Immune responses to

Abstract

Malaria has a high toll on the lives of infants and children under the age of five in endemic areas. Control, and more recently, elimination agendas consist on implementing several measures simultaneously, including vector control, vaccines and drugs. The current Millenium Development Goals aim at reducing malaria mortality and morbidity in the two most vulnerable groups: pregnant women and children.

Intermittent Preventive Treatment in Infants with Sulphadoxine‐Pyrimethamine (IPTi-SP) delivered through routine EPI vaccination programs has shown to be efficacious in different transmission settings and the WHO has recently recommended its implementation as a malaria control tool. However, one of the main concerns has been the potential impairment of acquisition of naturally acquired immunity, and this could be a concern regarding IPTi.

This thesis reports on a series of studies conducted in a malaria endemic area of Manhiça, Mozambique, to assess the impact of IPTi‐SP on the development of immune responses to the Plasmodium falciparum parasite. In this work, we measured antibody and cellular immune parameters considered to be the most appropriate markers of protective immunity against malaria identified to date.

The most consistent finding was that IPTi-SP does not modify the magnitude of the immune responses acquired over the first two years of age in Mozambican children. In addition, we described the factors that affect the antibody and cellular immune responses, and reported those that correlated with prospective malaria incidence.

Based on the studies presented herein, we can conclude that IPTi‐SP does not interfere with immune responses that are considered major contributors to the acquisition of protective immunity to malaria in early infancy.

In summary, this thesis contributes to a more complete assessment of IPTi as a control measure that will possibly be implemented in the near future in malaria endemic areas of Africa and of the world. In addition, it aims to contribute to advance the knowledge on the acquisition of natural immunity in infancy which is poorly understood. Furthermore, this information will help to understand the factors that should be taken into account when designing and deploying other control measures for this age group.