In the context of prioritization of therapeutics to be included in clinical research for Bundibugyo virus disease (BVD) the Technical Advisory Group on Therapeutics Prioritization (TAG-TP) has begun examining the landscape of immunomodulatory and host-directed new or repurposed agents. Currently, there are no studies in patients characterizing the downstream pathogenesis that follows infection with Bundibugyo virus (BDBV). The available evidence derives mainly from data collected with Ebola virus, specifically Zaire ebolavirus (EBOV) that provides relevant information from animal models and patients, but not sufficient to allow a proper assessment for the selection of immunomodulatory and host-directed candidates for clinical trials in BVD. In addition, it is noted that even corticosteroids have never been tested in a stringent filovirus animal model. For other infectious diseases leading to sepsis or other severe disease evolutions, it is also noted that immunomodulators can be beneficial or detrimental depending on the timing of the administration.
To allow for a proper scientific evaluation of the different potential interventions, the appropriate timing of administration and the appropriate patient selection for inclusion in large clinical trials, it is imperative to generate quality data on the natural history of BVD from people infected with BDBV. This would likely need to occur at select clinical sites that are adequately equipped to collect and analyze samples from patients with BVD. Suggested data for collection include immune makers associated with inflammation and innate/adaptive immunity, correlative viral load and clinical features, markers of coagulation perturbation and organ/tissue damage. This will help identify biomarkers pertaining to a pro-inflammatory status with co-relation to clinical phenotypes and organ dysfunction.
Only in this way will it be possible to identify and/or confirm potential pharmacological targets and related potential interventions. Collecting further evidence is paramount to minimizing risks to participants in clinical trials, as, depending on individual patient phenotypes and the status of disease evolution, the administration of some immunomodulatory agents may result in detrimental effects (e.g. on viral replication).
In addition, some of these clinical investigations may have to be tailored to specific immune phenotypes based on the pharmacological activity of the investigational candidate, but sophisticated biomarker testing should be avoided to ensure implementation of clinical trials at BDBV Treatment Units.
Lastly, timely availability of data from animal models would also provide evidence to facilitate the identification of the most promising therapies for inclusion in clinical trials.
