Medical Research Unit of Albert Schweitzer Hospital
	Name of Head of Institution: Dr. Saadou Issifou, MD, PhD Contact: Laboratoire de Recherches Hôpital Albert Schweitzer B.P.13901 Libreville, Gabon Tel: (00241) 07 98 91 91 Fax: (00241) 58 11 96 Email: foyakhiromen@lambarene.mimcom.net website: www.lambarene.org

Background
The Medical Research Unit of the Albert Schweitzer Hospital located in Lambaréné, Gabon is based on the historical site where Dr. Albert Schweitzer built his hospital and provided care to the local population for the rest of his life.
The Medical Research Unit of the Albert Schweitzer Hospital was established in 1981 with the mission to study major causes of disease burden in the local population. Since its foundation 25 years ago, it has become a leading African research centre, specialising in pathophysiology and treatment of highly prevalent infectious diseases found in sub-Saharan Africa. The initial goals have been broaden and now include training in clinical and laboratory research for local and international investigators.

Dr Issifou, Head of Unit

Malaria Research Program
Malaria research activities of the unit focus on the evaluation of new drugs or regimens, the pathophysiology, immunology of malaria infection and development of malaria vaccines.

Clinical Trials

Drugs. The site has extensive experience in clinical trials with antimalarials and has published in the field since almost 15 years. Examples include a series of studies with clindamycin as an antimalarial (Lell & Kremsner 2002), atovaquone/proguanil for treatment (Radloff et al. 1996) and prophylaxis (Lell et al. 1998) of malaria, tafenoquine for prophylaxis (Lell et al. 2000) and a series of trials establishing fosmidomycin (Missinou et al. 2002, Borrmann et al. 2004) as a promising antimalarial. An underlying principle of these studies has been the concept of combination therapy (Kremsner & Krishna 2004).

Vaccines. The African Malaria Network Trust (AMANET) conducted a clinical trial of a candidate malaria vaccine GMZ-2 in Lambaréné in compliance with international research and ethical standards. GMZ-2 is a hybrid malaria vaccine composed of merozoite surface protein (MSP3) and glutamate rich protein (GLURP). The vaccine is adjuvanted with Aluminium Hydroxide. This trial involved 40 healthy adult volunteers resident in Lambaréné. A study evaluating safety and immunogenicity of GMZ-2 in children is currently being planned.

In collaboration with the Malaria Vaccine Initiative and GSK Biologicals, the centre has recently conducted phase II trials of the RTS,S candidate vaccine. The center is member of the network of African centers preparing for the phase III vaccine efficacy.

MRU-ASH Staff

Pathophysiology
A major area of research focuses on identifying genetic or immunological risk factors for development of severe malaria. This work has succeed in identifying mutations in the promoter region of nitric oxide synthase 2 (Kun et al. 1998) and in the NADPH oxidase (Uhlemann et al. 2004) as well as differences in the capability to produce interferon-gamma (Luty et al. 1999) and oxygen radicals (Greve et al. 1999) that are associated with protection from severe disease.

Laboratory work at MRU-ASH

Financial support
The Research Unit receives no annual budget, and is funded solely through project grants. Current or recent funding agencies include, EDCTP, The Ministry of Education and Research, Germany; the WHO/TDR programme; Bill and Melinda Gates Foundation; Malaria Vaccine Initiative, Medicines for Malaria Venture, the National Institute of Health, USA; European Union;and the fortüne programme of the Medical Faculty of the University of Tübingen.
Industrial partners (for example: GSK and Sanofi-Aventis) are sponsors of current or recent clinical trials.
The Deutscher Hilfsverein für das Albert Schweitzer Hospital donated funds for a new research building which was inaugurated in 2007.

Collaboration
The MRU has a long list of local, regional and international collaborations including the Faculty of Health Science of Libreville, The Department of Parasitology/ Institute of Tropical Medicine of the Medical Faculty of the University of Tübingen and the Vienna School of Clinical Research (VSCR).

In collaboration with VSCR and other partners, the Medical Research Unit at the Albert Schweitzer Hospital in Lambaréné started a postgraduate educational program for African clinical researchers.
This training program aims at:

• improving and encouraging clinical research activities in Sub-Saharan Africa in the field of the poverty related diseases malaria, tuberculosis and HIV/AIDS
• training researchers from Sub-Saharan Africa on GCP, ethics, scientific aspects, legal requirements, data management (introduction to biostatistics), publication skills, and other clinical research related aspects.
• developing a well-selected group of African physicians/scientists to top level expertise in clinical research who would attract, initiate and lead clinical research within their African research centres and countries.

Publications
10 selected publications

1. Brandts CH, Ndjavé M, Graninger W, Kremsner PG. Effect of paracetamol on parasite clearance time in Plasmodium falciparum malaria. Lancet. 1997;350:704-9.
2. Brustoski K, Kramer M, Möller U, Kremsner PG, Luty AJ. Neonatal and maternal immunological responses to conserved epitopes within the DBL-gamma3 chondroitin sulfate A-binding domain of Plasmodium falciparum erythrocyte membrane protein 1. Infect Immun. 2005;73:7988-95.
3. Grobusch MP, Lell B, Schwarz NG, Gabor J, Dornemann J, Potschke M, Oyakhirome S, Kiessling GC, Necek M, Langin MU, Klouwenberg PK, Klopfer A, Naumann B, Altun H, Agnandji ST, Goesch J, Decker M, Salazar CL, Supan C, Kombila DU, Borchert L, Koster KB, Pongratz P, Adegnika AA, Glasenapp I, Issifou S, Kremsner PG. Intermittent preventive treatment against malaria in infants in Gabon - a randomized, double-blind, placebo-controlled trial. J Infect Dis. 2007;196:1595-602.
4. Helbok R, Issifou S, Matsiegui PB, Lackner P, Missinou MA, Kombila D, Dent W, Schmutzhard E, Kremsner PG. Simplified multi-organ dysfunction score predicts disability in African children with Plasmodium falciparum malaria. Am J Trop Med Hyg. 2006;75:443-7.
5. Lell B, Faucher JF, Missinou MA, Borrmann S, Dangelmaier O, Horton J, Kremsner PG. Malaria chemoprophylaxis with tafenoquine: a randomised study. Lancet. 2000;355:2041-5.
6. Matsiégui PB, Missinou MA, Necek M, Mavoungou E, Issifou S, Lell B, Kremsner PG. Antipyretic effect of ibuprofen in Gabonese children with uncomplicated falciparum malaria: a randomized, double-blind, placebo-controlled trial. Malar J. 2008;7:91.
7. Missinou MA, Borrmann S, Schindler A, Issifou S, Adegnika AA, Matsiegui PB, Binder R, Lell B, Wiesner J, Baranek T, Jomaa H, Kremsner PG. Fosmidomycin for malaria. Lancet. 2002;360:1941-2.
8. Planche T, Onanga M, Schwenk A, Dzeing A, Borrmann S, Faucher JF, Wright A, Bluck L, Ward L, Kombila M, Kremsner PG, Krishna S. Assessment of volume depletion in children with malaria. PLoS Med. 2004;1:1
9. Ramharter M, Oyakhirome S, Klouwenberg PK, Adégnika AA, Agnandji ST, Missinou MA, Matsiégui PB, Mordmüller B, Borrmann S, Kun JF, Lell B, Krishna S, Graninger W, Issifou S, Kremsner PG. Artesunate-clindamycin versus quinine-clindamycin in the treatment of Plasmodium falciparum malaria: a randomized controlled trial. Clin Infect Dis. 2005;40:1777-84.
10. Ramharter M, Schuster K, Bouyou-Akotet MK, Adegnika AA, Schmits K, Mombo-Ngoma G, Agnandji ST, Nemeth J, Afène SN, Issifou S, Onnas IN, Kombila M, Kremsner PG. Malaria in pregnancy before and after the implementation of a national IPTp program in Gabon. Am J Trop Med Hyg. 2007;77:418-22.