Over Robert Colebunders

Nodding syndrome (NS) is a neurological, incurable syndrome, currently affecting 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.

Since 2014, R Colebunders is engaged in research to identify the cause of the nodding syndrome (NS), an until then mysterious type of epilepsy known to occur only in northern Uganda, South Sudan and Tanzania. He discovered that NS is only one of the clinical presentations of epilepsy caused by onchocerciasis (river blindness), currently called onchocerciasis-associated epilepsy (OAE). He discovered that OAE is a major unrecognised public health problem in many onchocerciasis endemic regions in Africa with remaining high onchocerciasis transmission. He reported prevalence rates of epilepsy in onchocerciasis endemic villages in the DRC, Cameroon, Uganda, Tanzania and South Sudan varying between 2 and 11%, while the median prevalence of epilepsy in non-onchocerciasis endemic regions in Africa is 1.4%. He documented that the highest prevalences were found in villages located close to blackfly (the vector transmitting Onchocerca volvulus infection) breeding sites. In a case control study performed in onchocerciasis-endemic villages in the Logo health zone in Ituri province, in the DRC, persons with epilepsy were two times more likely to present skin O. volvulus microfilariae and had 10 times higher microfilarial skin densities than age, sex and village matched controls. He developed a clinical case definition of OAE that can be used by local health care workers for surveillance of this condition. Using this definition it was estimated that about 300,000 persons are currently affected by this form of epilepsy. In a study in Maridi, in South Sudan he showed that NS is the most severe form of OAE, characterised with more disabilities and higher skin microfilarial density.

He documented that despite many years of onchocerciasis elimination efforts in many remote onchocerciasis endemic regions, very little progress has been made and that strengthening onchocerciasis elimination efforts is urgently needed in areas with high OAE prevalence. He documented particularly low ivermectin (the treatment of onchocerciasis) use among 5-6 year-old children who are at risk of developing OAE. Currently children below the age of 5 or 15 kg are not considered to be eligible for ivermectin treatment because safety studies have never been performed in this age group. Based on R Colebunders study findings it is imperative to carry out clinical trials to investigate the safety of ivermectin treatment already below the age of 5 years or 15kg.

In collaboration with the team of M Boussinesq, he showed in a cohort study in Cameroon that the risk to develop epilepsy increased with increasing skin microfilarial density during childhood. This study, for the first time, showed the temporal relationship between onchocerciasis and epilepsy.

With Ugandan collaborators, he demonstrated that bi-annual community directed treatment with ivermectin (CDTI) and vector control was able to interrupt an OAE/NS epidemic in northern Uganda. Moreover, in Kabarole, western Uganda, with C Kaiser he documented that since the elimination of onchocerciasis in 2004, OAE including NS disappeared. With Cameroonian and French collaborators he showed that in Cameroon annual CDTI was also able to reduce the incidence of OAE, but insufficiently. Therefore bi-annual over annual CDTI should be preferred. Moreover, bi-annual CDTI has the advantage that it will increase ivermectin coverage and also decrease the frequency of seizures in persons with OAE, as recently demonstrated by his team in a randomized clinical trial in the Logo health zone, Ituri province, DRC.

With his PhD student JN Siewe Fodjo he showed in a meta-analysis of epilepsy surveys from West Africa that higher pre-control onchocerciasis endemicity and lower duration of onchocerciasis control were both associated with increased epilepsy prevalence. These findings suggest that before and during the early years of implementing onchocerciasis control, high onchocerciasis endemicity resulted in a high prevalence of OAE and that subsequent control efforts significantly reduced the prevalence of OAE.

In a post-mortem study, among persons who died of OAE in northern Uganda his team showed similar neuro-inflammatory lesions in persons with NS and persons with other forms of OAE confirming that NS and other forms of OAE are part of the same disease. Studies are ongoing on CSF and blood samples from persons with OAE/NS and controls to study the pathophysiological mechanism how O. volvulus may trigger the development of epilepsy. O. volvulus microfilariae and DNA were not detected in CSF. Therefore an auto-immune process triggered by O. volvulus seems to be the most likely mechanism.

Currently R Colebunders is involved in setting up prospective population based studies in onchocerciasis-endemic areas to investigate the effect of different onchocerciasis elimination strategies on the incidence of OAE. Moreover in those onchocerciasis-endemic areas with high epilepsy prevalence he is collaborating with local NGOs and the primary health care system to evaluate community based epilepsy treatment/care programmes.

 

 

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. He is initiator and coordinator of the International Citizen Project COVID-19, an initiative to investigate the impact of the COVID-19 pandemic on the lives of people living in Low and Middle income countries.  WWW.ICPcovid.com

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           

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)

Selected peer-reviewed publications (selected from 570 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 ]

Colebunders R, Tepage F, Rood E, Mandro M, Abatih EN, Musinya G, Mambandu G, Kabeya J, Komba M, Levick B, Mokili JL, Laudisoit A. Prevalence of River Epilepsy in the Orientale Province in the Democratic Republic of the Congo. PLoS Negl Trop Dis. 2016 May 3;10(5):e0004478.

Colebunders R, Mandro M, Mokili JL, Mucinya G, Mambandu G, Pfarr K, Reiter-Owona I, Hoerauf A, Tepage F, Levick B, Begon M, Laudisoit A. Risk factors for epilepsy in the Bas-Uélé Province in the Democratic Republic of the Congo: a case control study. Int J Infect Dis. 2016 May 19. pii: S1201-9712..

Colebunders R, Titulaer MJ. Nodding syndrome: Preventable and treatable. Sci Transl Med. 2017 Feb 15;9(377).

Colebunders R, Abd-Elfarag G, Carter JY, Olore PC, Puok K, Menon S, Joseph Nelson Fodjo Siewe JNF, Bhattacharyya S, Ojok M, Lako R, Logora MY. Clinical characteristics of onchocerciasis-associated epilepsy in villages in Maridi County, Republic of South Sudan. Seizure DOI 10.1016/j.seizure.2018.10.004

Colebunders R, Carter JY, Olore PC, Puok K, Bhattacharyya S, Menon S, Abd-Elfarag G, Ojok M, Ensoy-Musoro C, Lako R, Logora MY. High prevalence of onchocerciasis-associated epilepsy in villages in Maridi County, Republic of South Sudan: a community-based survey. Seizures 2018 Dec;63:93-101.

Colebunders R, Siewe Fodjo JN, Hopkins A, Hotterbeekx A, Lakwo TL, Kalinga A, Logora MY, Basáñez MG. From river blindness to river epilepsy: Implications for onchocerciasis elimination programmes. PLoS Negl Trop Dis. 2019 Jul 18;13(7):e0007407. JIF 4.45

Chapters in books: 38

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

Most infectious disease/AIDS/TB journals

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, HIV era, etc…