[leish-l] Fwd: Articles found by RefScout 03/08/2005 - 31/2005

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This is RefScout-Newsletter 31/2005.

REQUEST: [ leishmaniasis ]

(20 articles match this request)

PMID: 16041009

TITLE: Prevention and treatment of cutaneous leishmaniasis in primates by using
synthetic type D/A oligodeoxynucleotides expressing CpG motifs.

AUTHORS: Barbara Flynn, Vivian Wang, David L Sacks, Robert A Seder, Daniela

AFFILIATION: Division of Therapeutic Proteins, Center for Drug Evaluation and
Review, Food and Drug Administration, Washington, D.C., USA.

REFERENCE: Infect Immun 2005 Aug 73(8):4948-54

Oligodeoxynucleotides (ODN) containing CpG motifs mimic microbial DNA 
and are recognized by toll-like receptor 9 on immune cells. The 
resulting response limits the early spread of infectious organisms and 
promotes the development of adaptive immunity. In this regard, CpG ODN 
show promise as immunoprotective agents and as vaccine adjuvants. 
Previous studies of nonhuman primates showed that administration of CpG 
ODN type D (also known as type A) at the site of infection 3 days before
 and after a challenge with Leishmania major enhanced host resistance 
and reduced the lesion's severity. In this study, we show that systemic 
administration of D/A ODN limits the size of lesions following an 
intradermal infection with L. major. Importantly, the reduced morbidity 
was not associated with a reduction in long-term immunity, as such 
treated macaques were still protected following a secondary challenge. 
Finally, administration of D/A ODN to macaques that had established 
cutaneous lesions reduced the severity of the lesions, suggesting a 
potential role for CpG ODN in L. major treatment. Together, these 
findings support the development of clinical studies to assess the use 
of CpG ODN types D/A as immunoprotective and therapeutic agents.

PMID: 16040984

TITLE: Conditions influencing the efficacy of vaccination with live organisms
against Leishmania major infection.

AUTHORS: Khaled S Tabbara, Nathan C Peters, Farhat Afrin, Susana Mendez, Sylvie
Bertholet, Yasmine Belkaid, David L Sacks

AFFILIATION: NIAID, Laboratory of Parasitic Diseases, Bldg. 4, Rm. 126, Center
Dr. MSC 0425, Bethesda, MD 20892-0425, USA.

REFERENCE: Infect Immun 2005 Aug 73(8):4714-22

Numerous experimental vaccines have been developed with the goal of 
generating long-term cell-mediated immunity to the obligate 
intracellular parasite Leishmania major, yet inoculation with live, wild
-type L. major remains the only successful vaccine in humans. We 
examined the expression of immunity at the site of secondary, low-dose 
challenge in the ear dermis to determine the kinetics of parasite 
clearance and the early events associated with the protection conferred 
by vaccination with live L. major organisms in C57BL/6 mice. Particular 
attention was given to the route of vaccination. We observed that the 
rapidity, strength, and durability of the memory response following 
subcutaneous vaccination with live parasites in the footpad are even 
greater than previously appreciated. Antigen-specific gamma interferon (
IFN-gamma)-producing T cells infiltrate the secondary site by 1.5 weeks
, and viable parasites are cleared as early as 2.5 weeks following 
rechallenge, followed by a rapid drop in IFN-gamma(+) CD4(+) cell 
numbers in the site. In comparison, intradermal vaccination with live 
parasites in the ear generates immunity that is delayed in effector cell
 recruitment to the rechallenge site and in the clearance of parasites 
from the site. This compromised immunity was associated with a rapid 
recruitment of interleukin-10 (IL-10)-producing CD4(+) T cells to the 
rechallenge site. Treatment with anti-IL-10-receptor or anti-CD25 
antibody enhanced early parasite clearance in ear-vaccinated mice, 
indicating that chronic infection in the skin generates a population of 
regulatory cells capable of influencing the level of resistance to 
reinfection. A delicate balance of effector and regulatory T cells may 
be required to optimize the potency and durability of vaccines against 
Leishmaniasis and other intracellular pathogens.

PMID: 16041057

TITLE: Heterologous prime-boost vaccination with the LACK antigen protects
against murine visceral leishmaniasis.

AUTHORS: Blaise Dondji, Eva Pérez-Jimenez, Karen Goldsmith-Pestana, Mariano
Esteban, Diane McMahon-Pratt

AFFILIATION: Department of Epidemiology and Public Health, Yale University
School of Medicine, New Haven, CT 06520-8034, USA.

REFERENCE: Infect Immun 2005 Aug 73(8):5286-9

This study reports the efficacy of a heterologous prime-boost 
vaccination using DNA and vaccinia viruses (Western Reserve [WR] virus 
and modified [attenuated] vaccinia virus Ankara [MVA]) expressing the 
LACK antigen (Leishmania homologue of receptors for activated C kinase) 
and an intradermal murine infection model employing Leishmania infantum
. At 1 month postinfection, vaccinated mice showed high levels of 
protection in the draining lymph node (240-fold reduction in parasite 
burden) coupled with significant levels of gamma interferon (20 to 200 
ng/ml) and tumor necrosis factor alpha/lymphotoxin (8 to 134 pg/ml). 
Significant but lower levels of protection (6- to 30-fold) were observed
 in the spleen and liver. Comparable levels of protection were found for
 mice boosted with either LACK-WR or LACK-MVA, supporting the use of an 
attenuated vaccinia virus-based vaccine against human visceral 

PMID: 16020728

TITLE: The genome of the kinetoplastid parasite, Leishmania major.

AUTHORS: Alasdair C Ivens, Christopher S Peacock, Elizabeth A Worthey, Lee
Murphy, Gautam Aggarwal, Matthew Berriman, Ellen Sisk, Marie-Adele Rajandream,
Ellen Adlem, Rita Aert, Atashi Anupama, Zina Apostolou, Philip Attipoe,
Nathalie Bason, Christopher Bauser, Alfred Beck, Stephen M Beverley, Gabriella
Bianchettin, Katja Borzym, Gordana Bothe, Carlo V Bruschi, Matt Collins, Eithon
Cadag, Laura Ciarloni, Christine Clayton, Richard M R Coulson, Ann Cronin,
Angela K Cruz, Robert M Davies, Javier De Gaudenzi, Deborah E Dobson, Andreas
Duesterhoeft, Gholam Fazelina, Nigel Fosker, Alberto Carlos Frasch, Audrey
Fraser, Monika Fuchs, Claudia Gabel, Arlette Goble, André Goffeau, David
Harris, Christiane Hertz-Fowler, Helmut Hilbert, David Horn, Yiting Huang, Sven
Klages, Andrew Knights, Michael Kube, Natasha Larke, Lyudmila Litvin, Angela
Lord, Tin Louie, Marco Marra, David Masuy, Keith Matthews, Shulamit Michaeli,
Jeremy C Mottram, Silke Müller-Auer, Heather Munden, Siri Nelson, Halina
Norbertczak, Karen Oliver, Susan O'neil, Martin Pentony, Thomas M Pohl, Claire
Price, Bénédicte Purnelle, Michael A Quail, Ester Rabbinowitsch, Richard
Reinhardt, Michael Rieger, Joel Rinta, Johan Robben, Laura Robertson, Jeronimo
C Ruiz, Simon Rutter, David Saunders, Melanie Schäfer, Jacquie Schein, David C
Schwartz, Kathy Seeger, Amber Seyler, Sarah Sharp, Heesun Shin, Dhileep Sivam,
Rob Squares, Steve Squares, Valentina Tosato, Christy Vogt, Guido Volckaert,
Rolf Wambutt, Tim Warren, Holger Wedler, John Woodward, Shiguo Zhou, Wolfgang
Zimmermann, Deborah F Smith, Jenefer M Blackwell, Kenneth D Stuart, Bart
Barrell, Peter J Myler

AFFILIATION: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus,
Hinxton, Cambridgeshire CB10 1SA, UK. alicat at sanger.ac.uk

REFERENCE: Science 2005 Jul 309(5733):436-42

Leishmania species cause a spectrum of human diseases in tropical and 
subtropical regions of the world. We have sequenced the 36 chromosomes 
of the 32.8-megabase haploid genome of Leishmania major (Friedlin strain
) and predict 911 RNA genes, 39 pseudogenes, and 8272 protein-coding 
genes, of which 36% can be ascribed a putative function. These include 
genes involved in host-pathogen interactions, such as proteolytic 
enzymes, and extensive machinery for synthesis of complex surface 
glycoconjugates. The organization of protein-coding genes into long, 
strand-specific, polycistronic clusters and lack of general 
transcription factors in the L. major, Trypanosoma brucei, and 
Trypanosoma cruzi (Tritryp) genomes suggest that the mechanisms 
regulating RNA polymerase II-directed transcription are distinct from 
those operating in other eukaryotes, although the trypanosomatids appear
 capable of chromatin remodeling. Abundant RNA-binding proteins are 
encoded in the Tritryp genomes, consistent with active 
posttranscriptional regulation of gene expression.

PMID: 16033309

TITLE: Visceral leishmaniasis: new health tools are needed.

AUTHORS: Asrat Hailu, Ahmed Mudawi Musa, Catherine Royce, Monique Wasunna

AFFILIATION: Faculty of Medicine, Addis Ababa University, Addis Ababa, Ethiopia.
hailu_a2004 at yahoo.com

REFERENCE: PLoS Med 2005 Jul 2(7):e211

PMID: 15997368

TITLE: Imported leishmaniasis in Germany 2001-2004: data of the SIMPID
surveillance network.

AUTHORS: T Weitzel, N Mühlberger, T Jelinek, M Schunk, S Ehrhardt, C Bogdan, K
Arasteh, T Schneider, W V Kern, G Fätkenheuer, G Boecken, T Zoller, M Probst,
M Peters, T Weinke, S Gfrörer, H Klinker, M-L Holthoff-Stich, 

AFFILIATION: Institut für Tropenmedizin, Spandauer Damm 130, 14050, Berlin,
Germany, thomas.weitzel at charite.de.

REFERENCE: Eur J Clin Microbiol Infect Dis 2005 Jul 24(7):471-6

Leishmaniasis is a rare, non-notifiable disease in Germany. 
Epidemiological and clinical data, therefore, are scarce. Most 
infections seen in Germany are contracted outside the country. The 
German surveillance network for imported infectious diseases (
Surveillance Importierter Infektionen in Deutschland, or SIPMID) 
recorded 42 cases of imported leishmaniasis (16 visceral, 23 cutaneous, 
and 3 mucocutaneous) from January 2001 to June 2004. Although most 
infections were acquired in European Mediterranean countries, the risk 
of infection was highest for travelers to Latin America. HIV coinfection
 was observed significantly more often in patients with visceral 
leishmaniasis than in patients with cutaneous/mucocutaneous 
leishmaniasis (31 vs. 4%, p=0.02). The median time to a definitive 
diagnosis was 85 days in cases of visceral leishmaniasis and 61 days in 
cases of cutaneous/mucocutaneous leishmaniasis, reflecting the 
unfamiliarity of German physicians with leishmanial infections. Visceral
 leishmaniasis was treated most frequently with amphotericin B, whereas 
cutaneous/mucocutaneous leishmaniasis was treated with a variety of 
local and systemic therapies. The findings presented here should serve 
to increase awareness as well as improve clinical management of 
leishmaniasis in Germany.

PMID: 16048685

TITLE: Molecular and biochemical characterization of a sand fly population from
Sri Lanka: evidence for insecticide resistance due to altered esterases and
insensitive acetylcholinesterase.

AUTHORS: S N Surendran, S H P P Karunaratne, Z Adams, J Hemingway, N J Hawkes

AFFILIATION: Department of Zoology, University of Jaffna, Jaffna,Sri Lanka.

REFERENCE: Bull Entomol Res 2005 Jul 95(4):371-80

With an increasing incidence of cutaneous leishmaniasis in Sri Lanka, 
particularly in northern provinces, insecticide-mediated vector control 
is under consideration. Optimizing such a strategy requires the 
characterization of sand fly populations in target areas with regard to 
species composition and extant resistance, among other parameters. Sand 
flies were collected by human bait and cattle-baited net traps on Delft 
Island, used as an illegal transit location by many refugees returning 
to the north of Sri Lanka from southern India where leishmaniasis is 
endemic. For species identification, genomic DNA was extracted and a 
fragment of the ribosomal 18S gene amplified. The sequence from all 
flies analysed matched that of Phlebotomus argentipes Annandale & 
Brunetti, the primary vector in India and the most likely vector in Sri 
Lanka. Independent morphological analysis also identified P. argentipes
. To establish the current susceptibility status of vector species, data
 were obtained at the biochemical level, from which potential cross-
resistance to alternative insecticides can be predicted. The Delft 
Island collection was assayed for the activities of four enzyme systems 
involved in insecticide resistance (acetylcholinesterase, non-specific 
carboxylesterases, glutathione-S-transferases and cytochrome p450 
monooxygenases), establishing baselines against which subsequent 
collections can be evaluated. There was preliminary evidence for 
elevated esterases and altered acetylcholinesterase in this population, 
the first report of these resistance mechanisms in sand flies to our 
knowledge, which probably arose from the malathion-based spraying 
regimes of the Anti-Malarial Campaign.

PMID: 16020696

TITLE: Trypanosomes at the gates.

AUTHORS: George A M Cross

REFERENCE: Science 2005 Jul 309(5733):355

PMID: 15893068

TITLE: Detailed analysis of an experimental challenge model for Leishmania
infantum (JPC strain) in dogs.

AUTHORS: Jacqueline Poot, Matthew E Rogers, Paul A Bates, Arno Vermeulen

AFFILIATION: Intervet International B.V., Parasitology R&D, Wim de Körverstraat
35, 5831 AN Boxmeer, The Netherlands. jacqueline.poot at intervet.com

REFERENCE: Vet Parasitol 2005 Jun 130(1-2):41-53

In this study, disease progression after intravenous or subdermal 
infection of dogs with Leishmania infantum JPC strain was monitored. A 
challenge performed on 14 dogs via the intravenous route with 5 x 10(7) 
stationary phase promastigotes of the L. infantum JPC strain was 100% 
successful. During a follow up period of 1.5 years, several parameters 
were evaluated in order to find the most reliable disease markers. 
Parasite detection by culture and histology were found to be very 
sensitive (100%). Additionally, regular physical examination, serology 
and serum gamma-globulin levels were found to be useful parameters in 
the evaluation of disease severity and are recommended for inclusion in 
vaccination-challenge experiments. Although this intravenous challenge 
model has practical limitations, the data set confirms it is the best 
experimental model currently available for vaccine development. Two 
intravenously infected dogs were treated with corticosteroids for 5 
months. This treatment was shown to enhance all aspects of a Leishmania 
infection. Five more dogs were infected by sub-dermal injection of 
promastigotes mixed with a proteophosphoglycan-matrix (PSG) secreted by 
Leishmania that assists in transmission and infection by sand fly bite. 
The resulting parasite burdens were low and the animals remained 
asymptomatic during a 2-year follow up period. However, this procedure 
did result in infection in 80% of the dogs and is appealing for future 
development as a natural challenge model in vaccine development.

PMID: 15902687

TITLE: Regulation of the Leishmania-induced innate inflammatory response by the
protein tyrosine phosphatase SHP-1.

AUTHORS: Geneviève Forget, Claudine Matte, Katherine A Siminovitch, Serge
Rivest, Philippe Pouliot, Martin Olivier

AFFILIATION: Centre de Recherche en Infectiologie, Centre Hospitalier
Universitaire de Québec, Pavillon CHUL, Université Laval, Ste-Foy, Canada.

REFERENCE: Eur J Immunol 2005 Jun 35(6):1906-17

Modulation of the phagocyte protein tyrosine phosphatase (PTP) SHP-1 by 
the parasite Leishmania favors its survival and propagation within its 
mammalian host. In vivo, the absence of SHP-1 leads to virtually absent 
footpad swelling, accompanied by enhanced inducible nitric oxide 
synthase expression. In this study, using an air pouch model, we show 
that viable motheaten SHP-1-deficient mice harbored a stronger 
inflammatory response against Leishmania infection than wild-type mice. 
This response was portrayed by higher pro-inflammatory cytokine (TNF-
alpha, IL-1beta and IL-6) expression and secretion and by greater 
chemokine and chemokine receptor expression. These inflammatory 
molecules were probably responsible for the stronger cellular 
recruitment, mainly of neutrophils, seen at the site of infection in 
viable motheaten mice within 6 h post inoculation. We also provide 
strong evidence that protein tyrosine phosphatases in general, and SHP-1
 in particular, are important regulators of chemokine gene expression. 
Overall, this study suggests that the ability of Leishmania to induce 
SHP-1 activity in its host allows the taming of an otherwise strong 
innate inflammatory response that would be detrimental for its survival 
and progression.

PMID: 16048642

TITLE: Host humoral immune response to Leishmania lipid-binding protein.

AUTHORS: M Maache, S Azzouz, R Diaz DE LA Guardia, P Alvarez, R Gil, L M DE
Pablos, A Osuna

AFFILIATION: Instituto de Biotecnología, Grupo de Bioquímica y Parasitología
Molecular, Universidad de Granada, Granada, Spain.

REFERENCE: Parasite Immunol 2005 Jun 27(6):227-34

SUMMARY We report on the use of Leishmania donovani lipid-binding 
proteins (LBPs) as antigens capable of being recognized by serum from 
immunocompetent patients from southern Spain suffering from visceral 
leishmaniasis and from Peruvian patients with localized cutaneous 
leishmaniasis caused by Leishmania braziliensis. The absorbance found by
 immunoenzymatic techniques gave significantly different results for the
 serum samples from patients with and without leishmaniasis. Specificity
 by ELISA testing was 93.2% and sensibility 100%. Dot blots from human 
patient serum samples or naturally infected dogs from Spain gave 
similarly significant results. All the human serum samples from 
individuals with visceral leishmaniasis and the Leishmania-positive 
canine samples recognized two bands, with molecular weights of 8 and 57 
kDa. The serum from individuals with cutaneous leishmaniasis caused by L
. braziliensis recognized an additional band of 16 kDa. We discuss the 
role of Leishmania FABP and compare the immunological reactions found 
with serum samples from other protozoan infections such as toxoplasma 
and Chagas as well as bacterial infections such as tuberculosis and 

PMID: 15866472

TITLE: The involvement of neutrophils in the resistance to Leishmania major
infection in susceptible but not in resistant mice.

AUTHORS: Lin Chen, Zhi-Hui Zhang, Tadashi Watanabe, Takao Yamashita, Takatoshi
Kobayakawa, Akira Kaneko, Hiromi Fujiwara, Fujiro Sendo

AFFILIATION: Department of Immunology and Parasitology, Yamagata University
School of Medicine, 2-2-2 Iida-Nishi, Yamagata 990-9585, Japan.

REFERENCE: Parasitol Int 2005 Jun 54(2):109-18

To understand the immunomodulatory roles of neutrophils in Leishmania 
major infection, we examined the expression of cytokine and chemokine 
mRNAs from neutrophils of the infected resistant C3H/HeJ and susceptible
 BALB/c mice. We also examined the effects of neutrophil depletion on 
the expression of cytokine by peritoneal macrophages and draining lymph 
node cells and on the footpad lesions and parasite burdens in these mice
. Neutrophils from resistant C3H/HeJ but not from susceptible BALB/c 
mice expressed mRNAs for IL-12p40, IFN-gamma,TNF-alpha and monokine 
induced by IFN-gamma(MIG). Neutrophil depletion of the resistant mice 
reduced the expression of IFN-gammaandTNF-alpha in peritoneal 
macrophages but did not affect the expression of IL-12p40 and IFN-gamma 
in draining lymph node cells and the growth of footpad lesions. On the 
other hand, neutrophil depletion of susceptible BALB/c mice did not 
affect the expression of TNF-alpha and monocyte-derived chemokine (MDC) 
in peritoneal macrophages but induced the early stage expression of IL-4
 in draining lymph node cells and exacerbated the footpad lesions and 
increased the parasite burden. The exacerbation of footpad lesions 
induced by neutrophil depletion was abolished by rIL-12 treatment. Our 
results suggest that even in susceptible BALB/c but not in C3H/HeJ mice 
there is a certain resistance requiring neutrophils at the early stage 
of infection.

PMID: 16036304

TITLE: Targeted delivery of arjunglucoside I using surface hydrophilic and
hydrophobic nanocarriers to combat experimental leishmaniasis.

AUTHORS: Richa Tyagi, Sanchaita Lala, Anita K Verma, A K Nandy, Shashi Bhushan
Mahato, Amarnath Maitra, Mukul Kumar Basu

AFFILIATION: Department of Chemistry, University of Delhi, Delhi, 110 007,

REFERENCE: J Drug Target 2005 Apr 13(3):161-71

The purpose of the present study was to investigate the therapeutic 
efficacy of the indigenous drug arjunglucoside I (AG) against in vivo 
models of experimental leishmaniasis by incorporating it in surface 
hydrophilic co-polymeric nanogel particles of size less than 100 nm 
diameter and to compare its efficacy with that of the free drug as well 
as the drug encapsulated in hydrophobic poly-dl-lactide (PLA) 
nanoparticles. The drug AG, having glucose at the terminal end of the 
glycosidic chain, was isolated from an indigenous source. Drug-
incorporated ultra-low-sized nanogels (approximately 90 nm in diameter) 
composed of cross-linked random co-polymer of N-isopropylacrylamide (
NIPAAM) and N-vinyl pyrrolidone(VP) were prepared, characterized and 
used as delivery vehicles to combat experimental leishmaniasis in 
hamster models. For comparison, drug-encapsulated hydrophobic 
nanoparticles (approximately 250 nm in diameter) made from PLA were used
 as a control. The drug AG was incorporated in these nanocarriers and 
these drug-nanocarrier complexes were physically characterized. The 
efficacy of lowering spleen parasite load by the free drug, as well as 
that incorporated in nanogels and PLA nanoparticles were examined in 
vivo in equimolar concentration against hamsters undergoing experimental
 leishmaniasis. The reduction of drug toxicity by the nanogels and PLA 
nanoparticles was also assessed. The efficacy in the lowering of spleen 
parasite load with the free drug was found to be only 38% but was much 
higher when the drug was incorporated in co-polymeric nanogels (79%) or 
in polymeric nanoparticles (75%). Both the nanocarriers were found to be
 effective in reducing hepatotoxicity and nephrotoxicity nearly to the 
same extent. It was apparent that in addition to a smaller size and 
better drug release profile, the contribution of other parameters, e.g. 
overall surface hydrophilicity or hydrophobicity of the vehicles, also 
play an important role in the macrophage uptake of the drug. However, 
whatever be the exact mechanism, being highly efficient, non-hepatotoxic
 and non-nephrotoxic, AG in either of the two nanoparticulate forms may 
have useful application in humans

PMID: 16044686

TITLE: Remote sensing and geographic information systems and risk of American
visceral leishmaniasis in Bahia, Brazil.

AUTHORS: M E Bavia, D D Madureira Trabuco Carneiro, H da Costa Gurgel, C
Madureira Filho, M G Rodrigues Barbosa

AFFILIATION: Universidade Federal da Bahia, Brasil. newmeb2004 at yahoo.com.br

REFERENCE: Parassitologia 2005 Mar 47(1):165-9

The spatial distribution of American visceral leishmaniasis (VL) was 
studied within the context of the environmental characteristics of 
northwest Bahia State in Brazil during an epidemic year. Geographic 
Information Systems (GIS) and Remote Sensing (RS) were used to 
characterize the landscape epidemiology of VL in order to identify and 
map high risk areas and endemic zones in a northwestern Bahia study area
. Normalized Difference Vegetation Index (NDVI) was shown to be one of 
the most important risk factors in the area of study. Low NDVI values 
were related to high numbers of sand flies and high numbers of human and
 canine VL positive cases. Caatinga vegetation type was the dominant 
vegetation type in the endemic area. The use of RS and GIS allowed the 
identification of classes of VL risk that may be useful information to 
guide control program interventions.

PMID: 16040429

TITLE: Symmetrical cutaneous leishmaniasis.

AUTHORS: Claudio Guarneri, Fabrizio Guarneri

REFERENCE: Acta Derm Venereol 2005  85(3):281-2

PMID: 16052865

TITLE: Visceral leishmaniasis and pseudomonas septicemia associated with
hemophagocytic syndrome and myelodysplasia in a Turkish child.

AUTHORS: Tansu Sipahi, Betül Tavil, Ayşegül Oksal

AFFILIATION: Dr. Sami Ulus Children's Disease Center, Ankara, Turkey.

REFERENCE: Turk J Pediatr 2005 Apr-Jun 47(2):191-4

An 18-month-old boy presented with fever, hepatosplenomegaly, jaundice, 
pancytopenia, hyperferritinemia, hypertriglyceridemia and evidence of 
hemophagocytosis and trilineage myelodysplasia in the bone marrow 
aspiration. Appropriate treatment was begun but he died after 12 hours 
of hospitalization due to Gram-negative septicemia. Post-mortem 
examination of liver biopsy revealed diffuse hemaphagocytic 
lymphohistiocytosis and Leishmania-donovani bodies in macrophages.

PMID: 12759563

TITLE: Neuroimmunomodulatory effects of morphine in Leishmania donovani-infected

AUTHORS: Priya Singal, Arvind G Kinhikar, Savita Singh, Prati Pal Singh

AFFILIATION: Department of Biotechnology, National Institute of Pharmaceutical
Education and Research, S.A.S. Nagar, India.

REFERENCE: Neuroimmunomodulation 2002-2003 10(5):261-9

OBJECTIVE: The effect of morphine on host defense during Leishmania 
donovani infection in golden hamsters was studied. METHODS: Hamsters 
were intracardially infected with L. donovani amastigotes and then 
monitored by spleen touch print microscopic examination. Morphine and 
naloxone were administered subcutaneously and intraperitoneally, 
respectively. Leukocytes were counted by a hemocytometer, and ex vivo 
phagocytosis was determined by the examination of stained adherent 
macrophages. RESULTS: Low doses of morphine, 1.75 and 2.5 mg/kg x 2, 
administered subcutaneously on day 0 and day 15 significantly (p < 0.
05) suppressed the infection, whereas high doses (20.0 and 50.0 mg/kg x 
2) exacerbated the infection. On day 30, hamsters treated with low doses
 of morphine showed a significant (p < 0.05) increase in the number 
of circulating leukocytes and the pool size and phagocytic activity of 
peritoneal macrophages ex vivo; in hamsters treated with high doses, all
 these parameters appeared to be diminished. The bone marrow of morphine
-treated hamsters showed a fall in total cellularity and no change in 
the number of monocytes; however, in those treated with low doses, the 
infection was completely eliminated by day 30, and paradoxically, a 
significant (p < 0.05) potentiation of infection was observed in 
hamsters treated with high doses. The spleens of hamsters treated with 
both low and high doses of morphine showed a significant (p < 0.05) 
decrease and increase in weight, respectively; treatment with low doses 
also caused an almost 2-fold increase in the percentage of monocytes. 
Morphine apparently exerted its protective effects via naloxone-
sensitive opioid receptors; naloxone pretreatment did not affect the 
potentiation of infection. CONCLUSION: Conditional doses of morphine 
apparently biphasically modulated the course of L. donovani infection in
 hamsters, at least in part through macrophage-mediated mechanisms.


 The following references are revised files and are brought to you in accordance
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PMID: 15814719

TITLE: Prevention of relapse after chemotherapy in a chronic intracellular
infection: mechanisms in experimental visceral leishmaniasis.

AUTHORS: Henry W Murray

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

REFERENCE: J Immunol 2005 Apr 174(8):4916-23

In visceral leishmaniasis, chemotherapy probably seldom eradicates all 
parasites in tissue macrophages; nevertheless, most T cell-intact 
patients show long-lasting clinical cure after treatment despite 
residual intracellular infection. To characterize prevention of 
posttreatment relapse, amphotericin B was used to kill approximately 90-
95% of Leishmania donovani in livers of mice deficient in mechanisms of 
acquired antileishmanial resistance. Recrudescence subsequently 
developed 1) in animals deficient in both CD4 and CD8 T cells as well as
 CD40L-mediated T cell costimulation, but not in a) CD4 or CD8 cells 
alone, b) NK cell lytic activity, or c) ICAM-1-recruited monocytes; and 
2) in mice deficient in IFN-gamma, but not in the IFN-gamma-inducing 
cytokines, a) IL-12, b) IL-12 and IL-23, or c) IL-18. Posttreatment 
recrudescence also did not develop in animals deficient in macrophage 
phagocyte NADPH oxidase (phox) or inducible NO synthase (iNOS) alone or
, surprisingly, in those deficient in both phox and iNOS. Therefore, 
regulation of the intracellular replication of residual Leishmania 
donovani that escape chemotherapy evolves to a host mechanism 
distinguishable from initial acquired resistance at the T cell, cytokine
, and macrophage levels. Posttreatment, either CD8 or CD4 cells can 
direct the response, IL-12 is not required, and iNOS and phox, the 
activated macrophage's primary IFN-gamma-inducible leishmanicidal 
pathways, both become dispensable.

PMID: 1738359

TITLE: Viscerotropic leishmaniasis in persons returning from Operation Desert

REFERENCE: MMWR Morb Mortal Wkly Rep 1992 Feb 41(8):131-4

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