Reducing the Effects of Malaria in Children by Administering Repeated Preventive Doses

Malaria Clinical Trial

Official title:

A Longitudinal Study Assessing the Infectious Status and Immunity of Mothers and Their Children in Lambaréné, Including Intermittent Treatment of Children With Sulfadoxine-pyrimethamine for Malaria Control and Its Impact on Long-term Health

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00167843
• Other study ID #: 28574
• Status: Completed
• Phase: Phase 4
• First received: September 11, 2005
• Last updated: January 23, 2013
• Start date: December 2002
• Est. completion date: March 2007

Study information

• Verified date: January 2013
• Source: Albert Schweitzer Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Gabon: Direction Générale de la Santé
• Study type: Interventional

Clinical Trial Summary

The general goal of the project is to assess the infectious status and immunity of mothers and children living in a malaria region. A major part of the study involves administering an effective antimalarial, sulfadoxine-pyrimethamine (Fansidar®), to children at the same timepoints as vaccinations, i.e. at age 3, 9 and 15 months. The main objective is to study safety, efficacy, and consequences of such a strategy in particular the ability to reduce the risk of anemia.

Description:

More than 1.5 million deaths of African children under 5 years of age are due to Plasmodium falciparum malaria. There is an urgent need for available and affordable strategies to control malaria morbidity in childhood.

Malaria control measures have been assessed for their potential to reduce intensity of infection in order to decrease the risk of malaria. It has been shown that malaria prevention using drugs is potentially capable to reduce malaria morbidity, school absenteeism, and all-cause mortality. However, prevention using drugs in the first years of life can also result in the loss or delay of acquired resistance which can lead to a rebound phenomenon (i.e. an increased risk of severe malaria after the therapy ended). In a recent study on intermittent treatment with Fansidar® at 2, 3, and 9 months of age, the number of malaria cases during the first 12 months of life was significantly reduced and no rebound effect was observed. This study has demonstrated that the intermittent administration of Fansidar® is safe and has beneficial effects for the children. However, the effectiveness decreased some months after discontinuing the drug. The promising effect of the intermittent administration of fansidar shown in this study needs to be confirmed in areas of different endemicity such as Lambaréné, Gabon. It is assumed that a more extended intermittent application of Fansidar® than performed in the above example would likely result in a longer period of protection from malaria, and the extended intermittent administration of Fansidar should not lead to rebound effects resulting in a higher occurrence of malaria.

The framework of this study offers a unique opportunity to study characteristics of infectious disease of importance in the Lambaréné area and the development of resistance against microbes at the maternofetal (mother/foetus) interface. Comparable studies will simultaneously take place in two associated study sites (Kumasi and Tamale) with different malaria endemicity in Ghana, West Africa.

Comparison: Comparison of malaria attacks in children with and without intermittent Fansidar® treatment with drug administration at months 3 and 9 (alongside with routine vaccinations delivered through child vaccination programme) and an additional administration at month 15.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1189
• Est. completion date: March 2007
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: N/A to 5 Months

Eligibility

Inclusion Criteria:

• Informed consent

• Permanent residence in the study area

Exclusion Criteria:

• Allergy/hypersensitivity to sulfonamides or pyrimethamine

• Signs of severe hepatic or renal dysfunction not due to malaria

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Malaria

Intervention

Drug:
• sulfadoxine-pyrimethamine

Locations

Country	Name	City	State
Gabon	Medical Research Unit of the Albert Schweitzer Hospital	Lambaréné	Moyen Ogooué

Sponsors (6)

Lead Sponsor	Collaborator
Albert Schweitzer Hospital	Bill and Melinda Gates Foundation, Bundesministerium fuer Bildung und Forschung (BMBF), Deutscher Akademischer Austausch Dienst, German Research Foundation, Medical Research Unit, Lambarene

Country where clinical trial is conducted

Gabon, 

References & Publications (6)

Bradley-Moore AM, Greenwood BM, Bradley AK, Bartlett A, Bidwell DE, Voller A, Kirkwood BR, Gilles HM. Malaria chemoprophylaxis with chloroquine in young Nigerian children. I. Its effect on mortality, morbidity and the prevalence of malaria. Ann Trop Med Parasitol. 1985 Dec;79(6):549-62. — View Citation

Diagne N, Rogier C, Sokhna CS, Tall A, Fontenille D, Roussilhon C, Spiegel A, Trape JF. Increased susceptibility to malaria during the early postpartum period. N Engl J Med. 2000 Aug 31;343(9):598-603. — View Citation

Greenwood BM, Greenwood AM, Bradley AK, Snow RW, Byass P, Hayes RJ, N'Jie AB. Comparison of two strategies for control of malaria within a primary health care programme in the Gambia. Lancet. 1988 May 21;1(8595):1121-7. — View Citation

Menendez C, Kahigwa E, Hirt R, Vounatsou P, Aponte JJ, Font F, Acosta CJ, Schellenberg DM, Galindo CM, Kimario J, Urassa H, Brabin B, Smith TA, Kitua AY, Tanner M, Alonso PL. Randomised placebo-controlled trial of iron supplementation and malaria chemoprophylaxis for prevention of severe anaemia and malaria in Tanzanian infants. Lancet. 1997 Sep 20;350(9081):844-50. — View Citation

Schellenberg D, Menendez C, Kahigwa E, Aponte J, Vidal J, Tanner M, Mshinda H, Alonso P. Intermittent treatment for malaria and anaemia control at time of routine vaccinations in Tanzanian infants: a randomised, placebo-controlled trial. Lancet. 2001 May 12;357(9267):1471-7. — View Citation

WHO. In WHO report: Fostering Development, Geneva, 1996

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy:
Primary	The proportion of children with at least one episode of anemia from 3 to 18 months of life
Primary	The proportion of children with at least one episode of malaria from 3 to 18 months of life
Primary	Safety:
Primary	The proportion of children with at least one episode of an adverse event
Primary	The proportion of children with at least one episode of a serious adverse event
Primary	Rebound:
Primary	The proportion of children with at least one episode of anemia from 18-30 months of life, the proportion of children with at least one episode of malaria from 18-30 months of life
Secondary	Proportion of children with at least one episode of severe anemia
Secondary	Proportion of hospitalized children with anemia
Secondary	Proportion of hospitalized children with malaria
Secondary	Proportion of hospitalized children with any disease
Secondary	Proportion of children with at least one episode of anemia from 3 to 12 months of life
Secondary	Proportion of children with at least one episode of malaria from 3 to 12 months of life.
Secondary	Parasite drug resistance after intermittent sulfadoxine-pyrimethamine and placebo application
Secondary	Multiplicity of P. falciparum infections after the intermittent treatment
Secondary	Antibody responses against variable parasite genes after the intermittent treatment
Secondary	Specific responses to malaria vaccine candidates during the study period

External Links

•   Homepage of IPTi consortium
•   Homepage of the Medical Research Unit of the Albert Schweitzer Hospital