Grant Detail

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Molecular epidemiology of drug resistant malaria

Miriam K Laufer

1 July 2004 - 31 March 2009
NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

In 1993, Malawi was the first country to switch from choloroquine to sulfadoxine-pyrimethamine (SP) as first line anti-malarial therapy due to unacceptably high failure rates with chloroquine. Studies of SP efficacy in Malawi from 1998 to 2002 have documented approximately 80% therapeutic efficacy at 14 days, with a modest increase in parasitological resistance and 28 day therapeutic efficacy. These results attest to the durability of SP efficacy, but also warn that increasing failure rates are likely to occur in the future. Following the unexpected finding that chloroquine efficacy has re-emerged after discontinuing its use 10 years ago, the candidate's mentor, Dr. Christopher Plowe, will conduct a longitudinal trial to assess the clinical and parasitological efficacy of chloroquine monotherapy and chloroquine in combination with other drugs as compared to SP alone, the current standard of care. The candidate will be completing her fellowship in pediatric infectious diseases and has been working with Dr. Plowe in Malawi. She will conduct a molecular evaluation of the parasites isolated from the participants in this clinical trial to look for the single nucleotide polymorphisms associate with chloroquine and SP resistance. These data will be analyzed to assess the ability of combination therapy to protect against the emergence of resistance-conferring mutations in comparison to monotherapy. In addition, she will test the hypothesis that there is a stable relationship between prevalence rates of resistant mutations and in vivo resistance over time in order to validate a model that uses molecular markers for drug resistant malaria as a surveillance method to monitor changes in drug efficacy. The candidate's career development plan is to gain the skills necessary to conduct clinical trials and analyze complex epidemiological data. She will be mentored by Dr. Plowe at the Center for Vaccine Development at the University of Maryland and Dr. Terrie Taylor at the Blantyre Malaria Project in Malawi, and will complete a Master's degree in Public Health. The candidate's long-term career goals are to become an independent investigator in an academic setting and to conduct clinical and epidemiological research that applies molecular techniques to address public health problems in developing countries.

7 Resulting Publications

• 1.

  2012

  Miriam K Laufer; Phillip C Thesing; Fraction K Dzinjalamala; Osward M Nyirenda; Rhoda Masonga; Matthew B Laurens; Abbie Stokes-Riner; Terrie E Taylor; Christopher V Plowe

  A longitudinal trial comparing chloroquine as monotherapy or in combination with artesunate, azithromycin or atovaquone-proguanil to treat malaria.

  PloS one 2012;7(8):e42284.

• 2.

  2011

  Bethany L Hedt; Miriam K Laufer; Ted Cohen

  Drug resistance surveillance in resource-poor settings: current methods and considerations for TB, HIV, and malaria.

  The American journal of tropical medicine and hygiene 2011;84(2):192-9.

• 3.

  2011

  Anne E P Frosch; Meera Venkatesan; Miriam K Laufer

  Patterns of chloroquine use and resistance in sub-Saharan Africa: a systematic review of household survey and molecular data.

  Malaria journal 2011;10():116.

• 4.

  2010

  Miriam K Laufer; Shannon Takala-Harrison; Fraction K Dzinjalamala; O Colin Stine; Terrie E Taylor; Christopher V Plowe

  Return of chloroquine-susceptible falciparum malaria in Malawi was a reexpansion of diverse susceptible parasites.

  The Journal of infectious diseases 2010;202(5):801-8.

• 5.

  2009

  Mark A Travassos; Miriam K Laufer

  Resistance to antimalarial drugs: molecular, pharmacologic, and clinical considerations.

  Pediatric research 2009;65(5 Pt 2):64R-70R.

• 6.

  2007

  Miriam K Laufer; Joep J G van Oosterhout; Phillip C Thesing; Fraction K Dzinjalamala; Teresa Hsi; Lorraine Beraho; Stephen M Graham; Terrie E Taylor; Christopher V Plowe

  Malaria treatment efficacy among people living with HIV: the role of host and parasite factors.

  The American journal of tropical medicine and hygiene 2007;77(4):627-32.

• 7.

  2006

  Miriam K Laufer; Phillip C Thesing; Nicole D Eddington; Rhoda Masonga; Fraction K Dzinjalamala; Shannon L Takala; Terrie E Taylor; Christopher V Plowe

  Return of chloroquine antimalarial efficacy in Malawi.

  The New England journal of medicine 2006;355(19):1959-66.

Scientific Context

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