[leish-l] Fwd: Articles found by RefScout 2005/11/09 2005/45
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REQUEST: [ leishmaniasis ]
(16 articles match this request)
PMID: 16267771
TITLE: The Predictive Validity of Naturally Acquired Delayed-Type
Hypersensitivity to Leishmanin in Resistance to Leishmania major-Associated
Cutaneous Leishmaniasis.
AUTHORS: Afif Ben Salah, Hechmi Louzir, Sadok Chlif, Mourad Mokni, Amor Zaatour,
Mohamed Raouene, Riadh Ben Ismail, Koussay Dellagi
AFFILIATION: Laboratory of Epidemiology and Ecology of Parasitic Diseases,
Institut Pasteur de Tunis, Tunis-Belvedere, Tunisia.
hechmi.louzir at pasteur.rns.tn.
REFERENCE: J Infect Dis 2005 Dec 192(11):1981-7
To accurately quantify the different outcomes of Leishmania major
infection and to evaluate the fraction of zoonotic cutaneous
leishmaniasis (ZCL) cases prevented by naturally acquired leishmanin
skin test (LST) reactivity, a cohort of 470 children was followed up in
2 endemic foci, Remada and Dhiba, in southern Tunisia. During May 1997,
before the ZCL emergence season, LST was performed, and results were
reassessed 12 months later. Active case detection during the ZCL
emergence season showed a high incidence of ZCL: 57.0% in Remada and 13.
7% in Dhiba. The preventive fraction of ZCL conferred by LST reactivity
increased proportionally with the reaction size before the emergence
season, revealing a dose-response effect of ~70%. In addition,
asymptomatic L. major infection appeared to be a significant form of
natural immunization, particularly in the context of relatively low
transmission. These findings may help in the design and evaluation of
vaccines.
PMID: 16255674
TITLE: Clinical status of agents being developed for leishmaniasis.
AUTHORS: Jonathan Berman
AFFILIATION: National Center for Complementary and Alternative Medicine, 6707
Democracy Boulevard, Bethesda, MD 20892, USA. bermanjo at mail.nih.gov
REFERENCE: Expert Opin Investig Drugs 2005 Nov 14(11):1337-46
Leishmaniasis, which exists in both visceral and cutaneous forms, is
currently treated with intramuscular antimony or intravenous
amphotericin B. The primary unmet need is for oral therapy. Of the
several drugs in clinical development, miltefosine is unique in being an
oral agent with efficacy against both forms of the disease. Sitamaquine
is an oral agent with substantial but not sufficient efficacy against
visceral disease. Oral fluconazole has been shown to be more effective
than placebo in one instance: for Leishmania major cutaneous disease
from Saudi Arabia. Paromomycin is in widespread trial. Topical
paromomycin formulations are being tested for cutaneous disease, and
intramuscular paromomycin is in Phase III trial for Indian visceral
disease. The most likely replacements for present therapy are oral
miltefosine for many of the visceral and cutaneous syndromes,
intramuscular paromomycin for visceral disease and topical paromomycin
for some forms of cutaneous disease.
PMID: 16272479
TITLE: Evaluation of enzyme-linked immunosorbent assays, an
immunofluorescent-antibody test, and two rapid tests
(immunochromatographic-dipstick and gel tests) for serological diagnosis of
symptomatic and asymptomatic leishmania infections in dogs.
AUTHORS: Maik Mettler, Felix Grimm, Gioia Capelli, Heinrich Camp, Peter
Deplazes
AFFILIATION: Institute of Parasitology, University of Zurich, Winterthurerstr
266a, CH-8057 Zurich, Switzerland. deplazesp at access.unizh.ch.
REFERENCE: J Clin Microbiol 2005 Nov 43(11):5515-9
Enzyme-linked immunosorbent assays (ELISAs) based on soluble antigens
derived from promastigote or amastigote-like stages of Leishmania
infantum and on the recombinant rK39 antigen, each in combination with
different conjugates [anti-immunoglobulin G1 [IgG1], anti-IgG2, anti-IgG
(gamma), and anti-IgG heavy plus light chains], were compared to an
immunofluorescent-antibody test (IFAT) and two commercially available
rapid test systems (DiaMed-Vet-IT Leish and ID-PaGIA canine
leishmaniasis antibody test) for the detection of specific anti-
Leishmania antibodies in symptomatic and asymptomatic dogs with proven L
. infantum infections. ELISAs based on soluble promastigote and
amastigote antigens had very high sensitivities in symptomatic (n = 30;
100%) and asymptomatic dogs (n = 17; 94.1 to 100%), except when combined
with the anti-IgG1 conjugate (41.2 to 82.4%). Specificities were high
for all combinations (n = 50; 96 to 100%). The rK39 ELISA detected fewer
asymptomatic cases (sensitivities, 52.9 to 64.7%) but was highly
specific (96 to 100%). The IFAT was 90% sensitive in symptomatic dogs
but was significantly less sensitive in asymptomatic cases (29.4%).
However, it had an excellent specificity (100%). Test performances of
the rapid tests based on the rK39 antigen were comparable to the ELISAs
based on the same antigen. ELISAs based on soluble promastigote or
amastigote antigens seem to be most suited for the serological diagnosis
of canine Leishmania infections in both symptomatic and asymptomatic
dogs. IFAT and the rK39 ELISA lack sensitivity in asymptomatic cases but
are highly specific. Rapid tests like the rK39 dipstick test or the ID-
PaGIA are helpful for confirming clinically suspected cases because of
their high specificities in symptomatic animals.
PMID: 16272487
TITLE: Quantitative nucleic Acid sequence-based assay as a new molecular tool
for detection and quantification of leishmania parasites in skin biopsy
samples.
AUTHORS: Wendy F van der Meide, Gerard J Schoone, William R Faber, Jim E
Zeegelaar, Henry J C de Vries, Yusuf Ozbel, Rudy F M Lai A Fat, LeÃla I A R C
Coelho, Masoom Kassi, Henk D F H Schallig
AFFILIATION: Koninklijk Instituut voor de Tropen/Royal Tropical Institute, KIT
Biomedical Research, Meibergdreef 39, 1105 AZ Amsterdam, The Netherlands.
w.v.d.meide at kit.nl.
REFERENCE: J Clin Microbiol 2005 Nov 43(11):5560-6
Currently available methods for the diagnosis of cutaneous leishmaniasis
(CL) have low sensitivities or are unable to quantify the number of
viable parasites. This constitutes a major obstacle for the diagnosis of
the disease and for the study of the effectiveness of treatment
schedules and urges the development of improved detection methods. In
this study, quantitative nucleic acid sequence-based amplification (QT-
NASBA) technology was used to detect and quantify Leishmania parasites
in skin biopsy samples from CL patients. The assay is based on the
detection of a small subunit rRNA (18S rRNA), which may allow for the
detection of viable parasites. The QT-NASBA assay was evaluated using in
vitro-cultured promastigotes and amastigotes and 2-mm skin biopsy
samples from Old and New World CL patients. The study demonstrated that
the lower detection limit of the QT-NASBA was two parasites per biopsy
sample. Parasites could be quantified in a range of 2 to 11,300,000
parasites per biopsy sample. The QT-NASBA could detect levels of
parasites 100-fold lower than those detected by conventional PCR. Test
evaluation revealed that the QT-NASBA had a sensitivity of 97.5% and a
specificity of 100% in the present study. The QT-NASBA is a highly
sensitive and specific method that allows quantification of both Old and
New World Leishmania parasites in skin biopsy samples and may provide
an important tool for diagnosis as well as for monitoring the therapy of
CL patients.
PMID: 16266015
TITLE: Placentitis associated with leishmaniasis in a dog.
AUTHORS: J P Dubey, Alexa C Rosypal, Virginia Pierce, Stuart N Scheinberg, David
S Lindsay
AFFILIATION: Animal Parasitic Diseases Laboratory, Animal and Natural Resources
Institute, Agricultural Research Service, USDA, Bldg 1001, Beltsville, MD
20705, USA.
REFERENCE: J Am Vet Med Assoc 2005 Oct 227(8):1266-9, 1250
A 1.5-year-old Coonhound from Maryland aborted 7 fetuses. Placenta and
internal tissues of 1 fetus were examined histologically. The
predominant lesion was placentitis characterized by necrosis and
infiltration of mixed leukocytes. Numerous Leishmania spp amastigotes
were identified in placental trophoblasts, and the diagnosis was
confirmed by use of immunohistochemical staining with Leishmania-
specific antibodies. Protozoa were not found in the fetal tissues. An
indirect fluorescent antibody test yielded a serum titer of 1:100, and a
recombinant K39 immunoassay of serum yielded positive results for the
K39 Leishmania antigen.
PMID: 16156976
TITLE: Removal of bacterial and yeast contamination from Leishmania promastigote
cultures, by agar plating.
AUTHORS: M Muniaraj, A K Gupta, S Narayan, S Kumar, P K Sinha, K Kishore, P Das
AFFILIATION: Rajendra Memorial Research Institute of Medical Sciences, (Indian
Council of Medical Research), Agam Kuan, Patna. mmuniaraj at yahoo.com
REFERENCE: Ann Trop Med Parasitol 2005 Sep 99(6):617-21
PMID: 16267958
TITLE: [Dermatologic manifestations associated with immune reconstitution
syndrome in HIV+ patients starting HAART: a retrospective study in French
Guiana]
AUTHORS: E Sarazin, M Nacher, Y Toure, E Clyti, M El Guedj, C Aznar, T Vaz, D
Sainte-Marie, M Sobesky, B Carme, P Couppié
AFFILIATION: Service de dermatologie, Centre hospitalier Andrée-Rosemon, Avenue
des Flamboyants, 97306, Cayenne, Guyane française.
REFERENCE: Bull Soc Pathol Exot 2005 Sep 98(3):187-92
Immune reconstitution syndrome (IRIS) is an unusual inflammatory
reaction to an opportunistic infection in an HIV-positive patient. This
syndrome occurs when immunity is restored in the first months of an
effective highly active antiretroviral treatment (HAART). First, we
described all patients with a cutaneous form of IRIS. Then, between 1992
and 2004 we conducted a retrospective cohort study comparing Herpes
Zoster and Herpes Simplex infections among untreated patients, patients
treated by HAART for < or = six months, and patients treated for >
six months. We observed three cases of atypical leprosy and three
original observations: two of these were fistulisation of lymph node
histoplasmosis and tuberculosis, the third one reports the recurrence of
a treated cutaneous leishmaniasis. Multivariate analysis showed that,
after controlling for age, sex and CD4 counts, patients receiving HAART
for < or = six months were more likely to develop Herpes Zoster or
herpes simplex infections (p < 0.005). Herpes Simplex and Herpes
Zoster infections are the two most frequent dermatological
manifestations in our tropical setting. Although mycobacterial
infections are more rarely observed than in visceral IRIS, the increased
incidence of leprosy may be quite significant when the availability of
HAART spreads to developing countries.
PMID: 16156970
TITLE: Microculture for the isolation of Leishmania parasites from cutaneous
lesions -- Sri Lankan experience.
AUTHORS: R L Ihalamulla, U S Rajapaksa, N D Karunaweera
AFFILIATION: Department of Parasitology, Faculty of Medicine, University of
Colombo, Sri Lanka.
REFERENCE: Ann Trop Med Parasitol 2005 Sep 99(6):571-5
Novy, McNeal and Nicolle (NNN) medium and Evans' modified Tobie's medium
are two conventional media for the isolation of Leishmania parasites in
in-vitro cultures. Both are biphasic, with a solid layer of blood agar
, and are normally prepared in glass test-tubes. In Sri Lanka at least,
a monophasic microcapillary culture, based solely on RPMI 1640 medium
supplemented with foetal calf serum, has been found simpler, more
economical and more sensitive, for the isolation of L. donovani from
skin lesions, than the use of Evans' modified Tobie's medium.
PMID: 15978364
TITLE: [Leishmania transmission to children in Southern France]
AUTHORS: P Minodier, P Blanc, G Noël, N Galon, J-M Garnier
AFFILIATION: Urgences Pédiatriques, CHU Nord, Chemin des Bourrelly, 13915
Marseille Cedex 20, France.
REFERENCE: Med Mal Infect 2005 Jun 35 Suppl 2():S114-6
PMID: 15978395
TITLE: [Visceral leishmaniases: epidemiology and diagnosis]
AUTHORS: P Marty
AFFILIATION: Laboratoire de Parasitologie-Mycologie, Centre Hospitalier
Universitaire de Nice et Equipe de Recherche sur les Leishmanioses (ERLEISH),
Faculté de Médecine, Université de Nice-Sophia Antipolis, 28, avenue de
Valombrose 06107 Nice Cedex 2, France.
REFERENCE: Med Mal Infect 2005 Jun 35 Suppl 2():S72-3
PMID: 16252191
TITLE: A case of visceral leishmaniasis misdiagnosed as autoimmune hepatitis.
AUTHORS: Buket Dalgiç, Ismail Dursun, Gülen Akyol
REFERENCE: Turk J Gastroenterol 2005 Mar 16(1):52-3
PMID: 16020124
TITLE: Kala-azar associated with coombs-positive autoimmune hemolytic anemia in
the patients coming from the endemic area of this disease and successful
treatment of these patients with liposomal amphotericin B.
AUTHORS: Erol Erduran, Aysenur Bahadir, Yusuf Gedik
AFFILIATION: Karadeniz Technical University, School of Medicine, Department of
Pediatrics, Trabzon, Turkey. erduran at ktu.edu.tr
REFERENCE: Pediatr Hematol Oncol 2005 Jul-Aug 22(5):349-55
Kala-azar is an intracellular parasitic infection that infects and
multiplies in the macrophages of the liver, the spleen, and the bone
marrow. It is characterized by intermittent fever, hepatosplenomegaly,
pancytopenia, and hypergammaglobulinemia. Although anemia is a usual
finding, Coombs-positive autoimmune hemolytic anemia (AIHA) has rarely
been reported with this disease. Pentavalent antimonial compounds remain
the mainstay of treatment worldwide. Liposomal amphotericin B (L-AmB)
is currently preferred in the treatment of kala-azar because of the
resistance to pentavalent antimonals. The authors diagnosed kala-azar
associated with Coombs-positive AIHA in 3 patients and treated them with
L-AmB (1-5 mg/kg/day) for 30-36 days. Now, all of these patients are
healthy following up at the outpatient base for 18-34 months. Kala-azar
must be considered in patients with Coombs-positive AIHA and living in
and coming from the endemic region for this disease, and it can be
successfully treated with L-AmB.
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PMID: 15555069
TITLE: Spectrum of clinical disease in a series of 135 hospitalised HIV-infected
patients from north India.
AUTHORS: S K Sharma, Tamilarasu Kadhiravan, Amit Banga, Tarun Goyal, Indrish
Bhatia, P K Saha
AFFILIATION: Department of Medicine, All India Institute of Medical Sciences,
New Delhi, India. sksharma at aiims.ac.in
REFERENCE: BMC Infect Dis 2004 Nov 4():52
BACKGROUND: Literature on the spectrum of opportunistic disease in human
immunodeficiency virus (HIV)-infected patients from developing
countries is sparse. The objective of this study was to document the
spectrum and determine the frequency of various opportunistic infections
(OIs) and non-infectious opportunistic diseases, in hospitalised HIV-
infected patients from north India. METHODS: One hundred and thirty five
consecutive, HIV-infected patients (age 34 +/- 10 years, females 17%)
admitted to a tertiary care hospital in north India, for the evaluation
and management of an OI or HIV-related disorder between January 2000 and
July 2003, were studied. RESULTS: Fever (71%) and weight loss (65%)
were the commonest presenting symptoms. Heterosexual transmission was
the commonest mode of HIV-acquisition. Tuberculosis (TB) was the
commonest OI (71%) followed by candidiasis (39.3%), Pneumocystis
jiroveci pneumonia (PCP) (7.4%), cryptococcal meningitis and cerebral
toxoplasmosis (3.7% each). Most of the cases of TB were disseminated (64
%). Apart from other well-recognised OIs, two patients had visceral
leishmaniasis. Two cases of HIV-associated lymphoma were encountered.
CD4+ cell counts were done in 109 patients. Majority of the patients (82
.6%) had CD4+ counts <200 cells/microL. Fifty patients (46%) had CD4
+ counts <50 cells/microL. Only 50 patients (37%) received
antiretroviral therapy. Twenty one patients (16%) died during hospital
stay. All but one deaths were due to TB (16 patients; 76%) and PCP (4
patients; 19%). CONCLUSIONS: A wide spectrum of disease, including both
OIs and non-infectious opportunistic diseases, is seen in hospitalised
HIV-infected patients from north India. Tuberculosis remains the most
common OI and is the commonest cause of death in these patients.
PMID: 15546498
TITLE: Zinc/copper imbalance reflects immune dysfunction in human leishmaniasis:
an ex vivo and in vitro study.
AUTHORS: Johan Van Weyenbergh, Gisélia Santana, Argemiro D'Oliveira, Anibal F
Santos, Carlos H Costa, Edgar M Carvalho, Aldina Barral, Manoel Barral-Netto
AFFILIATION: LIMI, Gonçalo Moniz Research Center -Oswaldo Cruz Foundation
(FIOCRUZ), Rua Waldemar Falcao 121, 40295-001 Salvador-BA, Brazil.
johan at cpqgm.fiocruz.br
REFERENCE: BMC Infect Dis 2004 Nov 4():50
BACKGROUND: The process of elimination of intracellular pathogens, such
as Leishmania, requires a Th1 type immune response, whereas a dominant
Th2 response leads to exacerbated disease. Experimental human zinc
deficiency decreases Th1 but not Th2 immune response. We investigated if
zinc and copper levels differ in different clinical forms of
leishmaniasis, and if these trace metals might be involved in the immune
response towards the parasite. METHODS: Blood was collected from 31
patients with either localized cutaneous (LCL), mucosal (ML) or visceral
(VL) leishmaniasis, as well as from 25 controls from endemic and non-
endemic areas. Anti-Leishmania humoral and cellular immune response were
evaluated by quantifying specific plasma IgG, lymphoproliferation and
cytokine production, respectively. Plasma levels of Cu and Zn were
quantified by atomic absorption spectrophotometry. RESULTS: A
significant decrease in plasma Zn was observed in all three patient
groups (p < 0.01 for LCL and ML, p < 0.001 for VL), as compared to
controls, but only VL (7/10) and ML (1/7) patients displayed overt Zn
deficiency. Plasma Cu was increased in LCL and VL (p < 0.001) but not
in ML, and was strongly correlated to anti-Leishmania IgG (Spearman r
= 0.65, p = 0.0028). Cu/Zn ratios were highest in patients with
deficient cellular (VL<<LCL<ML) and exacerbated humoral (VL>LCL
>ML) immune response. Ex vivo production of parasite-induced IFN-gamma
was negatively correlated to plasma Cu levels in LCL (r = -0.57, p = 0.
01). In vitro, increased Cu levels inhibited IFN-gamma production.
CONCLUSIONS: 1. Zn deficiency in VL and ML indicate possible therapeutic
administration of Zn in these severe forms of leishmaniasis. 2. Plasma
Cu positively correlates to humoral immune response across patient
groups. 3. Environmentally or genetically determined increases in Cu
levels might augment susceptibility to infection with intracellular
pathogens, by causing a decrease in IFN-gamma production.
PMID: 15225352
TITLE: Visceral leishmaniasis caused by Leishmania infantum in a Spanish patient
in Argentina: What is the origin of the infection? Case report.
AUTHORS: Joaquina MartÃn-Sánchez, José M Navarro-Mari, Juan Pasquau-Liaño,
Oscar D Salomón, Francisco Morillas-Márquez
AFFILIATION: Departamento de ParasitologÃa, Facultad de Farmacia, Campus
Universitario de Cartuja 18,071, Universidad de Granada, Spain.
joaquina at ugr.es
REFERENCE: BMC Infect Dis 2004 Jun 4():20
BACKGROUND: The question "Where have you been?" is a common
one asked by doctors in Northern Europe and America when faced with
clinical symptoms not typical of their country. This question must also
arise in the clinics of developing countries in which non-autochthonous
cases such as the one described here can appear. Important outbreaks of
Leishmania infantum have been recorded in the last decade in several
Latin American countries but its presence has not yet been recorded in
Argentina. We report the first case of visceral leishmaniasis owing to L
. infantum in this country. CASE PRESENTATION: A 71-year-old Spanish
woman who has been living in Mendoza, Argentina, during the last 40
years presented with a history of high fever and shivering, anemia,
leukopenia and splenomegaly over two years. Argentinian doctors did not
suspect visceral leishmaniasis even when the histological analysis
revealed the presence of "intracytoplasmatic spheroid particles
compatible with fungal or parasitic infection". After a serious
deterioration in her health, she was taken to Spain where she was
evaluated and visceral leishmaniasis was established. Specific
identification of the parasite was done by PCR-ELISA, isoenzyme
electrophoresis and RAPD-PCR. CONCLUSION: We would like to point out
that: i) cases such as the one described here, which appear in non-
endemic areas, can pass unnoticed by the clinical physician. ii) in
countries in which these introduced cases reside, in-depth
parasitological studies are required into vectors and possible
reservoirs to rule out the rare case of local infection and, once
infection has taken place, to ensure that this does not spread by
anthroponotic transmission or a competent reservoir.
PMID: 7743663
TITLE: During active viscerocutaneous leishmaniasis the anti-P2 humoral response
is specifically triggered by the parasite P proteins.
AUTHORS: M Soto, J M Requena, L Quijada, S O Angel, L C Gomez, F Guzman, M E
Patarroyo, C Alonso
AFFILIATION: Centro de BiologÃa Molecular Severo Ochoa, Universidad Autónoma
de Madrid, Cantoblanco, Spain.
REFERENCE: Clin Exp Immunol 1995 May 100(2):246-52
In this work we show that in the sera from dogs naturally infected with
the protozoan parasite Leishmania infantum there are antibodies that
react specifically against the parasite acidic ribosomal proteins LiP2a
and LiP2b, and that each one of the Leishmania P proteins elicits a
specific humoral immune response. Using synthetic peptides, the
antigenic epitope of these proteins has been mapped in a single region
located adjacent to the C-terminal domain highly conserved among the
eukaryotic P proteins. The anti-P antibodies elicited during the
Leishmania infection do not recognize the conserved C-terminal domain of
the parasite P proteins, in contrast with the findings reported in
Chagas' disease or systemic lupus erythematosus. The antigenic epitopes
of the LiP2a and LiP2b are almost identical in amino acid sequence. No
reactivity against Trypanosoma cruzi and human P proteins was found in
sera from L. infantum-infected dogs.
REQUEST: [ leishmania ]
(20 articles match this request. 8 articles matching other requests removed)
PMID: 16215758
TITLE: Unexplained complexity of the mitochondrial genome and transcriptome in
kinetoplastid flagellates.
AUTHORS: Julius Lukes, Hassan Hashimi, Alena ZÃková
AFFILIATION: Institute of Parasitology, Czech Academy of Sciences, Faculty of
Biology, University of South Bohemia, Branisovská 31, 37005, Ceské
Budejovice, Czech Republic, jula at paru.cas.cz.
REFERENCE: Curr Genet 2005 Nov 48(5):277-99
Kinetoplastids are flagellated protozoans, whose members include the
pathogens Trypanosoma brucei, T. cruzi and Leishmania species, that are
considered among the earliest diverging eukaryotes with a mitochondrion
. This organelle has become famous because of its many unusual
properties, which are unique to the order Kinetoplastida, including an
extensive kinetoplast DNA network and U-insertion/deletion type RNA
editing of its mitochondrial transcripts. In the last decade,
considerable progress has been made in elucidating the complex machinery
of RNA editing. Moreover, our understanding of the structure and
replication of kinetoplast DNA has also dramatically improved. Much less
however, is known, about the developmental regulation of RNA editing,
its integration with other RNA maturation processes, stability of
mitochondrial mRNAs, or evolution of the editing process itself. Yet the
profusion of genomic data recently made available by sequencing
consortia, in combination with methods of reverse genetics, hold promise
in understanding the complexity of this exciting organelle, knowledge
of which may enable us to fight these often medically important
protozoans.
PMID: 16272301
TITLE: DM Peptide-Editing Function Leads to Immunodominance in CD4 T Cell
Responses In Vivo.
AUTHORS: Navreet K Nanda, Elizabeth K Bikoff
AFFILIATION: Departments of Microbiology and Immunology, and Oncology, Lombardi
Cancer Center, Georgetown University Medical Center, Washington DC 20057.
REFERENCE: J Immunol 2005 Nov 175(10):6473-80
DM functions as a peptide editor for MHC class II-bound peptides. We
examined the hypothesis that DM peptide editing plays a key role in
focusing the in vivo CD4 T cell responses against complex pathogens and
protein Ags to only one, or at most a few, immunodominant peptides. Most
CD4 T cells elicited in the wild-type BALB/c (H-2(d)) mice infected
with Leishmania major predominantly recognize a single epitope 158-173
within Leishmania homologue of activated receptor for c-kinase (LACK),
as is the case when these mice are immunized with rLACK. Using DM-
deficient (DM(-/-)) H-2(d) mice, we now show that in the absence of DM,
the in vivo CD4 T cell responses to rLACK are skewed away from the
immunodominant epitopes and are diversified to include two novel
epitopes (LACK 33-48 and 261-276). DM(-/-) B10.BR (H-2(k)) mice showed
similar results. These results constitute the first demonstration of the
role of DM peptide editing in sculpting the specificity and
immunodominance in in vivo CD4 T cell responses.
PMID: 16272476
TITLE: Use of Full-Length Recombinant Calflagin and Its C Fragment for
Improvement of Diagnosis of Trypanosoma cruzi Infection.
AUTHORS: Iván S Marcipar, Cintia Roodveldt, Gerardo Corradi, MarÃa L Cabeza,
Maria Edileuza F Brito, Lucile M Floeter Winter, Alberto J Marcipar, Ariel M
Silber
AFFILIATION: Departamento de Fisiologia, Instituto de Biociências, Universidade
de São Paulo, Rua do Matão, Travessa 14, 101 Cidade Universitária
(05509-800), São Paulo, SP, Brazil. asilber at iq.usp.br.
REFERENCE: J Clin Microbiol 2005 Nov 43(11):5498-503
Serological diagnosis of Trypanosoma cruzi infection is hampered by
issues related to test specificity due to the cross-reactivity of most
antigens with proteins of related parasites such as Leishmania spp. The
recombinant calflagins are considered relevant antigens for the
diagnosis of infection by Trypanosoma cruzi. In the present work, we
describe two genes coding for putative calflagins in Leishmania major
with the N-terminal moieties presenting high similarity with T. cruzi
genes. This fact raised questions about their role in some cross-
recognition of this antigen by sera from Leishmania spp.-infected
individuals. The complete T. cruzi calflagin and two fragments of the
protein, consisting of 146 amino acids of the N-terminal and 65 amino
acids of the C-terminal regions, were expressed and evaluated against a
panel of sera, which included well-characterized samples from T. cruzi,
and Leishmania-infected patients. We were able to show that sera from
Leishmania (Viannia) braziliensis-infected individuals recognized the
recombinant full-length calflagin. Both the N-terminal and the complete
protein presented the same high sensitivity (98.5% of sera from T. cruzi
-infected patients was detected) but different specificities (94% and 98
%, respectively, when evaluated against sera from people not infected by
T. cruzi, including 15 sera from people infected with L. braziliensis
). The C-terminal fragment presented low sensitivity (70%) but 100%
specificity. We propose the use of these antigens in two sequential
assays to optimize the serological diagnosis of T. cruzi infection in
humans in geographic areas where Leishmania spp. infection is coendemic.
PMID: 16259128
TITLE: Screening of Leishmania APRT enzyme inhibitors.
AUTHORS: A R P Ambrozin, A C Leite, M Silva, P C Vieira, J B Fernandes, O H
Thiemann, M F das G F da Silva, G Oliva
AFFILIATION: Departamento de QuÃmica, Universidade Federal de São Carlos,
Brazil.
REFERENCE: Pharmazie 2005 Oct 60(10):781-4
Adenine phosphoribosyltransferase (APRT) enzyme from Leishmania
tarentolae has been proposed as a target for the rational search of new
leishmanicidal drugs. In this paper, we describe the evaluation of the
inhibitory activity on L. tarentolae APRT enzyme of 46 crude extracts of
Meliaceae and Rutaceae plants, besides three furoquinolone alkaloids.
The results showed that 21 extracts were able to decrease the APRT
enzymatic activity (IA% > or = 50). The methanolic extracts from roots
and leaves of Cedrela fissilis and from fruits, branches and leaves of
Cipadessa fruticosa have showed strong activities. Therefore, these
species could be a promising source of lead compounds for the rational
design of new leishmanicidal drugs. The phytochemical investigation of
an active fraction from Almeidea rubra afforded the alkaloids
isodutaduprine, isoskimmianine and isokokusagine, which showed low to
moderate activity on APRT.
PMID: 16130613
TITLE: Magnitude of unresponsiveness to sodium stibogluconate in the treatment
of visceral leishmaniasis in Bihar.
AUTHORS: V N R Das, A Ranjan, Sanjeev Bimal, N A Siddique, K Pandey, Nawin
Kumar, Neena Verma, V P Singh, P K Sinha, S K Bhattacharya
AFFILIATION: Rajendra Memorial Research Institute of Medical Sciences, Indian
Council of Medical Research, Agamkuan, Patna 800007, Bihar, India.
dirrmris at sancharnet.in
REFERENCE: Natl Med J India 2005 May-Jun 18(3):131-3
BACKGROUND: The Indian government proposes to eliminate kala-azar, which
has been a serious public health problem in Bihar. This study aimed to
assess the magnitude of unresponsiveness to sodium stibogluconate in the
treatment of new cases of visceral leishmaniasis and to identify the
associated factors. METHODS: Patients with clinically and
parasitologically confirmed visceral leishmaniasis (n = 182) who had
received no prior treatment, were enrolled for the study. The patients
were treated with sodium stibogluconate (20 mg/kg body weight; upper
limit 850 mg), intramuscularly for 30 days. The vital parameters and
side-effects, if any, were monitored. Patients who developed toxicity
during treatment were excluded from the study but were given rescue
treatment with liposomal amphotericin B. All patients who completed the
treatment were followed up for 6 months. RESULTS: Unresponsiveness to
sodium stibogluconate at the end of treatment was 43%. It was higher in
women (48%) compared to men (40%). A significant association was
observed between unresponsiveness and level of endemicity (p = 0.0002),
large spleen size (p = 0.04) and immune response (migration inhibition
factor) (p = 0.00002). At the end of 6 months' follow up, 27% of
patients relapsed, giving a total unresponsiveness rate of 58%.
CONCLUSION: Unresponsiveness to sodium stibogluconate is a serious
problem in the management of patients with visceral leishmaniasis. In
patients with factors associated with nonresponse to sodium
stibogluconate, alternative drugs such as miltefosine or amphotericin B
should be considered as first-line drugs.
********************************************************************************************************************
The following references are revised files and are brought to you in accordance
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PMID: 12055851
TITLE: Genes coding structural proteins in the Leishmania braziliensis complex.
AUTHORS: C Padilla, T Barreto, M De Los Santos, D C Barker, C Carrillo, Y
Montoya
AFFILIATION: Instituto Nacional de Salud, Centro Nacional de Laboratorios de
Salud Pública, Jr Capac Yupanqui 1400, Jesus Maria, Lima, Perú.
REFERENCE: Trans R Soc Trop Med Hyg 2002 Apr 96 Suppl 1():S49-54
Acidic ribosomal P1 and P2b proteins, referred to as P proteins, and
histone H3 are reported for first time in the Leishmania braziliensis
complex. Deoxyribonucleic acid analysis and multiple sequence alignment
suggest that both P proteins may maintain their structural function in
the ribosomal stalk, in spite of the high rate of mutations detected.
The deduced amino acid sequence of protein P1 showed 51% identity with
Trypanosoma cruzi protein P1 and protein P2b showed 61% identity with T
. cruzi protein P2b. Another conserved protein, L. (Viannia)
braziliensis histone H3, showed 82% and 70% identity with histone H3 of
L. (Leishmania) infantum and T. cruzi, respectively. The N-terminal end
of this histone is divergent in comparison with the consensus eukaryotic
sequence. Their predicted tridimensional structure was designed.
PMID: 11689705
TITLE: Glycosylation defects and virulence phenotypes of Leishmania mexicana
phosphomannomutase and dolicholphosphate-mannose synthase gene deletion
mutants.
AUTHORS: A Garami, A Mehlert, T Ilg
AFFILIATION: Max-Planck-Institut für Biologie, Abteilung Membranbiochemie,
72076 Tübingen, Federal Republic of Germany.
REFERENCE: Mol Cell Biol 2001 Dec 21(23):8168-83
Leishmania parasites synthesize an abundance of mannose (Man)-containing
glycoconjugates thought to be essential for virulence to the mammalian
host and for viability. These glycoconjugates include lipophosphoglycan
(LPG), proteophosphoglycans (PPGs), glycosylphosphatidylinositol (GPI)-
anchored proteins, glycoinositolphospholipids (GIPLs), and N-glycans. A
prerequisite for their biosynthesis is an ample supply of the Man donors
GDP-Man and dolicholphosphate-Man. We have cloned from Leishmania
mexicana the gene encoding the enzyme phosphomannomutase (PMM) and the
previously described dolicholphosphate-Man synthase gene (DPMS) that are
involved in Man activation. Surprisingly, gene deletion experiments
resulted in viable parasite lines lacking the respective open reading
frames (DeltaPMM and DeltaDPMS), a result against expectation and in
contrast to the lethal phenotype observed in gene deletion experiments
with fungi. L. mexicana DeltaDPMS exhibits a selective defect in LPG,
protein GPI anchor, and GIPL biosynthesis, but despite the absence of
these structures, which have been implicated in parasite virulence and
viability, the mutant remains infectious to macrophages and mice. By
contrast, L. mexicana DeltaPMM are largely devoid of all known Man-
containing glycoconjugates and are unable to establish an infection in
mouse macrophages or the living animal. Our results define Man
activation leading to GDP-Man as a virulence pathway in Leishmania.
PMID: 11514622
TITLE: Regulated degradation of an endoplasmic reticulum membrane protein in a
tubular lysosome in Leishmania mexicana.
AUTHORS: K A Mullin, B J Foth, S C Ilgoutz, J M Callaghan, J L Zawadzki, G I
McFadden, M J McConville
AFFILIATION: Department of Biochemistry and Molecular Biology, The University of
Melbourne, Victoria 3010, Australia.
REFERENCE: Mol Biol Cell 2001 Aug 12(8):2364-77
The cell surface of the human parasite Leishmania mexicana is coated
with glycosylphosphatidylinositol (GPI)-anchored macromolecules and free
GPI glycolipids. We have investigated the intracellular trafficking of
green fluorescent protein- and hemagglutinin-tagged forms of dolichol-
phosphate-mannose synthase (DPMS), a key enzyme in GPI biosynthesis in L
. mexicana promastigotes. These functionally active chimeras are found
in the same subcompartment of the endoplasmic reticulum (ER) as
endogenous DPMS but are degraded as logarithmically growing
promastigotes reach stationary phase, coincident with the down-
regulation of endogenous DPMS activity and GPI biosynthesis in these
cells. We provide evidence that these chimeras are constitutively
transported to and degraded in a novel multivesicular tubule (MVT)
lysosome. This organelle is a terminal lysosome, which is labeled with
the endocytic marker FM 4-64, contains lysosomal cysteine and serine
proteases and is disrupted by lysomorphotropic agents. Electron
microscopy and subcellular fractionation studies suggest that the DPMS
chimeras are transported from the ER to the lumen of the MVT via the
Golgi apparatus and a population of 200-nm multivesicular bodies. In
contrast, soluble ER proteins are not detectably transported to the MVT
lysosome in either log or stationary phase promastigotes. Finally, the
increased degradation of the DPMS chimeras in stationary phase
promastigotes coincides with an increase in the lytic capacity of the
MVT lysosome and changes in the morphology of this organelle. We
conclude that lysosomal degradation of DPMS may be important in
regulating the cellular levels of this enzyme and the stage-dependent
biosynthesis of the major surface glycolipids of these parasites.
PMID: 10589730
TITLE: Impairment of sterol biosynthesis leads to phosphorus and calcium
accumulation in Leishmania acidocalcisomes.
AUTHORS: M A Vannier-Santos, A Martiny, U Lins, J A Urbina, V M Borges, W de
Souza
AFFILIATION: Programa de Biologia Celular e Parasitologia, Instituto de
BiofÃsica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil.
vannier at biof.ufrj.br
REFERENCE: Microbiology 1999 Nov 145 ( Pt 11)():3213-20
The induction of the formation of inclusion vesicles in Leishmania
amazonensis by the sterol biosynthesis inhibitors (SBI) ketoconazole and
terbinafine has been reported previously. These compartments were
recently identified as acidocalcisomes. By the use of electron
spectroscopic imaging and energy loss spectroscopy, the presence of
calcium, phosphorus and oxygen in the electron-dense inclusions located
within the acidocalcisomes has been demonstrated. Endoplasmic reticulum
cisternae formed membrane whorls which enclosed large portions of the
cytoplasm and sometimes circumscribed acidocalcisomes. In addition, acid
phosphatase activity, as well as the endocytic tracers horseradish
peroxidase and gold-labelled transferrin and cystatin C were detected
within these organelles in both SBI-treated and untreated parasites.
These data suggest that impairment of sterol biosynthesis induces the
biogenesis of acidocalcisomes and triggers an autophagic process that
leads to intersection of the endosomal/lysosomal system with the
acidocalcisomes.
PMID: 10393180
TITLE: Glycosylphosphatidylinositol biosynthetic enzymes are localized to a
stable tubular subcompartment of the endoplasmic reticulum in Leishmania
mexicana.
AUTHORS: S C Ilgoutz, K A Mullin, B R Southwell, M J McConville
AFFILIATION: Departments of Biochemistry and Molecular Biology, University of
Melbourne, Royal Parade, Parkville, Victoria 3052, Australia.
REFERENCE: EMBO J 1999 Jul 18(13):3643-54
Glycosylphosphatidylinositols (GPI) are essential components in the
plasma membrane of the protozoan parasite Leishmania mexicana, both as
membrane anchors for the major surface macromolecules and as the sole
class of free glycolipids. We provide evidence that L.mexicana dolichol-
phosphate-mannose synthase (DPMS), a key enzyme in GPI biosynthesis, is
localized to a distinct tubular subdomain of the endoplasmic reticulum (
ER), based on the localization of a green fluorescent protein (GFP)-DPMS
chimera and subcellular fractionation experiments. This tubular
membrane (termed the DPMS tubule) is also enriched in other enzymes
involved in GPI biosynthesis, can be specifically stained with the
fluorescent lipid, BODIPY-C5-ceramide, and appears to be connected to
specific subpellicular microtubules that underlie the plasma membrane.
Perturbation of microtubules and DPMS tubule structure in vivo results
in the selective accumulation of GPI anchor precursors, but not free
GPIs. The DPMS tubule is closely associated morphologically with the
single Golgi apparatus in non-dividing and dividing cells, appears to
exclude luminal ER resident proteins and is labeled, together with the
Golgi apparatus, with another GFP chimera containing the heterologous
human Golgi marker beta1,2-N-acetylglucosaminyltransferase-I. The
possibility that the DPMS-tubule is a stable transitional ER is
discussed.
PMID: 10329621
TITLE: Evidence that free GPI glycolipids are essential for growth of Leishmania
mexicana.
AUTHORS: S C Ilgoutz, J L Zawadzki, J E Ralton, M J McConville
AFFILIATION: Department of Biochemistry and Molecular Biology, The University of
Melbourne, Parkville, Victoria 3052, Australia.
REFERENCE: EMBO J 1999 May 18(10):2746-55
The cell surface of the parasitic protozoan Leishmania mexicana is
coated by glycosylphosphatidylinositol (GPI)-anchored glycoproteins, a
GPI-anchored lipophosphoglycan and a class of free GPI glycolipids. To
investigate whether the anchor or free GPIs are required for parasite
growth we cloned the L.mexicana gene for dolichol-phosphate-mannose
synthase (DPMS) and attempted to create DPMS knockout mutants by
targeted gene deletion. DPMS catalyzes the formation of dolichol-
phosphate mannose, the sugar donor for all mannose additions in the
biosynthesis of both the anchor and free GPIs, except for a alpha1-3-
linked mannose residue that is added exclusively to the free GPIs and
lipophosphoglycan anchor precursors. The requirement for dolichol-
phosphate-mannose in other glycosylation pathways in L.mexicana is
minimal. Deletion of both alleles of the DPMS gene (lmdpms) consistently
resulted in amplification of the lmdpms chromosomal locus unless the
promastigotes were first transfected with an episomal copy of lmdpms,
indicating that lmdpms, and possibly GPI biosynthesis, is essential for
parasite growth. As evidence presented in this and previous studies
indicates that neither GPI-anchored glycoproteins nor lipophosphoglycan
are required for growth of cultured parasites, it is possible that the
abundant and functionally uncharacterized free GPIs are essential
membrane components.
PMID: 8973660
TITLE: Synthetic phospho-oligosaccharide fragments of lipophosphoglycan as
acceptors for Leishmania major alpha-D-mannosylphosphate transferase.
AUTHORS: G M Brown, A R Millar, C Masterson, J S Brimacombe, A V Nikolaev, M A
Ferguson
AFFILIATION: Department of Biochemistry, University of Dundee, Scotland.
REFERENCE: Eur J Biochem 1996 Dec 242(2):410-6
Protozoan parasites of the genus Leishmania synthesise
lipophosphoglycans, phosphoglycans and proteophosphoglycans that contain
phosphosaccharide-repeat units of [-6Gal beta 1-4Man alpha 1-P-]. In
this study, a GDP-Man-dependent alpha-mannosylphosphate-transferase
activity was detected in washed Leishmania major membranes using
synthetic phospho-oligosaccharide fragments of lipophosphoglycan as
acceptor substrates. The divalent-cation-dependent alpha-
mannosylphosphate-transferase activity had an apparent K(m) for GDP-Man
of about 15-20 microM and a pH optimum of 7.0. The activity showed a
requirement for a non-reducing terminal beta Gal residue and for one or
more phosphodiester units preceding the acceptor site. Based on these
results, the activity may be defined as a GDP-Man: Gal beta 1-4Man alpha
1-P-R alpha-mannosylphosphate-transferase. This acceptor specificity is
consistent with a role for the alpha-mannosylphosphate transferase in
the elongation of phosphosaccharide-repeat domains of Leishmania
glycoconjugates rather than in the priming of these domains. An
identical or similar activity must exist in the amastigote forms of the
Leishmania that produce and secrete proteophosphoglycan material and the
activity therefore represents a feasible target for the development of
chemotherapeutics.
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