Adherence to malaria treatment policy and prevalence of Pfkelch13 and background mutations associated with artemisinin resistance emergence in Plasmodium falciparum parasites in Uganda
| ISRCTN | ISRCTN12267960 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN12267960 |
| Secondary identifying numbers | SBS 803 |
- Submission date
- 25/03/2022
- Registration date
- 01/04/2022
- Last edited
- 28/03/2022
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Plain English Summary
Background and study aims
Malaria is a serious and sometimes fatal disease caused by a parasite that commonly infects a certain type of mosquito which feeds on humans.
Malaria remains a serious public health problem in Uganda, accounting for 30-50% of out-patient visits, 15-20% of hospital admissions and up to 20% of in-patient deaths. Malaria treatment is threatened by resistance to artemisinin agents, the cornerstone of current treatment modalities. Artemisinins are derived from extracts of sweet wormwood (Artemisia annua) and are well established for the treatment of malaria, including highly drug-resistant strains.
Efforts to track and contain artemisinin resistance especially in sub-Saharan Africa are hindered by lack of valid molecular markers coupled with inadequate capacity to perform routine parasite sensitivity analysis. Additionally, lack of information on local drivers of artemisinin resistance development and spread further limit development of containment and eradication strategies.
The study is screening for the presence of artemisinin resistance in Plasmodium falciparum parasites among symptomatic malaria patients in low and high malaria transmission settings in Uganda
Who can participate?
Adult (18 years and above) malaria patients
What does the study involve?
Participants provide a blood sample at a single time point
What are the possible benefits and risks of participating?
There are no anticipated direct benefits and risks to participating in this study. However, participating in the study will help in advancing scientific knowledge on artemisinin resistance.
Where is the study run from?
Makerere University, College of Health Sciences, Department of Pharmacology & Therapeutics (Uganda)
When is the study starting and how long is it expected to run for?
August 2019 to December 2023
Who is funding the study?
European & Developing Countries Clinical Trials Partnership (the Netherlands)
Who is the main contact?
Dr Moses Ocan, ocanmoses@gmail.com
Contact information
Principal Investigator
Upper Mulago Hill Road
Kampala
-
Uganda
 ORCID ID |
0000-0002-8852-820X |
|---|---|
| Phone | +256 782355302 |
| moses.ocan@mak.ac.ug |
Study information
| Study design | Single center observational cross-sectional cohort study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Cross sectional study |
| Study setting(s) | Hospital |
| Study type | Screening |
| Scientific title | Predictors of local emergence and spread of artemisinin resistance among Ugandan plasmodium falciparum parasites |
| Study acronym | Pfkelch13 emergence |
| Study hypothesis | Research questions 1. What is the extent of adherence to national malaria treatment guidelines/policy in malaria treatment in private hospitals, private pharmacies and public hospitals in low and high malaria transmission settings in Uganda 2. What is the prevalence of Pfkelch13 single nucleotide polymorphisms and background mutations fd (ferredoxin), arps10 (apicomplast ribosomal protein S10), mdr-2 (multi-drug resistance protein-2) and crt (chloroquine resistance protein) in Plasmodium falciparum parasites in low and high malaria transmission settings in Uganda |
| Ethics approval(s) | Approved 07/10/2020, School of Biomedical Science Research Ethics Committee (P.O. Box 7072, Kampala, Uganda; +256 752575050; biomedicalresearch62@gmail.com), ref: SBS 803 |
| Condition | Screening for occurrence of artemisinin resistance among symptomatic malaria patients |
| Intervention | The study is screening for the presence of artemisinin resistance in Plasmodium falciparum parasites among symptomatic malaria patients in low and high malaria transmission settings in Uganda. Microscopy is being used to screen for the presence of Plasmodium falciparum parasites in blood samples collected from malaria symptomatic patients. For blood samples where malaria parasites are confirmed, the sample is collected in a dried blood spot Whatman filter paper. The DNA of the parasites are then extracted from the filter paper and screened for the presence of K13 mutations (markers for artemisinin resistance) and background mutations (crt, arps10, fd, mdr-2) using Sanger sequencing method Approach: (i) Treatment of malaria patients in health facilities (public and private) will be assessed using a checklist to establish adherence to national malaria treatment guidelines, (ii) P. falciparum infected blood samples collected in high and low malaria transmission settings in Uganda will be used. P. falciparum infection will be established using PfHRP-2 Rapid Diagnostic Test (HRP-2 RDT) and microscopy. (iii) Parasite DNA will be extracted and purified using Qiagen-Max kit. Next generation sequencing platform will be used to establish Pfkelch13 Single nucleotide polymorphisms (SNPs) and genetic background mutations (fd, arps10, mdr2 and crt) in P. falciparum parasites. |
| Intervention type | Other |
| Primary outcome measure | Artemisinin resistance is measured using K13 gene mutations and background mutations (crt, arps10, fd, mdr-2) at baseline. This being a cross-sectional study, the outcome will be measured once at baseline. |
| Secondary outcome measures | 1. Level of adherence to malaria treatment policy measured using a questionnaire and interview guide at baseline 2. Pharmacopoeial quality of ACTs measured using LC-MS at baseline |
| Overall study start date | 10/08/2019 |
| Overall study end date | 31/12/2023 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Total number of patients 385 (Tororo general hospital, 150; Apac general hospital, 150; Mbarara regional referral hospital, 45; Kabale regional referral hospital, 40) |
| Participant inclusion criteria | 1. Symptomatic malaria patients 2. Age 18 years and above 3. Patients with malaria treatment given at a hospital |
| Participant exclusion criteria | 1. Severely ill adult malaria patients 2. Anemic patients (males, Hb < 13g/100ml; non-pregnant females, Hb <12g/100ml; pregnant females, Hb <11g/100ml) 3. Patients with low parasite load (<1000 parasites/µl of blood) |
| Recruitment start date | 05/06/2021 |
| Recruitment end date | 05/06/2022 |
Locations
Countries of recruitment
- Uganda
Study participating centre
Department of Pharmacology & Therapeutics
Upper Mulago Hill Road
Kampala
-
Uganda
Sponsor information
Research organisation
PO Box 93015
The Hague
2509 AA
Netherlands
| Phone | +31 70 344 0880 |
|---|---|
| edctpgrants@edctp.org | |
| Website | http://www.edctp.org/ |
"ROR" |
https://ror.org/031jv9v19 |
Funders
Funder type
Government
Private sector organisation / International organizations
- Alternative name(s)
- Le partenariat Europe-Pays en développement pour les essais cliniques, A Parceria entre a Europa e os Países em Desenvolvimento para a Realização de Ensaios Clínicos, The European & Developing Countries Clinical Trials Partnership, European and Developing Countries Clinical Trials, EDCTP
- Location
- Netherlands
Results and Publications
| Intention to publish date | 31/12/2022 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Published as a supplement to the results publication |
| Publication and dissemination plan | The research outputs will be communicated to, Ministry of Health (Malaria Control Program), Scientific community, Community engagement. In community engagement, different stakeholders such as Non-governmental organizations (MeTA, HEPS-Uganda), healthcare professionals through professional organizations (Uganda Medical Association, Uganda Pharmaceutical Society, Uganda Pharmacological Society, Uganda Nurses and Midwives Union), patients/local communities. This will be done through workshops with the stakeholders. For patient/local communities, one member of a Village Health Team (VHT) from each of the study districts will be invited for the stakeholder dialogue and results dissemination. The invited VHTs will then organize local workshops with other VHTs in the study districts. The VHTs will then share key study findings with local communities during their routine service to communities. In addition, the project website will provide a platform for the public to know about the study. The website will be developed at project month 1. Stakeholder meetings: The research outputs will be shared with the stakeholders (Ministry of Health, Scientific community/researchers, Non-governmental organizations, and healthcare professionals) through meetings. The meeting will involve oral presentation of project research outputs and dialogue with the audience. This will be done once every 6 months throughout the project duration. Report writing: The key research findings will summarized in a book (research report). The report will then be distributed to the libraries of Ministry of Health and Universities that train Medical Students in Uganda. The report will also be shared with the Non-governmental organizations and health professional organizations. Publications: Three articles from the findings of the project will be published in open access peer reviewed journal. |
| IPD sharing plan | Primary data will be shared with open access journals where the study will be published. |
Editorial Notes
28/03/2022: Trial's existence confirmed by Makerere University
