My goal is to have a rewarding career in pediatric infectious diseases by improving the health of children through clinical care and patient oriented malaria research. I became drawn to malaria because of the tremendous global burden of this disease in children and because recent interest in malaria elimination has brought forth exciting questions on how countries can interrupt transmission. I am particularly interested in re-active surveillance, a strategy whereby community members around index cases are screened as a way to identify and target asymptomatic carriers that perpetuate transmission. Building on my fellowship research which focused on surveillance for malaria elimination, and building on existing infrastructure and collaboration with the Swaziland National Malaria Control Program, I propose the following specific aims: 1) Compare pooled PCR to rapid diagnostic test (RDT) for improved detection of secondary malaria infections, 2) Identify epidemiological factors associated with the detection of secondary infections in re-active surveillance, and 3) Build and test a model for predicting the location of hot spots utilizing RDT, PCR, epidemiological data, and malaria serology. These findings will help guide best practices for re-active surveillance, clarifying which diagnostic test to use, when to investigate an index case, and who in the community should be screened during these investigations. Improved prediction of hot spots will also enable countries to anticipate potential outbreaks, target limited resources to remaining foci, and ultimately interrupt malaria transmission. The proposed project will also enable me to collect the preliminary data necessary for a subsequent R01 submission to test the effectiveness of focal interventions targeting hot spots identified by these surveillance methods (e.g. screening and treatment, mass drug administration, or intensive indoor residual spraying). To perform these cluster-randomized clinical trials would be the culmination of many positive and productive research, programmatic, and clinical experiences that I have had in the past. However, in order to achieve this career goal and the aims of my K23, there are two major areas where I require additional training, mentoring, and experience: 1) Advanced skills in clinical and epidemiologic research, and 2) Expertise in malaria diagnostic and surveillance laboratory assays. In this proposal, I present a detailed career development plan that includes mentorship in these areas, a Master's in Clinical Research, and practical laboratory experience at UCSF and in Swaziland. The skills and experience acquired from this training will enable me to independently design a clinical trial and compete successfully for R01 funding. I have assembled a highly experienced and well-resourced mentorship team that is committed to the proposed project and my career development. Furthermore, I already have a track record of productivity with my mentors and collaborators. I have full and enthusiastic support from UCSF, my home institution, which has a rich and enduring tradition of excellence in biomedical science, clinical and translational research, and global health. The training and research opportunities available at UCSF and through my mentorship team will no doubt prepare me for a successful career as an independent malaria researcher, addressing clinical and epidemiologic challenges of malaria elimination, and ultimately contributing to improved health of children and larger populations currently threatened by malaria.

Public Health Relevance

The global burden of disease caused by malaria is tremendous. The proposed research program will take place in Swaziland, a country in southern Africa endeavoring to eliminate malaria, and will critically evaluate re-active surveillance, a strategy whereby the communities of known malaria cases are screened as a way to identify other cases and hot spots. The results will help to focus future research and malaria interventions in Swaziland and many other countries aiming to eliminate malaria.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23AI101012-03
Application #
8662187
Study Section
Microbiology and Infectious Diseases B Subcommittee (MID)
Program Officer
Rao, Malla R
Project Start
2012-06-01
Project End
2017-05-31
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
3
Fiscal Year
2014
Total Cost
$131,490
Indirect Cost
$9,740
Name
University of California San Francisco
Department
Pediatrics
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Zelman, Brittany W; Baral, Ranju; Zarlinda, Iska et al. (2018) Costs and cost-effectiveness of malaria reactive case detection using loop-mediated isothermal amplification compared to microscopy in the low transmission setting of Aceh Province, Indonesia. Malar J 17:220
Herdiana, Herdiana; Cotter, Chris; Coutrier, Farah N et al. (2016) Malaria risk factor assessment using active and passive surveillance data from Aceh Besar, Indonesia, a low endemic, malaria elimination setting with Plasmodium knowlesi, Plasmodium vivax, and Plasmodium falciparum. Malar J 15:468
Hsiang, Michelle S; Greenhouse, Bryan; Rosenthal, Philip J (2015) Reply to Goyal et al. J Infect Dis 211:1687
Hsiang, Michelle S; Gosling, Roly D (2015) Striding Toward Malaria Elimination in China. Am J Trop Med Hyg 93:203-4
Reiner, Robert C; Le Menach, Arnaud; Kunene, Simon et al. (2015) Mapping residual transmission for malaria elimination. Elife 4:
Liu, Yaobao; Hsiang, Michelle S; Zhou, Huayun et al. (2014) Malaria in overseas labourers returning to China: an analysis of imported malaria in Jiangsu Province, 2001-2011. Malar J 13:29
Smith Gueye, Cara; Sanders, Kelly C; Galappaththy, Gawrie N L et al. (2013) Active case detection for malaria elimination: a survey among Asia Pacific countries. Malar J 12:358
Baltzell, Kimberly A; Shakely, Deler; Hsiang, Michelle et al. (2013) Prevalence of PCR detectable malaria infection among febrile patients with a negative Plasmodium falciparum specific rapid diagnostic test in Zanzibar. Am J Trop Med Hyg 88:289-91
Hsiang, Michelle S; Hwang, Jimee; Tao, Amy R et al. (2013) Mass drug administration for the control and elimination of Plasmodium vivax malaria: an ecological study from Jiangsu province, China. Malar J 12:383
Gosling, Roly D; Hsiang, Michelle S (2013) Malaria and severe anemia: thinking beyond Plasmodium falciparum. PLoS Med 10:e1001576

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