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 language | English |
|---|---|
| Pages (from-to) | 1718-1721 |
| Number of pages | 4 |
| Journal | American Journal of Tropical Medicine and Hygiene |
| Volume | 98 |
| Issue number | 6 |
| DOIs | |
| State | Published - 1 Jan 2018 |
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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 journal › Article
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 -