Mass-Drug Administration to Reduce Malaria Transmission

NCT00509015 | Completed DMC

• 1 other identifier: APRIORI1/01
• Study Type: interventional
• Target: 6,000
• Locations: 1 country
• Sites: 1

Brief Summary

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..

Conditions

Malaria, Falciparum

Keywords

antimalarials; malaria transmission; mass drug administration; artemisinin-based combination therapy; primaquine; gametocytes; QT-NASBA

Outcome Measures

Primary Outcomes (5)

• malaria morbidity by active and passive case detection.

  during the entire study period

• asexual parasite prevalence and density by microscopy, rapid diagnostic test and molecular QT-NASBA

  monthly during the entire study period

• gametocyte prevalence and density by QT-NASBA and microscopy

  monthly during the entire study period

• transmission intensity quantified by entomologic inoculation rate

  continuously during the study period

• human infectious reservoir

  prior to the intervention and several months after the intervention

Secondary Outcomes (4)

• asexual parasite and gametocyte density by microscopy and molecular QT-NASBA

  monthly during the study period

• human immune responses to malaria antigens

  prior to the intervention and several months after the intervention

• the prevalence of drug resistant parasite strains

  prior to the intervention and several months after the intervention

• Possible side effects of intervention with primaquine, notably hemolysis

  one week after the intervention

Study Arms (2)

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); Drug: Artesunate (day 1,2,3: 4 mg/kg); Drug: Primaquine-base (day 3: 0.75 mg/kg)

2

PLACEBO COMPARATOR

Placebo: lactose tablets (Albochin)

Drug: placebo tablets

Interventions

Sulphadoxine-pyrimethamine (day 1: 500mg S&25mg P/20 kg) DRUG

500mg S\&25mg P/20 kg, 1 day, single dose

1

Artesunate (day 1,2,3: 4 mg/kg) DRUG

4 mg/kg, daily single dose over three days

1

Primaquine-base (day 3: 0.75 mg/kg) DRUG

single dose at 0.75 mg/kg on day 3

1

placebo tablets DRUG

3 days of lactose tablets (160mg) albochin

2

Eligibility Criteria

• Age: 1 Year+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• permanent resident of the research area
• age \>1 years

You may not qualify if:

• severe anemia
• pregnancy

Sponsors & Collaborators

• Radboud University Medical Center: lead
• Kilimanjaro Christian Medical Centre, Tanzania: collaborator
• London School of Hygiene and Tropical Medicine: collaborator

Study Sites (1)

Kilimanjaro Christian Medical Centre

Moshi, Tanzania

Location

Related Publications (5)

• 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. doi: 10.1016/s0035-9203(03)90125-8.

  PMID: 14584381 BACKGROUND

• 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. doi: 10.4038/cmj.v47i3.3434.

  PMID: 12449772 BACKGROUND

• Shah MP, Hwang J, Choi L, Lindblade KA, Kachur SP, Desai M. Mass drug administration for malaria. Cochrane Database Syst Rev. 2021 Sep 29;9(9):CD008846. doi: 10.1002/14651858.CD008846.pub3.

  PMID: 34585740 DERIVED

• Shekalaghe SA, Drakeley C, van den Bosch S, ter Braak R, van den Bijllaardt W, Mwanziva C, Semvua S, Masokoto A, Mosha F, Teelen K, Hermsen R, Okell L, Gosling R, Sauerwein R, Bousema T. A cluster-randomized trial of mass drug administration with a gametocytocidal drug combination to interrupt malaria transmission in a low endemic area in Tanzania. Malar J. 2011 Aug 24;10:247. doi: 10.1186/1475-2875-10-247.

  PMID: 21864343 DERIVED

• Shekalaghe SA, ter Braak R, Daou M, Kavishe R, van den Bijllaardt W, van den Bosch S, Koenderink JB, Luty AJ, Whitty CJ, Drakeley C, Sauerwein RW, Bousema T. In Tanzania, hemolysis after a single dose of primaquine coadministered with an artemisinin is not restricted to glucose-6-phosphate dehydrogenase-deficient (G6PD A-) individuals. Antimicrob Agents Chemother. 2010 May;54(5):1762-8. doi: 10.1128/AAC.01135-09. Epub 2010 Mar 1.

  PMID: 20194698 DERIVED

MeSH Terms

Conditions

Malaria, Falciparum

Interventions

fanasil, pyrimethamine drug combination; Artesunate

Condition Hierarchy (Ancestors)

Malaria; Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Sesquiterpenes; Terpenes; Hydrocarbons

Study Officials

• Seif Shekalaghe, MPH MD

  Kilimanjaro Christian Medical Centre

  PRINCIPAL INVESTIGATOR

• Robert Sauerwein, Prof MD PhD

  Radboud University Medical Center

  STUDY CHAIR

• Frank Mosha, PhD

  Kilimanjaro Christian Medical Centre

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: July 30, 2007
• First Posted: July 31, 2007
• Study Start: February 1, 2008
• Primary Completion: August 1, 2008
• Study Completion: August 1, 2008
• Last Updated: August 13, 2008

Record last verified: 2008-08

Locations

TA (1)