[leish-l] Fwd: Articles found by RefScout 27/04/2004 - 17/2005
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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
Peru.
AUTHORS: C Miranda-Verástegui, A Llanos-Cuentas, I Arévalo, B J Ward, G
Matlashewski
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 <
; 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
lesions.
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
Brazil.
AUTHORS: Fernanda S Oliveira, Claude Pirmez, Marize Q Pires, Reginaldo P Brazil,
Raquel S Pacheco
AFFILIATION: Laboratório de Sistemática BioquÃmica, Departamento de
BioquÃmica 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 PiauÃ, 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
Française.
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 ElÃas, R G Miniet, M E Garcia, A A
DomÃnguez
AFFILIATION: Instituto de Medicina Tropical "Pedro KounrÃ", 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 BioclÃnicas, 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,
Iran.
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,
Italy.
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
enzyme.
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
Subunit.
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
Roosje
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
results.
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PMID: 15463609
TITLE: Leishmania: sex, lies and karyotype.
AUTHORS: P Bastien, C Blaineau, M Pages
AFFILIATION: Laboratoire de Parasitologie, Faculté de Médecine, Montpellier,
France.
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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