Can Treatment of Malaria be Restricted to Parasitologically Confirmed Malaria?

This study has been completed.
Sponsor:
Collaborator:
Institut de Médecine et d'Epidémiologie Appliquée - Fondation Internationale Léon M'Ba
Information provided by:
Institut de Recherche pour le Developpement
ClinicalTrials.gov Identifier:
NCT00913146
First received: June 3, 2009
Last updated: NA
Last verified: June 2009
History: No changes posted
  Purpose

The investigators performed a prospective study, in order to assess the feasibility and safety of restricting antimalarials to rapid diagnostic test (RDT)-confirmed cases in children aged 5 to 15 years-old


Condition
Malaria

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: Can Treatment of Malaria be Restricted to Parasitologically Confirmed Malaria? A School-Based Prospective, Exposed/Non Exposed to Fever, Study in Benin.

Resource links provided by NLM:


Further study details as provided by Institut de Recherche pour le Developpement:

Primary Outcome Measures:
  • malaria incidence in the 2 groups (index and control) [ Time Frame: after 14 days of follow-up ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • malaria incidence in children with a positive Plasmodium falciparum PCR at baseline [ Time Frame: after 14 days of follow-up ] [ Designated as safety issue: Yes ]

Biospecimen Retention:   Samples With DNA

whole blood dried on filter papers


Enrollment: 484
Study Start Date: February 2008
Study Completion Date: March 2009
Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)
Groups/Cohorts
index
child with fever and a negative malaria RDT
control
apparently healthy child with a negative RDT

  Hide Detailed Description

Detailed Description:

This study was designed to measure the incidence of malaria attacks during a 2-week follow-up period in 2 populations of patients. First, an index group (IG, exposed to fever) constituted by schoolchildren attending the school nursery for fever and not diagnosed malaria, based on a negative HRP2-based RDT. Second, a control group (CG, not exposed to fever) constituted of apparently healthy schoolchildren paired with index cases on gender, age, week of inclusion and malaria status (ie: negative HRP2-based RDT).

In a pragmatic purpose, the subjects were selected for inclusion if no malaria diagnosis was made by the means accessible to a clinician in routine practice, i.e., RDT and body temperature assessment. During the follow-up, malaria was defined as the association of fever and parasitemia, using any malaria diagnostic method, whatever its availability on the field: (blood smear and/or PCR).

Hence, the primary objective of the study was to show that applying the algorithm of management of fevers in the school setting is safe, in the way it does not lead to an excessive number of undiagnosed (and thus untreated) malaria attacks, by comparing the number of malaria attacks between the two groups (exposed and non exposed to fever).

The secondary objective was to compare malaria incidence between children at high risk for malaria during follow-up in the IG and CG respectively. Children at high risk for malaria in these 2 groups were defined by the detection of Plasmodium falciparum infection at enrollment, using the most sensitive diagnostic tool currently available (i.e., PCR). Based on data from the literature, we estimated to about 15% the proportion of children attending for fever with a negative RDT and a positive PCR for malaria, and we assumed this proportion to be roughly the same in apparently healthy children. Twenty-eight children at high risk for malaria in each group (corresponding to187 children in each group) are needed to detect an 8% difference in proportion between the 2 groups (α = 0.05 and β = 0.8). Assuming a maximum of 5% in the dropout rate, we aimed at including a minimum of 200 children in each group.

Study site: This study was performed from February through June 2008 in 4 schools, located at Allada, Southern-Benin, where malaria transmission is intense and perennial. Altogether, the 4 study schools received about 2600 schoolchildren of 5 years-old and above.

Conduct of the study: Ethical clearance was obtained from the Faculty of Medicine ethics committee, Benin National University, Cotonou. Children attended school nurseries on their own, or led by their parents/guardians. Care was provided for any child from a school participating to the study. Children from the IG were included and actively followed only if individual informed consent was obtained (within 24 hours from the initial visit) from a parent or guardian. Asymptomatic children were screened for the CG on gender, age, week of inclusion. The first child with a negative RDT and for whom an informed consent was obtained, was included in the CG. Asymptomatic children (screened for inclusion into the CG) and with a positive RDT were advised to quickly attend at the school nursery as soon as symptoms of malaria would appear. Children treated for malaria within the prior month were not included in either group.

All children were examined by a study nurse. Children with danger signs were referred to a health centre. Children attending the school nurseries were managed for fever only if fever was stated (tympanic temperature at 37.8°C or above) or if an history of fever in the preceding 24 hours was reported. For each schoolchild managed for fever, a RDT (Paracheck®, ORCHID Diagnostics) was performed and children were given artemether-lumefantrine (AL) if the RDT result was positive, according to national guidelines in this age group. At enrolment and during follow-up, medications with antimalarial activity for the treatment of non malarial illnesses were avoided when acceptable alternatives were available.

Follow-up visits were on day 3, 7 and 14. A blood smear and a blood spot were collected at enrolment and at each scheduled visit. An additional blood spot for pharmacological data was collected for 100 children in each group on day 0 and day 14. When fever was reported and/or stated at a follow-up visit, a RDT was performed.

We estimated the number of undiagnosed P falciparum malaria at enrolment, by taking into account both baseline data (all cases with P falciparum parasitemia >1000/µL) and follow-up data with fever with concomitant occurrence of at least one test (including PCR) positive for a P falciparum infection.

Laboratory analysis: RDTs were red by the study nurse, as recommended by manufacturer 15 minutes after it was performed. Microscopy examination was done retrospectively (patients were managed according to RDT results in terms of antimalarials prescriptions and IG or CG group assignment) and blinded to the patient's identity.

DNA was prepared from blood collected at day 0 and on the last day of follow-up, as well as at occurrence of fever during follow-up.

On day 0 and day 14 in the 100 first children from each group, whole blood was sampled on filter paper spots and dried at room temperature. Using these dried blood spot (DBS), chloroquine (and monodesethylchloroquine) and quinine were detected by high pressure liquid chromatography with UV detection to 254 nm using ammonium acetate (40 mM, pH =5.5)/acetonitrile (85/15 % v/v).

Statistics: Parametric tests (Pearson's chi-square and chi-square for the comparison of crude rates) and non-parametric (Fischer) tests were used. A logistic regression on PCR positivity at enrollment was performed, taking into account variables likely to influence the malarial status: gender, age, school, clinical status, declared bednet use.

  Eligibility

Ages Eligible for Study:   5 Years to 15 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

2600 schoolchildren of 5 years-old and above

Criteria

Inclusion Criteria in the index group:

  • School children aged 5 to 15 years.
  • Tympanic temperature at 37.8°C or above, or if a history of fever in the preceding 24 hours was reported.
  • A negative malaria (Paracheck® Plasmodium falciparum) RDT.
  • Informed consent.
  • Asymptomatic children were screened for the Control Group on gender, age, week of inclusion. The first child with a negative RDT and for whom an informed consent was obtained, was included in the CG.

Exclusion Criteria:

  • Adequate malaria treatment within a month prior screening.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00913146

Locations
Benin
Centre de Santé de Commune
Allada, Benin
Sponsors and Collaborators
Institut de Recherche pour le Developpement
Institut de Médecine et d'Epidémiologie Appliquée - Fondation Internationale Léon M'Ba
Investigators
Principal Investigator: Jean-François Faucher, MD, PhD IRD
  More Information

Publications:
Responsible Party: Jean-François Faucher, MD, Institut de Recherche pour le Developpement
ClinicalTrials.gov Identifier: NCT00913146     History of Changes
Other Study ID Numbers: IMEA5982FAU90
Study First Received: June 3, 2009
Last Updated: June 3, 2009
Health Authority: France: IRD

Keywords provided by Institut de Recherche pour le Developpement:
Management of fever
Malaria
Malaria rapid diagnostic test
Clinical trial

Additional relevant MeSH terms:
Malaria
Protozoan Infections
Parasitic Diseases

ClinicalTrials.gov processed this record on August 21, 2014