Effectiveness of Intermittent Preventive Treatment for Malaria in Children
Condition: Malaria
MeSH terms: Malaria
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      Intermittent preventive treatment for malaria in children (IPTc) is a promising new approach
      to malaria control. Preliminary studies of IPTc in Senegal and Mali indicate that this
      approach can be very effective. Although the results of these studies suggest that IPTc with
      sulphadoxine-pyrimethamine (SP) plus artesunate (AS) or SP alone is an efficacious and safe
      intervention for reducing the burden of malaria and anaemia in children in high transmission
      areas with short transmission periods, there is no data from areas with long transmission
      periods. This study aims to evaluate the effectiveness of IPTc in reducing anaemia and
      malaria in an area with up to 6 months of transmission in Ghana. Two thousand two hundred
      forty children aged 3-59 months will be randomly allocated to four groups (560 per arm) to
      receive amodiaquine plus artesunate (AQ+AS), given at two different intervals (monthly or
      bimonthly), SP or placebo. The children will also be followed to determine if there is any
      rebound in the incidence of severe malaria and anaemia in the year following IPTc.
    

Detailed description: 
      Background:

      In high transmission areas, where a major proportion of deaths and severe morbidity from
      malaria occurs during the first year of life, intermittent preventive treatment for infants
      (IPTi) could make a major contribution to reducing the burden of malaria as a whole. However,
      in many areas in Africa, where mortality and morbidity from malaria in children under five
      years of age is very high and the burden of malaria is not predominantly in infants, IPTi,
      even if highly effective, would have only a limited impact on the overall burden of malaria
      in children.

      Few community trials have evaluated the effect of IPTc in the prevention of malaria. Dicko
      and his colleagues in Mali, an area of seasonal malaria transmission gave two doses of SP to
      children aged 6 months to 9 years at an interval of two months and found a protective
      efficacy of 40% against clinical attacks of malaria among children in the intervention group
      compared to the placebo group. Recent work in Niakhar, Senegal has assessed IPTc in an area
      of intense but short seasonal malaria transmission. The study used a combination of SP plus
      one dose of AS, which was given every month for three months during the rainy season which
      lasted for only four months. This study showed that IPTc using AS+SP was well tolerated
      without any drug-attributable adverse events and that IPTc can reduce the incidence of
      clinical malaria by 86%. Although these results suggest that IPTc with SP+one dose of AS is
      an efficacious and safe intervention for reducing the burden of malaria and anaemia in
      children, there is no data on the effectiveness of IPTc in areas with prolonged transmission
      seasons and on the use of other forms of combination therapy in IPTc.

      Study overview:

      The study aims to determine the optimum drug schedule for IPTc in an area of prolonged
      seasonal malaria transmission in Ghana. The main study will compare the effectiveness of IPTC
      using SP, monthly AQ+AS or bimonthly AQ+AS. In order to facilitate the interpretation of the
      results of this trial, two ancillary studies will be done. The first will be a conventional
      in vivo drug efficacy study of SP and AQ+AS in children with clinical malaria to ensure the
      efficacy of the drugs used in the IPTc trial within the study area. The second subsidiary
      study will be an investigation of whether or not administration of IPTc over one malaria
      transmission season is followed by an increase in the incidence of malaria or anaemia during
      the following malaria transmission season.

      Study Objectives:

        1. To investigate whether IPTc using monthly or bimonthly AQ+AS or SP can improve mean Hb
           level and decrease anaemia and malaria morbidity in young children in an area of intense
           and prolonged seasonal malaria transmission.

        2. To compare the incidence of severe malaria among children aged 3-59 months using the
           three treatment regimens.

      Study area:

      The study will be carried out in Hohoe district, Ghana. The major rainy season lasts from
      April to July and the minor one from September to November. The rest of the year is
      relatively dry. Malaria is the most common disease in this area. For the past four years
      malaria has accounted for 32% of the out patient attendances out of which 45% were children
      under five years. Twenty five percent (25%) of malaria cases required inpatient care and 37%
      of the cases were children under five years and 57% of them reported with anaemia. The peak
      of OPD malaria and anaemia cases occurs between June and October.

      Study procedures:

      A cross-sectional survey will be carried out after informed consent has been obtained from
      the guardians of all children aged between 3 to 59 months in the selected villages.
      Information will be collected on the background of the child and guardian, hypersensitivity
      to the study drugs and bednet use. Anthropometric indices will be measured.

      Drugs will be administered to the study children every month from May to October. Field
      workers and coordinators will visit the participants once a week from May to October. Parents
      and guardians will be strongly advised to come directly to a health centre if their child
      develops any symptoms or signs of illness between the field workers' weekly home-visits.
      Passive surveillance will be performed by six medical assistants and twelve nurses based in
      the health centres in the sub-districts within the district. Malaria clinical attacks will be
      documented and treatment for malaria and any other illness will be provided free of charge to
      study participants in all the health centres that are in the catchment area of the selected
      communities.

      If the child has fever or any features suggestive of malaria, a finger prick blood sample
      will be collected for Hb and malaria parasite detection. Two slides will be prepared for each
      child. At the health centre, one slide will be examined on the same day for deciding on
      appropriate treatment. The second slide will be kept and sent to the central laboratory for
      reading to provide a definitive diagnosis. Those who have malaria will be treated with oral
      quinine 10mg/kg every 8 hours for 7days and will be followed on days 3 and 7 for outcome
      measurement.

      At the end of the malaria transmission season, a cross-sectional survey will be undertaken
      involving all children who have remained in the study. Following administration of a short
      questionnaire, a finger prick blood sample will be obtained for preparation of a blood film
      and for determination of Hb. A filter paper sample will be collected for molecular studies.
    

Intervention name(s): artesunate-amodiaquine; sulphadoxine-pyrimethamine
Intervention type(s): Drug; Drug
Intervention MeSH terms: Artesunate; Pyrimethamine; Sulfadoxine; Fanasil, pyrimethamine drug combination; Amodiaquine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary purpose: Prevention
Keywords: intermittent preventive treatment; effectiveness; malaria