Dr Alexis Nzila

Dr Alexis Nzila is Head of the Molecular Parasitology Group at the KEMRI Wellcome Trust Research Programmme in Kilifi, Kenya. He was trained in France and started in Postdoctoral work at the KEMRI/Wellcome Programme in Kenya in 1996. His research focused on the understanding of the mechanism of resistance to pyrimethamine/ sulfadoxine and chlorproguanil/ dapsone, 2 antifolate drugs used to treat malaria. He has made substantial contribution in our understanding of the mechanism of antifolate resistance and helped in developing simple ways of tracking drug resistance against malaria.

He has developed an innovative approach in discovering new drugs by using experience in cancer research. Indeed malaria and cancer cells have one similarity in that they rely heavily on the availability of folate. Thus, many strategies to inhibit cancer cells by blocking folate metabolism can also be applied in malaria. He has exploited this approach, and this has led lead some important discoveries.

He has identified simple of ways of reversing pyrimethamine/sulfadoxine resistance in malaria using the ucosuric agent probenecid. This finding has been confirmed in vivo, in children suffering from malaria. His group has recently shown that this compound can increase the activity of the new antimalarial drug, piperaquine, which has been combined with dihydroartemesine as Artekin®. Thus, this a potential of using probenecid to chemosensitve malaria parasite to antimalarials in vivo.

Still using experience in cancer research, he has also proposed that low and safe dose of some anticancer drugs can also be used to treat malaria. Recently he and his colleagues at KEMRI have carried out a Phase I evaluation of one of this anticancer drugs, methotrexate, in adult healthy volunteers. Others anticancer drugs are in the pipeline to be tested. His work has demonstrated that that there is a possibility of discovering new drugs against malaria by using anticancer pharmacopeia.

Extending on his knowledge on antifolate resistance, Dr Nzila is now working on understanding the mechanism of resistance to other antimalarial drugs, including lumefantrine and piperaquine.

Dr Nzila is also actively involved in training and capacity building of young scientists in Kenya. One of his students, Leah Mwai, is a recipient of EDCTP studentship.

But winning is not new to Dr Nzila. In 2006, he won the Royal Society Pfizer Award, UK – for ” contribution In drug resistance and drug discovery in malaria”

Dr Dominique J Pepper

Dr Dominique J Pepper is a physician-in-training at the University of Cape Town and has already completed the Part 1 Fellow of College of Physicians (South Africa) Examinations. He is affiliated with the Wilkinson Laboratory at the Institute of Infectious Diseases and Molecular Medicine (Cape Town) and has 3 years research experience as a lead investigator for a study entitled ‘Clinical deterioration during TB treatment in HIV-infected South Africans’.

Understanding how complex systems interact is why this 28-year-old with first class honours from the University of Cape Town chose a career in infectious diseases research. His preliminary work, conducted in 2007 at a district hospital in Cape Town, found that clinical deterioration during TB treatment is an important clinical entity. In this study, 352 patients were assessed with clinical deterioration over a 3-month period, accounting for 17% of total medical admissions. More than 70% of patients had an additional illness to tuberculosis. Rifampin-resistant tuberculosis, tuberculosis- associated immune reconstitution inflammatory syndrome (TB-IRIS) and drug resistant bacterial infections (other than tuberculosis) were found in 12%, 14% and 4% of cases, respectively.

In light of this overwhelming burden of disease and the need to mitigate the associated co-morbidity and mortality, Dr Pepper investigated the incidence, causes and risk factors for clinical deterioration. A 9-month prospective cohort study was conducted at Site B Khayelitsha tuberculosis clinic. This clinic is an exceptionally busy, integrated TB-HIV service in Cape Town, South Africa.

After 24 weeks of follow-up, the findings were compelling: 40% (117/292) of patients experienced clinical deterioration, 26% of whom (30/117) required hospital admission for new AIDS-defining illnesses and TB-IRIS. Significant risk factors for deterioration and death were HIV infection and a low CD4 count at tuberculosis diagnosis. Surprisingly, multi-drug resistant tuberculosis, which is frequently encountered in Cape Town, was not a common reason for clinical deterioration or hospital admission. While MDR-TB is an important health care problem in South Africa, it is a facet of the much larger problem of clinical deterioration during TB treatment.

These findings have broader public health implications. This study highlights the need for more progressive strategies in ART and tuberculosis programs. Currently, HIV-infected patients present to health care services when they are already profoundly immune-suppressed. This results in a high burden of tuberculosis, which is accompanied by multiple complications during TB treatment. Dr Pepper’s work suggests that initiation of antiretroviral treatment at higher CD4 counts could alleviate the burden on overwhelmed health care services.

Further laboratory work is underway. This includes determining: 1) the unique metabolomic signatures for frequent causes of clinical deterioration, and 2) the frequency of sub-therapeutic TB drug levels in patients presenting with TB-IRIS.

Dr Pepper is passionate about scientific research which influences global practice. He intends to successfully address the health care challenges facing South Africa by combining first world technologies with novel research projects.

In addition to this prestigious EDCTP award, Dr Pepper was recently acknowledged as one of the Top 300 Young South Africans (Mail and Guardian, June issue 2009). He is also the recipient of a number of research awards, including a Fogarty International Clinical Operational Health Services Research Training Award at Johns Hopkins University, as well as a South African Tuberculosis AIDS Training grant and research training scholarship (NIH/FIC 1U2RTW007373-01A1, 1U2RTW007370)