I am associate professor of Pharmacology (2009), currently working as senior researcher and leader of my own research group at the division of clinical pharmacology, Department of laboratory Medicine, Karolinska Institutet. My research is on global health pharmacology including maternal and child health in Sub Saharan Africa, where the disease burden is paramount and yet little is known about the impact of host-genetic factors, drug interactions, coinfections and comorbidity, and nutrition on both the safety and efficacy of therapy. I have conducted several prospective observational studies, randomized clinical trials, drug interaction and dose optimization studies focusing on major public health problems including treatment of the three most deadly infectious diseases (HIV/AIDS, tuberculosis, and malaria), neglected tropical diseases and antimicrobial resistance that claim millions of lives worldwide, especially in low-income countries. I have conducted several pharmacogenetics, pharmacokinetics, pharmacodynamics and drug interaction studies, biomarker discovery and validation studies for drug-induced liver injury, antimicrobial resistance and Hospital-acquired infections; pharmacovigilance and postmarking surveillance involving mass drug administration and immunization in resource-limited countries.
I have recived several national and international external research grants in competition as a principal investigator. My research projects and external funding has created opportunities for 10 completed and 3 ongoing PhD students at Karolinska Institutet, and > 95 original research publications in peer-reviewed scientific journals.
Currently I am member of the scientific advisory board for EDCTP, and member of the committee for development research at the Swedish research council.
Project 1: Pharmacovigilance infrastructure and post-marketing surveillance system capacity building for regional medicine regulatory harmonization in East Africa- PROFORMA (http://proforma.ki.se/).
In sub-Saharan Africa, access to medicine including new drugs, vaccines, microbicides for treatment of poverty-related diseases (PRD) is increasing. However, capacities of the National Medicine Regulatory Authorities (NMRAs) to monitor the quality and public safety of new drugs and interventions are not coping with, partly due to a shortage of qualified personnel and limited resources. PRORFORMA aims to strengthen the national pharmacovigilance infrastructure and post-marketing surveillance system in Ethiopia, Kenya, Tanzania, and Rwanda by forging partnerships with local academic institutions (training-of-the-trainers for sustainable training programs), national medicine regulatory authorities (practical training to change policy into practice) and public health programs. We aim to generate a cohort of pharmacovigilance-trained human resources from all stockholders including patients, healthcare providers, regulatory staffs that are engaged in pharmacovigilance data collection, analysis, interpretation, and data sharing. Our specific objective to strengthen pharmacovigilance and post-marketing surveillance system focusing on public health programs involving mass drug administration for neglected tropical diseases and mass immunization programs. Twelve postgraduates will be trained to serves as part of the future PV expert regional task force in East Africa aligned with the large-scale African medicine regulatory harmonization and WHO’s Pharmacovigilance program.
PROFORMA project is funded by the European Union’s Framework Programme for Research and Innovation Horizon 2020 via the European and Developing Countries Clinical Trials Partnership Association (EDCTP2), with co-funding from Sida.
Project 2: Effectiveness dihydroartemisinin -piperaquine versus sulfadoxine-pyrimethamine for prevention of falciparum malaria infection during pregnancy in Tanzania.
Intermittent Preventive Treatment in pregnancy (IPTp) with Sulfadoxine/Pyrimethamine (SP) is the current chemoprophylaxis intervention recommended by WHO for malaria prevention in pregnancy. However, the high prevalence Sulfadoxin/Pyrimethamine (SP) resistance in high malaria endemic areas including Tanzania are likely to undermine the use of IPTp-SP in improving birth outcomes. We investigate whether the combination of dihydroartemisinin-piperaquine (DHP) is superior to SP and co-trimoxazole alone for prevention of malaria in pregnancy among HIV negative and HIV positive pregnant women respectively. The study design is an open-label, two-arm, prospective randomized controlled trial. HIV negative pregnant women are randomized to receive either IPTp-SP or IPTp-DHP. In parallel, HIV positive pregnant women are randomized to receive either co-trimoxazole (CTX) with DHP (IPTp-DHP+CMX) or CTX alone. Result from this study will establish if DHP can be a suitable alternative to replace SP for IPTp for malaria prevention in HIV negative pregnant women, and the addition of DHP to daily cotrimoxazole is significant in preventing malaria among HIV positive pregnant women.
This study is funded by grant from Sida.
Project 3: Randomized clinical trial to determine the effectiveness the efficacy and safety of Praziquantel combined with Dihydroartemisinin-Piperaquine versus Praziquantel alone for the treatment of schistosomiasis in Tanzania.
Neglected tropical diseases (NTDs) such as schistosomiasis remain a burden in Sub-Saharan Africa (SSA), creating a public health concern. NTDs are linked to almost all Millennium development goals (MDGs), and their control is associated with a direct impact on the achievement of the MDGs such as reduction of poverty and education. Prevalence of schistosomiasis remains high in SSA, affecting more than 200 million people worldwide, of which more than 80% found in the SSA. Despite the use of praziquantel (PZQ) for mass treatment and disease control, the prevalence of schistosomiasis remains high in some endemic settings. PZQ is effective against mature Schistosoma species but has low efficacy against immature schistosomes (juvenile schistosomes). Previous studies report that artemisinin and its derivatives are effective against immature schistosomes. In a randomized clinical trial, we are investigating the efficacy and safety of praziquantel combined with Dihydroartemisinin-Piperaquine versus Praziquantel alone for the treatment of schistosomiasis. Our hypothesis is PZQ plus dihydroartemisinin-piperaquine (DHP) will improve schistosomiasis treatment outcome by covering both matured and immature forms of a parasite and eventually control of the disease achieved.
This study is funded by grant from Sida.
Project 4: Factors affecting malaria treatment outcome among pregnant women treated with artemether-lumefantrine in Tanzania
The expression and metabolic profile of serval hepatic drug metabolizing enzymes are altered by hormonal and physiological changes during pregnancy. Enhanced antimalarial drug metabolism and lower plasma drug exposure may increase the risks of treatment failure, development of resistance and negative birth outcomes. Receiving the same therapy, the pharmacokinetics and treatment outcome of antimalarial drugs may differ between pregnant and non-pregnant women. Knowledge on the pharmacokinetics of antimalarial drugs and its impact on treatment response in pregnant women is still minimal. In addition, the impact of pharmacogenetic variations on malaria treatment outcome in pregnant women remains to be explored. We are conducting a pharmacogenetic and pharmacokinetic prospective cohort study in pregnant women with uncomplicated Plasmodium falciparum infection treated with artemisinin lumefantrine combination therapy in Tanzania.
This study is funded by grant from Sida.
Project 5: Optimization of pediatric antiretroviral therapy in sub-Saharan Africa.
Efavirenz (EFV), a potent antiretroviral drug is approved by US-FDA and WHO to treat HIV infected children > 3 years of age. US-FDA has recently expanded the use of efavirenz (EFV) based ART for children aged ≥ 3 months weighing > 3.5 kg. However, waiting for more pharmacokinetic (PK) safety and efficacy data in children, WHO continues to limit the use of EFV in children < 3 years of age. The current body weight based EFV dose recommendation to treat infant and children is a scaled-down prediction from population PK modeling of data obtained from adults treated with the standard maximum EFV dose (600mg/day). We are conducting a three-phase efavirenz pharmacokinetics, pharmacogenetics and pharmacodynamics based dose optimization study in HIV and HIV-TB co-infected children in Uganda and Ethiopia. Result from this study will provide an evidence-based recommendation for policymakers to develop effective pediatric HIV treatment guidelines, particularly in Sub-Saharan Africa.
This study is funded by a grant from the Swedish research council.
Project 6: Pharmacokinetics and Pharmacogenetics of Cyclophosphamide and tamoxifen for the treatment of Breast Cancer patients in Ethiopia.
Breast cancer in women of black African origin is characterized by the younger age of onset, clinically aggressive with a high prevalence of triple-negative tumor, and higher mortality rates than age-matched Caucasian women. Cyclophosphamide and tamoxifen are the cornerstones of breast cancer chemotherapy. Both drugs are metabolized by genetically polymorphic cytochrome P450 enzymes and display wide between patient variations in their plasma concentrations. In a cross-sectional study design, we investigate the impact of pharmacogenetics on the pharmacokinetics of cyclophosphamide and tamoxifen, as we as the incidence and predictors of chemotherapy-induced hematologic toxicities and reduced relative dose intensity in Ethiopian breast cancer patients.
This study is funded by a grant from Sida.
- Five year postdoctoral training in clinical pharmacology, Karolinska Institutet
- PhD degree in molecular genetics (2003) from Karolinska Institutet.
- MSc degree in biochemistry (1996), and Bachelor of pharmacy (1987) from Addis Ababa University, Ethiopia.
Academic honours, awards and prizes
Since 2016 - Memeber of committee for development research at the Swedish research council.
Since 2014 - Memeber of the Strategic Advisory Committee for European and Developing Countries Clinical Trial partnership (EDCTP)
2015- Fellow of the Royal Collage of Physicians of Edinburgh: FRCP (Edin) http://www.rcpe.ac.uk/membership/fellowship
2013 - Honorary Professor of clinical Pharmacology at Department of Pharmacology and Toxicology, Faculty of Medical Sciences, University of Kragujevac, Serbia.