Research Areas:

Tuberculosis

Tuberculosis (TB) is a bacterial infection that causes lung disease. TB is currently the deadliest infectious disease in the world. In 2017 1.6 million died of TB. In addition, over 10 million people fell ill from TB and approximately 25% of the world population is latently infected with TB. In Western countries TB patients are treated with a cocktail of antibiotics. However, anti-microbial drug resistance in TB is increasing, which makes it harder to treat. Overall, a growing number of TB infected people cannot be treated and die of the disease. Prevention by vaccination is the only means to break the cycle of TB transmission and infection. Read more >

BPRC uses TB models in the rhesus monkey and the cynomolgus monkey to get a better insight in how the disease develops and to evaluate new treatments of TB. The two models represent two different disease manifestations. TB in rhesus monkeys develops as a progressive active form of the disease, while infection of cynomolgus monkeys can develop as a latent disease.

Local administration of BCG-vaccine superior to classical skin immunization

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For the evaluation of new vaccine candidates, we work with the rhesus monkey. Over the last 2 decades the TB group has been working to refine the rhesus monkey model by challenging the animals with smaller amounts of tuberculosis bacteria. Last year we reported on the development of a repetitive limiting dose challenge model in the rhesus monkey (read more; article and commentary). This model more closely represents what happens in real life where people in endemic areas are repeatedly challenged with low doses of mycobacteria. This year we used the repetitive limiting dose infection to compare the efficacy of two immunization routes of the BCG-vaccine. We observed that local immunization in the lung was superior to classical immunization in the skin. Some animals were even protected from infection. Moreover, in the animals that were not fully protected, a reduced bacterial burden and disease was observed. Currently, we are investigating the adaptive and innate immune responses in the animals. The results from these experiments are expected to be published in 2019.

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PET/CT to visualize successful treatment

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Active TB infection poses a major public health risk. Patients are contagious and spread bacteria by coughing. Therefore, patients with active TB are treated with antimicrobial drugs. However, bacterial resistance is on the rise. Long-term use of antimicrobial drugs is the most important cause of the development of drug resistance and should be avoided. However, this calls for new therapeutic strategies. In 2018 we successfully visualized the reduction of TB disease after treatment of an established infection. Longitudinal PET/CTs imaging were used during a combination therapy of 2 commonly used antibiotics. We will further develop PET/CT to evaluate therapeutic strategies, which can be vaccination or host directed therapy (HDT). In this way we aim to hope to improve anti-microbial drug regimens and identify strategies that can help in the fight against drug resistant TB.

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