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Memórias do Instituto Oswaldo Cruz
Fundação Oswaldo Cruz, Fiocruz
ISSN: 1678-8060 EISSN: 1678-8060
Vol. 92, Num. 6, 1997, pp. 867-870
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Mem Inst Oswaldo Cruz, Rio de Janeiro, Vol. 92(6),
November/December 1997, pp. 867-870
First World Congress on Leishmaniasis-World Leish1
Istanbul, Turkey
May 5-9, 1997
Antonia Maria Ramos Franco
Departamento de Imunologia, Instituto Oswaldo Cruz, Av. Brasil 4365,
21045-900 Rio de Janeiro, RJ, Brasil
Code Number:OC97161
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The leishmaniases are a widespread group of parasitic diseases, which
pose serious health problems that still remain unsolved in the 1990's. The
parasite Leishmania, is responsible for a wide spectrum of
morbidity, in over 12 million people. It is estimated that 350 million
people are at risk, and that some 1.5-2 million people are infected
annually. This parasite has proven to be an excellent model for studies on
host-parasite and host-vector interactions, immunological mechanisms,
molecular biology, and epidemiology. The aim of the congress was to promote
interaction and cooperation among scientists resulting in new solutions to
regional or global problems on leishmaniasis. The place chosen for this
first world meeting on leishmaniasis, Istanbul, is the only city in the
world on two continents, Asia and Europe. This eclectic city provided for
all the participants an unforgettable scientific and cultural experience.
The Congress benefited from the active participation of scientists from at
least 36 countries. This participation is fully reflected by the content of
the 411 abstracts published.
It is not possible to comment on all the presentations, and this report
is a selective list of some of the highlights.
CL Jaffe (Hebrew University-Hadassah Medical School, Jerusalem, Israel)
opened the proceedings with a conference about the protein kinases (PK) and
parasite survival. These proteins have important roles in the regulation of
cellular metabolism, differentiation, growth and signal transduction.
Little is known regarding their host-parasite interactions. Environmental
changes, such as temperature and pH affect PK activity. These proteins can
also affect host response to the parasite. Jaffe showed some assays related
with these enzyme activities and discussed how the intra- and extracellular
PK function, in parasite survival, growth and response to host
environmental changes.
Vaccine Development
The development of a vaccine against Leishmania has been a
complex process and one of the principal aims of studies on leishmaniasis.
Recombinant DNA technology has been successfully applied to the development
of vaccines against a number of diseases. Different methods to select
leishmanial antigens as vaccine candidate were presented. YAW Skeiky
(Corixa Corp. Seattle, WA) with other collaborators (J Webb, R Badaro, A
Campos-Neto & SG Reed) have tested recombinant antigens, identified by
expression cloning or by reverse genetic approaches. The selection was
carried out by the ability of these antigens to stimulate immune responses
in cells from patients as well as to elicit Th1 associated responses from
lymphocytes from infected BALB/c mice. They showed the results of
protective immune responses against L. major in BALB/c mice with a
combination of three antigens. SCF Mendonca (Fiocruz, Brazil) reported the
results of comparison between autoclaved and non-autoclaved preparations of
a vaccine composed of whole antigens from killed promastigotes of L.
amazonensis in two groups of immunized individuals from an endemic area
in Brazil. Promastigotes of autoclaved L. major were used as a
vaccine in volunteers in endemic areas infected with L. major, L.
tropica and L. donovani (Iran, Pakistan and Sudan). RF
Hashemi (Razi Research Vaccine and Serum Institute, Iran) showed that the
immunogenicity of the vaccine was satisfactory and adverse effects in
vaccinated volunteers were not observed. The efficacy of an autoclaved
L. major vaccine (ALM), mixed with BCG was showed in volunteers
against natural cutaneous leishmaniasis in Isfahan (AZ Momeni, Isfahan
University of Medical Sciences, Iran) and in schoolchildren, in Bam, Iran
(I Sharifi et al., Medical School, Kerman University of Medical Sciences).
In Baluchistan, Pakistan, where both anthroponotic and zoonotic cutaneous
leishmaniasis are endemic, a randomized double-blinded-placebo-controlled
vaccine efficacy trial using this killed L.major vaccine was
conducted among the individuals tested. A Firooz et al. (Pasteur Institute,
Iran) reported that the use of three injections of ALM with BCG, 30 days
apart, are completely safe and significantly more immunogenic than BCG
alone in adults.
Several animal models have been tested with different vaccination
schedules and vaccine preparations. D Rivier et al. (University of
Lausanne, Switzerland) showed the importance of adjuvants and the site of
immunization for vaccination using CBA (inbred strains of mice, that
develop a cutaneous ulcer caused by L. major, such as in the human
disease) as a model animal. The animals were immunized with a purified
amphiphilic leishmanolysin gp63 and infected with L. major, the
results show that the protection against L. major could be obtained
following subcutaneous injection of gp63 at a distance from the site of
infection only when adjuvants (C. parvum or BCG) were omitted from
the vaccine. Currently, Leishmania antigens have been tried in
several primate models as well as in humans, however, they have been
ineffective as vaccines. RT Kenney, AA Gam and DL Sacks, reported the
immunogenic effect of a vaccine that combines a killed preparation of L.
amazonensis (produced by Biobras) and recombinant interleukin-12, that
has a marked effect as an adjuvant in the BALB/c model of CL adsorbed to
aluminum hydroxide fluid gel and tested in Macaca mulatta. They
suggest the need for an adjuvant to stimulate an effective immune response
in this primate model. The relative value of different animals models for
Leishmania vaccine trials was discussed. Two aspects of the model
system in particular need consideration: the first of these is whether the
host animal is capable of mimicking human infection and subsequent immune
response sufficiently closely; the second is whether the appropriate
parasite stage and method of delivery is used.
Canine Leishmaniasis
Visceral leishmaniasis (VL), or kala-azar is a zoonosis in most regions
where it occurs. Dogs are the most important vertebrate reservoir of the
disease and are mainly responsible for the persistence of VL in the
Paleartic and Neotropical regions. Canine leishmaniasis is a
viscerocutaneous disease and therefore it is incorrect to call it VL. As in
man, there are some cases of assymptomatic infection. No specific
Leishmania drug exists to treat canine visceral leishmaniasis (CVL).
However, several human drugs were tested. The development of effective
treatments for canine visceral leishmaniasis is essential to eradicate the
disease in humans, nevertheless, very little is known about the immune
cells implicated in CVL and its protective role. P Abranches (Tropical
Medicine and Hygiene Institute, Portugal) stressed the importance of
knowing when canine cutaneous parasitism becomes infectious to the insect
vector. JA Rioux indicated later periods of the disease, J Alvar showed by
xenodiagnosis that it is possible that transmission might occur earlier.
The finding of animals without humoral response means that the prevalence
of canine leishmaniasis found in epidemiological surveys by search of
antibodies may be underestimated, and that the spontaneous development of
resistance (related with active cellular immunity) in these infected
animals is interesting for research studies aiming at a canine vaccine.
Some presentations showed studies of the humoral response against L.
infantum in vaccinated or treated dogs. Results obtained with the
use of autoclaved L. major mixed with BCG as adjuvant
revealed a partial protection in vaccinated dogs in which a cell-mediated
response was established as well as asymptomatic dogs spontaneously
recovered from leishmaniasis. Animals treated with pentamidine reveal that
after treatment the immune cellular response which is involved in
protection against L. infantum infection was established (A Rhalem
et al., Institut Agronomique et Veterinaire Hassan II, Morocco).
HIV and Leishmaniasis The occurrence of human individuals
infected with both diseases has increased. HIV-VL coinfection is usual in
some Spanish regions. The diagnosis is hampered by its coexistence with
other opportunistic infections as well as the poor sensitivity of serology
versus Leishmania spp. This coinfection is accompanied by severe
immunodepression stronger than that caused by other diseases. The presence
of p24 antigen and the bicytopenia (platelets and leucocytes) are
discriminatory criteria in the diagnosis of HIV-VL (J Hernandez, Andalusian
Group for Study of Infectious Diseases, Spain).
Kinetoplast DNA
Studies of kinetoplast-DNA (KDNA), showed that this extrachromosomal DNA
structure, have associated proteins (histone H1-like), where genes have
been cloned (DS Ray, University of California, USA). Replication of the
individual kDNA minicircle initiates at a 12-nucleotide sequence, termed
the universal minicircle sequence (UMS), which was conserved in all the
trypanosomatids species studied. Computer analyses confirm the location of
the origin-associated UMS within a local sequence-directed curved DNA
structure, and revealed the potential of the DNA double-helix at the
minicircle origin region to generate a stable intrastrand secondary
structure. Kinetoplast segregation is co-ordinated with other structural
events in the cell cycle. The segregation is mediated by attachment of the
mitochondrion/kinetoplast complex to the flagellum basal bodies. Through
sequence analysis the mitochondrial genome is encoded in the maxicircle
while the minicircle has been shown to encode small RNA molecules (guides
RNAs) which are involved in the process of RNA editing. Models of kDNA
replication were also discussed (Y Tzfati et al., The Hebrew University,
Israel; K Gull et al., University of Manchester, UK; K Stuart et al.,
University of Washington, USA).
Taxonomy of Leishmania
JA Rioux and N Leger (Montpellier-Reims, France), discussed
nomenclatural problems, where considerations about species and genus were
raised. K Victoir et al. (Laboratoire de Genetique Moleculaire des
Parasites et des Vecteurs, Montpellier) showed that the combination of
analysis by restriction enzymes (RFLP) and PCR amplification of the
conserved part of the gp63 gene, when compared with MLEE data, might be an
epidemiological and diagnostic tool to differentiated between L.
(V.) peruviana and L. (V.) braziliensis
(two genetically close species with different pathogenicity). Studies to
show the differences between both species was carried out using molecular
karyotyping, the limits for using this method were discussed. Results were
presented suggesting mating between both species which are considered to
reproduce mainly clonally (JC Dujardin et al., Prince Leopold Institute of
Tropical Medicine, Belgium). Through the MLEE and RAPD analysis the data
support the view that these species correspond to two closely related but
distinct phylogenetic lines (clades).
Sand Fly Vectors and Non-vector Transmission
Female sandflies salivate as they probe the skin for blood. Sand fly
saliva is known to supress immune functions of macrophages and exarcebate
experimental cutaneous leishmaniasis. The saliva of Phlebotomus
papatasi, the vector of L. major contains a potent inhibitor of
protein phosphatase (PP)-1 and PP-2A. Saliva of this sand fly also,
down-regulated the expression of the inducible nitric oxide synthase gene
and reduced the production of nitric oxide by activated macrophage. J
Waitumbi and A Warburg (Hebrew University, Israel) suggest that the
supression of nitric oxide production caused by P. papatasi saliva,
is achieved via the inhibition of PP activity in macrophages. Another
interesting subject is the presence of apyrase (an ATP/ADPase that inhibits
platelet aggregation) and maxadilan (a potent vasoactive peptide with
proved pharmacological and immuno-modulatory activites) in the saliva of
some species of sandflies (including all L. longipalpis
spp.). Both facilitate the location of blood vessels in the skin, prevent
hemostasis and assure an adequate blood supply to the bite site. The same
authors discussed the properties and functions of different sand fly saliva
among P. papatasi and Lu. longipalpis spp. They suspected
that maxadilan may be the exacerbating factor in saliva, in fact, their
studies showed that lesion exacerbation is not attributable to any single
salivary component. Many studies have suggested L. longipalpis as a
complex of species. Azevedo et al. (Fiocruz, Brazil) compared populations
from different regions in Brazil by morphological methods, suggesting a
polymorphism among specimens from these areas (PA, MA, RN, CE and MG) in
Brazil. The transmission of the Leishmania parasite without the sand
fly vector has been reported, by blood transfusion, sexual intercourse,
direct contact or congenital transfer. Meinecke et al. (Olgahospital,
Germany) reported a rare case of VL where the mother of an infected child
never showed signs of the disease but was shown to be subclinically
infected. The authors emphasize that congenital infection with VL may be
much more common than is thought.
Diagnosis
Different methods of Leishmania diagnosis were presented, such
as, parasitological, immunological (IFAT, ELISA, TR-FIA/time resolved
fluoro immuno assay, TRALd/rapid test antibody L. donovani,
SPEEDLEISH/Bio veto test), DNA hybridization and PCR. PCR-based methods,
have been used with the intention of identification of different species of
Leishmania by detection of DNA polymorphisms in Leishmania
and the use of sequences from the conserved region of minicircle kDNA (G
Schönian et al., Humboldt University, Berlin; Barker et al., Cambridge
University, UK; O Fernandes et al., Fiocruz, Brazil; OF Osman et al.,
University of Khartoum, Sudan; R Piarroux, University of French Country,
France). In conclusion, PCR-based methods have become an essential tool for
the diagnosis of leishmaniasis. This rapid and sensitive method allows the
detection of parasite DNA from different material, and can be used for a
wide variety of situations.
Finally, MA Ozcel presented the economic importance of parasitic
diseases. The information of prevalence and incidence on the the various
aspects of the parasitic diseases in certain areas in the world, such as
transmission, disease characteristics and control measures, provide
baseline points for social and economic studies to determine the role of
human behaviour in the incidence, transmission and control of diseases.
The full proceedings of the conference are published in a supplementary
issue of Acta Parasitologica Turcica (the official Journal of the
Turkish Society for Parasitology).
Acknowledgements: to Dr H Momen for critical reading of the
original manuscript. To the Brazilian funding agency FAPERJ for travel
support. This report represents an personal view of the Congress.
Copyright 1997 Fundacao Oswaldo Cruz
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