NSETHIO, project funded by ERC, Horizon 2020
Nodding Syndrome: a trans-disciplinary approach to identify the cause and decrease the incidence of river epilepsy
Nodding syndrome (NS) is a neurological, incurable syndrome, currently affecting mainly children between 5 and 18 years of age, initially described in South Sudan, Uganda and Tanzania. https://www.youtube.com/watch?v=5S7QLocaS0M. NS is characterized by head-nodding (an atonic form of epilepsy), often followed by clonic - tonic seizures, developmental retardation and faltering growth. In the affected regions, NS is a major public health problem associated with severe socio-economic consequences. In South Sudan, in the West Equatoria State, in Mvolo, we found that 1 in 6 children had epilepsyand at least one in 2 families had at least one child with epilepsy.
In many onchocerciasis endemic areas a high prevalence of epilepsy is found. We hypothesize that NS is part of a spectrum of different types of seizures in onchocerciasis endemic areas, and that several of the different types most likely have a related etiology as a direct and/or indirect (potentially immune mediated) consequence of OV infection. We propose to call this form of epilepsy associated with onchocerciasis “river epilepsy”.
We recently discovered a high prevalence of epilepsy in several onchocerciasis endemic areas in the Democratic Republic of the Congo (DRC) (e.g. in the Oriental Province, Ituri, and Katanga). In Titule in Bas Uélé region, Orientale Province the epilepsy prevalence was 2.3%. A case control study showed that, daily bathing in the local rivers was an important risk factor for epilepsy (OR 3.07, 95% CI 1.19-7.93). In a prospective study in Cameroon by the NSETHIO consortium, O. volvulus microfilariae density (larval stage residing under the skin) in childhood was found to be strongly associated with the risk of either seizures or epilepsy in an onchocerciasis focus in Cameroon. Moreover, in a study in the DRC a correlation between skin microfilariae density and seizure frequency.
Recently, others found that serum autoantibodies against leiomodin-1, (a protein present in the human brain), were more likely to be present in NS cases than in controls. These antibodies were also present in the cerebrospinal fluid of certain patients with NS, and were found to be neurotoxic in vitro, and cross-reacting with OV-specific proteins. Whether these antibodies are instrumental in the pathogenesis of NS and epilepsy and/or are a consequence of damage to the central nervous system caused by the O volvulus, needs to be investigated. Recently in a postmortem study A Hotterbeekx, postdoc at the NSETHIO project, detected O volvulus DNA by PCR in brain tissue of children with nodding syndrome who died.
The African Programme for Onchocerciasis Control estimates there are currently 36 million people with onchocerciasis. Therefore, if 1% (equivalent to the approximate excess prevalence over non-endemic areas) were to develop epilepsy, the number of excess cases of epilepsy due to onchocerciasis would be on the order of 360,000. We hypothesize that most of this excess in prevalence of epilepsy is potentially preventable by increasing the coverage of ivermectin treatment and larviciding rivers, and by maintaining it over many years. If it is confirmed that O volvulus infection increases the risk of epilepsy, this will be an additional argument to strengthen onchocerciasis elimination plans. In a population based trials we will investigate whether with bi-anual ivermectin distribution with or without larviciding rivers will decrease the incidence of river epilepsy.
Data of the NSETHIO project can be obtained by contacting robert.colebunders@uantwerpen.be
Curriculum vitae
R Colebunders was among the first to describe the clinical manifestations of HIV infection in Africa. In 2004 he spent a sabbatical year in Uganda at the infectious diseases Institute to assist this institution to scale up ART. He published numerous studies about how to improve the quality of care in persons with HIV and HIV TB co-infection and how to organise care/treatment more effectively. He initiated the international network for the study of HIV related IRIS (INSHI). He was a member of the international team that investigated the Kikwit Ebola and the Durba Marburg outbreak. Currently he is involved in research to identify the cause of the nodding syndrome and epilepsy in onchocerciasis endemic regions.
A.Positions and Honors
Positions
1974 Setif, Algeria: Head of department of paediatrics in large urban hospital.
1974‑1975 Bougaa, Algeria: responsible for the health care of a large rural area.
1976-1982 Medical Residency, Internal Medicine, St Pierre Brussels
1982‑1984 Senior fellow in Internal Medicine, University Hospital Antwerp (department of cardiology) and Hospital St.-Mariagasthuis, Berchem, Belgium.
1984‑1987 Coordinator of the clinical studies on HIV/AIDS of "Projet SIDA" in Kinshasa, Zaire.
1988 Visiting scientist, International Activities HIV/AIDS program, Centers for Disease Control (CDC), Atlanta, GA, USA.
1989-2004 Coordinator of the HIV/AIDS patient care and clinical research, Institute of Tropical Medicine (ITM), Antwerp.
1995- Professor in Tropical Diseases and STD, Institute of Tropical Medicine, Antwerp.
1996- Professor in Infectious Diseases, University of Antwerp (UA).
2004-3.05 Senior Clinical investigator, Infectious Disease Institute, Kampala, Uganda (Sabbatical)
4.2005-4.14 Head clinical HIV/STD Unit, department clinical Sciences, Institute of Tropical Medicine, Antwerp
10.2014 – Emeritus Professor ITM
Consultancies
Consultancies concerning HIV, TB and viral haemorrhagic fevers. for WHO, UNAIDS, Family Health International (FHI), European Commission (EC), University of North Carolina (UNC), Institut de Recherche pour le Développement (IRD), EDCTP, Pasteur Institute, ANRS, etc...
Honors
W.R.O. Goslingsprize 1993. Infectious Diseases Society of the Netherlands and Flanders.
Membership in professional societies
-2008 Chairman of the Flemish Clinical AIDS Research Group, Belgian Society of Infectious Diseases
Member of the most Scientific Committees of European, International and African AIDS conferences
Academic Alliance Member, Infectious Diseases Institute, Makerere University, Uganda
-2014 Coordinator International Network for the Study of HIV-associated IRIS (INSHI)
2018 International society of Infectious diseases (ISID) Council Member
Selected peer-reviewed publications (selected from 688 publications)
Colebunders R, Mann JM, Francis H et al. Evaluation of a Clinical Case Definition of AIDS in Africa. Lancet 1987; i: 492‑4.
Colebunders R, Lusakumunu K, Nelson AM et al. Persistent diarrhoea in Zairian AIDS patients: an endoscopical and histological study. GUT 1988; 29: 1687-91.
Colebunders RL, Ryder RW, Nzilambi N, Dikilu K, Willame JC, Kaboto M, Bagala N, Jeugmans J, Muepu K, Francis HL, Mann JM, Quinn TC and Piot P. HIV infection in patients with tuberculosis in Kinshasa, Zaire. Am Rev Respir Dis 1989; 139: 1082-5.
Colebunders R, Hodossy B, Burger D, Daems T, Roelens K, Pelgrom J, Coppens M, Van Bulck B, Jacquemyn Y, Van Wijngaerden E, Fransen K. The effect of highly active antiretroviral treatment on viral load and antiretroviral drug levels in breast milk. AIDS. 2005 Nov 4;19(16):1912-1915.
Colebunders R, Tshomba A, Van Kerkhove M, Bausch D, Libande M, Pirard P, Tshioko F, Mardel S, Mulangu S, Sleurs H, Rollin P, Muyembe-Tamfum J-J, Borchert M. Marburg Haemorrhagic Fever in Watsa, Democratic Republic of Congo: Clinical Documentation, Symptomatology and Treatment. J Infect Dis 2007; 196: S148-S153
Castelnuovo B, Byakwaga H, Menten J, Schaefer P, Kamya M, Colebunders R. Can response of a Pruritic Papular Eruption to antiretroviral therapy be used as a clinical parameter to monitor virological outcome? AIDS 2008 Jan 11;22(2):269-73
Meintjes G, Lawn SD, Scano F, Maartens G, French MA, Worodria W, Elliott J, Murdoch D, Wilkinson RJ, Seyler C, John L, Schim van der Loeff M, Reiss P, Lynen L, Janoff EN, Gilks C, Colebunders R. Tuberculosis Immune Reconstitution Inflammatory Syndrome (TB-IRIS): Case Definitions for Adults in Resource-Limited Settings. Lancet Infect Dis 2008 Aug;8(8):516-523.
Renggli V, De Ryck I, Jacob S, Yeneneh H, Sirgu S, Mpanga Sebuyira L, Pfitzer A, Downing J, Portillo C, Murray J, Gove S, Colebunders R. HIV education for health care professionals in high prevalence countries: time to integrate a pre-service approach into overall training models, Viewpoint, Lancet 2008 Jul 26;372(9635):341-3.
Lynen L, Sokkab A, Koole O, Sopheak T, Seilavath R, De Munter P, Sculier D, Arnould L, Fransen K, Menten J, Boelaert M, Van den Ende J, Colebunders R. An algorithm to optimize viral load testing in HIV-positive patients with suspected first-line antiretroviral therapy failure in Cambodia. J Acquir Immune Defic Syndr. 2009 Sep 1;52(1):40-8
Colebunders R, Hendy A, Nanyunja M, Wamala JF, van Oijen M. Nodding Syndrome – a new hypothesis and new direction for research. Intern J Infect Dis. 2014 Intern J Infect Dis. DOI: 10.1016/j.ijid.2014.08.001. [JIF: 1.938 ]
Chapters in books: 40
H index 57
Supervisor of PhD students: 49 obtained their PhD
Ongoing research projects
1. Advanced ERC grant (AdG671055) (20015-20) Nodding syndrome: a trans-disciplinary approach to identify the cause and decrease the incidence of river epilepsy (NSETHIO project). PI
2. VLIR Team project Tanzania PI Multi-disciplinary approach to control onchocerciasis-associated epilepsy in the Mahenge area in Morogoro region, Tanzania 1.09.17-31.12.20. PI
3. VLIR-Joint project PI African network to study, treat and prevent onchocerciasis associated epilepsy (OAE-Africa). 1.01.19-31.12.21. PI
4. Research for health in humanitarian crisis R2hc/elrrha grant (DIFID, NHS and Welcome trust). Evaluation of a community-based comprehensive epilepsy prevention and treatment programme in onchocerciasis endemic villages in South Sudan. 1.09.19- 31.08.21. Co-PI
5. VLIR Joint project Improving diagnostics and care for childhood onset epilepsies and its common neurological co-morbidities in Tanzania. 1.02.20-31.01.22. Co-investigator.
Reviewer Journals
About 20 papers per year
Research protocols
FWO, WHO, AIDS Task Force of the European Community, British Medical Research Council, ANRS, Aids Care Research in Africa (ACRiA), MRC (UK and S Africa), Bill and Melinda Gates Foundation, EDCTP, Wellcome Trust, etc…
