Tropical Pharmacology and Therapeutics

Gulu Regional Referral Hospital, Uganda. Photo: Thomas Dorlo

We develop and optimize treatment regimens for poverty-related and neglected tropical diseases by using pharmacometric mathematical models.

Nearly one million people die each year from poverty-related and ‘neglected’ tropical diseases (NTDs), caused by parasites and fungi, such as malaria, leishmaniasis and mycetoma. This is mainly due to a lack of safe and effective drugs. Underserved and understudied patient groups such as children and pregnant women are worst affected, but these groups are often excluded from clinical trials in the development of drugs. This means that there is a lack of good treatment options for those patients who actually need them the most.

Our research aims to find optimal treatment regimens for these poverty-related diseases. For this, we use pharmacometric mathematical models that describe all the processes a drug goes through once it is inside the body, and the desirable and undesirable effects that the drug has on both the patient and the disease-causing microorganism.
Our research provides answers to important clinical questions such as: What dose should be used to treat young children or pregnant women? What biomarkers in the blood should we measure to confirm that a patient is cured? How can parasites in the skin of patients be treated most effectively?

The new tools and biomarkers we are developing also make drug development for these neglected diseases more efficient and successful, so that new drugs and drug combinations can be made available to patients faster.

Current research

Optimizing Treatment of Leishmaniasis

We develop pharmacometric and model-based strategies to improve therapies for parasitic infections such as visceral leishmaniasis. Our focus is on optimized, shortened, combination regimens. We also optimize treatment for children, where we are evaluating specific weight-band based dosing regimens for miltefosine and other drugs, accounting for scaling of both PK and PD (host response) interactions from adults to children.

Skin Neglected Tropical Diseases

We develop state-of-the-art bioanalytical methods to measure target site drug exposure in skin lesions from skin NTD patients and develop semi-mechanistic PKPD models that describe relationships between skin PK, parasite/fungal clearance, and lesion healing. We lead clinical pharmacology and pharmacometric dose optimization in many Phase 2 and 3 trials on post-kala-azar dermal leishmaniasis, cutaneous leishmaniasis, and mycetoma, with partners in e.g. Ethiopia, India, Sudan, & Latin America. An example is the recently started MAMS4CL consortium to optimize therapy for cutaneous leishmaniasis caused by L. aethiopica, funded by EDCTP3.

Zoom image

Malaria in Pregnancy

We develop physiologically based PK (PBPK) models to decipher the impact of pathophysiological changes and parasite infection dynamics on intracellular drug distribution of drugs, e.g. for pyronaridine for malaria. Together with partners in DR Congo, Mozambique, Mali, Gambia, Burkina Faso, we investigate the need for dosing adjustments for the antimalarial pyronaridine-artesunate in pregnant women, through the PYRAPREG consortium.

Zoom image

Biomarkers & Treatment Response

We identify and characterize the dynamics of early (bio)markers of treatment response in parasitic diseases such as leishmaniasis, including parasite load and host immunological responses in visceral leishmaniasis in Eastern Africa, to enable faster and more accurate assessment of therapy success and to guide adaptive treatment and drug development strategies.