TY - JOUR
T1 - Sulfamethoxazole levels in HIV-Exposed uninfected Ugandan children
AU - Kasule, Jingo
AU - Gabriel, Erin E.
AU - Anok, Aggrey
AU - Neal, Jillian
AU - Eastman, Richard T.
AU - Penzak, Scott
AU - Newell, Kevin
AU - Serwadda, David
AU - Duffy, Patrick E.
AU - Reynolds, Steven J.
AU - Hobbs, Charlotte V.
N1 - Funding Information:
Financial support: This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E (K. N.), and in part by the Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health and Division of Intramural Research, National Institute of Allergy and Infectious Diseases, and National Institutes of Health. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.
Funding Information:
This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E (K. N.), and in part by the Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health and Division of Intramural Research, National Institute of Allergy and Infectious Diseases, and National Institutes of Health. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.
Publisher Copyright:
Copyright © 2018 by The American Society of Tropical Medicine and Hygiene.
PY - 2018
Y1 - 2018
N2 - Trimethoprim–sulfamethoxazole (TMP–SMX) prophylaxis in HIV-uninfected, exposed (HUE) children variably reduces clinical malaria burden despite antifolate resistance, but data regarding achieved serum levels and adherence are lacking. Serum samples from 70 HUE children aged 3–12 months from Rakai, Uganda, enrolled in an observational study were assayed for random SMX levels using a colorimetric assay. Adherence with TMP–SMX prophylaxis data (yes/no) was also collected. Of 148 visits with concurrent SMX levels available, 56% had self-reported adherence with TMP–SMX therapy. Among these 82 visits, mean (standard deviation) level was 19.78 (19.22) µg/mL, but 33% had SMX levels below half maximal inhibitory concentrations (IC50) for Plasmodium falciparum with some, but not all, of the reported antifolate resistance mutations reported in Uganda. With TMP–SMX prophylaxis, suboptimal adherence is concerning. Sulfamethoxazole levels below IC50s required to overcome malaria parasites with multiple antifolate resistance mutations may be significant. Further study of TMP–SMX in this context is needed.
AB - Trimethoprim–sulfamethoxazole (TMP–SMX) prophylaxis in HIV-uninfected, exposed (HUE) children variably reduces clinical malaria burden despite antifolate resistance, but data regarding achieved serum levels and adherence are lacking. Serum samples from 70 HUE children aged 3–12 months from Rakai, Uganda, enrolled in an observational study were assayed for random SMX levels using a colorimetric assay. Adherence with TMP–SMX prophylaxis data (yes/no) was also collected. Of 148 visits with concurrent SMX levels available, 56% had self-reported adherence with TMP–SMX therapy. Among these 82 visits, mean (standard deviation) level was 19.78 (19.22) µg/mL, but 33% had SMX levels below half maximal inhibitory concentrations (IC50) for Plasmodium falciparum with some, but not all, of the reported antifolate resistance mutations reported in Uganda. With TMP–SMX prophylaxis, suboptimal adherence is concerning. Sulfamethoxazole levels below IC50s required to overcome malaria parasites with multiple antifolate resistance mutations may be significant. Further study of TMP–SMX in this context is needed.
UR - http://www.scopus.com/inward/record.url?scp=85048288464&partnerID=8YFLogxK
U2 - 10.4269/ajtmh.17-0933
DO - 10.4269/ajtmh.17-0933
M3 - Article
AN - SCOPUS:85048288464
VL - 98
SP - 1718
EP - 1721
JO - American Journal of Tropical Medicine and Hygiene
JF - American Journal of Tropical Medicine and Hygiene
SN - 0002-9637
IS - 6
ER -