Evaluation of the safety and effectiveness of EPI-linked
malaria intermittent chemotherapy and iron supplementation

Location           :Kassena-Nankana District of Northern Ghana

Investigators    :Chandramohan D, Brugha R, Shulman C, Greenwood B

On-site Investigators:Dr. K. Amponsa- Achiano (kamponsa-achiano@navrongo.mimcom.net)
                                 Dr. Rita Adomako-Bamfi (radomako-bamfi@navrongo.mimcom.net)

Collaboration     :London School of Tropical Medicine and Hygiene

Funding               :Department for International Development (DFID - UK)

Status              :On-going

Period Covered :2000-3

 Scientific summary

Anaemia is one of the main disease burdens of children in developing countries.  Severe anaemia is often fatal, while moderate anaemia leads to growth and cognitive disorders.  The incidence of anaemia in children is extremely high in malaria endemic areas since episodes of clinical malaria and asymptomatic parasitaemia result in red cell destruction.  It has been shown in Tanzania that the incidence of severe anaemia in infants can be reduced by 30% by regular administration of iron supplements and by 60% if regular malaria chemoprophylaxis is given in addition.  One way to operationalise this research finding, with minimal additional cost to governments and communities, is to link the distribution of iron and antimalarial drugs to the EPI programme. 

This is a community-randomised trial to study the effectiveness of intermittent iron supplements and malaria chemotherapy in reducing the incidence of anaemia and clinical malaria, and to investigate any possible interactions of iron and antimalarial drugs with EPI vaccines.  The study has two arms: children in both arms receive monthly supplies of twice weekly iron supplements when they attend EPI and growth monitoring clinics.  In addition, children in arm 1 receive a placebo when they receive Polio/DPT 1, Polio/DPT 3 and measles vaccines, while those in arm 2  receive sulfadoxine-pyremethamine (SP).  The baseline incidence of anaemia and malaria, and immune response to EPI vaccines has been estimated in a sample of children from a non-intervention area adjacent to the study area.

The immune response to EPI vaccines, drug side effects, and the incidence of anaemia and malaria will be compared between the two arms of the study and with the non-intervention area.  Any possible ‘rebound’ in malaria incidence due to impairment of immunity will be monitored and treated during the six months after stopping the chemotherapy and supplementation.

Outcome measures 

1. Comparison of mean Hb levels and the proportion of children having an Hb <7 g/dl at 12 and 18 months of age between the study groups and with the Hb levels in children in the non-intervention areas.

2. 2. Comparison of the incidence of clinical malaria [ (history of fever during previous 2 days or axillary temperature ³ 37.5°C) + parasitaemia]  reported through passive case detection systems in the comparison groups during the period of 3-12 months and 13-18 months of age.

3. Comparison of the incidence of moderately severe or severe malaria [(history of fever during previous 2 days or axillary temperature ³ 37.5°C)+ parasitaemia + (unable to drink or very sleepy or unconscious or Hb<5 g/dl)] reported through passive case detection systems during the period of 3-12 months and 13-18 months of age.

4. Comparison of the sero conversion rates for polio and DPT at 9 months (four months after the 3rd dose of the vaccines) and for measles at 12 months (3 months after vaccination) between the two study groups.

5. Determination of the incidence of accidental ingestion of drugs.

6. Description of the characteristics of children who defaulted attending EPI-growth monitoring clinic at 2, 4,9 and 12 months of age.

Person to whom correspondence should be addressed

Chandramohan Daniel Dr.

Clinical Lecturer, Department of Infectious and Tropical Diseases, LSHTM

Keppel Street, London WC1E 7HT

Tele: 0171 927 2322; Fax: 0171 580 9075;

email: dchandra@lshtm.ac.uk