[leish-l] Fwd: Articles found by RefScout 2005/009/07 - 36/2005

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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 Biología 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 Clínica 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 Biología 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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