Research Robert Colebunders

Abstract

Onchocerciasis, caused by the parasite Onchocerca volvulus, is still endemic in Cameroon despite long-term annual community-directed treatment with ivermectin (CDTI). Low CDTI coverage and frequency (once a year) resulted in a high prevalence of onchocerciasis-associated morbidity (skin, eye, and neurological disease). Children infected with O. volvulus between the ages of 5-12 years are at risk of developing onchocerciasis-associated epilepsy. Moreover, O. volvulus infection during pregnancy induces "parasite tolerance" in the neonate and an increased risk to become infected with high parasitic loads, predisposing the child to develop onchocerciasis-associated morbidities. We hypothesize that maternal onchocerciasis has a negative impact on the neuro-cognitive development of the child. This will be investigated by recruiting nursing mothers with different exposures to onchocerciasis during pregnancy, and by monitoring the neurocognitive evolution of their children at 12 and 24 months of age. We also will evaluate a school-based ivermectin distribution strategy (adding to annual CDTI) to obtain six monthly intake of ivermectin by 5-12 year old children to prevent infection and ensuing morbidity. Understanding the impact of onchocerciasis on neurocognitive development during infancy and the possible benefits of an additional ivermectin dose in older children is expected to lead to interventions to preserve the intellectual capital of children in onchocerciasis-endemic regions.

Researcher(s)

• Promoter: Van geertruyden Jean-Pierre
• Co-promoter: Colebunders Robert
• Co-promoter: Weckhuysen Sarah
• Fellow: Siewe Fodjo Joseph Nelson

Research team(s)

• Global Health Institute (GHI)

Project type(s)

• Research Project

Abstract

Objectives 1. Evaluate Onchocerciasis RDTs under development. 2. Collect, analyse and store blood samples from individuals in onchocerciasis endemic areas. Activities Onchocerciasis results in severe itching, blindness and poor socioeconomic development. It has been targeted for elimination by 2030 by the WHO. Current diagnostics for onchocerciasis, including the skin-snipping microscopy, Ov16 ELISA and Ov16 RDT, are limited in their sensitivities. Improved versions of the Ov16 RDT are in development and need to be evaluated to assess their diagnostic performance. Moving these tests along the development pipeline will greatly enhance the diagnostic needs for onchocerciasis and contribute to its elimination. We propose to advance the development of these tests, and evaluate them against current tools through: • Establishing a diagnostic biorepository for onchocerciasis. The availability of a repository for well characterized samples continues to be a challenge for the development and evaluation of new diagnostics for onchocerciasis • Coordination with existing product development partners to evaluate tools in development. This early coordination among partners and evaluation will help identify the best tool to move further in the development pipeline.

Researcher(s)

• Promoter: Colebunders Robert

Research team(s)

• Global Health Institute (GHI)

Project type(s)

• Research Project

Abstract

There is growing epidemiological evidence that onchocerciasis (river blindness) can cause epilepsy (onchocerciasis-associated epilepsy, OAE), a major unrecognized public health problem in sub-Saharan Africa. However, the pathophysiological mechanism remains unknown. Neither the Onchocerca volvulus, nor its endosymbiont Wolbachia, appear to be able to pass the blood brain barrier (BBB). Annual community-directed treatment with ivermectin (CDTI), has limited efficacy in reducing OAE incidence. Therefore, we will 1] Investigate in onchocerciasis-endemic areas, in Cameroon, whether a community based vector control method "slash & clear" combined with CDTI is superior to CDTI alone to decrease the incidence of OAE; 2] Explore whether O. volvulus excretory/secretory products can cross the BBB and possibly trigger OAE, by comparing proteomic profiles of cerebro-spinal fluid of children with OAE with those of different stages of the parasite; 3] Explore whether O. volvulus infected blackflies may transmit a neutrotropic virus causing OAE, by testing blackflies and sera from OAE cases with Q-PCR targeting potential OAE specific viral sequences identified during a metagenomic case-control study in South Sudan. Our findings will provide context-specific evidence about a complementary strategy to accelerate onchocerciasis elimination and new insights into the underlying mechanisms of OAE, and as such contribute to reducing the burden and stigma of 'river epilepsy'.

Researcher(s)

• Promoter: Mertens Inge
• Co-promoter: Colebunders Robert

Research team(s)

• Center for Oncological Research (CORE)

Project type(s)

• Research Project

Abstract

The aim of this project is to conduct series of investigate Psycho-Social and Behavioral Response and Compliance to Restriction Measures to Prevent and Control of Covid-19 and compose sets of recommendation to governments for further manage country crisis management and recovering plans. The study objectives are: 1. To describe the psychosocial burden and coping capabilities, risk of contracting the diseases and level of adherence behaviors, the current measures recommended by governments and during the first 6 months following implementation 2. To describe the determinants of adherence to the measures recommended by governments (baseline covariates and time-varying covariates) 3. To assess the overall effectiveness of adherence to the measures recommended by governments on the incidence of severe COVID-19 disease 4. To identify the most effective measure (or combination of measures) to reduce the incidence of severe COVID-19 disease and NCD risk and NCDs management during post-covid-19 epidemic. 5. Assess knowledge, understanding and acceptability related to Covid-19 vaccine 6. Psycho-social, stress, performance, and other impacts of covid-19 epidemics during, between and post pandemics of each waves among various samples such as health workers.

Researcher(s)

• Promoter: Colebunders Robert

Research team(s)

• Global Health Institute (GHI)

Project type(s)

• Research Project

Abstract

Responding to a number of urgent problems noted in the area of Covid-19 contact tracing (reluctance to give information, lack of care orientation, script-dominated talk), this project analyses and seeks to optimize the interactional functioning of the contact tracing phone call services coordinated by the Flemish Agency for Health & Care. It combines 4 objectives: (i) diagnosis of interactional practice in 3 cycles of data collection and analysis (incl. 1 cycle on encounters in other languages than Dutch); (ii) recommendations for practice, the development of training materials and a recruitment package; (iii) a pilot implementation followed by an efficacy measurement; and (iv) societal impact on the general public's support for contact tracing. The project inserts itself in an applied, interactional sociolinguistic and conversation analytic research tradition on medical encounters and institutional interviewing on sensitive topics. It addresses a current gap in (i) fundamental knowledge about the linguistic interactional dynamics of contact tracing calls as a specific type of institutional encounter and (ii) applied knowledge on how to improve task-oriented efficiency and enhance pragmatic awareness of practitioners as a dimension of professional reflexivity in a currently, important domain of combatting and containing the Covid-19 pandemic. The project benefits from close collaboration between relevant linguistic, medical and ethical expertise.

Researcher(s)

• Promoter: Vandenbroucke Mieke
• Co-promoter: Bastiaens Hilde
• Co-promoter: Colebunders Robert

Research team(s)

• Grammar and Pragmatics

Project type(s)

• Research Project

Abstract

Recently, the consortium involved in this project collected strong clinical and epidemiological evidence that nodding syndrome is one of the clinical presentations of onchocerciasis (river blindness)-associated epilepsy (OAE) and that this form of epilepsy is preventable by strengthening onchocerciasis elimination programs. Despite this evidence there is still little awareness about the important public health problem caused by OAE and a complete lack of interventions to address the problem. Eight African partners of the Democratic Republic Congo, Uganda and Tanzania, all with complementary OAE expertise, will be involved in the project. By increas-ing their research capacity and through multi-country studies we hope to solve the remaining OAE research questions. Moreover, by joining forces, including the organisation of a high profile international workshop on OAE, we aim to put OAE on the international development agenda. This project will increase OAE awareness among affected communities, local health care workers, health policymakers and hopefully funders in order to take appropriate actions.

Researcher(s)

• Promoter: Colebunders Robert

Research team(s)

• Global Health Institute (GHI)

Project type(s)

• Research Project

Abstract

Despite the use of ivermectin (IVM) once annually for control of onchocerciasis (oncho) (= river blindness) in Mahenge Tanzania, the prevalence of oncho and epilepsy remains high. There is increasing evidence that epilepsy is a complication of oncho and that treatment of oncho can not only eliminate blindness but also reduce epilepsy. Our proposed project aims to: 1) strengthen the multi-disciplinary research capacity for the prevention of oncho and epilepsy in Tanzania. We will establish an oncho-associated epilepsy (OAE) research group to support a master and a PhD-level student in the development of research protocols addressing OAE in the Mahenge region; 2) reduce the prevalence of oncho and the incidence of epilepsy in the Mahenge area by: a) establishing a surveillance system for early diagnosis of epilepsy; b) strengthening and implementing an effective community distribution of IVM; 3) Implement evidence-based guidelines to treat OAE by training local health care workers; 4) introduce community advocacy on epilepsy, epilepsy-associated stigma and discrimination.

Researcher(s)

• Promoter: Colebunders Robert
• Co-promoter: Weckhuysen Sarah

Research team(s)

• Global Health Institute (GHI)

Project type(s)

• Research Project

Abstract

Nodding syndrome (NS) is a form of epilepsy, characterized by head-nodding, often associated with severe intellectual disability, psychiatric problems, and early death. Initially, NS was reported only in onchocerciasis-endemic regions in Tanzania, Uganda and South Sudan. Until recently, the cause of the syndrome was unknown. Therefore, no strategy for prevention and cure was possible. Our ERC project (NSETHIO) discovered that NS is only one of the clinical presentations of onchocerciasis associated epilepsy (OAE) and that this form of epilepsy is probably present in all onchocerciasis endemic regions where onchocerciasis is insufficiently controlled. We estimate that the number of excess cases of epilepsy due to onchocerciasis could be as much as 100,000. Based on NSETHIO findings we will develop an innovative comprehensive OAE policy plan that will prevent children from developing OAE and that will reduce the negative consequences of OAE for the economy and society. This plan includes the following components: strengthening community directed ivermectin (IVM) treatment programs (IVM will stop OAE), establishing an SMS based epilepsy surveillance system by epilepsy trained community-directed IVM distributors, developing a community-based care system using evidence based OAE treatment algorithms, and a community-awareness program. We will fine tune the plan during 2 OAE stakeholder workshops, field test it in a high OAE prevalence health zone and calculate its cost. We will create an international OAE alliance including scientists and health care workers, representatives of communities and advocacy groups, WHO, Ministries of Health, non-governmental organizations, the pharmaceutical industry and donors to scale up the implementation of these interventions after the end of the NSstop project. Reducing the burden of disease caused by OAE will have great positive cultural, societal and economic impacts on affected families and villages in many parts of Africa.

Researcher(s)

• Promoter: Colebunders Robert

Research team(s)

• Global Health Institute (GHI)

Project type(s)

• Research Project

Abstract

Nodding syndrome (NS) is a neurological, incurable syndrome, currently affecting mainly children between 5 and 15 years of age in South Sudan, Uganda and Tanzania. Since 1950, when NS was first described, its cause has remained a mystery. 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. After exploratory missions to South Sudan, Uganda and the Democratic Republic of the Congo (DRC), we gathered epidemiological evidence that supports the hypothesis that NS is a disease caused by a pathogen transmitted by blackflies, the vectors that transmit the parasitic worm that causes onchocerciasis. This pathogen could be an unknown neurotropic virus or another pathogen that is transmitted either independently or as a symbiont of the worm. We postulate that this pathogen is able to cause typical NS, but also other forms of epidemic epilepsy. We hypothesise that the same disease is also endemic in other onchocerciasis hyper-endemic regions e.g. in the Mbam valley, Cameroon and the Orientale Province, DRC (where it is referred to as "river epilepsy"). In this project we aim to investigate our hypotheses in South Sudan, Uganda, Tanzania, Cameroon and the DRC with a trans-disciplinary approach including clinical-epidemiological, post-mortem, eco-entomological, and metagenomic studies. We will study the effect of vector control methods and ivermectin distribution on the incidence of river epilepsy. So far a multi-country study on NS was never done and nearly all previous studies were cross-sectional, carried out during short country visits. With this long term research plan we hope to finally discover the cause of NS and detect effective control strategies to decrease the incidence of epilepsy in onchocerciasis endemic areas.

Researcher(s)

• Promoter: Colebunders Robert

Research team(s)

• Global Health Institute (GHI)

Project website

Project type(s)

• Research Project

Abstract

Notre projet a pour but d'aider les chercheurs de l'Université de Kisangani dans leurs efforts d'identifier la cause de l'épilepsie des rivières qui est un problème de santé publique majeur, récemment détecté dans la Province Orientale dans une région hyper-endémiques pour l'onchocercose (maladie parasitaire qui cause la « cécité de rivières ») et de développer une stratégie pour diminuer la souffrance et la stigmatisation lié à l'épilepsie des rivières.

Researcher(s)

• Promoter: Van geertruyden Jean-Pierre
• Co-promoter: Colebunders Robert

Research team(s)

Project type(s)

• Research Project

Abstract

Background: Nodding syndrome (NS) is a life threatening neurological disorder, currently affecting an increasing number of children between 5 and 15 years in South Sudan, Northern Uganda and Southern Tanzania. NS is characterized by head-bobbing spells often followed by other types of seizures, developmental retardation and growth faltering. In the affected regions, NS is becoming a major public health problem with high morbidity and mortality rates and with severe social-economic implications. Despite detailed investigations in a limited number of Ugandan children, the aetiology and pathogenesis of NS remains unknown. Aside from questions regarding the aetiology, questions regarding the disease incidence, prevalence and long-term course remain outstanding. Proposed study: It is proposed to conduct an integrate program combining a case- control design with a detailed descriptive study using a phased approach. In the first phase a pathogen discovery programme will be applied on a limited number of NS patients and a group of controls using state of the art next generation sequencing and microarray-based methods on samples obtained from children and black flies. The focus of the second phase of the study will depend, in part, on the outcome of first phase: If a possible pathogen is identified the focus in the second phase will be on further identification of this pathogen. If no pathogen is identified, a detailed descriptive aetiology studies will be started using a case- control design and investigating all possible aetiologies previously indicated. Irrespective of the outcome of phase 1, in the second phase a surveillance study will also be started of all NS cases in the four most affected counties of South Sudan, next to a long term follow up of a selected group of NS cases and controls. This 3 years program will be conducted in close collaboration with South Sudanese, Dutch and Belgium NS and paediatric research experts and will be built on existing NS research and support activities already in place in South Sudan. Expected outcome: There is a significant chance that the true aetiology and the risk factors for NS will be identified and that the NS epidemiology in South Sudan will be clarified with respect to incidence, prevalence and disease progression. In addition, the study will create a platform for treatment intervention studies and will inform local health authorities how to improve their disease management and prevention strategies.

Researcher(s)

• Promoter: Van geertruyden Jean-Pierre
• Co-promoter: Colebunders Robert

Research team(s)

Project type(s)

• Research Project

Abstract

Our group has discovered a new species of dimorphic fungal infection in South Africa. This is the first new species of dimorphic fungus that infects humans to be found for over 50 years. We have named the organism Emmonsia hoerikwaggiana. It causes severe disease and, if untreated, death in persons with poor immune function such as those infected with HIV. We know very little about this fungus. We will investigate its ecological niches, its geographical range, which organisms it usually infects, what the prevalence is of human infections and how these infections manifest. In addition we want to do further investigations into the risk factors for human infection and the optimal diagnostic and therapeutic strategies.

Researcher(s)

• Promoter: Colebunders Robert

Research team(s)

Project type(s)

• Research Project

Abstract

Within this project the management of patients with HIV in South Africa will be studied. Intervention studies will be performed to define the value of weight monitoring before and during antiretroviral treatment. Specifically studies will be looking at obese patients and patients who use alcohol.

Researcher(s)

• Promoter: Colebunders Robert
• Fellow: Huis in 't Veld Diana

Research team(s)

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand Erasmus Mundus. UA provides Erasmus Mundus research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Colebunders Robert

Research team(s)

Project type(s)

• Research Project

Abstract

The main aim of this study is to provide a comprehensive picture of the level of clinical relevant antibiotic resistant bacteria (ARB) in the environment and commensal flora in Gauteng/South Africa. Besides, the genetic relatedness of these ARB will be studied to understand the mechanisms of antibiotic resistance dissemination in the community.

Researcher(s)

• Promoter: Goossens Herman
• Co-promoter: Colebunders Robert
• Co-promoter: Malhotra Surbhi
• Fellow: Paasch Fabienne

Research team(s)

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand VLIR. UA provides VLIR research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Colebunders Robert
• Co-promoter: de Deckere Eric
• Co-promoter: Goossens Herman
• Co-promoter: Meulemans Herman
• Co-promoter: Van geertruyden Jean-Pierre
• Co-promoter: van Sprundel Marc

Research team(s)

Project type(s)

• Research Project

Abstract

This is a fundamental research project financed by the Research Foundation - Flanders (FWO). The project was subsidized after selection by the FWO-expert panel.

Researcher(s)

• Promoter: Colebunders Robert
• Fellow: Huis in 't Veld Diana

Research team(s)

Project type(s)

• Research Project

Abstract

The pathogenesis, the clinical manifestations and the public health aspects of the Immune reconstitution inflammatoy syndrome (WS) will be studied. In Uganda and Ethiopia we will study how frequent a smear negative pulmonary TB patient with IRIS can become smear positive, and what the effect is of lRIS on the health service and the treatment adherence of the patient. Using blood samples obtained during a cohort study in Uganda, we will study whether VitD deficient; and the M. tuberculosis (TB) genotype/"antigen load" plays a role in the pathogenesis of TB-IRIS.

Researcher(s)

• Promoter: Colebunders Robert
• Fellow: Conesa Botella Anali

Research team(s)

Project type(s)

• Research Project

Abstract

Researcher(s)

• Promoter: Colebunders Robert

Research team(s)

Project type(s)

• Research Project

Abstract

Between 10% and 40% of HIV infected patients who start highly active antiretroviral therapy (HAART) experience a syndrome characterized by an excessive inflammatory response and a paradoxical deterioration in clinical status1. This phenomenon is thought to be due to a HAART-associated recovery of pathogen-specific immune responses to pre-existing or latent infections, and has been termed immune reconstitution inflammatory syndrome (IRIS). The clinical spectrum is diverse and cases of IRIS associated with more than 20 infectious pathogens have been described. IRIS represents a major diagnostic challenge in patients with new clinical symptoms who have recently started HAART and severe IRIS may result in organ failure, hospitalization or death. Patients in particular experience this syndrome as treatment failure whereas it is related to unbalanced restoration of the immune system, leading to disproportionate or aberrant cellular immune responses against pre-existing opportunistic infection2,3,4. IRIS is particularly a problem in antiretroviral therapy (ART) roll-out programmes in less developed countries where the underlying prevalence of infections such as Mycobacterium tuberculosis (MTB) is high, and where patients initiating HAART are more likely to have advanced immunodeficiency. So far there have been only few systematic, in depth studies on the incidence, risk factors and clinical course of IRIS undertaken in resource limited settings5. Moreover, a better understanding of the immunopathogenesis of IRIS is urgently needed to develop more effective strategies to diagnose, manage and prevent IRIS6. In this project we propose to study the pathogenesis, diagnosis and management of different manifestations of IRIS in a multidisciplinary way. The focus will be on Mycobacterium tuberculosis infection as one of the most prominent manifestations of IRIS. The work will be divided in two parts. One oriented to the immunological characteristics of TB-IRIS patients and the second one more epidemiological (study the characteristics of Mycobacterium tuberculosis in TB-IRIS patients compare to TB non IRIS patients).

Researcher(s)

• Promoter: Colebunders Robert
• Fellow: Conesa Botella Anali

Research team(s)

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand VLIR. UA provides VLIR research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Colebunders Robert
• Fellow: De Ryck Iris

Research team(s)

Project type(s)

• Research Project

Abstract

Mortality related to AIDS remains very high in Africa. Organizing optimal HIV treatment/care is particularly difficult when resources are limited and when there is little scientific evidence how to treat persons with HIV infection. The aim of this project is to improve the capacity of the Infectious Diseases Institute (IDI) of Makerere University in Kampala, Uganda to diagnose opportunistic infections/ malignancies and to train clinicians/pathologists in HIV research. To do so we will strengthen the microbiological and pathology laboratory, improve the endoscopy services of Mulago hospital and train clinicians/pathologists in research by involving them in several research projects (using the learning by doing methodology).

Researcher(s)

• Promoter: Colebunders Robert

Research team(s)

Project type(s)

• Research Project

Abstract

Améliorer le suivi des patients sous traitement ARV en développant une méthode de suivi standardisée des patients sous ARV dans toute la RDC; améliorer l'accès aux ARV en RDC ; renforcer l'expertise des chercheurs de l'UNIKIN et de I'ESP dans l'utilisation des ARV et de la recherche opérationnelle concernant l'accès et la distribution des ARV en DRC.

Researcher(s)

• Promoter: Colebunders Robert

Research team(s)

Project type(s)

• Research Project

Abstract

Researcher(s)

• Promoter: Colebunders Robert

Research team(s)

Project type(s)

• Research Project

Abstract

It has been shown that HIV-1 seropositive patients without disease progression exhibit a strong HIV-specific CD4+ and CD8+ T-cell immunity. Moreover, even HIV-specific CD8+ cytototoxic T-lymphocytes (CTL) can be observed in HIV-1 patients with a progressive disease course. These cells however appear to be functionally deficient. This suggests that the qualitative enhancement and boosting of T cell responses against HIV may have a beneficial influence on the disease progression. Treatment with `highly active anti-retroviral therapy' (HAART) drugs suppresses the viral replication, but is not able to eradicate the virus completely. Furthermore, HAART diminishes the anti-HIV CTL response and does not lead to a complete reconstitution of the HIV-specific CD4+ T-helper cells. Eliciting a strong cellular immune response against the regulatory HIV proteins Tat and Rev may be of great importance in the elimination of the virus. Hence, the main goal of this project is the ex vivo sensitisation of T cells of HAART patients by loading of autologous monocyte-derived dendritic cells (Mo-DCs) with mRNA coding for the regulatory HIV proteins Tat and Rev (alone or in combination with the structural HIV protein Gag). We will not only focus on the induction of CD8+ HIV-specific CTLs, but also on the specific conditioning of DCs for the activation CD4+ T helper cells, which can enhance the anti-HIV CTL response. Our laboratories are experienced in the in vitro culturing of DCs, and also in the electroporation transfection technique which will be used for loading of the obtained dendritic cells with HIV-1 mRNA. So, in this project we would like to demonstrate that eliciting and/boosting of the cellular immune response against the early HIV antigens Tat and Rev plays a key role in the development of a HIV immunotherapy.

Researcher(s)

• Promoter: Berneman Zwi
• Co-promoter: Colebunders Robert
• Co-promoter: Van Tendeloo Vigor

Research team(s)

Project type(s)

• Research Project

Abstract

A one year hospital based observation study will be carried out on Senegalese patients attending the St. Louis Hospital in Richard Toll, an area endemic for S. mansoni. In this population the clinical manifestation associated with Schistosoma mansoni infection will be described. A case control study will be performed, comparing asymptomatic and severely diseased individuals with Schistosoma mansoni infection. This study will be used to determine riskfactors for developing severe S. mansoni disease.

Researcher(s)

• Promoter: Van Marck Eric
• Co-promoter: Colebunders Robert

Research team(s)

Project type(s)

• Research Project