Comparison of Two Strategies for the Delivery of IPTc
Condition: Malaria
MeSH terms: Malaria
Study type: Interventional
Phase: Phase 4

Summary: 
      Antimalarial chemoprophylaxis can reduce morbidity and mortality from malaria in children.
      However, this approach to malaria control has not been implemented widely because of concerns
      over its possible effect on the development of resistance and natural immunity. Intermittent
      preventive treatment (IPT) may be able to achieve some of the beneficial effects of
      chemoprophylaxis without its drawbacks. Recently, it has been shown that IPT given to
      Senegalese children under the age of five years on three occasions during the malaria
      transmission season reduced the incidence of clinical malaria by approximately 90%. However,
      it is uncertain how this intervention can be most effectively delivered. Therefore, 26
      Maternal and Child Health (MCH) trekking clinics in Upper River Division, south of the River
      Gambia, each with an average catchment population of 400-500 children under 5 years of age,
      will be randomly allocated to receive IPT from the MCH trekking team or from a IPT dispenser
      (village health worker, traditional birth attendant or a community mother based in a primary
      health care village). Treatment with a single dose of sulfadoxine /pyrimethamine (SP) plus
      three doses of amodiaquine will be given to all study subjects at monthly intervals on three
      occasions during the months of September, October and November. The primary end points will
      be the incidence of clinical attacks of malaria detected by passive case detection, and
      cost-effectiveness of the delivery methods. Important secondary endpoints will be the
      coverage and the equity of coverage of IPT in preventing malaria morbidity.
    

Detailed description: 
      3. OBJECTIVES

      The objective of this trial is to study the effectiveness and cost-effectiveness of two
      approaches to the administration of intermittent preventive treatment to Gambian children -
      distribution by village volunteers or through EPI trekking teams.

      5 STUDY DESIGN AND METHODOLOGY

      The unit of randomization will be the catchment population of the monthly EPI trekking
      clinics. There are 33 trekking clinics in total on the south bank of URD of which 27 are
      rural. The rural trekking clinics will be selected for randomization. 26 rural clusters (two
      will be merged to give an even number) will be stratified by health facility catchment area
      (Gambissara, Basse, Fatoto). Constrained randomization will be used to ensure balance within
      strata with regard to distribution of PHC key villages and population size.

      The bednet coverage in URD is estimated to 65%. However, during the enumeration, details of
      bed net usage by the community will be assessed. In collaboration with the malaria control
      programme, we will facilitate the provision of bed nets to households without one. At the
      beginning of the rainy season permethrin will be provided to all households with bednets.

      5.1 Malaria card

      After the enumeration has been completed, a database containing the list of eligible children
      will be established. The database will be used to generate the list of participating study
      children in each village. A record system using appropriate visual aids will be devised that
      can be used by an IPTc dispenser. This will consist of a "malaria card" held by the mother or
      guardian of each child and an IPT register held by IPTc dispenser or staff of the DHT
      trekking team. On the malaria card held by the mother, the compound number and study number
      will be written in Arabic and English, together with the child's name and the name of his or
      her parents. The dosage of trial medication to be given will be indicated on the malaria card
      and the register using coloured circles and semi-circles (full circle for one tablet and
      semi-circle for half a tablet). The register held by the IPTc dispenser or DHT staff will
      contain similar information to that on the malaria card.

      When a child presents to a health facility for medication, the DHT staff or the IPTc
      dispenser will examine the malaria card of the study subject. Medication will only be given
      to study subjects after correct identification and after matching the information on the
      malaria card held by the mother and that on the register held by the IPTc dispenser or the
      DHT. It is envisaged that the DHT staff and IPTc dispenser taking part in the study will be
      paid modest salary supplements for their contribution to the project. However, the details of
      payment will be discussed with the EPI unit and Basse DHT.

      5.2 Cross-section survey

      In December, at the end of the malaria transmission season, a cross-sectional survey of
      children less than 6yrs will be undertaken in all the 26 clusters. A questionnaire to
      determine asset rating and wealth index will be completed. Information on demographic, bed
      net usage, socio-economic status, health seeking behaviour and utilisation patterns profiles
      will be collected, a clinical history will be obtained and a physical examination will be
      performed, including abdominal palpation for splenomegaly and measurement of height, weight
      and axillary body temperature.

      5.3 Distribution of tablets

      5.3.1 Distribution of tablets in the villages

      Each key PHC village has a health post staffed by a community health nurse. There are 29 PHC
      villages and the majority of these have a village health worker and a traditional birth
      attendant. The three towns with basic health facilities (Basse, Fatoto and Gambisara) will be
      excluded from the evaluation, and the trial will focus on other communities in the study
      area. The trial medication will be administered by IPTc dispenser based in a PHC village. The
      IPTc dispenser will distribute the trial medication at a central point (usually a health
      post) on the first Wednesday of the month during September, October and November. Mothers and
      carers will be asked to bring their children to the central point during the morning when the
      IPTc dispenser will be available to distribute the drugs. When a child presents to the
      central point for medication, the IPTc dispenser will identify the study subject using the
      malaria card held by the mother and match the information on the malaria card with that on
      her register. When she is satisfied that she has correctly identify the study subject and
      that the information on the malaria card matches those on her register, the correct dosage of
      the trial medication will be given to the study subject.

      The first dose of treatment will be taken under direct supervision of the IPTc dispenser and
      she will mark her register and the malaria card to show that the child has received the
      tablets. The remaining two doses will be given to the mother or guardian of the child with
      clear instructions on how to administer the drugs.

      5.3.2 Distribution of tablets in the trekking clinics A member of the MCH trekking team
      (designated as an IPTc officer) of each of the 3 basic health facilities (Basse, Fatoto and
      Gambissara) will be identified by the EPI team and given responsibility for delivery of IPT
      at the trekking clinics, which are allocated by randomization to deliver IPTc. Thus, each EPI
      team will deliver IPTc in some of its trekking clinics but not in others.

      The dates of each monthly treatment will be written in Arabic and English on the "malaria
      cards". To ensure that children do not receive more doses of IPTc than they should, different
      coloured "malaria cards" will be issued to children in villages where children will receive
      their medication from IPTc dispenser and to those allocated to receive medication from the
      MCH trekking clinic. IPTc dispensers and IPTc officers will be taught how to give medication
      only to children who have the correct coloured cards.

      At the end of the malaria transmission season, the total number of complete treatment doses
      each child in the trial has taken will be recorded. Compliance will be checked on a rolling
      basis throughout the study by assessing the number of correct doses of medication received.
      In addition, urine samples will be collected from a random sample of 100 children each month
      in the two-week period following administration of IPTc to test for the presence of SP in the
      urine using Eggelte dipsticks.

      5.4 Morbidity surveillance during the rainy season

      Passive surveillance for malaria will be maintained throughout the transmission season.

      5.5 Surveillance for severe malaria

      Records will be kept of admission of study children to Basse and Fatoto Health Centres.
      Physicians and nurses based at these facilities will be asked to look out for any child with
      severe malaria, and any admission attributed to malaria will be carefully documented.

      5.6 Surveillance for overall and cause specific mortality

      Deaths will be investigated using postmortem questionnaire techniques and cause of death
      established wherever possible.

      5.7 Nested case control study

      To estimate the effect of inequalities in wealth on malaria morbidity and its prevention by
      intermittent treatment, -a nested case control approach will be used to determine
      distribution of malaria morbidity in relation to two measures of socioeconomic status - a
      wealth rating scale and an asset index.

      5.8 Study of cost-effectiveness

      A cost-effectiveness analysis will be undertaken from a societal perspective, meaning that
      all costs and effects, no matter to whom they accrue, will be measured and valued.

      5.8.1 Programme costs:

      The costs of the two modes of delivering IPTc will be assessed using the bottom-up or
      'ingredients' approach which involves the identification of all the resources required by the
      two modes of delivery.

      5.8.2 Resource savings:

      The modes of delivery will be compared with respect to the resource savings resulting from
      fewer children being treated for malaria related illnesses as a result of better IPTc
      coverage.

      5.8.3 Cost-effectiveness:

      For both modes of delivery, two cost-effectiveness ratios will be calculated: (i) cost per
      child who fully adheres to treatment; (ii) cost per case of malaria averted. In addition, net
      cost-effectiveness ratios will be calculated by subtracting resources saved from the total
      programme cost divided by the relevant outcome measure. The incidence of malaria and the
      costs will be compared between the two delivery arms and the cost per additional case averted
      calculated.

      5.9 Equity

      The impact of the different delivery strategies on alleviating (or exacerbating) three forms
      of equity will be measured. Equity outcomes and the cost of each delivery mode will also be
      compared using benefit-incidence analysis.

      5.9.1 Equality of utilization or adherence:

      To determine impact in terms of IPT coverage, levels of adherence will also be compared
      across the two delivery strategies; a cross-section survey will be used.

      5.9.2 Equality of access:

      Here we are measuring whether households have the same opportunity to benefit from each mode
      of delivery. This involves defining and measuring financial access, geographical access,
      informational access and cultural/gender barriers to access. Approximately 25 compliers and
      25 non-compliers from a sub-sample of 12 clusters will be interviewed about factors
      influencing access to each delivery strategy.

      5.9.3 Benefit-incidence-analysis:

      Utilization and access data for rich and poor households will be compared with the cost of
      providing the service. This will involve the use of benefit-incidence-analysis to analyze the
      impact of government expenditure on poverty.

      5.9.4 Cost-effectiveness data collection:

      Health service costing data including capital costs, consumables, salaries etc. will be
      collected by careful review of health facility records and through consultation with
      administration staff. Costs to the community will be collected using an interviewer
      administered questionnaire recently developed by a GMP PhD student.
    

Intervention name(s): sulfadoxine /pyrimethamine plus amodiaquine
Intervention type(s): Drug
Intervention MeSH terms: Pyrimethamine; Sulfadoxine; Amodiaquine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: malaria; prevention; intermittent; drugs