Partner 1:

Prince Leopold Institute of Tropical Medicine (ITMA), Belgium

The Prince Leopold Institute of Tropical Medicine in Antwerp, Belgium (ITMA) is one of the world's leading institutes for training, research and assistance in tropical medicine and health care in developing countries. The overall goals of ITMA are to: (i) strengthen the rational basis of medical and veterinary health care in developing countries, and (ii) provide reference clinical services for the management of tropical diseases, import pathology and AIDS in Belgium. Its fields of activity include all health problems related to the specific ecological and socio-economic conditions of developing countries.

• Clinical and preventive services for tropical diseases and related pathology.
• Advanced education in tropical human and veterinary medicine and in the management of health care in developing countries.
• Research on biomedical, clinical and operational aspects of tropical diseases and their control, and on the management of health care in developing countries.
• Supporting and strengthening national and international bodies concerned with human and animal health in developing countries.

The Department of Parasitology is one of the 5 departments of ITMA. The overall objective of the department is to "generate, disseminate and apply knowledge of human parasitic diseases, in particular malaria, leishmaniasis, sleeping sickness and schistosomiasis and to strengthen the capacities in those fields in developing countries". The department pursues this objective through innovative and applied research, post-graduate training and scientific support to research and control programmes, as well as by seeking international added value and competitiveness.
The Unit of Molecular Parasitology was created in 2002 on the base of the former Protozoology Unit (Prof. D. Le Ray). It aims at implementation research addressing the needs of disease control programmes for leishmaniasis (Old World and New World) along two main avenues: genomics and diagnostics, that are further oriented towards epidemiology and health services. In the past, the unit performed a pioneer work in deciphering the significance of chromosomal polymorphism in natural populations of Leishmania. Later on, we performed several studies aiming to understand the contribution of the parasite to the tremendous clinical pleomorphism observed among leishmaniases. By exploring "non-conventional" genetic markers, we made some interesting findings, like (i) the possible role of chromosomal rearrangements in the pathogenicity of the parasite and (ii) the importance of the polymorphism of specific antigen genes. Currently, the unit is involved in four major activities: (i) the promotion of transborder surveillance of the three major risk factors (drug resistance, immune status, human and environmental factors) for spreading of leishmaniasis around the Mediterranean basin, (ii) the understanding of treatment failure and natural drug resistance and (iii) the development and evaluation of molecular tools for diagnostics, species identification, fingerprinting and detection of drug resistance, and (iv) the molecular tracking of parasites in support to intervention studies (bednets). Jean-Claude Dujardin is currently the head of the Molecular Parasitology Unit, with the close support of Saskia Decuypere and Thierry Laurent.

Prof. Dr. J.C. Dujardin is an expert on molecular parasitology research, both at the basic (genome structure, dynamics and function) and the applied levels (molecular diagnosis and epidemiology). He is particularly adapted to work succesfully at that particular interphase between cutting edge molecular biology technology and its application to solve problems of clinical and epidemiological relevance. He has the relevant laboratory experience in (i) parasitology and (ii) molecular biology both in the high-tech context of a modern lab and in the working conditions of a laboratory in a tropical context. He is deeply involved in several networks active on leishmaniasis and is fanatic of multidisciplinary research.
Dr. Thierry Laurent is the post-doc assistant at the Unit of Molecular Parasitology. He has the theoretical and practical knowledge of both molecular biology and serology. His main subject of expertise are diagnostic, typing and finger printing molecular tools. He has a great technical and practical experience in high tech laboratory.
Saskia Decuypere is currently working at the Unit of Molecular Parasitoly as a PhD-student of the University of Antwerp. She is a biochemist and her main expertise is drug resistance. Particularly in this project, she has studied the mechanism of SbV resistance on transcriptomic level.
Simonne De Doncker is a technician specialised in basic and molecular parasitology of trypanosomatids. She is responsible for the logistics of the project, and is the manager of the reference cryobank. During the project, she participated to the technological tranfer and training of oversea colleagues.

	Unit of Molecular Parasitology Prof. Dr. Jean-Claude Dujardin Simonne De Doncker Dr. Thierry Laurent Saskia Decuypere	Department of Public Health Dr. Marleen Boelaert
Go to publications ITMA

Partner 2:

B.P. Koirala Institute of Health Sciences (BPKIHS), Nepal

BPKIHS, an autonomous health sciences university, established in 1993 through an act of the Nepalese parliament with a mandate to produce socially responsible and competent health force and thus continuously strive forward to meet the health need of eastern Nepal at all primary, secondary and tertiary level.

Objectives of BPKIHS:

• To develop a pattern of teaching in undergraduate and postgraduate medical education in all its branches so as to demonstrate a high standard medical education to all medical colleges and other allied institutions in Nepal.
• To bring together in one place educational facilities of the highest order for the training of personnel in all the important branches of health activity.
• Attain self sufficiency in postgraduate medical education.

Functions of BPKIHS:

• Undergraduate and postgraduate teaching in medical and related physical and biological sciences
• Nursing and dental education
• Innovations in education
• Producing medical teachers for the nation
• Research and medical sciences
• Health care: preventive, promotive and curative; primary, secondary and tertiary
• Community based teaching and research

The institute has also been envisoned to develop as a center of excellence in tropical and infectious diseases for the region. Located within the midst of the endemic Terai region for vector borne diseases, malaria, kala-azar and Japanese encephalitis, the institute has been conducting reearch in kala-azar for over a decade. A 34 bed tropical and infectious diseases ward has been established along with a specialized kala-azar laboratory.

Dr. Suman Rijal is currently in charge of the tropical and infectious disease unit. He is a physician with a special interest in tropical and infectious diseases including kala-azar. Has been associated with conducting research in kala-azar since 1999. The major fields of research include epidemiology, evaluation of diagnostic tests, development of molecular markers for drug resistance and conducting drug trials.

	Department of Medicine Dr. Suman Rijal	Department of Microbiology Dr. Bashuda Khanal Kamal Parajuli Ranjit Karna
Go to publications BPKIHS

Partner 3:

Centro Universitario de Medicina Tropical (CUMETROP), Bolivia

CUMETROP belongs to the Institute for Biomedical Investigation at the Universidad Mayor de San Simon. The centre aims at developing research on tropical medicine, performing medical care for patients with tropical diseases and improving teaching of tropical pathology. Extensive research has already been performed in epidemiological and entomological research on leishmaniasis with particular attention for the development of research in accordance with the national reality.

	Director Dr. Hernan Bermudez
Go to publications CUMETROP

Partner 4:

London School of Hygiene and Tropical Medicine (LSHTM), UK

The mission of the London School of Hygiene & Tropical Medicine is to contribute to the improvement of health worldwide through the pursuit of excellence in research, postgraduate teaching, advanced training and consultancy in international public health and tropical medicine. To achieve this mission the School will enhance its role as:

• Britain's national school of public health,
• a leading institution in Europe for research and postgraduate education in public health and tropical medicine
• an international centre of excellence in public health and medicine in developing countries.

The Department of Infectious and Tropical Diseases (ITD) was formed in August 1997 and encompasses all of the laboratory-based research in the School as well as that on the clinical and epidemiological aspects of infectious and tropical diseases. It is currently headed by Hazel Dockrell, who is Professor of Immunology. The Department is organised into five large research units. The range of disciplines represented in the department is very broad and inter-disciplinary research is a feature of much of our activity.
The research interests of the Drug Discovery Group, headed by Professor Simon Croft, range from drug resistance (Leishmania-SbV, Leishmania-miltefosine), to screening of drugs form a variety of sources against Plasmodium spp., Leishmania spp., Trypanosoma brucei sp. and Trypanosoma cruzi. Members of the group are also involved in novel drug development and new formulations of existing anti-protozoals.

Dr. Vanessa Yardley has worked at the School for over 10 years setting up the TDR/WHO-funded integrated screen. She completed her PhD and has maintained an interest in new formulations of amphotericin B (and antimonials) as potential anti-leishmanials. As a partner of the LeishNatDrug-R project, her role has been to carry out in vitro evaluation of the isolates as well as provide material for partners carrying out molecular techniques.

	Department of Infectious and Tropical Diseases Prof. Dr. Simon Croft Dr. Vanessa Yardley
Go to publications LSHTM

Partner 5:

Instituto de Medicina Tropical 'Alexander von Humboldt'(IMTAvH), Peru

The Institute of Tropical Medicine “Alexander von Humboldt” (IMTAvH), in Lima, Peru, is the leading institution for training and research on infectious diseases in Peru. It is part of the Universidad Peruana Cayetano Heredia, a private university specialized on biomedical sciences. The IMTAvH is located adjacent to the University Northern Campus, within the Hospital Nacional Cayetano Heredia in Lima, Peru. Below is the general description for research activities and clinical capacity in IMTAvH. IMTAvH occupies a roofed area of 1 900 m² within a 10 000 m² area and comprises research laboratories, library, computational facilities, hospitalization beds, outpatient clinics and teaching facilities.

A. Training Activities

The IMTAvH of the Universidad Peruana Cayetano Heredia has developed several training activities as international opportunities:

1. An 8-12 week long “extracurricular” clinical course on Infectious and Tropical Diseases. This course offers instruction on the diagnosis, epidemiology, clinical manifestations, treatment and prevention of the infectious and parasitic diseases prevalent in Peru. It emphasizes clinical duties and laboratory work, and may include visits to several field sites, where research and training activities are ongoing. Iquitos, a large city in the Peruvian jungle, where many tropical diseases are endemic, is normally visited for two weeks, as part of the in-service teaching-training program for Medical undergraduate students.
2. Long-term clinical training, under special arrangement. At present, 3 fellows are funded for one year by the Spanish Government undertaking training similar to that of Peruvian residents. Occasionally, a full four year residency in Infectious and Tropical Diseases, involving a 3-month field-work experience, may be arranged for foreign physicians.
3. Research training and field work on epidemiology, entomology, diagnosis, clinical studies, on human leishmaniasis and bartonellosis, which are present in the same endemic areas in the Andes.
4. Other research collaboration on a multitude of specific diseases, including malaria, Chagas' disease, hepatitis, yellow fever, measles, enteric viral diseases, dengue, typhoid fever, shigellosis, cholera, brucellosis, mycobacterial diseases, superficial and deep mycoses, and several others.
5. Research collaboration on nutritional aspects of infectious diseases, a line which is receiving increasing interest at IMTAvH.

B. Clinical Capacity for Leishmaniasis

The Leishmania Working Group (LWG) started its activities in 1984. Research has focused in clinical, epidemiological and laboratorial areas. It works in close collaboration with the Trypanosomatid Molecular and Cell Biology Lab, having lately undertaken together the four year LeishNatDrug study to investigate the clinical and parasitic genetic polymorphisms associations in the development of treatment resistance.
Over the past 20 years, IMTAvH has been one of the reference centers for difficult cases of leishmaniasis, especially treatment failures. A number of clinical and laboratory research projects have taken place through the years. Personnel from LWG have served in the diagnosis, patient enrollment, treatment and follow-up procedures. On average, 250 patients per year are seen at our facilities, 90% of them with a firm diagnosis of either CL or ML, in which 75% are CL patients. For inpatient support (severe leishmaniasis cases), LWG offers its diagnostic media to ward physicians at the hospital and remains during the patient's hospitalization period constantly monitoring its improvement. LWG has access to inpatient treatment in a 36 bed facility. These are reserved for leishmaniasis patients that require close monitoring (severe ML illness, systemic illnesses in association with leishmaniasis, etc).
Among the various research groups at IMTAvH, LWG is the only one that offers both diagnostic procedures and treatment facilities for patients. Patients with proven diagnosis of leishmaniasis are given either pentavalent antimonials or Amphotericin B treatment, overseen always by a full-time employed clinician. Their cases are individually followed to monitor cure and failure rates and given subsequent treatments when deemed necessary. LWG routinely offers the following exams for diagnosis:

1) Montenegro skin test (Leishmanin)
2) Direct smear (Giemsa stain)
3) Parasite culture (needle aspiration of lesions or biopsy culture)
4) Punch skin biopsy for PCR, RNA studies and culture
5) mucosal biopsy from nasal, oral and pharyngeal lesions

Leishmania cultures are performed in very few institutions in Peru, and LWG is one of the facilities that routinely offer this service, usually free of charge to patients from all over the country. Depending on the study conditions, blood samples from patients for serological studies can be taken by the personnel.

C. Laboratory Research for Leishmaniasis

The Unit of Cellular and Molecular Biology of Trypanosomatids started in 1981, with the aim to understand the role of the parasites in the different clinical manifestations of the disease. A multidisciplinary approach is carried out to understand the molecular basis of parasite virulence in Leishmania subgenus Viannia, the intracellular parasite responsible of American tegumantary leishmaniasis. At a lesser extent we also conducted some studies on Trypanosoma cruzi, the causative agent of Chagas disease. Among the side products of our research are molecular tools that permit a more rapid and specific diagnosis of these diseases. The following topics in these parasites are being studied:

Genetic polymorphism of Leishmania
Isolates from different endemic areas of Peru are being characterized by isoenzymes, RFLP (Restriction Lenght Polymorphism), PCR (Polymerase Chain Reaction) and molecular karyotype. We have been able to build up dendrograms that show correlation between geography and genetic polymorphism. Now we are attempting to establish if a correlation with virulence does exist. Special emphasis is given to the chromosome bearing gp63 which showed an interesting genetic polymorphism. This chromosome encodes a parasite protease that has been implied in parasite virulence.
Design for molecular tools for diagnosis in leishmaniasis
We have developed a diagnostic method based on PCR, using our own primers, which was able to be performed in the field with minimal laboratory facilities. It has been applied also for detection of parasites in their insect vectors and to conduct studies to assess the predictive value of PCR for disease relapse. Other important research line is the development of diagnostic test based on recombinant antigens. For this, we have cloned and characterized parasite proteins that are strongly recognized by sera of infected patients.
Host-parasite relationship
We have established experimental in vitro and in vivo infection systems to evaluate the capability of parasites to invade macrophages or to cause disease. These systems are being used to evaluate natural products as potential chemotherapeutic agents.
Oxygen radicals in Trypanosoma cruzi, biological effects and detoxifying mechanisms
We have demonstrated that different stages of the parasite have a differential susceptibility to oxygen radicals. Furthermore, the infective forms present a higher concentration of ascorbic acid, most of it in the reduced form. Dehydroascorbate reductase, the enzyme that is responsible of the balance between oxidized and reduced forms of ascorbate is being purified from T. cruzi for subsequent characterization.
Signal transduction in the differentiation of Leishmania parasites
Protein phosphorylation is the most important post-translational process that controls cell growth and metabolism. Protein kinases, specially those which are involved in the cell cycle and differentiation are most probably also essential for parasite survival. Study of this group of enzymes for Leishmania might uncover important processes in this parasite. This is a new research line and we expect to generate through this project: a) Information on the mechanisms of parasite development within its host; b) identification of novel molecules that are essential for parasite development and survival; c) identification of molecules, such as kinases, either common to all Leishmania species or specific for some particular Leishmania (genes corresponding to these molecules might be useful for the development of diagnostic methods for leishmaniasis); d) the characterization of protein kinases could provide targets to design specific inhibitor peptides that could be used for innovative therapeutic strategies.

	Unit of Cellular and Molecular Biology of Trypanosomatids Dr. Jorge Arevalo Raul Loayza Denis Castillo Vanessa Adaui	Leishmaniasis Working Group Dr. Alejandro Llanos-Cuentas Marcela Lazo Cesar Miranda Gianfranco Tulliano
Go to publications IMTAvH

Partner 6:

Hôpitaux Universitaires de Genève (HUG), Switzerland

The "Hôpitaux Universitaires de Genève" (HUG), or Geneva University hospital, is the reference medical centre for the population of Geneva and surroundings. Their mission, defined by law, comprises the diagnosis and treatment of the sick, teaching and research, preventive medicine and social help for patients. In 2003, the HUG undertook 750 000 consultations and 45 000 patients were admitted in the 2 200 beds hospitals.
The "Unité de Médecine des Voyages et des Migrations" (UMVM), or Travel and Migration Medicine Unit, is part of the Department of Community Medicine and undertake around 13 000 consultations yearly. Its activities comprise a travellers' clinic (e.g. vaccinations, malaria prevention), consultations of tropical medicine for out and in-patients, care to migrants and refugees, coordination of humanitarian activities of the HUG, pre and post graduate teaching and research. Since 1998, the UMVM has developed partnerships with the Swiss section of Médecins Sans Frontières (MSF) and with the B. P. Koirala Institute of Health Sciences (BPKIHS), a teaching hospital located in Dharan, Nepal.
The research activities of the UMVM in the field of tropical diseases deal with clinical and public health aspects of snake bites, human African trypanosomiasis and visceral leishmaniasis (kala-azar). Studies on kala-azar in Nepal and Uganda have focused on diagnostic tests and antimonial therapy. In the frame of the ongoing LeishNatDrug project, research activities on immunological aspects of cutaneous and visceral leishmaniasis are being developed with the Division of Immunology of the HUG.

	Travel and Migration Medicine Unit Dr. François Chappuis Dr. Louis Loutan	Division of Immunology Carlo Chizzolini Coralie Durieux Anne Maurer
Go to publications HUG