Research

Silvie-HuijbenI’m interested in the evolution of drug resistance in general and in the context of malaria in particular. While all tools for theoretical malaria eradication exist, in practice it proofs to be more complicated due to natural selection of drug resistant parasites and insecticide resistant mosquitoes. I am interested in understanding which factors are involved in driving resistance through the population and how we can utilize this knowledge to maximize the useful life span of drugs and insecticides. My work can be divided in the following different topics.

The controversy of aggressive treatment

treatment3Resistance against most antimalarials is widespread and resistance against artemisinins, the ‘magic bullet, appears to be on the rise. Much effort is put into R&D of new antimalarials, but, as of yet, there are no alternatives available for when artemisinins fully lose their efficacy. The question I’m asking is ‘Are there ways to slow the evolution of drug resistant parasites?’
We believe there might be, by harnessing the within-host ecology of the parasites: drug sensitive parasites are natural suppressors of drug resistant parasites in a co-infection. Rather than removing all susceptible parasites with the conventional way of aggressive chemotherapy that results in the greatest possible selection for resistant parasites, lower dosages of drug treatment will result in less selection for drug resistant parasites but possibly still equivalent improvement of host health. My work involves studying the competitive interactions between a drug resistant and drug susceptible Plasmodium chabaudi strain under various ecological scenario’s and following different treatment regimes.

The majority of this work was carried out during my PhD and post-doc in Andrew Read´s lab in Pennstate.
Key publications: Huijben, S., Bell, A.S., Sim, D.G., Salathe, R., Tomasello, D., Mideo, N., Day, T., & Read, A.F. (2013). Aggressive chemotherapy and the selection of drug resistant pathogens. PLoS Pathogens 9: e1003578.
Read, A.F., Day, T., & Huijben, S. (2011). The evolution of drug resistance and the curious orthodoxy of aggressive chemotherapy. PNAS 108: 10871-10877.

HIV-malaria co-infections

milennium-goals-smallMalaria-HIV co-infections can play an important role in the emergence and spread of malaria drug resistance. Given the level of geographical overlap between malaria-endemic areas, the current Human Immunodeficiency Virus (HIV) pandemic and the resulting increased frequency of co-infections, this could be a serious health problem. Unfortunately, the degree to which the immune status of the host affects the selection for resistant malaria parasites is largely unknown. In this project, I aim to address the question whether HIV infections increase the prevalence of antimalarial resistance either within the individual patient (using samples of pregnant women with known HIV status) or on the population level (using data on HIV prevalence and antimalarial resistance in Sub-Saharan Africa from published data).

This work is carried out at ISglobal, under supervision of Alfredo Mayor.
Funding: Branco Weiss Fellowship, Marie Curie IIF Fellowship.
Key publication: Birger S., Kouyos R.D., Cohen T., Griffiths E., Huijben S., Mina M., Volkova V., Grenfell B., and Metcalf C.J.E. (in press). The potential impact of coinfection on antimicrobial chemotherapy and drug resistance. Trends in Microbiology.

Insecticide stewardship

mossieInsecticides were one of the key tools that led to successful eradication of malaria in many countries during the middle of last century. However, in the current new ambitious goal of global malaria eradication, the high level of insecticide resistance will be a major obstacle. In this project, the goal is to understand the effect of selective pressures on the evolution of insecticide resistance in both the laboratory setting and in the field. I aim to study how rapidly resistance emerges and spreads under different monotherapeutic selection pressures and how fast mosquitoes regain insecticide susceptibility when selection pressures are released. Ultimately, the aim is to assess which insecticide resistance management strategy maximally delays the evolution of resistance. Furthermore, we aim to study the evolutionary consequences of intense insecticide use in real-time in areas targeted for malaria elimination.

This work is planned to commence in 2016 and will be carried out at ISglobal, Barcelona, Spain and CISM, Manhiça, Mozambique, in collaboration with Krijn Paaijmans.
Funding: Branco Weiss Fellowship.

Multidisciplinary resistance workshop

multidis1The evolution of drug and pesticide resistance is a global phenomenon, impacting the control of insect pests, weeds and pathogens in agriculture, compromising the efficacy of antimicrobial and antiretroviral drugs and resulting in failure of chemotherapy in cancer treatment. Although our understanding of the molecular mechanisms of drug resistance is rapidly increasing, our knowledge of the factors that determines the evolutionary trajectory of these mechanisms lags behind. Understanding this ecological context in which resistance evolves provides prospects for reducing the emergence and spread of resistance. Whilst the particular mutations and mechanisms that give rise to resistance may be drug- and system-specific, the basic genetic and evolutionary principles underlying the development and spread of resistance may share common features. Yet, interdisciplinary knowledge sharing is currently far from common practice. In January 2016, we will hold a workshop with the major objective to assemble a diverse group of researchers (<30) working across disciplines in agriculture and healthcare to consider the eco-evolutionary drivers for the selection and spread of resistance. In doing so, we aim to identify common ecological and evolutionary principles which underpin the selection and spread of drug resistance. These principles will be considered with a view to the design and testing of resistance management principles with broad application in agricultural and healthcare settings.

Workshop “Running to stand still: Evolution and management of drug resistance in healthcare and agriculture”
17-19 January 2016, Barcelona, Spain.
Collaborator: Paul Neve, Rothamsted Research, UK
Funding: BBSRC – International Workshop