Condition category
Infections and Infestations
Date applied
31/01/2005
Date assigned
22/07/2005
Last edited
04/02/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Malaria is a serious tropical disease spread by mosquitoes. Previous studies monitoring the success of drug treatment in curing malaria in African children had found that drugs differed in whether the cured children were prevented from passing on malaria to mosquitoes. With the new generation of combination drugs becoming widely available in the early 2000s we sought to compare these with the older drugs, and to test whether these were more effective at not only curing the disease, but in preventing further mosquito infections.

Who can participate?
Children under 12 years of age who were brought to the Farafenni hospital, in The Gambia, for malaria treatment.

What does the study involve?
The children are randomly allocated to one of the study medications, and sent home with all the drugs they would need. Our health worker team then visits each child at home (by motorbike) on subsequent days to assist with the continuing treatment, and to monitor the cure by taking small finger-prick blood samples to test for persisting parasites. Seven days after treatment the children are brought in to the study clinic and lab for a thorough check, and those with any potentially infectious parasites in their blood after checking under the microscope are asked to give an additional blood sample. This sample is then used to experimentally feed mosquitoes to check whether this child is still potentially infectious to the insects which spread malaria.

What are the possible benefits and risks of participating?
Not provided at time of registration

Where is the study run from?
Farafenni hospital in The Gambia

When is the study starting and how long is it expected to run for?
January 2000 to December 2003

Who is funding the study?
The Wellcome Trust and MRC Laboratories (UK)

Who is the main contact?
Dr Colin Sutherland
colin.sutherland@lshtm.ac.uk

Trial website

Contact information

Type

Scientific

Primary contact

Dr Colin Sutherland

ORCID ID

Contact details

London School of Hygiene & Tropical Medicine
Keppel St
London
WC1E 7HT
United Kingdom
+44 (0)20 7927 2338
colin.sutherland@lshtm.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

061910

Study information

Scientific title

The impact of anti-malarial treatment upon the development and persistence of Plasmodium falciparum gametocytes in vitro and in vivo

Acronym

Study hypothesis

That use of artemisinin combination chemotherapy for treating uncomplicated falciparum malaria in children will reduce transmissibility of malaria to mosquitoes, compared to other combinations or to monotherapies.

Ethics approval

1. LSHTM Ethics Committee, 05/09/2000, ref: 708
2. Joint Gambia Government/MRC Laboratories Ethics Committee, 06/08/2000, ref: SCC/EC 838/798. Approved annually on 20/09/2001 (ref: SCC/EC 887/844) and 14/08/2002 (ref: SCC/EC 910)

Study design

Randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Other

Trial type

Treatment

Patient information sheet

Condition

Malaria

Intervention

Combination antimalarial therapy versus established monotherapy. Single-blind open-label randomised controlled trial run over three consecutive transmission seasons in Farafenni, The Gambia.

Intervention type

Drug

Phase

Not Applicable

Drug names

Artemisinin combination chemotherapy

Primary outcome measures

Major endpoints were:
1. Post-treatment gametocyte carriage over 28 days
2. Infectiousness to mosquitoes of children carrying gametocytes seven days after treatment

Secondary outcome measures

Minor endpoints were:
1. Clinical and parasitological drug efficacy over 28 days of follow-up

Overall trial start date

01/01/2000

Overall trial end date

31/12/2003

Reason abandoned

Eligibility

Participant inclusion criteria

1. Children one to ten years of age (either sex) attending Farafenni Health Centre, The Gambia, from September to December in each of 2000, 2001 and 2002
2. Children with a temperature more than 37.5°C, or a history of fever
3. Blood-film positive for P. falciparum at a density greater than 500 parasites per ml
4. Signed informed consent was obtained

Participant type

Patient

Age group

Child

Gender

Both

Target number of participants

600

Participant exclusion criteria

1. An inability to take drugs orally
2. Treatment with antimalarial chemotherapy within the past two weeks
3. Carriage of circulating gametocytes at presentation
4. Any evidence of chronic disease or acute infection other than malaria
5. Domicile outside the study area (approximately 10 km radius)
6. Any signs or symptoms of severe malaria:
6.1. Severe anaemia (peripheral blood Packed Cell Volume [PCV] less than 20%)
6.2. Hyper-parasitaemia (more than 250,000 per ml peripheral blood)
6.3. Respiratory distress (respiratory rate more than 40 with two of the following: nasal flaring, intercostal indrawing, subcostal recession or grunting)
6.4. Repeated generalised convulsions (three or more per 24 hours or two witnessed seizures in 24 hours)
6.5. Haemoglobinuria (dark red/black urine)
6.6. Jaundice
6.7. Prostration
6.8. Circulatory collapse

Recruitment start date

01/01/2000

Recruitment end date

31/12/2003

Locations

Countries of recruitment

Gambia

Trial participating centre

London School of Hygiene & Tropical Medicine
London
WC1E 7HT
United Kingdom

Sponsor information

Organisation

London School of Hygiene and Tropical Medicine (UK)

Sponsor details

Research Grants and Contracts Office
Keppel Street
London
WC1E 7HT
United Kingdom
+44 (0)20 7827 2678
Penny.Ireland@lshtm.ac.uk

Sponsor type

University/education

Website

http://www.lshtm.ac.uk

Funders

Funder type

Charity

Funder name

The Wellcome Trust (UK) (grant ref: 061910)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

MRC Laboratories (The Gambia) - Scientific Coordinating Committee (Projects: 838, 887 and 910)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

1. 2002 results in http://www.ncbi.nlm.nih.gov/pubmed/12518847
2. 2003 results in http://www.ncbi.nlm.nih.gov/pubmed/12932091
3. 2004 results in http://www.ncbi.nlm.nih.gov/pubmed/14728607
4. 2004 results in http://www.ncbi.nlm.nih.gov/pubmed/15388456
5. 2008 results in http://www.ncbi.nlm.nih.gov/pubmed/18509532

Publication citations

  1. Results

    Sutherland CJ, Alloueche A, Curtis J, Drakeley CJ, Ord R, Duraisingh M, Greenwood BM, Pinder M, Warhurst D, Targett GA, Gambian children successfully treated with chloroquine can harbor and transmit Plasmodium falciparum gametocytes carrying resistance genes., Am. J. Trop. Med. Hyg., 2002, 67, 6, 578-585.

  2. Results

    Sutherland CJ, Drakeley CJ, Obisike U, Coleman R, Jawara M, Targett GA, Milligan P, Pinder M, Walraven G, The addition of artesunate to chloroquine for treatment of Plasmodium falciparum malaria in Gambian children delays, but does not prevent treatment failure., Am. J. Trop. Med. Hyg., 2003, 69, 1, 19-25.

  3. Results

    Drakeley CJ, Jawara M, Targett GA, Walraven G, Obisike U, Coleman R, Pinder M, Sutherland CJ, Addition of artesunate to chloroquine for treatment of Plasmodium falciparum malaria in Gambian children causes a significant but short-lived reduction in infectiousness for mosquitoes., Trop. Med. Int. Health, 2004, 9, 1, 53-61.

  4. Results

    Hallett RL, Sutherland CJ, Alexander N, Ord R, Jawara M, Drakeley CJ, Pinder M, Walraven G, Targett GA, Alloueche A, Combination therapy counteracts the enhanced transmission of drug-resistant malaria parasites to mosquitoes., Antimicrob. Agents Chemother., 2004, 48, 10, 3940-3943, doi: 10.1128/AAC.48.10.3940-3943.2004.

  5. Results

    Saeed M, Roeffen W, Alexander N, Drakeley CJ, Targett GA, Sutherland CJ, Plasmodium falciparum antigens on the surface of the gametocyte-infected erythrocyte., PLoS ONE, 2008, 3, 5, e2280, doi: 10.1371/journal.pone.0002280.

Additional files

Editorial Notes

04/02/2016: Publication reference added.