Evidence map›Paper›PMID 30897090›Full record

Trial reportPLoS neglected tropical diseases2019

The prevalence and antifolate drug resistance profiles of Plasmodium falciparum in study participants randomized to discontinue or continue cotrimoxazole prophylaxis.

Dennis W Juma, Peninah Muiruri, Krista Yuhas, Grace John-Stewart, Ronald Ottichilo, John Waitumbi, Benson Singa, Christina Polyak, Edwin Kamau

Registry-linked trialOpen access · goldAbstract readComparative StudyRandomized Controlled TrialEquivalence Trial
In one paragraph

Trial report in PLoS neglected tropical diseases, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01425073 (Discontinuation of Trimethoprim-sulfamethoxazole Prophylaxis in Adults on Antiretroviral Therapy in Kenya), which is not on this map. Cited by 16 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 1 pooled it
2.7field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01425073 nacompletednot on this map

Discontinuation of Trimethoprim-sulfamethoxazole Prophylaxis in Adults on Antiretroviral Therapy in Kenya: a Randomized Trial

TypeinterventionalSponsorUniversity of WashingtonRan2012 to 2013Enrolled500ConditionsHIV Infections, Acquired Immunodeficiency Syndrome, Disease Progression, Immune System DiseasesArmsDiscontinue TMP/SMZ prophylaxis
3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Genomic characterization ofFrontiers in cellular and infection microbiology · 2022
    Article
  9. Article
  10. Review
  11. Cotrimoxazole Prophylaxis Selects for Antimicrobial Resistance in Human Immunodeficiency Virus-Exposed, Uninfected Infants.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2020
    Article
  12. Article
  13. BMJ global health · 2020
    Article
  14. Article
  15. Frontiers in cellular and infection microbiology · 2020
    Article
  16. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 5 institutions in 2 countries.

Dennis W JumaDepartment of Emerging and Infectious Diseases (DEID), United States Army Medical Research Directorate-Africa (USAMRD-A), Kenya Medical Research Institute (KEMRI) Kisumu, Kenya.
Peninah MuiruriDepartment of Emerging and Infectious Diseases (DEID), United States Army Medical Research Directorate-Africa (USAMRD-A), Kenya Medical Research Institute (KEMRI) Kisumu, Kenya.
Krista YuhasDepartment of Global Health, University of Washington, Seattle, Washington United States of America.
Grace John-StewartDepartments of Global Health, Medicine, Epidemiology, and Pediatrics, University of Washington, Seattle, Washington, United States of America.ORCID 0000-0002-4301-1573
Ronald OttichiloDepartment of Emerging and Infectious Diseases (DEID), United States Army Medical Research Directorate-Africa (USAMRD-A), Kenya Medical Research Institute (KEMRI) Kisumu, Kenya.
John WaitumbiDepartment of Emerging and Infectious Diseases (DEID), United States Army Medical Research Directorate-Africa (USAMRD-A), Kenya Medical Research Institute (KEMRI) Kisumu, Kenya.
Benson SingaCentre for Clinical Research, KEMRI, Nairobi, Kenya.
Christina PolyakU.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, United States of America.
Edwin KamauDepartment of Emerging and Infectious Diseases (DEID), United States Army Medical Research Directorate-Africa (USAMRD-A), Kenya Medical Research Institute (KEMRI) Kisumu, Kenya.ORCID 0000-0002-5761-7883
United States Army Medical Research Directorate - Africa · KEUniversity of Washington · USHenry M. Jackson Foundation · USJomo Kenyatta University of Agriculture and Technology · KEKenya Medical Research Institute · KE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveCotrimoxazole prevents opportunistic infections including falciparum malaria in HIV-infected individuals but there are concerns of cross-resistance to other antifolate drugs such as sulphadoxine-pyrimethamine (SP). In this study, we investigated the prevalence of antifolate-resistance mutations in Plasmodium falciparum that are associated with SP resistance in HIV-infected individuals on antiretroviral treatment randomized to discontinue (STOP-CTX), or continue (CTX) cotrimoxazole in Western Kenya.

designSamples were obtained from an unblinded, non-inferiority randomized controlled trial where participants were recruited on a rolling basis for the first six months of the study, then followed-up for 12 months with samples collected at enrollment, quarterly, and during sick visits.

methodPlasmodium DNA was extracted from blood specimens. Initial screening to determine the presence of Plasmodium spp. was performed by quantitative reverse transcriptase real-time PCR, followed by genotyping for the presence of SP-resistance associated mutations by Sanger sequencing.

resultsThe prevalence of mutant haplotypes associated with SP-resistant parasites in pfdhfr (51I/59R/108N) and pfdhps (437G/540E) genes were significantly higher (P = 0.0006 and P = 0.027, respectively) in STOP-CTX compared to CTX arm. The prevalence of quintuple haplotype (51I/59R/108N/437G/540E) was 51.8% in STOP-CTX vs. 6.3% (P = 0.0007) in CTX arm. There was a steady increase in mutant haplotypes in both genes in STOP-CTX arm overtime through the study period, reaching statistical significance (P < 0.0001).

conclusionThe frequencies of mutations in pfdhfr and pfdhps genes were higher in STOP-CTX arm compared to CTX arm, suggesting cotrimoxazole effectively controls and selects against SP-resistant parasites.

trial registrationClinicalTrials.gov NCT01425073.

Indexed as

AdolescentAdultAntimalarialsDihydropteroate SynthaseDrug CombinationsDrug ResistanceFolic Acid AntagonistsHaplotypesHIV InfectionsHumansKenyaMalaria, FalciparumMutationPlasmodium falciparumPre-Exposure ProphylaxisPrevalenceAntimalarialsDHFR protein, Plasmodium falciparumDihydropteroate SynthaseDrug Combinationsfanasil, pyrimethamine drug combinationFolic Acid AntagonistsProtozoan ProteinsPyrimethamineSulfadoxineTetrahydrofolate DehydrogenaseTrimethoprim, Sulfamethoxazole Drug Combination

Identifiers

PMID30897090
PMCPMC6445470
OpenAlexW2925250049

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.