Sulfamethoxazole levels in HIV-Exposed uninfected Ugandan children

Jingo Kasule, Erin E. Gabriel, Aggrey Anok, Jillian Neal, Richard T. Eastman, Scott Robert Penzak, Kevin Newell, David Serwadda, Patrick E. Duffy, Steven J. Reynolds, Charlotte V. Hobbs

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)1718-1721
Number of pages4
JournalAmerican Journal of Tropical Medicine and Hygiene
Volume98
Issue number6
DOIs
StatePublished - 1 Jan 2018

Fingerprint

Folic Acid Antagonists
Sulfamethoxazole
Uganda
HIV
Malaria
Mutation
Plasmodium falciparum
Serum
Inhibitory Concentration 50
Observational Studies
Parasites
Therapeutics

Cite this

Kasule, J., Gabriel, E. E., Anok, A., Neal, J., Eastman, R. T., Penzak, S. R., ... Hobbs, C. V. (2018). Sulfamethoxazole levels in HIV-Exposed uninfected Ugandan children. American Journal of Tropical Medicine and Hygiene, 98(6), 1718-1721. https://doi.org/10.4269/ajtmh.17-0933
Kasule, Jingo ; Gabriel, Erin E. ; Anok, Aggrey ; Neal, Jillian ; Eastman, Richard T. ; Penzak, Scott Robert ; Newell, Kevin ; Serwadda, David ; Duffy, Patrick E. ; Reynolds, Steven J. ; Hobbs, Charlotte V. / Sulfamethoxazole levels in HIV-Exposed uninfected Ugandan children. In: American Journal of Tropical Medicine and Hygiene. 2018 ; Vol. 98, No. 6. pp. 1718-1721.
@article{e9f927273839433aa6d3a3206676b65c,
title = "Sulfamethoxazole levels in HIV-Exposed uninfected Ugandan children",
abstract = "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.",
author = "Jingo Kasule and Gabriel, {Erin E.} and Aggrey Anok and Jillian Neal and Eastman, {Richard T.} and Penzak, {Scott Robert} and Kevin Newell and David Serwadda and Duffy, {Patrick E.} and Reynolds, {Steven J.} and Hobbs, {Charlotte V.}",
year = "2018",
month = "1",
day = "1",
doi = "10.4269/ajtmh.17-0933",
language = "English",
volume = "98",
pages = "1718--1721",
journal = "American Journal of Tropical Medicine and Hygiene",
issn = "0002-9637",
publisher = "American Society of Tropical Medicine and Hygiene",
number = "6",

}

Kasule, J, Gabriel, EE, Anok, A, Neal, J, Eastman, RT, Penzak, SR, Newell, K, Serwadda, D, Duffy, PE, Reynolds, SJ & Hobbs, CV 2018, 'Sulfamethoxazole levels in HIV-Exposed uninfected Ugandan children', American Journal of Tropical Medicine and Hygiene, vol. 98, no. 6, pp. 1718-1721. https://doi.org/10.4269/ajtmh.17-0933

Sulfamethoxazole levels in HIV-Exposed uninfected Ugandan children. / Kasule, Jingo; Gabriel, Erin E.; Anok, Aggrey; Neal, Jillian; Eastman, Richard T.; Penzak, Scott Robert; Newell, Kevin; Serwadda, David; Duffy, Patrick E.; Reynolds, Steven J.; Hobbs, Charlotte V.

In: American Journal of Tropical Medicine and Hygiene, Vol. 98, No. 6, 01.01.2018, p. 1718-1721.

Research output: Contribution to journalArticle

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 Robert

AU - Newell, Kevin

AU - Serwadda, David

AU - Duffy, Patrick E.

AU - Reynolds, Steven J.

AU - Hobbs, Charlotte V.

PY - 2018/1/1

Y1 - 2018/1/1

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 -