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.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Mentored Patient-Oriented Research Career Development Award (K23)
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Microbiology and Infectious Diseases B Subcommittee (MID)
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Rao, Malla R
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University of Maryland Baltimore
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United States
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Gilliams, Elizabeth A; Jumare, Jibreel; Claassen, Cassidy W et al. (2014) Chloroquine-azithromycin combination antimalarial treatment decreases risk of respiratory- and gastrointestinal-tract infections in Malawian children. J Infect Dis 210:585-92
Kalilani-Phiri, Linda; Thesing, Phillip C; Nyirenda, Osward M et al. (2013) Timing of malaria infection during pregnancy has characteristic maternal, infant and placental outcomes. PLoS One 8:e74643
Mathanga, Don P; Walker, Edward D; Wilson, Mark L et al. (2012) Malaria control in Malawi: current status and directions for the future. Acta Trop 121:212-7
Laufer, Miriam K; Thesing, Phillip C; Dzinjalamala, Fraction K et al. (2012) A longitudinal trial comparing chloroquine as monotherapy or in combination with artesunate, azithromycin or atovaquone-proguanil to treat malaria. PLoS One 7:e42284
Hedt, Bethany L; Laufer, Miriam K; Cohen, Ted (2011) Drug resistance surveillance in resource-poor settings: current methods and considerations for TB, HIV, and malaria. Am J Trop Med Hyg 84:192-9
Frosch, Anne E P; Venkatesan, Meera; Laufer, Miriam K (2011) Patterns of chloroquine use and resistance in sub-Saharan Africa: a systematic review of household survey and molecular data. Malar J 10:116
Laufer, Miriam K; Takala-Harrison, Shannon; Dzinjalamala, Fraction K et al. (2010) Return of chloroquine-susceptible falciparum malaria in Malawi was a reexpansion of diverse susceptible parasites. J Infect Dis 202:801-8
Laufer, Miriam K (2009) Monitoring antimalarial drug efficacy: current challenges. Curr Infect Dis Rep 11:59-65
Travassos, Mark A; Laufer, Miriam K (2009) Resistance to antimalarial drugs: molecular, pharmacologic, and clinical considerations. Pediatr Res 65:64R-70R
Laufer, Miriam K; van Oosterhout, Joep J G; Thesing, Phillip C et al. (2007) Malaria treatment efficacy among people living with HIV: the role of host and parasite factors. Am J Trop Med Hyg 77:627-32

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