Date of Award

1-1-2019

Document Type

Thesis

Degree Name

Master of Public Health (MPH)

Department

School of Public Health

First Advisor

Sunil Parikh

Second Advisor

Amy K. Bei

Abstract

Malaria remains one of the most challenging infections globally. Malaria RDTs have had the largest impact on malaria detection in recent years with almost 245 million RDTs delivered globally. (1) They work by detecting either the histidine-rich protein (HRP2) or the Plasmodium lactate-dehydrogenase (pLDH). (2) Following a malaria infection, the HRP2 and pLDH antigens often circulate in the blood stream for several weeks. (3) As new RDTs are constantly being developed, each with a better sensitivity, specificity and lower limit of detection than its predecessor, the need to understand the persistence of their positivity, following a malaria infection, remains. The latest RDT on the market is produced by Alere™ and is called the ultra-sensitive RDT (uRDT). To test how long this new RDT remains positive following a malaria diagnosis and treatment, we prospectively followed children for 42 days. Children were either HIV positive or negative and either placed on a 3-day or 5-day artemether-lumefantrine regimen. Microscopy and the uRDT were performed on days 0, 7, 14, 21, 28, 35, and 42. The mean length of uRDT positivity was 9.2 days with a standard deviation of 11.3 days. Approximately 50% of all uRDTs remained positive for 11 days post-treatment of malaria. Neither HIV status nor AL duration impacted the length of uRDT positivity. Only parasite density was directly correlated with uRDT positivity with an increase in parasite density of 1 parasite/l resulting in 0.6 additional days of uRDT positivity. Microscopy (considered the gold standard in our study) and uRDT outcomes matched 67.5% of the time (320/474). The true positive rate (sensitivity) was calculated to be 91.3% and the true negative rate (specificity) was 55.3%. The uRDT was also able to predict treatment failure in children 7 days prior (p = 0.015). Due to its positive persistence that can lead to false positive, we recommend that the use of Alere’s uRDT be limited to low transmission and elimination settings only.

Comments

This thesis is restricted to Yale network users only. It will be made publicly available on 08/28/2020

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