmaniasis is rarely seen in 
Australia, but an index of suspicion is warranted when treating persons 
with typical clinical features who are from endemic regions.

PMID: 15837614

TITLE: Second-generation vaccines against leishmaniasis.

AUTHORS: Rhea N Coler, Steven G Reed

AFFILIATION: The Infectious Disease Research Institute, 1124 Columbia Street,
Suite 600, Seattle, WA 98104, USA; TheraVax, 1124 Columbia Street, Suite 600,
Seattle, WA 98104, USA.

REFERENCE: Trends Parasitol 2005 May 21(5):244-9

Several species of Leishmania cause human diseases that range from self-
healing cutaneous lesions to fatal visceral leishmaniasis, mucosal 
leishmaniasis and diffuse cutaneous leishmaniasis. Drug resistance and 
toxicities associated with chemotherapy emphasize the need for a safe, 
effective vaccine. Studies of the immunopathogenesis and mechanisms of 
protective immunity define several features that should be met by an 
effective vaccine. The leishmaniases are unique among parasitic diseases
 because a single vaccine has the potential to protect against more than
 one species (disease) and be successful at both treating and preventing
 disease. In addition, several antigens have been identified and 
characterized that might be potential vaccine candidates. In this 
article, we focus on advances made with second-generation vaccines 
against leishmaniasis.

PMID: 15844060

TITLE: Randomized, double-blind clinical trial of topical imiquimod 5% with
parenteral meglumine antimoniate in the treatment of cutaneous leishmaniasis in

AUTHORS: C Miranda-Verástegui, A Llanos-Cuentas, I Arévalo, B J Ward, G

AFFILIATION: Department of Microbiology and Immunology, McGill University,
Montreal, Canada.

REFERENCE: Clin Infect Dis 2005 May 40(10):1395-403

BACKGROUND: Current treatments for cutaneous leishmaniasis are limited 
by their toxicity, high cost, and discomfort and the emergence of drug 
resistance. New approaches, including combination therapies, are 
urgently needed. We performed a double-blind, randomized trial of 
therapy with parenteral antimony plus topical imiquimod, an innate 
immune-response modulator, versus therapy with antimony alone, in 
subjects with cutaneous leishmaniasis for whom an initial course of 
antimony therapy had failed. METHODS: Forty subjects with clinical 
resistance to antimony were recruited in Lima, Peru, between February 
2001 and December 2002. All subjects received meglumine antimoniate (20 
mg/kg/day im or iv) and were randomized to receive either topical 
imiquimod 5% cream (Aldara; 3M Pharmaceuticals) or vehicle control every
 other day for 20 days. Lesions and adverse events were evaluated during
 treatment and at 1, 2, 3, 6, and 12 months after the treatment period. 
RESULTS: The mean number of lesions was 1.2 per person; 71% of the 
lesions were facial and 76% were ulcerative. There were no major 
differences between the groups, and all but 2 subjects completed therapy
. Mild adverse events were reported by 73% of the subjects, but only 
erythema occurred more commonly in the imiquimod group (P < or = .02
). Lesions resolved more rapidly in the imiquimod group: 50% of the 
imiquimod group achieved cure at 1 month after the treatment period 
versus 15% of the vehicle cream group (P < or = .02); 61% of the 
imiquimod group at 2 months versus 25% of the vehicle cream group (P &lt
; or = .03); and 72% of the imiquimod group at 3 months versus 35% of 
the vehicle cream group (P < or = .02). Residual scarring in the 
imiquimod group was less prominent than in the vehicle cream group. 
CONCLUSIONS: Combined antimony plus imiquimod treatment was well 
tolerated, accelerated healing of lesions, and improved scar quality. 
This therapy may have particular advantages for subjects with facial 

PMID: 15845276

TITLE: PCR-based diagnosis for detection of Leishmania in skin and blood of
rodents from an endemic area of cutaneous and visceral leishmaniasis in

AUTHORS: Fernanda S Oliveira, Claude Pirmez, Marize Q Pires, Reginaldo P Brazil,
Raquel S Pacheco

AFFILIATION: Laboratório de Sistemática Bioquímica, Departamento de
Bioquímica e Biologia Molecular (DBBM), Instituto Oswaldo Cruz (IOC),
Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, Brasil.

REFERENCE: Vet Parasitol 2005 May 129(3-4):219-27

The technique of polymerase chain reaction (PCR) associated to 
hybridization was used to screen 123 samples collected from wild and 
synanthropic rodents captured in a cutaneous and visceral leishmaniasis 
endemic area in the State of Minas Gerais, Brazil. The detection of 
Leishmania spp in naturally infected rodents is of fundamental 
importance for incriminating them as possible reservoir hosts of the 
diseases in Minas Gerais. A total of 62 specimens belonging to wild (
Thrichomys apereoides, Oryzomys subflavus, Galea spixii, Bolomyslasiurus
 and Wiedomys pyrrhorhinos) and synanthropic (R. rattus) rodent species 
were captured in different ecotopes. Blood and skin samples were 
submitted for PCR analyses followed by molecular hybridization with 
specific probes for the three Leishmania-species complexes. Fifteen 
samples were found positive after PCR-hybridization and identified as 
follows: nine belonging to the L. mexicana complex, three to the L. 
braziliensis complex and three to the L. donovani complex. Positive PCR 
results were found in 11 out of the 61 (18%) blood samples and in four 
out of the 62 (6.4%) skin fragments screened. R. rattus and T. 
apereoides were the most abundant species in the area also presenting 
high prevalence of natural infection. The presence of parasite DNA 
belonging to L. braziliensis, L. mexicana and L. donovani complexes was 
confirmed in several individuals of a rodent species, R. rattus. This 
work is the first report of the detection of L. (L.) chagasi in a 
naturally infected T. apereoides. The utility of filter paper as a 
substrate for PCR analyses and the efficacy of the procedure associated 
to the hybridization is emphasized.

PMID: 15848765

TITLE: Biphenylquinuclidines as inhibitors of squalene synthase and growth of
parasitic protozoa.

AUTHORS: Silvia Orenes Lorente, Rosario Gómez, Carmen Jiménez, Simon Cammerer,
Vanessa Yardley, Kate de Luca-Fradley, Simon L Croft, Luis M Ruiz Perez, Julio
Urbina, Dolores Gonzalez Pacanowska, Ian H Gilbert

AFFILIATION: Welsh School of Pharmacy, Cardiff University, Redwood Building,
King Edward VII Avenue, Cardiff CF10 3XF, UK.

REFERENCE: Bioorg Med Chem 2005 May 13(10):3519-29

In this paper we describe the preparation of some biphenylquinuclidine 
derivatives and their evaluation as inhibitors of squalene synthase in 
order to explore their potential in the treatment of the parasitic 
diseases leishmaniasis and Chagas disease. The compounds were screened 
against recombinant Leishmania major squalene synthase and against 
Leishmania mexicana promastigotes, Leishmania donovani intracellular 
amastigotes and Trypanosoma cruzi intracellular amastigotes. Compounds 
that inhibited the enzyme, also reduced the levels of steroids and 
caused growth inhibition of L. mexicana promastigotes. However there was
 a lower correlation between inhibition of the enzyme and growth 
inhibition of the intracellular parasites, possibly due to delivery 
problems. Some compounds also showed growth inhibition of T. brucei 
rhodesiense trypomastigotes, although in this case alternative modes of 
action other than inhibition of SQS are probably involved.

PMID: 15834984

TITLE: Social impact of leishmaniasis, Afghanistan.

AUTHORS: Richard Reithinger, Khoksar Aadil, Jan Kolaczinski, Mohammad Mohsen,
Samad Hami

REFERENCE: Emerg Infect Dis 2005 Apr 11(4):634-6

PMID: 15844420

TITLE: Autochthonous visceral leishmaniasis in dogs in North America.

AUTHORS: Peter M Schantz, Francis J Steurer, Zandra H Duprey, Katherine P
Kurpel, Stephen C Barr, Joan E Jackson, Edward B Breitschwerdt, Michael G Levy,
J C Fox

AFFILIATION: CDC, Division of Parasitic Diseases, National Center For Infectious
Diseases, 4770 Buford Hwy, Atlanta, GA 30341, USA.

REFERENCE: J Am Vet Med Assoc 2005 Apr 226(8):1316-22

PMID: 15829132

TITLE: Household structure and urban services: neglected targets in the control
of visceral leishmaniasis.

AUTHORS: C H N Costa, G L Werneck, L Rodrigues, M V Santos, I B Araújo, L S
Moura, S Moreira, R B B Gomes, S S Lima

AFFILIATION: Instituto de Doenças Tropicais Nathan Portella and Universidade
Federal do Piauí, Rua Governador Raimundo Artur de Vasconcelos, 151, CEP
64001-450, Teresina, PI, Brazil.

REFERENCE: Ann Trop Med Parasitol 2005 Apr 99(3):229-36

Visceral leishmaniasis (VL) caused by Leishmania chagasi is a growing 
public-health problem in many parts of the New World. Although several 
studies have focused on the consequences of environmental damage, human 
migration and land occupation on the incidence of VL, the effects on the
 disease of the substandard living conditions that often result from the
 process of urbanization have not been investigated in detail. The 
present study was based in the Brazilian city of Teresina, where, since 
1980, there have been two large outbreaks of VL (one in 1981-1985 and 
the other in 1993-1996), each involving at least 1000 newly reported 
cases. The role of household structure and the provision of urban 
services in the city, as predictors of the occurrence of VL, was studied
 in a case-control investigation. After controlling for age, crowding, 
and the background incidence of VL in the area where the subjects lived
, the risk of acquiring the disease was found to be significantly higher
 for those who lived in houses with an inadequate sewage system and 
those who had no regular rubbish collection. Improving household 
structure and providing basic urban services might be effective 
strategies for controlling the spread of VL in urban areas.

PMID: 15772867

TITLE: Curcumin overcomes the inhibitory effect of nitric oxide on Leishmania.

AUTHORS: Marion Man-Ying Chan, Naga Suresh Adapala, Dunne Fong

AFFILIATION: Department of Microbiology and Immunology, Temple University School
of Medicine, 3400 North Broad St., Philadelphia, PA, 19140, USA,
marion.chan at temple.edu.

REFERENCE: Parasitol Res 2005 Apr 96(1):49-56

Upon Leishmania infection, macrophages are activated to produce nitrogen
 and oxygen radicals simultaneously. It is well established that the 
infected host cells rely on nitric oxide (NO) as the major weapon 
against the intracellular parasite. In India where leishmaniasis is 
endemic, the spice turmeric is used prolifically in food and for insect 
bites. Curcumin, the active principle of turmeric, is a scavenger of NO
. This report shows that curcumin protects promastigotes and amastigotes
 of the visceral species, Leishmania donovani, and promastigotes of the 
cutaneous species, L. major, against the actions of S-nitroso-N-acetyl-D
,L-penicillamine (SNAP) and DETANONOate, which release NO, 3-morpholino-
sydnonimine hydrochloride (SIN-1), which releases NO and superoxide, and
 peroxynitrite, which is formed from the reaction of NO with superoxide
. Thus, curcumin, as an antioxidant, is capable of blocking the action 
of both NO and NO congeners on the Leishmania parasite.

PMID: 15789648

TITLE: Efficacy of the treatment of dogs with leishmaniosis with a combination
of metronidazole and spiramycin.

AUTHORS: M G Pennisi, M De Majo, M Masucci, D Britti, F Vitale, R Del Maso

AFFILIATION: Dipartimento di Scienze Mediche Veterinarie, Università degli
Studi di Messina, Messina, Italy.

REFERENCE: Vet Rec 2005 Mar 156(11):346-9

Twenty-seven dogs infected naturally with Leishmania infantum were used 
in a randomised controlled trial to compare the clinical and 
parasitological efficacy of an oral treatment with a combination of 
metronidazole and spiramycin (13 dogs) with the efficacy of conventional
 treatment with meglumine antimonate and allopurinol (14 dogs) as 
controls. In the test group one dog had to be withdrawn from the 
treatment because it developed pemphigus foliaceus; 10 of the dogs were 
clinically responsive but none was cured parasitologically. In the 
control group four dogs were withdrawn from the treatment because of 
side effects; eight of the dogs were clinically responsive but none was 
cured parasitologically. The control group showed signs of improvement 
after an average of 30 days, whereas the test group did not show signs 
of improvement until after an average of 45 days.

PMID: 15721831

TITLE: Targeting cell regulation promotes pathogen survival in macrophages.

AUTHORS: Neil E Reiner

AFFILIATION: Department of Medicine (Division of Infectious Diseases),
University of British Columbia Faculties of Medicine and Science, Rm 452D, 2733
Heather Street, Vancouver, British Columbia, Canada V5Z 3J5.
ethan at interchange.ubc.ca

REFERENCE: Clin Immunol 2005 Mar 114(3):213-5

PMID: 15721837

TITLE: Leishmania donovani engages in regulatory interference by targeting
macrophage protein tyrosine phosphatase SHP-1.

AUTHORS: Devki Nandan, Neil E Reiner

AFFILIATION: Division of Infectious Diseases, Department of Medicine, Vancouver
Coastal Health Research Institute (VCHRI), The University of British Columbia,
Room 452D, 2733 Heather Street, Vancouver, BC, Canada, V5Z 3J5.
dnandan at interchange.ubc.ca

REFERENCE: Clin Immunol 2005 Mar 114(3):266-77

Protozoan parasites of the genus leishmania are obligate intracellular 
parasites of monocytes and macrophages. These pathogens have evolved to 
invade the mammalian immune system and typically survive for long 
periods of time. Leishmania have developed a variety of remarkable 
strategies to prevent their elimination by both innate and acquired 
immune effector mechanisms. One particular strategy of interest involves
 manipulation of host cell regulatory pathways so as to prevent 
macrophage activation required for efficient microbicidal activity. 
These interference mechanisms are the main focus of this review. Several
 lines of evidence have been developed to show that the Src homology-2 
domain containing tyrosine phosphatase-1 (SHP-1) becomes activated in 
leishmania-infected cells and that this contributes to disease 
pathogenesis. Recent studies aimed at understanding the mechanism 
responsible for the change in activation state of SHP-1 led to the 
identification of leishmania EF-1alpha as an SHP-1 binding protein and 
SHP-1 activator. This was a surprising finding given that this 
ubiquitous and highly conserved protein plays an essential role in 
protein translation in both prokaryotic and eukaryotic cells. The role 
of leishmania EF-1alpha as an SHP-1 activator and its contribution to 
pathogenesis are reviewed with particular attention to the properties 
that distinguish it from host EF-1alpha.

PMID: 15833054

TITLE: Applications of molecular methods for Leishmania control.

AUTHORS: Sarman Singh, Ayan Dey, Ramu Sivakumar

AFFILIATION: All India Institute of Medical Sciences, New Delhi-110029, India.
sarman_singh at yahoo.com

REFERENCE: Expert Rev Mol Diagn 2005 Mar 5(2):251-65

This article reviews the recent advances made in the field of human 
leishmaniasis. Special emphasis is placed upon the application of 
various molecular tools for accurate and rapid diagnosis, understanding 
the mechanisms of drug resistance and identification of vaccine 
candidates. The focus will be on the major role played by recombinant 
antigens in the immunoserodiagnosis and progress of the Leishmania 
genome project, which has enabled researchers to design better PCR 
primers and molecular probes for microarrays. A special interest is 
placed on the recombinant antigen (rK39) cloned from the Leishmania 
chagasi kinesin gene and a very recently cloned recombinant antigen (
KE16) from the Old World Leishmania donovani species with high 
sensitivity and specificity. Advances made in the specific PCR primer 
designed to diagnose and differentiate various species and strains of 
Leishmania causing visceral and post-kala-azar-dermal leishmaniasis have
 been covered. Molecular methods (e.g., DNA and protein microarrays) 
applied to understanding the pathobiology of the parasite, mechanism of 
host invasion, drug interaction and drug resistance to develop effective
 therapeutic molecules, gene expression profiling studies that have 
opened doors to understand many host-parasite relations, effective 
therapy and vaccine candidates are extensively covered in this review.

PMID: 15798564

TITLE: [Cutaneous-mucosal paracoccidio-domycosis: the first case diagnosed in
French Guiana]

AUTHORS: F Sarazin, D Sainte-Marie, M Demar, C Aznar, J Sarrouy, R Pradinaud, B
Carme, P Couppié

AFFILIATION: Service de Dermatologie, Centre Hospitalier, Cayenne, Guyane

REFERENCE: Ann Dermatol Venereol 2005 Feb 132(2):136-9

INTRODUCTION: Paracoccidio-domycosisis a deep mycosis due to a dimorphic
 fungus:Paracoccidioides brasiliensis. The principle endemic country is 
Brazil. We describe the first case of paracoccidio-domycosis, in its 
cutaneous-mucosal form, diagnosed in French Guiana. OBSERVATION: A 20 
year-old Brazilian man, having mover to French Guiana a few months 
earlier, presented with multiple disseminated cutaneous lesions, 
predominating on the face, and composed of multiple nodules and two 
ulcerations. The clinical examination also revealed voluminous 
superficial lymph nodes and ulcerations of the pharynx and larynx. 
Direct examination, anatomopathology and culture of cutaneous biopsies 
revealed specific images of Paracoccidioides brasiliensis. HIV serology 
was negative. Treatment combining cotrimoxazole and itraconazole 
eliminated the lesions in one month. DISCUSSION: Because the patient had
 just moved to Guiana, this observation probably corresponded to an 
imported disease. The principle differential diagnosis was leishmaniosis.

PMID: 15841653

TITLE: Evaluation of oxidative stress in cutaneous leishmaniasis.

AUTHORS: Hatice Ozbilge, Nurten Aksoy, Eser Kilic, Recep Saraymen, Süleyman
Yazar, Huseyin Vural

AFFILIATION: Harran University, Medical Faculty, Department of Microbiology,
Sanliurfa, Turkey.

REFERENCE: J Dermatol 2005 Jan 32(1):7-11

Oxidative stress occurs when there is excessive free-radical production 
or a low antioxidant level. The role of free radicals in the 
pathogenesis and in the progression of many diseases has often been 
discussed, but it has not been widely investigated in leishmaniasis. 
However, measurement of oxidants and antioxidants in the serum seems to 
be of great value. In this study, we aimed to determine lipid 
peroxidation levels as markers of oxidative stress in the serum of 
patients suffering from cutaneous leishmaniasis, which is a common 
health problem in our region of Southern Anatolia, Turkey. Forty 
patients aged between 5-50 years and forty controls aged between 5-50 
years were included in the study. The LPO levels of the patients with 
active cutaneous leishmaniasis were significantly higher (p<0.001) 
than those of healthy controls. As a result, it is possible to conclude 
that patients with cutaneous leishmaniasis are affected by oxidative 
stress, which may contribute to the progression of the disease.

PMID: 15544167

TITLE: The heat shock protein HSP70 and heat shock cognate protein HSC70
contribute to antimony tolerance in the protozoan parasite leishmania.

AUTHORS: Christian Brochu, Anass Haimeur, Marc Ouellette

AFFILIATION: Centre de Recherche en Infectiologie du Centre de Recherche du CHUL
and Division de Microbiologie, Faculté de Médecine, Université Laval, CHUQ,
Pavilion CHUL, 2705, Boulevard Laurier, Sainte-Foy, Québec, Canada.

REFERENCE: Cell Stress Chaperones 2004  9(3):294-303

Antimony-containing drugs are still the drugs of choice in the treatment
 of infections caused by the parasite Leishmania. Resistance to antimony
 is now common in some parts of the world, and several mechanisms of 
resistance have been described. By transfecting cosmid banks and 
selecting with potassium antimonyl tartrate (SbIII), we have isolated a 
cosmid associated with resistance. This cosmid contains 2 copies of the 
heat shock protein 70 (HSP70) and 1 copy of the heat shock cognate 
protein 70 (HSC70). Several data linked HSP70 to antimony response and 
resistance. First, several Leishmania species, both as promastigotes and
 amastigotes, increased the expression of their HSP70 proteins when 
grown in the presence of 1 or 2 times the Effect Concentration 50% of 
SbIII. In several mutants selected for resistance to either SbIII or to 
the related metal arsenite, the HSP70 proteins were found to be 
overexpressed. This increase was also observed in revertant cells grown 
for several passages in the absence of SbIII, suggesting that this 
increased production of HSP70 is stable. Transfection of HSP70 or HSC70 
in Leishmania cells does not confer resistance directly, though these 
transfectants were better able to tolerate a shock with SbIII. Our 
results are consistent with HSP70 and HSC70 being a first line of 
defense against SbIII until more specific and efficient resistance 
mechanisms take over.

PMID: 15748079

TITLE: Factors affecting variations in exposure to infections by Leishmania
donovani in eastern Sudan.

AUTHORS: D E A Elnaiem, A M Mukhawi, M M Hassan, M E Osman, O F Osman, M S
Abdeen, M A Abdel Raheems

AFFILIATION: Department of Zoology, Faculty of Science, University of Khartoum,
Khartoum, Sudan.

REFERENCE: East Mediterr Health J 2003 Jul 9(4):827-36

A cross-sectional survey was carried out in Gedaref state, eastern Sudan
 to investigate the prevalence of positive leishmanin skin tests and 
environmental factors related to Leishmania donovani infection. A total 
of 3835 people living in 11 villages in 3 regions were screened. Soil 
types and tree densities were determined in 33 villages inhabited by 44 
different tribes. The highest rates of positive skin tests were in Rahad
 region (33.9%), Atbara (21.6%) and Gedaref (10.6%), with an average of 
21.1% for the state. Risk of infection by L. donovani varied 
significantly between different tribes. Higher densities of Acacia and 
Balanites spp. trees were in Masaleet villages, suggesting that the 
relatively high risk of L. donovani exposure in this tribe is due to 
environmental factors.

PMID: 15846918

TITLE: [Building of a genomic library of Leishmania amazonensis and its
expression in BALB/c mice's muscle]

AUTHORS: A M Alvarez, E A Amador, M M Elías, R G Miniet, M E Garcia, A A

AFFILIATION: Instituto de Medicina Tropical "Pedro Kounrí", Apartado 601,
Marianao, Ciudad de La Habana, Cuba. amontalvo at ipk.sld.cu

REFERENCE: Rev Cubana Med Trop 2001 Sep-Dec 53(3):154-60

A genomic library of Leishaminia amazonensis was built through a pcDNA3 
vector, with expression promoter in eukaryot cells, to contribute to the
 application of immunization technology with nucleic acids in 
leishmaniasis. To show the expression genomic library in the muscles of 
mice immunized with it, the indirect immunofluoresce technique was used
. A mix of sera with high antileishmania titers from an area where L.
braziliensis infection is predominant was used as primary antibody. A 
library of 80% recombinant clones was obtained. Antigen determinant 
expression was confirmed in immunized BALB/c mice's muscles, according 
to the results of immunofluorescence testing.


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PMID: 15642973

TITLE: Treatment of visceral leishmaniasis in 2004.

AUTHORS: Henry W Murray

AFFILIATION: Department of Medicine, Weill Medical College of Cornell
University, New York, New York 10021, USA. hwmurray at med.cornell.edu

REFERENCE: Am J Trop Med Hyg 2004 Dec 71(6):787-94

In 2004, visceral leishmaniasis (kala-azar) maintains its status as a 
neglected, if not "most neglected" disease. Lack of affordable
 new drugs, still a basic unsolved problem, has also been joined by 
additional therapeutic obstacles including large-scale resistance to 
pentavalent antimony (Sb) in India and coinfection with human immuno-
deficiency virus in all endemic regions. Nevertheless, available 
treatment options have actually expanded because the energetic clinical 
trials effort of the past decade has yielded tangible advances. This 
progress includes successful application of less expensive generic Sb; 
rediscovery of the high-level efficacy of amphotericin B; implementation
 of short-course parenteral regimens (lipid formulations of amphotericin
 B); potential to replace Sb and amphotericin B with price-capped 
paromyomycin; and identification of the first effective oral agent (
miltefosine). How to sustain and move this progress ahead, make new 
advances practical (e.g., affordable, and therefore, deployable), and 
how to translate promising experimental approaches into actual therapy 
remain difficult next steps in the treatment of kala-azar.

PMID: 15569787

TITLE: Comparison of generic to branded pentavalent antimony for treatment of
new world cutaneous leishmaniasis.

AUTHORS: J Soto, L Valda-Rodriquez, J Toledo, L Vera-Navarro, M Luz, H
Monasterios-Torrico, J Vega, J Berman

AFFILIATION: Consorcio de Investigaciones Bioclínicas, Calle 60 A 5-54, Suite
201, Bogota, Colombia. jaime.soto at cable.net.co

REFERENCE: Am J Trop Med Hyg 2004 Nov 71(5):577-81

The cost of generic pentavalent antimony (generic stibogluconate) is 
approximately one-sixth that of branded pentavalent antimony (
stibogluconate in the form of Pentostam or meglumine antimoniate in the 
form of Glucantime. We compared generic stibogluconate to Pentostam and 
Glucantime for the treatment of cutaneous leishmaniasis patients in 
Bolivia and Colombia. For all 114 patients, the per-protocol cure rates 
were 83-91% and the intent-to-treat cure rates were 75-83%. The highest 
values were in the generic stibogluconate group. The incidence of 
pancreatic enzyme abnormalities was 48-88% and the incidence of liver 
enzyme abnormalities was 48-87%. The lowest incidences were in the 
generic stibogluconate group. The efficacy and tolerance of inexpensive 
generic stibogluconate appears comparable to branded formulations for 
the treatment of cutaneous leishmaniasis in these endemic regions.

REQUEST: [ leishmania ]

(19 articles match this request. 8 articles matching other requests removed)

PMID: 15845273

TITLE: Seroepidemiology of leptospirosis, toxoplasmosis, and leishmaniosis among
dogs in Ankara, Turkey.

AUTHORS: Ozkan Aslantaş, Vildan Ozdemir, Selçuk Kiliç, Cahit Babür

AFFILIATION: Mustafa Kemal University, Faculty of Veterinary Medicine,
Department of Microbiology, 31040 Antakya-Hatay, Turkey.

REFERENCE: Vet Parasitol 2005 May 129(3-4):187-91

Seroprevalence of five different Leptospira interrogans serovars, 
Toxoplasma gondii and Leishmania infantum in stray dogs in Ankara was 
investigated. A total of 116 dog sera collected from apparently healthy 
stray dogs were tested for L. interrogans serovars by microscopic 
agglutination test (MAT), for T. gondii antibodies by Sabin-Feldman dye 
test (SFDT), and for L. infantum antibodies by indirect fluoresence 
antibody test (IFAT). Of the 116 dogs, 51 (43.96%) were seropositive for
 leptospirosis, 72 (62.06%) for T. gondii and 3 (2.58%) for L. infantum
. No statistically significant difference was observed between male and 
female dogs in the seroprevalences of toxoplasmosis and leptospirosis (P
>0.05), but statistically significant difference was observed among 
different age groups in the seroprevalences of toxoplasmosis and 
leptospirosis (P<0.05). Although the seroprevalence of L. infantum 
was low, asymptomatic animals should be considered as a reservoir for 
the spread of the disease.

PMID: 15838793

TITLE: DC-SIGN-Mediated Transfer of HIV-1 Is Compromised by the Ability of
Leishmania infantum to Exploit DC-SIGN as a Ligand.

AUTHORS: Chenqi Zhao, Rejean Cantin, Marie Breton, Barbara Papadopoulou, Michel
J Tremblay

AFFILIATION: Research Center in Infectious Diseases, CHUL Research Center, and
Faculty of Medicine, Laval University, Quebec, Canada.

REFERENCE: J Infect Dis 2005 May 191(10):1665-9

DC-SIGN (dendritic cell-specific intercellular adhesion molecule 3-
grabbing nonintegrin) binds human immunodeficiency virus type 1 (HIV-1) 
and facilitates transfer of virus to permissive cells. Leishmania 
parasites also exploit DC-SIGN as a receptor. Here, we report that 
transfer of HIV-1 to target cells is markedly reduced when DC-SIGN(+) 
cells are preincubated with Leishmania amastigotes before pulsing with 
virions. Moreover, binding of HIV-1 to DC-SIGN(+) cells is diminished by
 the presence of Leishmania amastigotes. Our findings provide novel 
insight into the complex interactions between HIV-1 and Leishmania 
parasites. The ability of both HIV-1 and Leishmania parasites to bind to
 the same cell-surface constituent to gain entry into dendritic cells 
might have an impact on the immunological and pathological events 
associated with HIV-1 infection.

PMID: 15845279

TITLE: Epidemiological aspects of canine visceral leishmaniosis in the Islamic
Republic of Iran.

AUTHORS: Mehdi Mohebali, Homa Hajjaran, Yazdan Hamzavi, Iraj Mobedi, Shahnam
Arshi, Zabih Zarei, Behnaz Akhoundi, Koroush Manouchehri Naeini, Reza Avizeh,
Mehdi Fakhar

AFFILIATION: School of Public Health Research, Tehran University of Medical
Sciences, Department of Medical Parasitology, P.O. Box 14155-6446, Tehran,

REFERENCE: Vet Parasitol 2005 May 129(3-4):243-51

An epidemiological study to examine the sero-prevalence of zoonotic 
visceral leishmaniosis (ZVL) among domestic and wild canines in endemic 
foci of Iran was carried out during 1999-2003 to assess the distribution
 of the disease and the possible association between infection in dogs, 
wild canines and people. Anti-leishmanial antibodies were detected by 
the direct agglutination test (DAT). Parasitological study was performed
 for all captured wild canines and were detected in some of the 
seropositive dogs with specific clinical signs (n=107). Serum samples (n
=1568) were collected from domestic dogs in villages that are known 
endemic foci of human visceral leishmaniosis (HVL). Wild canine sera 
were collected from jackals (Canis aureus,n=10), foxes (Vulpes vulpes,n=
10) and wolves (Canis lupus,n=10). Of the 1568 serum sampled collected 
from domestic dogs, 222 (14.2%) were positive by DAT (1:320 and above). 
No statistically significant difference was found between male (15.2%) 
and female (11.8%) sero-prevalence (P=0.083). Dogs of 8 years and above 
showed the highest sero-prevalence (40.6%). Only 23.9% of the 
seropositive domestic dogs had clinical signs. Parasitology and serology
 tests that were performed in 30 wild canines showed 10% these animals 
were infected by Leishmania infantum. Ten out of 11 Leishmania spp. 
isolated from the dogs and wild canines were identified as L. infantum 
and one other as L. tropica by molecular and biochemical techniques. For
 the first time in Iran, L. infantum and L. tropica were isolated from 
viscera of both a wolf and a domestic dog.

PMID: 15848791

TITLE: Altered platelet aggregation and coagulation disorders related to
clinical findings in 30 dogs naturally infected by Leishmania infantum.

AUTHORS: P Ciaramella, A Pelagalli, L Cortese, M E Pero, M Corona, P Lombardi, L
Avallone, A Persechino

AFFILIATION: Department of Veterinary Clinical Science, Section of Internal
Medicine, University of Naples, Federico II, Via Delpino 1, 80137 Napoli,

REFERENCE: Vet J 2005 May 169(3):465-7

PMID: 15606359

TITLE: Mutational analysis of the active-site residues crucial for catalytic
activity of adenosine kinase from Leishmania donovani.

AUTHORS: Rupak Datta, Ishita Das, Banibrata Sen, Anutosh Chakraborty, Subrata
Adak, Chhabinath Mandal, Alok K Datta

AFFILIATION: Division of Infectious Diseases, Leishmania Group, Indian Institute
of Chemical Biology, 4, Raja S.C. Mullick Road, Kolkata 700 032, India.

REFERENCE: Biochem J 2005 May 387(Pt 3):591-600

Leishmania donovani adenosine kinase (LdAdK) plays a pivotal role in 
scavenging of purines from the host. Exploiting interspecies homology 
and structural co-ordinates of the enzyme from other sources, we 
generated a model of LdAdK that led us to target several amino acid 
residues (namely Gly-62, Arg-69, Arg-131 and Asp-299). Replacement of 
Gly-62 with aspartate caused a drastic reduction in catalytic activity, 
with decreased affinity for either substrate. Asp-299 was found to be 
catalytically indispensable. Mutation of either Arg-131 or Arg-69 caused
 a significant reduction in k(cat). R69A (Arg-69-->Ala) and R131A 
mutants exhibited unaltered K(m) for either substrate, whereas ATP K(m) 
for R69K increased 6-fold. Importance of both of the arginine residues 
was reaffirmed by the R69K/R131A double mutant, which exhibited approx. 
0.5% residual activity with a large increase in ATP K(m). Phenylglyoxal
, which inhibits the wild-type enzyme, also inactivated the arginine 
mutants to different extents. Adenosine protected both of the Arg-69 
mutants, but not the R131A variant, from inactivation. Binding 
experiments revealed that the AMP-binding property of R69K or R69A and 
D299A mutants remained largely unaltered, but R131A and R69K/R131A 
mutants lost their AMP binding ability significantly. The G62D mutant 
did not bind AMP at all. Free energy calculations indicated that Arg-69 
and Arg-131 are functionally independent. Thus, apart from the mandatory
 requirement of flexibility around the diglycyl (Gly-61-Gly-62) motif, 
our results identified Asp-299 and Arg-131 as key catalytic residues, 
with the former functioning as the proton abstractor from the 5'-OH of 
adenosine, while the latter acts as a bidentate electrophile to 
stabilize the negative charge on the leaving group during the phosphate 
transfer. Moreover, the positive charge distribution of Arg-69 probably 
helps in maintaining the flexibility of the alpha-3 helix needed for 
proper domain movement. These findings provide the first comprehensive 
biochemical evidence implicating the mechanistic roles of the 
functionally important residues of this chemotherapeutically exploitable

PMID: 15711017

TITLE: N-terminal Region of the Large Subunit of Leishmania donovani Bisubunit
Topoisomerase I Is Involved in DNA Relaxation and Interaction with the Smaller

AUTHORS: Benu Brata Das, Nilkantha Sen, Somdeb Bose Dasgupta, Agneyo Ganguly,
Hemanta K Majumder

AFFILIATION: Department of Molecular Parasitology, Indian Institute of Chemical
Biology, 4 Raja S. C. Mullick Road, Kolkata 700032, India.

REFERENCE: J Biol Chem 2005 Apr 280(16):16335-44

Leishmania donovani topoisomerase I is an unusual bisubunit enzyme. We 
have demonstrated earlier that the large and small subunit could be 
reconstituted in vitro to show topoisomerase I activity. We extend our 
biochemical study to evaluate the role of the large subunit in 
topoisomerase activity. The large subunit (LdTOP1L) shows a substantial 
degree of homology with the core DNA binding domain of the topoisomerase
 IB family. Two N-terminal truncation constructs, LdTOP1Delta39L (
lacking amino acids 1-39) and LdTOP1Delta99L (lacking amino acids 1-99) 
of the large subunit were generated and mixed with intact small subunit
 (LdTOP1S). Our observations reveal that residues within amino acids 1-
39 of the large subunit have significant roles in modulating 
topoisomerase I activity (i.e. in vitro DNA relaxation, camptothecin 
sensitivity, cleavage activity, and DNA binding affinity). Interestingly
, the mutant LdTOP1Delta99LS was unable to show topoisomerase I activity
. Investigation of the loss of activity indicates that LdTOP1Delta99L 
was unable to pull down glutathione S-transferase-LdTOP1S in an Ni(2+)-
nitrilotriacetic acid co-immobilization experiment. For further analysis
, we co-expressed LdTOP1L and LdTOP1S in Escherichia coli BL21(DE3)pLysS
 cells. The lysate shows topoisomerase I activity. Immunoprecipitation 
revealed that LdTOP1L could interact with LdTOP1S, indicating the 
subunit interaction in bacterial cells, whereas immunoprecipitation of 
bacterial lysate co-expressing LdTOP1Delta99L and LdTOP1S reveals that 
LdTOP1Delta99L was significantly deficient at interacting with LdTOP1S 
to reconstitute topoisomerase I activity. This study demonstrates that 
heterodimerization between the large and small subunits of the bisubunit
 enzyme appears to be an absolute requirement for topoisomerase activity
. The residue within amino acids 1-39 from the N-terminal end of the 
large subunit regulates DNA topology during relaxation by controlling 
noncovalent DNA binding or by coordinating DNA contacts by other parts 
of the enzyme.

PMID: 15828834

TITLE: Pyridinium-1-yl bisphosphonates are potent inhibitors of farnesyl
diphosphate synthase and bone resorption.

AUTHORS: John M Sanders, Yongcheng Song, Julian M W Chan, Yonghui Zhang, Samuel
Jennings, Thomas Kosztowski, Sarah Odeh, Ryan Flessner, Christine
Schwerdtfeger, Evangelia Kotsikorou, Gary A Meints, Aurora Ortiz Gómez,
Dolores González-Pacanowska, Amy M Raker, Hong Wang, Ermond R van Beek,
Socrates E Papapoulos, Craig T Morita, Eric Oldfield

AFFILIATION: Department of Chemistry, 600 South Mathews Avenue, University of
Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.

REFERENCE: J Med Chem 2005 Apr 48(8):2957-63

We report the design, synthesis and testing of a series of novel 
bisphosphonates, pyridinium-1-yl-hydroxy-bisphosphonates, based on the 
results of comparative molecular similarity indices analysis and 
pharmacophore modeling studies of farnesyl diphosphate synthase (FPPS) 
inhibition, human Vgamma2Vdelta2 T cell activation and bone resorption 
inhibition. The most potent molecules have high activity against an 
expressed FPPS from Leishmania major, in Dictyostelium discoideum growth
 inhibition, in gammadelta T cell activation and in an in vitro bone 
resorption assay. As such, they represent useful new leads for the 
discovery of new bone resorption, antiinfective and anticancer drugs.

PMID: 15849344

TITLE: Two cases of feline leishmaniosis in Switzerland.

AUTHORS: S Rüfenacht, H Sager, N Müller, V Schaerer, A Heier, M M Welle, P J

AFFILIATION: Dermatology Unit, Department of Clinical Veterinary Medicine.

REFERENCE: Vet Rec 2005 Apr 156(17):542

Two cats with Leishmania species infections were investigated. The first
 had been imported from Spain with a non-healing, ulcerated nodule on a 
hindleg. The presence of Leishmania species was detected by 
histopathology and pcr on samples of skin. The lesion was unresponsive 
to treatment with allopurinol for three months but the cat was treated 
successfully by removing the lesion surgically. The second cat had lived
 in both Spain and Switzerland, and had a history of recurrent skin 
lesions on its head and neck. A diagnosis of pemphigus foliaceus was 
made on the basis of histopathology, but Leishmania species serology (
elisa) and pcr of skin were positive, leading to a diagnosis of a 
Leishmania species infection combined with pemphigus foliaceus.

PMID: 15846906

TITLE: [Immunization with Leishmania amazonensis subgenomic libraries protects
BALB/c mice against the challenge]

AUTHORS: Ana M MontalvoAlvarez, Lianet Monzote Fidalgo, Lisset Fonseca Géigel,
Ivón Montano Goodridge, Luis Fonte Galindo, Manuel Soto, José M Requena

AFFILIATION: Instituto de Medicina Tropical "Pedro Kouri" Ciudad de La Habana,
Cuba. amontalvo at ipk.sld.cu

REFERENCE: Rev Cubana Med Trop 2004 May-Aug 56(2):103-10

A genomic library of Leishmania amazonensis in expression vector of 
eukaryote cells (pEF1HisA, pEF1HisB, pEF1HisC) was prepared. Also two 
subgenomic libraries having each 500 clones approximately were created 
and BALB/c mice were immunized with 50 mg/0,1 mL of DNA from each. Two 
immunizations were administered intramuscularly at 15-day interval. 
Groups of control mice were immunized with DNA from empty plasmid 
pEF1His, with soluble parasite antigen (100 mg/0,1 mL) and saline 
solution. The size of lesions was measured for 12 weeks and at the end 
of the experiment, the parasite load at lesion sites was determined by 
plaque microtitration method. In mice immunized with subgenomic library 
DNAI and with soluble antigens,the size of lesions was controlled, which
 reached an statistical difference (p< 0,05) in relation to the rest 
of groups whose lesions increased. The parasite load found in lesion 
sites confirmed the previous results; the number of promastigots was 
significantly lower in those mice already protected. It was concluded 
that in subgenomic library DNA1 there should be genes or gene fragments 
whose in vivo expression induces protective immune response against the 
challenge in the murine model used.

PMID: 15748081

TITLE: Field evaluation of latex agglutination test for detecting urinary
antigens in visceral leishmaniasis in Sudan.

AUTHORS: S H El-Safi, A Abdel-Haleem, A Hammad, I El-Basha, A Omer, H G Kareem,
M Boelaert, M Chance, M Hommel

AFFILIATION: Faculty of Medicine, University of Khartoum, Khartoum, Sudan.

REFERENCE: East Mediterr Health J 2003 Jul 9(4):844-55

A latex agglutination test to detect urinary antigens for visceral 
leishmaniasis (VL) was studied. In 204 patients with suspected VL, KAtex
 had a sensitivity of 95.2% with good agreement with microscopy smears 
but poor agreement with 4 different serology tests. It was also positive
 in 2 confirmed VL cases co-infected with HIV. In all K4tex-positive 
confirmed cases actively followed up after treatment, the test became 
negative 1 month after completion of treatment. While IC4tex had a 
specificity of 100% in healthy endemic and non-endemic controls, the 
direct agglutination test (DAT) was positive in 14% of the KAtex-
negative healthy endemic controls. KAtex is a simple addition to the 
diagnostics of VL particularly at field level and as a complementary 
test for the diagnosis of VL in smear-negative cases with positive DAT 


 The following references are revised files and are brought to you in accordance
to license agreement with the NLM.


PMID: 15463609

TITLE: Leishmania: sex, lies and karyotype.

AUTHORS: P Bastien, C Blaineau, M Pages

AFFILIATION: Laboratoire de Parasitologie, Faculté de Médecine, Montpellier,

REFERENCE: Parasitol Today 1992 May 8(5):174-7

The exploration of the genome of the tryponosomotid protozoan Leishmania
 has been difficult until recently owing to a number of obstacles, not 
least our ignorance of the ploidy and of the number of chromosomes (as 
in many other protozoa, the latter do not condense during mitosis), the 
uncertainty of the species concept in these allegedly asexual protozoa 
and the absence of classical genetic studies. Here, Patrick Bastien, 
Christine Bloineou and Michel Pages discuss the advances in this field 
brought about by the advent of molecular biology and its techniques, 
with on emphasis on ploidy and genetic exchange. In particular, they 
discuss the data from pulsed field gel electrophoresis (PFGE). When 
coupled with DNA restriction analysis, PFGE constitutes a powerful tool 
for the direct examination o f chromosomes of protozoa.

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