Effect of trimethoprim-sulphamethoxazole on the risk of malaria in HIV-infected Ugandan children living in an area of widespread antifolate resistance
Abstract Background Daily trimethoprim-sulfamethoxazole (TS) protects against malaria, but efficacy may be diminished as anti-folate resistance increases. This study assessed the incidence of falciparum malaria and the prevalence of resistance-conferring Plasmodium falciparum mutations in HIV-infect...
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ftdoajarticles:oai:doaj.org/article:309af99fef2f456bb978a9505308594c 2023-05-15T15:14:29+02:00 Effect of trimethoprim-sulphamethoxazole on the risk of malaria in HIV-infected Ugandan children living in an area of widespread antifolate resistance Kateera Fredrick Ruel Theodore Charlebois Edwin Achan Jane Vora Neil Ochong Edwin O Kamya Moses R Gasasira Anne F Meya Denise N Havlir Diane Rosenthal Philip J Dorsey Grant 2010-06-01T00:00:00Z https://doi.org/10.1186/1475-2875-9-177 https://doaj.org/article/309af99fef2f456bb978a9505308594c EN eng BMC http://www.malariajournal.com/content/9/1/177 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-9-177 1475-2875 https://doaj.org/article/309af99fef2f456bb978a9505308594c Malaria Journal, Vol 9, Iss 1, p 177 (2010) Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2010 ftdoajarticles https://doi.org/10.1186/1475-2875-9-177 2022-12-31T08:47:55Z Abstract Background Daily trimethoprim-sulfamethoxazole (TS) protects against malaria, but efficacy may be diminished as anti-folate resistance increases. This study assessed the incidence of falciparum malaria and the prevalence of resistance-conferring Plasmodium falciparum mutations in HIV-infected children receiving daily TS and HIV-uninfected children not taking TS. Materials and methods Subjects were 292 HIV-infected and 517 uninfected children from two cohort studies in Kampala, Uganda observed from August 2006 to December 2008. Daily TS was given to HIV-infected, but not HIV-uninfected children and all participants were provided an insecticide-treated bed net. Standardized protocols were used to measure the incidence of malaria and identify markers of antifolate resistance. Results Sixty-five episodes of falciparum malaria occurred in HIV-infected and 491 episodes in uninfected children during the observation period. TS was associated with a protective efficacy of 80% (0.10 vs. 0.45 episodes per person year, p < 0.001), and efficacy did not vary over three consecutive 9.5 month periods (81%, 74%, 80% respectively, p = 0.506). The prevalences of dhfr 51I, 108N, and 59R and dhps 437G and 540E mutations were each over 90% among parasites infecting both HIV-infected and uninfected children. Prevalence of the dhfr 164L mutation, which is associated with high-level resistance, was significantly higher in parasites from HIV-infected compared to uninfected children (8% vs. 1%, p = 0.001). Sequencing of the dhfr and dhps genes identified only one additional polymorphism, dhps 581G, in 2 of 30 samples from HIV-infected and 0 of 54 samples from uninfected children. Conclusion Despite high prevalence of known anti-folate resistance-mediating mutations, TS prophylaxis was highly effective against malaria, but was associated with presence of dhfr 164L mutation. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Malaria Journal 9 1 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
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Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Kateera Fredrick Ruel Theodore Charlebois Edwin Achan Jane Vora Neil Ochong Edwin O Kamya Moses R Gasasira Anne F Meya Denise N Havlir Diane Rosenthal Philip J Dorsey Grant Effect of trimethoprim-sulphamethoxazole on the risk of malaria in HIV-infected Ugandan children living in an area of widespread antifolate resistance |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Abstract Background Daily trimethoprim-sulfamethoxazole (TS) protects against malaria, but efficacy may be diminished as anti-folate resistance increases. This study assessed the incidence of falciparum malaria and the prevalence of resistance-conferring Plasmodium falciparum mutations in HIV-infected children receiving daily TS and HIV-uninfected children not taking TS. Materials and methods Subjects were 292 HIV-infected and 517 uninfected children from two cohort studies in Kampala, Uganda observed from August 2006 to December 2008. Daily TS was given to HIV-infected, but not HIV-uninfected children and all participants were provided an insecticide-treated bed net. Standardized protocols were used to measure the incidence of malaria and identify markers of antifolate resistance. Results Sixty-five episodes of falciparum malaria occurred in HIV-infected and 491 episodes in uninfected children during the observation period. TS was associated with a protective efficacy of 80% (0.10 vs. 0.45 episodes per person year, p < 0.001), and efficacy did not vary over three consecutive 9.5 month periods (81%, 74%, 80% respectively, p = 0.506). The prevalences of dhfr 51I, 108N, and 59R and dhps 437G and 540E mutations were each over 90% among parasites infecting both HIV-infected and uninfected children. Prevalence of the dhfr 164L mutation, which is associated with high-level resistance, was significantly higher in parasites from HIV-infected compared to uninfected children (8% vs. 1%, p = 0.001). Sequencing of the dhfr and dhps genes identified only one additional polymorphism, dhps 581G, in 2 of 30 samples from HIV-infected and 0 of 54 samples from uninfected children. Conclusion Despite high prevalence of known anti-folate resistance-mediating mutations, TS prophylaxis was highly effective against malaria, but was associated with presence of dhfr 164L mutation. |
format |
Article in Journal/Newspaper |
author |
Kateera Fredrick Ruel Theodore Charlebois Edwin Achan Jane Vora Neil Ochong Edwin O Kamya Moses R Gasasira Anne F Meya Denise N Havlir Diane Rosenthal Philip J Dorsey Grant |
author_facet |
Kateera Fredrick Ruel Theodore Charlebois Edwin Achan Jane Vora Neil Ochong Edwin O Kamya Moses R Gasasira Anne F Meya Denise N Havlir Diane Rosenthal Philip J Dorsey Grant |
author_sort |
Kateera Fredrick |
title |
Effect of trimethoprim-sulphamethoxazole on the risk of malaria in HIV-infected Ugandan children living in an area of widespread antifolate resistance |
title_short |
Effect of trimethoprim-sulphamethoxazole on the risk of malaria in HIV-infected Ugandan children living in an area of widespread antifolate resistance |
title_full |
Effect of trimethoprim-sulphamethoxazole on the risk of malaria in HIV-infected Ugandan children living in an area of widespread antifolate resistance |
title_fullStr |
Effect of trimethoprim-sulphamethoxazole on the risk of malaria in HIV-infected Ugandan children living in an area of widespread antifolate resistance |
title_full_unstemmed |
Effect of trimethoprim-sulphamethoxazole on the risk of malaria in HIV-infected Ugandan children living in an area of widespread antifolate resistance |
title_sort |
effect of trimethoprim-sulphamethoxazole on the risk of malaria in hiv-infected ugandan children living in an area of widespread antifolate resistance |
publisher |
BMC |
publishDate |
2010 |
url |
https://doi.org/10.1186/1475-2875-9-177 https://doaj.org/article/309af99fef2f456bb978a9505308594c |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 9, Iss 1, p 177 (2010) |
op_relation |
http://www.malariajournal.com/content/9/1/177 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-9-177 1475-2875 https://doaj.org/article/309af99fef2f456bb978a9505308594c |
op_doi |
https://doi.org/10.1186/1475-2875-9-177 |
container_title |
Malaria Journal |
container_volume |
9 |
container_issue |
1 |
_version_ |
1766344935786676224 |