Mass-Drug Administration to Reduce Malaria Transmission - Full Text View

Sponsors and Collaborators:	Radboud University Kilimanjaro Christian Medical Centre, Tanzania London School of Hygiene and Tropical Medicine
Information provided by:	Radboud University
ClinicalTrials.gov Identifier:	NCT00509015

Purpose

In the 1950s, the WHO included mass drug administration (MDA) with antimalarial drugs as a tool for malaria control in 'exceptional conditions when conventional control strategies have failed'. Subsequently, MDA has received little attention until the introduction of artemisinin based combination therapy (ACT). The principle aim of MDA is to interrupt malaria transmission by clearing the population of sexual stage parasites, gametocytes, prior to the transmission season. Gametocytes are essential for propagation of the disease and elimination of gametocytes will result in a reduction in malaria transmission. As a consequence, a successful MDA will reduce the burden of disease in a population and is expected to have little influence on the development of protective immunity in areas of low transmission intensity. In Africa, only one large scale MDA study was conducted in the last 10 years. That study, conducted in The Gambia using sulphadoxine-pyrimethamine (SP) plus a single dose of artesunate (AS), failed to show a significant impact of MDA on malaria transmission. Possible reasons for this failure are the limited impact of the drug regimen (a single dose of AS) on malaria transmission, the incomplete coverage, the relatively high transmission intensity in the area and the migration of individuals between villages. Here, we propose to conduct an MDA study in an area of very low malaria transmission intensity in Tanzania. We use the highly active drug combination SP+AS (3 days) followed by a single dose of primaquine..

Condition	Intervention
Malaria, Falciparum	Drug: Sulphadoxine-pyrimethamine (day 1: 500mg S&25mg P/20 kg) Drug: Artesunate (day 1,2,3: 4 mg/kg) Drug: Primaquine-base (day 3: 0.75 mg/kg) Drug: placebo tablets

MedlinePlus related topics: Malaria

Drug Information available for: Pyrimethamine Sulfadoxine Artesunate Fansidar Artemisinin Lactose Primaquine Primaquine phosphate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Prevention, Randomized, Single Blind (Subject), Placebo Control, Parallel Assignment, Efficacy Study
Official Title:	Mass-Drug Administration With a Gametocytocidal Drug Combination, a Model for a Transmission Blocking Vaccine

Further study details as provided by Radboud University:

Primary Outcome Measures:

malaria morbidity by active and passive case detection. [ Time Frame: during the entire study period ] [ Designated as safety issue: Yes ]
asexual parasite prevalence and density by microscopy, rapid diagnostic test and molecular QT-NASBA [ Time Frame: monthly during the entire study period ]
gametocyte prevalence and density by QT-NASBA and microscopy [ Time Frame: monthly during the entire study period ]
transmission intensity quantified by entomologic inoculation rate [ Time Frame: continuously during the study period ]
human infectious reservoir [ Time Frame: prior to the intervention and several months after the intervention ]

Secondary Outcome Measures:

asexual parasite and gametocyte density by microscopy and molecular QT-NASBA [ Time Frame: monthly during the study period ]
human immune responses to malaria antigens [ Time Frame: prior to the intervention and several months after the intervention ]
the prevalence of drug resistant parasite strains [ Time Frame: prior to the intervention and several months after the intervention ]
Possible side effects of intervention with primaquine, notably hemolysis [ Time Frame: one week after the intervention ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	6000
Study Start Date:	February 2008
Study Completion Date:	August 2008
Primary Completion Date:	August 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator Sulphadoxine-pyrimethemine (day 1) artesunate (day 1-3) primaquine (day 3)	Drug: Sulphadoxine-pyrimethamine (day 1: 500mg S&25mg P/20 kg) 500mg S&25mg P/20 kg, 1 day, single dose Drug: Artesunate (day 1,2,3: 4 mg/kg) 4 mg/kg, daily single dose over three days Drug: Primaquine-base (day 3: 0.75 mg/kg) single dose at 0.75 mg/kg on day 3
2: Placebo Comparator Placebo: lactose tablets (Albochin)	Drug: placebo tablets 3 days of lactose tablets (160mg) albochin

Show Detailed Description

Eligibility

Ages Eligible for Study:	1 Year and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

permanent resident of the research area
age >1 years

Exclusion Criteria:

severe anemia
pregnancy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00509015

Locations

Tanzania
Kilimanjaro Christian Medical Centre
Moshi, Tanzania

Sponsors and Collaborators

Radboud University

Kilimanjaro Christian Medical Centre, Tanzania

London School of Hygiene and Tropical Medicine

Investigators

Principal Investigator:	Seif Shekalaghe, MPH MD	Kilimanjaro Christian Medical Centre
Study Chair:	Robert Sauerwein, Prof MD PhD	Radboud University Medical Centre
Study Director:	Frank Mosha, PhD	Kilimanjaro Christian Medical Centre

More Information

Publications:

von Seidlein L, Walraven G, Milligan PJ, Alexander N, Manneh F, Deen JL, Coleman R, Jawara M, Lindsay SW, Drakeley C, De Martin S, Olliaro P, Bennett S, Schim van der Loeff M, Okunoye K, Targett GA, McAdam KP, Doherty JF, Greenwood BM, Pinder M. The effect of mass administration of sulfadoxine-pyrimethamine combined with artesunate on malaria incidence: a double-blind, community-randomized, placebo-controlled trial in The Gambia. Trans R Soc Trop Med Hyg. 2003 Mar-Apr;97(2):217-25.

Weerasinghe KL, Galappaththy G, Fernando WP, Wickremasinghe DR, Faizal HM, Wickremasinghe AR. A safety and efficacy trial of artesunate, sulphadoxine-pyrimethamine and primaquine in P falciparum malaria. Ceylon Med J. 2002 Sep;47(3):83-5.

Responsible Party:	Kilimanjaro Christian Medical Centre ( Seif Shekalaghe )
Study ID Numbers:	APRIORI1/01
Study First Received:	July 30, 2007
Last Updated:	August 12, 2008
ClinicalTrials.gov Identifier:	NCT00509015
Health Authority:	Tanzania: Food & Drug Administration

Keywords provided by Radboud University:

antimalarials
malaria transmission
mass drug administration
artemisinin-based combination therapy

primaquine
gametocytes
QT-NASBA

Study placed in the following topic categories:

Folic Acid
Artesunate
Pyrimethamine
Protozoan Infections
Sulfadoxine-pyrimethamine
Primaquine

Artemisinins
Artemisinine
Parasitic Diseases
Malaria
Sulfadoxine
Malaria, Falciparum

Additional relevant MeSH terms:

Anti-Infective Agents
Antimalarials
Antiparasitic Agents
Antiprotozoal Agents
Molecular Mechanisms of Pharmacological Action
Coccidiosis

Therapeutic Uses
Anti-Infective Agents, Urinary
Enzyme Inhibitors
Renal Agents
Folic Acid Antagonists
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009