[leish-l] Fwd: Articles found by RefScout 2005/009/07 - 36/2005
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Date: Wed, 7 Sep 2005 02:52:42
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This is RefScout-Newsletter 36/2005.
REQUEST: [ leishmaniasis ]
(15 articles match this request)
PMID: 16135192
TITLE: Control of mucocutaneous leishmaniasis, a neglected disease: results of a
control programme in Satipo Province, Peru.
AUTHORS: Jean-Paul Guthmann, Doris Arlt, Luis Miguel Leon Garcia, Milena
Rosales, Juan Jesus Sanchez, Eugenia Alvarez, Sylvaine Lonlas, Mado Conte,
Guillermo Bertoletti, Christophe Fournier, Roberto Huari, Els Torreele,
Alejandro Llanos-Cuentas
AFFILIATION: Epicentre, Paris, France.
REFERENCE: Trop Med Int Health 2005 Sep 10(9):856-62
Mucocutaneous leishmaniasis (MCL) is an important health problem in many
rural areas of Latin America, but there are few data on the results of
programmatic approaches to control the disease. We report the results of
a control programme in San Martin de Pangoa District, which reports one
of the highest prevalences of MCL in Peru. For 2 years (2001-2002), the
technicians at the health post were trained in patient case management
, received medical support and were supplied with antimonials. An
evaluation after 2 years showed the following main achievements: better
diagnosis of patients, who were confirmed by microscopy in 34% (82/240)
of the cases in 2001 and 60% of the cases (153/254) in 2002; improved
follow-up during treatment: 237 of 263 (90%) patients who initiated an
antimonial therapy ended the full treatment course; improved follow-up
after treatment: 143 of 237 (60%) patients who ended their full
treatment were correctly monitored during the required period of 6 (
cutaneous cases) or 12 (mucosal cases) months after the end of treatment
. These achievements were largely due to the human and logistical
resources made available, the constant availability of medications and
the close collaboration between the Ministry of Health, a national
research institute and an international non-governmental organization.
At the end of this period, the health authorities decided to register a
generic brand of sodium stibogluconate, which is now in use. This should
allow the treatment of a significant number of additional patients,
while saving money to invest in other facets of the case management.
PMID: 16138106
TITLE: Opportunities and challenges in antiparasitic drug discovery.
AUTHORS: Richard Pink, Alan Hudson, Marie-Annick Mouriès, Mary Bendig
AFFILIATION: TDR (the UNICEF/UNDP/World Bank/WHO/Special Programme for Research
and Training in Tropical Diseases), Geneva 1211, Switzerland.
REFERENCE: Nat Rev Drug Discov 2005 Sep 4(9):727-40
New antiparasitic drugs are urgently needed to treat and control
diseases such as malaria, leishmaniasis, sleeping sickness and
filariasis, which affect millions of people each year. However, because
the majority of those infected live in countries in which the prospects
of any financial return on investment are too low to support market-
driven drug discovery and development, alternative approaches are needed
. In this article, challenges and opportunities for antiparasitic drug
discovery are considered, highlighting some of the progress that has
been made in recent years, partly through scientific advances, but also
by more effective partnership between the public and private sectors.
PMID: 16113301
TITLE: Toward a novel experimental model of infection to study American
cutaneous leishmaniasis caused by Leishmania braziliensis.
AUTHORS: Tatiana R de Moura, Fernanda O Novais, Fabiano Oliveira, Jorge
Clarêncio, Almério Noronha, Aldina Barral, Claudia Brodskyn, Camila I de
Oliveira
AFFILIATION: Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Rua
Waldemar Falcão, 121, Salvador, BA 40295-001, Brazil.
REFERENCE: Infect Immun 2005 Sep 73(9):5827-34
Leishmania spp. cause a broad spectrum of diseases collectively known as
leishmaniasis. Leishmania braziliensis is the main etiological agent of
American cutaneous leishmaniasis (ACL) and mucocutaneous leishmaniasis
. In the present study, we have developed an experimental model of
infection that closely resembles ACL caused by L. braziliensis. In order
to do so, BALB/c mice were infected in the ear dermis with 10(5)
parasites and distinct aspects of the infection were evaluated.
Following inoculation, parasite expansion in the ear dermis was
accompanied by the development of an ulcerated dermal lesion which
healed spontaneously, as seen by the presence of a scar. Histological
analysis of infected ears showed the presence of a mixed inflammatory
infiltrate consisting of both mononuclear and polymorphonuclear cells.
In draining lymph nodes, parasite replication was detected throughout
the infection. In vitro restimulation of draining lymph node cells
followed by intracellular staining showed an up-regulation in the
production of gamma interferon (IFN-gamma) and in the frequency of IFN-
gamma-secreting CD4(+) and CD8(+) T cells. Reverse transcription-PCR of
ears and draining lymph node cells showed the expression of CC
chemokines. The dermal model of infection with L. braziliensis herein is
able to reproduce aspects of the natural infection, such as the
presence of an ulcerated lesion, parasite dissemination to lymphoid
areas, and the development of a Th1-type immune response. These results
indicate that this model shall be useful to address questions related to
the concomitant immunity to reinfection and parasite persistence
leading to mucocutaneous leishmaniasis.
PMID: 16113303
TITLE: Vaccination with the Leishmania infantum acidic ribosomal P0 protein plus
CpG oligodeoxynucleotides induces protection against cutaneous leishmaniasis in
C57BL/6 mice but does not prevent progressive disease in BALB/c mice.
AUTHORS: Salvador Iborra, Javier Carrión, Charles Anderson, Carlos Alonso,
David Sacks, Manuel Soto
AFFILIATION: Centro de BiologÃa Molecular "Severo Ochoa," Universidad Autónoma
de Madrid, 28049 Madrid, Spain.
REFERENCE: Infect Immun 2005 Sep 73(9):5842-52
We have examined the efficacy of the administration in mice of a
molecularly defined vaccine based on the Leishmania infantum acidic
ribosomal protein P0 (rLiP0). Two different challenge models of murine
cutaneous leishmaniasis were used: (i) subcutaneous inoculation of L.
major parasites in susceptible BALB/c mice (a model widely used for
vaccination analysis) and (ii) the intradermal inoculation of a low
infective dose in resistant C57BL/6 mice (a model that more accurately
reproduces the L. major infection in natural reservoirs and in human
hosts). First, we demonstrated that C57BL/6 mice vaccinated with LiP0-
DNA or rLiP0 protein plus CpG oligodeoxynucleotides (ODN) were protected
against the development of dermal pathology and showed a reduction in
the parasite load. This protection was associated with production of
gamma interferon (IFN-gamma) in the dermal site. Secondly, we showed
that immunization with rLiP0 plus CpG ODN is able to induce only partial
protection in BALB/c, since these mice finally developed a progressive
disease. Further, we demonstrated that LiP0 vaccination induces a Th1
immunological response in both strains of mice. In both cases, the
antibodies against LiP0 were predominantly of the immunoglobulin G2a
isotype, which was correlated with an rLiP0-stimulated production of IFN
-gamma in draining lymph nodes. Finally, we demonstrated that LiP0
vaccination does not prevent the Th2 response induced by L. major
infection in BALB/c mice. Taken together, these data indicate that the
BALB/c model of cutaneous leishmaniasis may undervalue the potential
efficacy of some vaccines based on defined proteins, making C57BL/6 a
suitable alternative model to test vaccine candidates.
PMID: 16113329
TITLE: Arginase I induction during Leishmania major infection mediates the
development of disease.
AUTHORS: Virginia Iniesta, Jesualdo Carcelén, Isabel Molano, Pablo M V Peixoto,
Eloy Redondo, Pilar Parra, Marina Mangas, Isabel Monroy, Maria Luisa Campo,
Carlos Gómez Nieto, Inés Corraliza
AFFILIATION: Facultad de Veterinaria, Universidad de Extremadura. Avda. de la
Universidad s/n, Cáceres 10071, Spain.
REFERENCE: Infect Immun 2005 Sep 73(9):6085-90
In a previous work, we demonstrated that the induction of arginase I
favored the replication of Leishmania inside macrophages. Now we have
analyzed the differential expression of this enzyme in the mouse model
of L. major infection. Ours results show that arginase I is induced in
both susceptible and resistant mice during the development of the
disease. However, in BALB/c-infected tissues, the induction of this
protein parallels the time of infection, while in C57BL/6 mice, the
enzyme is upregulated only during footpad swelling. The induction of the
host arginase in both strains is mediated by the balance between
interleukin-4 (IL-4) and IL-12 and opposite to nitric oxide synthase II
expression. Moreover, inhibition of arginase reduces the number of
parasites and delays disease outcome in BALB/c mice, while treatment
with l-ornithine increases the susceptibility of C57BL/6 mice. Therefore
, arginase I induction could be considered a marker of disease in
leishmaniasis.
PMID: 16135144
TITLE: Treatment of cutaneous leishmaniasis with cryosurgery.
AUTHORS: Antonios Panagiotopoulos, Panagiotis G Stavropoulos, Vassiliki Hasapi,
Anastasia-Metaxia Papakonstantinou, Athanassios Petridis, Andreas Katsambas
AFFILIATION: From the Department of Cryosurgery, Third Department of Dermatology
and Venereology, and Academic Department of Dermatology and Venereology,
University of Athens School of Medicine, "A. Syggros" Hospital, Athens,
Greece.
REFERENCE: Int J Dermatol 2005 Sep 44(9):749-52
Background The management of cutaneous leishmaniasis with topical
methods, if effective, can spare patients from long and costly inpatient
treatments. Methods Seventeen patients with cutaneous leishmaniasis
were treated with cryosurgery using liquid nitrogen as the cryogen. Two
cycles of 10-30 s freezing time were used and repeated at 3-week
intervals. Results All patients responded well to therapy with excellent
cosmetic results and no relapse in any case. Side-effects were rare.
Conclusions Cutaneous leishmaniasis can be successfully treated with a
simple protocol of cryosurgery with minor side-effects.
PMID: 15986254
TITLE: Is Leishmania (Viannia) braziliensis preferentially restricted to the
cutaneous lesions of naturally infected dogs?
AUTHORS: Maria de Fátima Madeira, Armando de O Schubach, Tânia M P Schubach,
Cathia M B Serra, Sandro A Pereira, Fabiano B Figueiredo, Eliame Mouta Confort,
Leonardo P Quintella, Mauro C A Marzochi
AFFILIATION: Instituto de Pesquisa ClÃnica Evandro Chagas, Serviço de
Parasitologia, Fundação Oswaldo Cruz. Av. Brasil, 4365, 21040-900, Rio de
Janeiro, Brasil, fmadeira at ipec.fiocruz.br.
REFERENCE: Parasitol Res 2005 Aug 97(1):73-6
Nineteen dogs naturally infected with Leishmania (Viannia) braziliensis
were studied in order to determine the presence of the parasite outside
cutaneous lesions. Eleven (57.9%) animals showed single cutaneous or
mucosal lesions and eight (42.1%) presented two or three lesions. Twenty
-eight active lesions were biopsied. Isolation in culture and
characterization by enzyme electrophoresis were possible in 100% of
cases and amastigote forms were visualized upon histopathological
examination in three samples (n=25, 12%). Isolation of the parasite in
culture from peripheral blood and intact skin fragments obtained from
the scapular region was negative in all animals, as was the
histopathological analysis of skin from this region. Serological
reactivity determined by an immunofluorescent antibody test and/or
enzyme-linked immunosorbent assay was demonstrated in 15 animals. The
results obtained suggest that L. braziliensis preferentially remains at
the site of lesion, in contrast to the systemic distribution of
parasites observed in dogs infected with L. (Leishmania) chagasi. A
better understanding of this aspect may help direct diagnostic and
control strategies applicable to areas characterized by the simultaneous
occurrence of the cutaneous and visceral forms of leishmaniasis, as is
the case for the Municipality of Rio de Janeiro, Brazil.
PMID: 15953097
TITLE: Basal cell carcinoma in a leishmanial scar.
AUTHORS: M S Gurel, L Inal, I Ozardali, S A Duzgun
REFERENCE: Clin Exp Dermatol 2005 Jul 30(4):444-5
PMID: 16047575
TITLE: Leishmaaniasis: early diagnosis is key.
AUTHORS: Michael Roscoe
AFFILIATION: US Army, USA.
REFERENCE: JAAPA 2005 Jul 18(7):47-50, 53-4
A patient presents with nasal congestion, a history of nosebleed, and
painful lesions on his body and in his mouth. What questions should you
ask to ensure that you make an accurate diagnosis?
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.
PMID: 16117959
TITLE: A neglected disease of humans: a new focus of visceral leishmaniasis in
Bakool, Somalia.
AUTHORS: M V L Marlet, F Wuillaume, D Jacquet, K W Quispe, J C Dujardin, M
Boelaert
AFFILIATION: Médecins sans Frontières, Dupréstraat 94, B-1090 Brussels,
Belgium.
REFERENCE: Trans R Soc Trop Med Hyg 2003 Nov-Dec 97(6):667-71
Visceral leishmaniasis (VL) was observed in children in Bakool region,
Somalia, an area where VL has not been reported before. We describe the
extent of the problem in this war- and famine-stricken area. A
retrospective analysis was done of all cases admitted to a VL treatment
centre between July 2000 and August 2001. Patients with longstanding
fever, splenomegaly and a positive direct agglutination test (DAT; titre
> 1:3200) were treated as suspected VL cases. A rapid epidemiological
and entomological assessment was performed in the area. Species
identification was attempted from blood samples by polymerase chain
reaction-restriction fragment length polymorphism analysis of cysteine
proteinase B genes. In 1 year, 230 serologically-positive cases were
diagnosed as VL, and response to therapy was good in 91.6% of the 225
treated with sodium stibogluconate. Parasitological confirmation was
attempted and obtained in 2 cases. Parasites were found to be most
similar to Sudanese and Ethiopian reference strains of the Leishmania
donovani complex. In a serological survey of 161 healthy displaced
persons, 15% were positive by the leishmanin skin test and 3 (2%) were
positive by the DAT. The sandfly captures showed Phlebotomus martini and
P. vansomerenae. VL seems to be a longstanding and serious health
problem in Bakool region. Food insecurity might have contributed to the
emergence and detection of VL in this area.
PMID: 16134257
TITLE: Royal Society of Tropical Medicine and Hygiene joint meeting with
Médecins Sans Frontières at Manson House, London, 20 March 2003: field
research in humanitarian medical programmes. Médecins Sans Frontières
interventions against kala-azar in the Sudan, 1989-2003.
AUTHORS: K Ritmeijer, R N Davidson
AFFILIATION: Médecins Sans Frontières-Holland, Max Euweplein 40, PO Box 10014,
1001 EA Amsterdam, The Netherlands. koert_ritmeijer at amsterdam.msf.org
REFERENCE: Trans R Soc Trop Med Hyg 2003 Nov-Dec 97(6):609-13
Since 1989, Médecins Sans Frontières (MSF) has provided medical
humanitarian assistance during outbreaks of visceral leishmaniasis (VL;
kala-azar) in Sudan. First, in western Upper Nile in southern Sudan,
where a VL epidemic occurred after the resumption of the civil war in
Sudan in 1983, with an estimated 100,000 deaths. Later, MSF started
interventions in eastern Upper Nile and Gedaref State. In these two
endemic regions VL incidence has risen markedly since 2001, which could
be the start of a new epidemic cycle. Outbreaks of VL in Sudan remain
unpredictable, and access to affected populations in war-torn southern
Sudan is often hampered by insecurity. Therefore, MSF takes a flexible
approach, establishing treatment centres where patients can be accessed
. From 1989 to 2002, MSF treated >51,000 VL cases in Sudan. Despite very
basic field conditions, high cure rates of 95% are being achieved. Lack
of diagnostics is a major obstacle to treatment, especially during
epidemic situations. Therefore, development of simple and rapid
technologies is required, allowing reliable diagnosis under field
conditions. For treatment of VL there is a limited choice of effective,
affordable drugs. There are strong indications of an emerging resistance
to antimonials in Malakal. Introduction of combination therapies is
urgently needed to prevent the further emergence and spread of
resistance to antimonials, which are still the mainstay of VL treatment
in eastern Africa. Experience with combination therapy with sodium
stibogluconate (SSG) and paromomycin is promising, and combinations of
SSg with liposomal amphotericin B and miltefosine are currently being
explored.
PMID: 16117962
TITLE: Standardization of a rapid immunochromatographic test with the
recombinant antigens K39 and K26 for the diagnosis of canine visceral
leishmaniasis.
AUTHORS: Roberto Teodoro da Costa, João Carlos França, Wilson Mayrink, Evaldo
Nascimento, Odair Genaro, Antonio Campos-Neto
AFFILIATION: Laboratory of Leishmaniasis and Vaccines, Department of
Parasitology, Institute of Biological Sciences, UFMG, Belo Horizonte, Minas
Gerais, Brazil.
REFERENCE: Trans R Soc Trop Med Hyg 2003 Nov-Dec 97(6):678-82
The serological diagnosis of canine visceral leishmaniasis (CVL) remains
problematic because there areno reliable commercially available tests.
Most laboratories use domestically prepared tests such as the enzyme-
linked immunosorbent assay (ELISA) or the indirect immunofluorescent
antibody test (IFAT). We evaluated rapid immunochromatographic (RICH)
test kits for the diagnosis of CVL. The tests were assembled with either
Leishmania chagasi recombinant antigens K39 or K26 and with either gold
-labelled Staphylococcus aureus protein A or Streptococcus pyogenes
protein G. Fifty sera from dogs with CVL, 14 sera from dogs with Chagas
disease, and 50 sera from normal healthy dogs were tested. The results
show that the RICH test using recombinant antigen K39 has a sensitivity
of 96% and 100% specificity for the diagnosis of CVL. No significant
differences were observed in the tests assembled with either protein A
or protein G. The RICH tests using recombinant antigen K26 were equally
specific but less sensitive than those using K39. However, the 2
antigens complemented each other and increased the overall sensitivity
of the test. Because of its simplicity and performance the RICH test is
a quick and reliable alternative for the diagnosis of CVL either in
conventional laboratories or for remote areas where laboratories are not
readily accessible for conventional assays.
PMID: 16117969
TITLE: Randomized, double-blind, placebo-controlled study on the immunogenicity
of the leishmanin skin test.
AUTHORS: P M De Luca, W Mayrink, M A Santiago, R Nogueira, F Conceição-Silva,
G Mélo, S C F Mendonça
AFFILIATION: Department of Immunology, Oswaldo Cruz Institute, FIOCRUZ, Av.
Brasil 4365, Manguinhos, 21045-900 Rio de Janeiro, RJ, Brazil.
REFERENCE: Trans R Soc Trop Med Hyg 2003 Nov-Dec 97(6):709-12
A positive reaction to the leishmanin skin test (LST) indicates previous
contact with Leishmania antigens and is a useful criterion for the
diagnosis of cutaneous leishmaniasis. In leishmaniasis vaccine trials,
selection of volunteers has always been based on skin testing. During
1999 we performed a randomized controlled study in order to evaluate the
immunogenicity of the LST. Fifty-nine (29 male and 30 female) healthy
volunteer undergraduate students from the Medical School of Volta
Redonda, Rio de Janeiro State, Brazil, with no evidence of previous
infection with Leishmania, were randomly assigned into 2 groups: 29
subjects received LST and 30 received a placebo (merthiolate-phosphate-
buffered saline). All volunteers received LST 41 d after the first
injection of LST or placebo. Blood samples were taken immediately before
the applications of LST or placebo for the assessment of Leishmania
antigen-induced proliferation and cytokine production in peripheral
blood mononuclear cell cultures. A significant increase in proliferative
responses to L. braziliensis (P < 0.005) and L. amazonensis (P = 0.
01) antigens as well as in L. braziliensis antigen-induced interferon-
gamma production (P < 0.01) followed the application of LST but not
the administration of the placebo. A single LST application is therefore
able to induce Leishmania-specific cell-mediated immune responses. This
observation should be considered in human trials of candidate vaccines
against leishmaniasis.
PMID: 16117955
TITLE: Cutaneous leishmaniasis vector control perspectives using
lambdacyhalothrin residual house spraying in El Ingenio, Miranda State,
Venezuela.
AUTHORS: M Dora Feliciangeli, Milena B Mazzarri, Diarmid Campbell-Lendrum,
Michele Maroli, Rhaiza Maingon
AFFILIATION: BIOMED-CNRFV, Universidad de Carabobo, Núcleo Aragua, Apartado
4873, Maracay, Venezuela. mdora at telcel.net.ve
REFERENCE: Trans R Soc Trop Med Hyg 2003 Nov-Dec 97(6):641-6
An indoor vector control trial was carried out between December 1996 and
February 1997, with the aim of reducing the population densities of
Lutzomyia ovallesi, the proven vector of cutaneous leishmaniasis (CL) in
El Ingenio, Miranda State, Venezuela. Houses were matched according to
their structure ("bahareque" [mud and straw], concrete, and
wood) and randomly assigned to a control group (n = 19) or a treated
group (n = 20) that was sprayed with 25 mg/m(2) of lambdacyhalothrin.
This dose was selected on the basis of a laboratory susceptibility test
of Lu. ovallesi to pyrethroids. Sandfly abundance was measured using CDC
light traps 7-79 d post-intervention, by which time the sandfly
population in control houses had declined to very low levels, at what
was the end of the transmission season. Catches of total females, fed
females, and males were significantly lower in sprayed than in control
houses immediately after treatment. Catches of total females and males
in sprayed houses recovered, reaching the level of control houses after
7 and 11 weeks, respectively. Bioassays following WHO protocols using
contact cones on a sandfly laboratory colony showed a short residual
effect of the insecticide explaining these results. In contrast, there
was no tendency for catches of fed females in the sprayed houses to
recover during the course of the trial. Previous studies of adult
population dynamics showed a short season of high abundance. Combined
with these results, we believe that 2 indoor sprayings with
lambdacyhalothrin, the first at the beginning of November and the second
at the beginning of January, would considerably reduce the Lu. ovallesi
population, and control CL transmission in this and other foci where
this sandfly is considered to be the main vector.
REQUEST: [ leishmania ]
(19 articles match this request. 8 articles matching other requests removed)
PMID: 16113310
TITLE: Transforming growth factor {beta}1 production by CD4(+) CD25(+)
regulatory T cells in peripheral blood mononuclear cells from healthy subjects
stimulated with Leishmania guyanensis.
AUTHORS: A Kariminia, E Bourreau, H Pascalis, P Couppié, D Sainte-Marie, F
Tacchini-Cottier, P Launois
AFFILIATION: Immunologie des Leishmanioses, Institut Pasteur de la Guyane, 97306
Cayenne, French Guyana.
REFERENCE: Infect Immun 2005 Sep 73(9):5908-14
Transforming growth factor beta (TGF-beta) has been shown to be a
central immunomodulator used by leishmaniae to escape effective
mechanisms of protection in human and murine infections with these
parasites. However, all the information is derived from studies of
established infection, while little is known about TGF-beta production
in response to Leishmania stimulation in healthy subjects. In this study
, TGF-beta1 production was demonstrated in peripheral blood mononuclear
cells from healthy subjects never exposed to leishmaniae in response to
live Leishmania guyanensis, and the TGF-beta1-producing cells were
described as a distinct subpopulation of CD4(+) CD25(+) regulatory T
cells. The suppressive properties of CD4(+) CD25(+) T cells were
demonstrated in vitro by their inhibition of production of interleukin 2
(IL-2) and IL-10 by CD4(+) CD25(-) T cells in the presence of either
anti-CD3 or L. guyanensis. Although neutralization of TGF-beta1 did not
reverse the suppressive activity of CD4(+) CD25(+) T cells activated by
anti-CD3, it reversed the suppressive activity of CD4(+) CD25(+) T cells
activated by L. guyanensis. Altogether our data demonstrated that TGF-
beta1 is involved in the suppressive activity of L. guyanensis-
stimulated CD4(+) CD25(+) T cells from healthy controls.
PMID: 16135234
TITLE: Modulation in aquaglyceroporin AQP1 gene transcript levels in
drug-resistant Leishmania.
AUTHORS: Nathalie Marquis, Benjamin Gourbal, Barry P Rosen, Rita Mukhopadhyay,
Marc Ouellette
AFFILIATION: Centre de recherche en Infectiologie du Centre de recherche du CHUL
and Division de Microbiologie, Faculté de Médecine, Université Laval,
Québec, Canada.
REFERENCE: Mol Microbiol 2005 Sep 57(6):1690-9
Antimonial-containing drugs are the first line of treatment against the
parasite Leishmania. Resistance to antimonials has been correlated to
its reduced accumulation. We used a dominant negative functional cloning
strategy where a Leishmania mexicana expression cosmid bank was
transfected in cells resistant to trivalent antimony (SbIII). Cells were
selected for increased sensitivity to SbIII. One cosmid was isolated
that could bestow SbIII sensitivity to resistant cells. The gene part of
this cosmid that is responsible for increased SbIII sensitivity
corresponds to AQP1, an aquaglyceroporin. AQP1 was recently shown to be
a route by which SbIII can accumulate in Leishmania cells. Transport
studies have shown that the L. mexicana AQP1 can restore SbIII transport
in resistant cells. Southern blot analysis indicated that the copy
number of neither the AQP1 gene nor the other AQP homologues was changed
in antimony-resistant mutants of several Leishmania species. The AQP1
gene sequence was also unchanged in mutants. However, the AQP1 RNA
levels were downregulated in several Leishmania promastigote species
resistant to antimonials. In general, but not always, the level of AQP1
transcript levels correlated well with the accumulation of SbIII and
resistance levels in Leishmania cells. AQP1 thus appears to be a key
determinant of antimonials accumulation and susceptibility in Leishmania.
PMID: 16127040
TITLE: Purine nucleobase transport in amastigotes of Leishmania mexicana:
involvement in allopurinol uptake.
AUTHORS: Mohammed I Al-Salabi, Harry P de Koning
AFFILIATION: Institute of Biomedical and Life Sciences, Division of Infection
and Immunity, Joseph Black Building, University of Glasgow, Glasgow G12 8QQ,
United Kingdom.
REFERENCE: Antimicrob Agents Chemother 2005 Sep 49(9):3682-9
Nucleobase and nucleoside transporters play central roles in the
biochemistry of parasitic protozoa, as they lack the ability to
synthesize purines de novo and are absolutely reliant upon purine
salvage from their hosts. Furthermore, such transporters are potentially
critical to the pharmacology of these important human pathogens,
because they mediate the uptake of purine analogues, as well as some
nonpurine drugs, that can be selectively cytotoxic to the parasites. We
here report the first identification and characterization of a purine
nucleobase transporter in Leishmania amastigotes. Uptake of [3H]
hypoxanthine by Leishmania mexicana amastigotes was mediated by a single
high-affinity transporter, LmexNBT1, with a Km of 1.6 +/- 0.4 microM
and high affinity for adenine, guanine, and xanthine but low affinity
for nucleosides and pyrimidine nucleobases. Allopurinol, an
antileishmanial hypoxanthine analogue, was apparently taken up by the
same transporter. Using [3H]allopurinol, a Km value of 33.6 +/- 6.0
microM was obtained. All evidence was compatible with a model of a
single purine nucleobase transporter being expressed in amastigotes.
Using various purine nucleobase analogues, a model for the interactions
between hypoxanthine and the transporter's permeant binding site was
constructed. The binding interactions were compared with those of the
LmajNBT1 transporter in Leishmania major promastigotes and found to be
very similar.
PMID: 16131481
TITLE: Use of Leishmania donovani Field Isolates Expressing the Luciferase
Reporter Gene in In Vitro Drug Screening.
AUTHORS: Ashutosh, Suman Gupta, Ramesh, Shyam Sundar, Neena Goyal
AFFILIATION: Division of Biochemistry, Central Drug Research Institute, Chatter
Manzil Palace, M. G. Road, Lucknow 226 001 (UP), India. neenacdri at yahoo.com.
REFERENCE: Antimicrob Agents Chemother 2005 Sep 49(9):3776-83
Currently available primary screens for the selection of candidate
antileishmanial compounds are not ideal. These techniques are time-
consuming, laborious, and difficult to scale and require macrophages,
which limit their use for high-throughput screening. We have developed
Leishmania donovani field isolates that constitutively express the
firefly luciferase reporter gene (luc) as a part of an episomal vector.
An excellent correlation between parasite number and luciferase activity
was observed. luc expression was stable, even in the absence of drug
selection, for 4 weeks. The transfectants were infective to macrophages
, and intracellular amastigotes exhibited luciferase activity. The
suitability of these recombinant field isolates for in vitro screening
of antileishmanial drugs was established. The luciferase-expressing
sodium stibogluconate-resistant cell lines offer a model for the
screening of compounds for resistance. The system is in routine use at
the Central Drug Research Institute, Lucknow, India, for high-throughput
screening of newly synthesized compounds.
PMID: 16131378
TITLE: Leishmania inactivation in human pheresis platelets by a psoralen
(amotosalen HCl) and long-wavelength ultraviolet irradiation.
AUTHORS: Richard T Eastman, Lynn K Barrett, Kent Dupuis, Frederick S Buckner,
Wesley C Van Voorhis
AFFILIATION: From the Departments of Pathobiology and Medicine, University of
Washington, Seattle, Washington.
REFERENCE: Transfusion 2005 Sep 45(9):1459-63
BACKGROUND: Leishmania spp. are protozoans that cause skin and visceral
diseases. Leishmania are obligate intracellular parasites of mononuclear
phagocytes and have been documented to be transmitted by blood
transfusion. STUDY DESIGN AND METHODS: This study examines whether
Leishmania can be inactivated in human platelet (PLT) concentrates by a
photochemical treatment process that is applicable to blood bank use.
Human PLT concentrates were contaminated with Leishmania mexicana
metacyclic promastigotes or mouse-derived Leishmania major amastigotes
and were exposed to long-wavelength ultraviolet (UV) A light (320-400 nm
) plus the psoralen amotosalen HCl. RESULTS: Neither treatment with
amotosalen nor UVA alone had an effect on Leishmania viability; however
, treatment with 150 micromol per L amotosalen plus 3 J per cm(2) UVA
inactivated both metacyclic promastigotes and amastigotes to
undetectable levels, more than a 10,000-fold reduction in viability.
CONCLUSIONS: This study demonstrates the effectiveness of photochemical
treatment to inactivate Leishmania in PLT concentrates intended for
transfusion. Both metacylic promastigotes, which represent the
infectious form from the sand fly vector, and amastigotes, which
represent the form that grows in mononuclear phagocytes, were extremely
susceptible to photochemical inactivation by this process. Thus, the
photochemical treatment of PLT concentrates inactivates both forms of
Leishmania that would be expected to circulate in blood products
collected from infected donors.
PMID: 16134072
TITLE: Cytologic patterns of lymphadenopathy in dogs infected with Leishmania
infantum.
AUTHORS: Mathios E Mylonakis, Nikolaos Papaioannou, Manolis N Saridomichelakis,
Alexander F Koutinas, Charalambos Billinis, Vassilios I Kontos
REFERENCE: Vet Clin Pathol 2005 Sep 34(3):243-7
BACKGROUND: Lymphadenopathy in canine leishmaniosis has been reported as
reactive lymphoid hyperplasia or granulomatous (histiocytic)
lymphadenitis. However, we are unaware of information on the effect of
latent Leishmania infection on lymph node cytology compared with
clinically affected dogs. OBJECTIVES: The aim of the present study was
to investigate cytologic patterns of lymphadenopathy in dogs with
clinical and subclinical forms of leishmaniosis and to correlate
cytologic findings with the density of Leishmania amastigotes in fine
needle aspiration (FNA) smears. METHODS: FNA cytology of prescapular or
popliteal lymph nodes was evaluated on 32 dogs with clinical evidence of
leishmaniosis (group A), 24 subclinically infected dogs (group B), and
17 clinically healthy noninfected dogs (group C); groups were based on
the results of serologic and PCR tests for Leishmania sp. Differential
nucleated cell counts (based on 300 cells) and amastigote density were
determined microscopically. Cytologic findings were categorized and
compared among groups. RESULTS: Cytologic abnormalities were found in 19
of 32 (59.4%) dogs in group A, 1 of 24 (4.2%) dogs in group B, and 2 of
17 (11.8%) dogs in group C and were significantly more frequent in
group A than group B (P <.001) or C (P = .001). In group A, 68.7% of
the dogs had lymphoid hyperplasia, 12.5% had lymphoid hyperplasia and
histiocytic lymphadenitis, 6.3% had histiocytic lymphadenitis, and 3.1%
had lymphoid hyperplasia and neutrophilic lymphadenitis. Lymphoid
hyperplasia was also noted in 1 dog in group B, and lymphoid hyperplasia
and eosinophilic lymphadenitis were each found in 1 dog in group C.
Lymph node smears from 31 (96.9%) dogs in group A and 6 (25%) dogs in
group B were positive for Leishmania amastigotes; however, no
correlation was found between the density of amastigotes and
cytopathologic patterns of lymphadenopathy. CONCLUSION: Abnormal lymph
node cytology is much more common in dogs with clinical leishmaniosis
than in dogs with subclinical infection, and primarily involves lymphoid
hyperplasia. Despite finding no association between the density of
amastigotes and type of lymphadenopathy, lymph node cytology still is a
valuable diagnostic tool for diagnosing canine leishmaniosis.
PMID: 16134981
TITLE: Phlebotomine sand flies from Ouagadougou, Burkina Faso: first record of
Phlebotomus (Larroussius) longicuspis south of the Sahara.
AUTHORS: J Depaquit, F Muller, J-C Gantier, N Leger, H Ferte, P Ready, A-A
Niang
AFFILIATION: Faculté de Pharmacie, Reims, France.
REFERENCE: Med Vet Entomol 2005 Sep 19(3):322-5
Abstract. During a brief entomological survey carried out in Ouagadougou
, Burkina Faso, in March 2002, 178 phlebotomine sand flies (Diptera,
Psychodidae) were caught using CDC miniature light traps. They were
identified as Phlebotomus duboscqi Neveu-Lemaire, P. longicuspis
Nitzulescu, Sergentomyia adleri (Theodor), S. affinis vorax (Parrot), S
. antennata (Newstead), S. bedfordi (Newstead), S. christophersi (Sinton
), S. fallax (Parrot), S. magna (Sinton) and S. schwetzi (Adler, Theodor
& Parrot). This is the first record south of the Sahara of P.
longicuspis sensu lato. This proven vector of Leishmania infantum
Nicolle is a species closely related to P. perniciosus. It was
identified by morphology and by the sequencing of a fragment of
mitochondrial cytochrome b. There was 100% sequence homology with
typical Tunisian specimens, and all characters identified the specimen
as P. longicuspis sensu stricto. Epidemiological and biogeographical
consequences are discussed.
PMID: 15972660
TITLE: TLR-dependent activation stimuli associated with Th1 responses confer NK
cell stimulatory capacity to mouse dendritic cells.
AUTHORS: Ivan Zanoni, Maria Foti, Paola Ricciardi-Castagnoli, Francesca
Granucci
AFFILIATION: Department of Biotechnology and Bioscience, University of
Milano-Bicocca, Milan, Italy.
REFERENCE: J Immunol 2005 Jul 175(1):286-92
Dendritic cells (DCs) have an important role in the activation of NK
cells that exert direct antitumor and antimicrobial effects and can
influence the development of adaptive T cell responses. DCs acquire NK
cell stimulatory capacity after exposure to various stimuli. In this
study we investigated the nature of the stimuli that confer to DCs the
NK cell-activating capacity. After exposure of DCs to TLR-dependent and
-independent microbial stimuli and to nonmicrobial stimuli, we
evaluated the ability of activated DCs to elicit IFN-gamma production
from NK cells in vitro and to promote NK cell activation in vivo. We
show in this study that only TLR-dependent microbial stimuli typically
associated with Th1 responses confer to DCs the ability to activate NK
cells, whereas stimuli associated with Th2 responses do not have this
property.
PMID: 16003841
TITLE: Antileishmanial agents part-IV: synthesis and antileishmanial activity of
novel terpenyl pyrimidines.
AUTHORS: Naveen Chandra, Ramesh, Ashutosh, Neena Goyal, S N Suryawanshi, Suman
Gupta
AFFILIATION: Division of Medicinal Chemistry, Central Drug Research Institute,
Lucknow 226001, India.
REFERENCE: Eur J Med Chem 2005 Jun 40(6):552-6
Some novel N- and O-substituted terpenyl pyrimidines 4 (a-j) have been
synthesized and screened for in vitro antileishmanial activity profile
in promastigote model. Some of the compounds exhibited 100% inhibition
at 10 microg ml(-1) concentration.
PMID: 16128611
TITLE: Sequence-based discovery of the human and rodent peroxisomal proteome.
AUTHORS: Igor V Kurochkin, Takeshi Nagashima, Akihiko Konagaya, Christian
Schönbach
AFFILIATION: Immunoinformatics Team, RIKEN Genomic Sciences Center, RIKEN
Yokohama Institute, Yokohama, Japan.
REFERENCE: Appl Bioinformatics 2005 4(2):93-104
BACKGROUND: Peroxisomes are metabolic organelles present in virtually
all eukaryotic cells. They contain enzymes involved in hydrogen peroxide
-based respiration and lipid metabolism. At present, only a small number
of peroxisomal enzymes that are associated with oxidative stress
response and metabolic disorders have been characterised biochemically.
Therefore, we devised a sequence-based, multistep knowledge discovery
strategy to identify potential novel peroxisomal protein candidates in
small rodent model organisms and human. METHODS: Screening of 130 629
putative translations of GenBank((R)) rodent and primate mRNA sequences
was limited to the classical type-1 peroxisomal targeting signal [SA]-K-
L. This motif is over-represented among peroxisomal proteins and has a
high targeting efficiency. Subsequent steps of identifying co-occurring
motifs, secondary structure properties, orthologues and variants, in
combination with literature searching and visual inspection by domain
experts, aimed at reduction of both false positive and negative
validation targets. RESULTS: Our method yielded 117 known peroxisome-
targeted proteins and 29 novel candidate proteins. Of special interest
were the mouse C530046K17Rik and 1300019N10Rik protein sequences that
contain domains associated with enzymatic functions. C530046K17Rik
showed no similarity to any known sequence of the animal kingdom, but
weak similarity to the possible Leishmania quinone oxidoreductase and a
putative cyanobacterium nicotinamide adenine dinucleotide phosphate (
NADP)-dependent oxidoreductase. 1300019N10Rik contains two protease-
related domains, glutamyl endopeptidase I and trypsin-like serine and
cysteine proteases, which may have unique specificities to achieve
efficient breakdown of proteins in the peroxisomes. CONCLUSION: One
mouse C57BL/6J strain-specific isocitrate dehydrogenase 1 isoform might
be suitable to investigate potential phenotypes associated with the
deficit of the intraperoxisomal reduced form of NADP (NADPH) and 2-
oxoglutarate. Our biological knowledge discovery strategy enabled not
only the identification of peroxisomal enzymes already described in the
literature, but also the prediction of several novel proteins with
possible roles in peroxisomal biochemistry and metabolism that are
currently under experimental validation.
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PMID: 15176985
TITLE: The expression of HSP83 genes in Leishmania infantum is affected by
temperature and by stage-differentiation and is regulated at the levels of mRNA
stability and translation.
AUTHORS: Ruth Larreta, Manuel Soto, Luis Quijada, Cristina Folgueira, Daniel R
Abanades, Carlos Alonso, Jose M Requena
AFFILIATION: Centro de BiologÃa Molecular Severo Ochoa, Universidad Autónoma
de Madrid, 28049, Spain. rlarreta at cbm.uam.es
REFERENCE: BMC Mol Biol 2004 Jun 5():3
BACKGROUND: Exposure of Leishmania promastigotes to the temperature of
their mammalian hosts results in the induction of a typical heat shock
response. It has been suggested that heat shock proteins play an
important role in parasite survival and differentiation. RESULTS: Here
we report the studies on the expression of the heat shock protein 83 (
HSP83) genes of Leishmania infantum. Confirming previous observations
for other Leishmania species, we found that the L. infantum HSP83
transcripts also show a temperature-dependent accumulation that is
controlled by a post-transcriptional mechanism involving sequences
located in the 3'-untranslated region (3'-UTR). However, contrary to
that described for L. amazonensis, the accumulation of the HSP83
transcripts in L. infantum is dependent on active protein synthesis. The
translation of HSP83 transcripts is enhanced during heat shock and, as
first described in L. amazonensis, we show that the 3'-UTR of the L.
infantum HSP83 gene is essential for this translational control.
Measurement of the steady-state levels of HSP83 transcripts along the
promastigote-to-amastigote differentiation evidenced a specific profile
of HSP83 RNAs: after an initial accumulation of HSP83 transcripts
observed short after (2 h) incubation in the differentiation conditions
, the amount of HSP83 RNA decreased to a steady-state level lower than
in undifferentiated promastigotes. We show that this transient
accumulation is linked to the presence of the 3'-UTR and flanking
regions. Again, an 8-fold increase in translation of the HSP83
transcripts is observed short after the initiation of the axenic
differentiation, but it is not sustained after 9 h. CONCLUSIONS: This
transient expression of HSP83 genes could be relevant for the
differentiation of Leishmania, and the underlying regulatory mechanism
may be part of the developmental program of this parasite.
REQUEST: [ sand fly ]
(2 articles match this request. 1 article matching other requests removed)
PMID: 16009374
TITLE: Fossil evidence of insect pathogens.
AUTHORS: George Poinar, Roberta Poinar
AFFILIATION: Department of Zoology, Oregon State University, Corvallis, OR
97331, USA.
REFERENCE: J Invertebr Pathol 2005 Jul 89(3):243-50
The present report describes fossil evidence of insect pathogens,
heretofore, almost non-existent, from six samples of amber ranging in
age from 15 to 100 million years. They include a cytoplasmic
polyhedrosis virus and trypanosomatid infection in an adult biting midge
(Diptera: Ceratopogonidae), and a nuclear polyhedrosis virus in an
adult sand fly (Diptera: Phlebotomidae), both from Early Cretaceous
Burmese amber, several types of fungal thalli on the cuticle of an adult
mosquito (Culicidae: Diptera), as well as a fungal growth on the
prothorax of a fungus gnat (Mycetophilidae: Diptera) in Dominican amber
and large tumors in the body cavity of a caterpillar (Lepidoptera) in
Mexican amber. These discoveries suggest that insect polyhedrosis
viruses were present 100 million years ago and present the possibility
that vertebrate arboviruses (especially those in the family Reoviridae)
could have evolved from cytoplasmic polyhedrosis viruses infecting
biting insects. The flagellates in the Early Cretaceous biting midge
represent the first fossil record of monogenetic trypanosomatid
infections of arthropods.
REQUEST: [ sandfly ]
(2 articles match this request. 2 articles matching other requests removed)
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