Evidence map›Paper›PMID 33588295›Full record

ArticleInternational journal for parasitology. Drugs and drug resistance2021

Physiological and proteomic profiles of Trypanosoma brucei rhodesiense parasite isolated from suramin responsive and non-responsive HAT patients in Busoga, Uganda.

Catherine N Mutuku, Rosemary Bateta, Martin K Rono, James M Njunge, Erick O Awuoche, Kariuki Ndung'u, Clarence M Mang'era, Modesta O Akoth, Vincent O Adung'a, Bartholomew N Ondigo and 1 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in International journal for parasitology. Drugs and drug resistance, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.6field-weighted citation impact, top 33% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 4 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
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

11 authors at 4 institutions in 1 country.

Catherine N MutukuBiotechnology Research Institute, Kenya Agricultural and Livestock Research Organization, P.O. Box 362, Kikuyu, Kenya; Department of Biochemistry and Molecular Biology, Egerton University, P.O. Box 536, Njoro, Kenya.
Rosemary BatetaBiotechnology Research Institute, Kenya Agricultural and Livestock Research Organization, P.O. Box 362, Kikuyu, Kenya. Electronic address: batetarw@gmail.com.
Martin K RonoCentre for Geographic Medicine Research - Coast, Kenya Medical Research Institute, PO Box 230-80108 Kilifi, Kenya.
James M NjungeCentre for Geographic Medicine Research - Coast, Kenya Medical Research Institute, PO Box 230-80108 Kilifi, Kenya.
Erick O AwuocheDepartment of Biological Sciences, School of Pure and Applied Science, Meru University of Science and Technology, Meru, Kenya.
Kariuki Ndung'uBiotechnology Research Institute, Kenya Agricultural and Livestock Research Organization, P.O. Box 362, Kikuyu, Kenya.
Clarence M Mang'eraDepartment of Biochemistry and Molecular Biology, Egerton University, P.O. Box 536, Njoro, Kenya.
Modesta O AkothBiotechnology Research Institute, Kenya Agricultural and Livestock Research Organization, P.O. Box 362, Kikuyu, Kenya; Department of Biochemistry and Molecular Biology, Egerton University, P.O. Box 536, Njoro, Kenya.
Vincent O Adung'aDepartment of Biochemistry and Molecular Biology, Egerton University, P.O. Box 536, Njoro, Kenya.
Bartholomew N OndigoDepartment of Biochemistry and Molecular Biology, Egerton University, P.O. Box 536, Njoro, Kenya.
Paul O MirejiBiotechnology Research Institute, Kenya Agricultural and Livestock Research Organization, P.O. Box 362, Kikuyu, Kenya; Centre for Geographic Medicine Research - Coast, Kenya Medical Research Institute, PO Box 230-80108 Kilifi, Kenya. Electronic address: mireji.paul@gmail.com.
Egerton University · KEKenya Medical Research Institute · KEKenya Agricultural and Livestock Research Organization · KEMeru University of Science and Technology · KE

Funding

Control of Tsetse Fly Transmitted Diseases in KenyaU01AI115648 · NIAID · YALE UNIVERSITY · PI AKSOY, SERAP · 2015 to 2019
$3.6M
NIAID NIH HHS U01 AI115648
6 · The paper itself

Abstract

Human African Trypanosomiasis (HAT) is a disease of major economic importance in Sub-Saharan Africa. The HAT is caused by Trypanosoma brucei rhodesiense (Tbr) parasite in eastern and southern Africa, with suramin as drug of choice for treatment of early stage of the disease. Suramin treatment failures has been observed among HAT patients in Tbr foci in Uganda. In this study, we assessed Tbr parasite strains isolated from HAT patients responsive (Tbr EATRO-232) and non-responsive (Tbr EATRO-734) to suramin treatment in Busoga, Uganda for 1) putative role of suramin resistance in the treatment failure 2) correlation of suramin resistance with Tbr pathogenicity and 3) proteomic pathways underpinning the potential suramin resistance phenotype in vivo. We first assessed suramin response in each isolate by infecting male Swiss white mice followed by treatment using a series of suramin doses. We then assessed relative pathogenicity of the two Tbr isolates by assessing changes pathogenicity indices (prepatent period, survival and mortality). We finally isolated proteins from mice infected by the isolates, and assessed their proteomic profiles using mass spectrometry. We established putative resistance to 2.5 mg/kg suramin in the parasite Tbr EATRO-734. We established that Tbr EATRO-734 proliferated slower and has significantly enriched pathways associated with detoxification and metabolism of energy and drugs relative to Tbr EATRO-232. The Tbr EATRO-734 also has more abundantly expressed mitochondrion proteins and enzymes than Tbr EATRO-232. The suramin treatment failure may be linked to the relatively higher resistance to suramin in Tbr EATRO-734 than Tbr EATRO-232, among other host and parasite specific factors. However, the Tbr EATRO-734 appears to be less pathogenic than Tbr EATRO-232, as evidenced by its lower rate of parasitaemia. The Tbr EATRO-734 putatively surmount suramin challenges through induction of energy metabolism pathways. These cellular and molecular processes may be involved in suramin resistance in Tbr.

Indexed as

ParasitesTrypanosoma brucei bruceiTrypanosomiasis, AfricanAnimalsHumansMaleMiceProteomicsSuraminTrypanosoma brucei rhodesienseUgandaSuraminDrug resistanceDrug sensitive, Trypanosoma brucei rhodesienceSuramin

Identifiers

PMID33588295
PMCPMC7895675
OpenAlexW3126923003

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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 Socratic graph.