Clin. exp. Immunol. (1992) 89, 296-300
Severe malaria in Gambian children is not due to lack of previous exposure to malaria 0. A. ERUNKULU*, A. V. S. HILLt, D. P. KWIATKOWSKI*t, J. E. TODD*, J. IQBALt, K. BERZINSt, E. M. RILEY* & B. M. GREENWOOD* *Medical Research Council Laboratories, Banjul, The Gambia, tInstitute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK, and +Department of Immunology, University of Stockholm, Stockholm, Sweden (A ccepted for publication 23 March 1992)
SUMMARY The reasons why only a small proportion of African children infected with Plasmodiumfalciparum develop severe or fatal malaria are not known. One possible reason is that children who develop severe disease have had less previous exposure to malaria infection, and hence have less acquired immunity, than children who develop a mild clinical attack. To investigate this possibility we have measured titres of a wide range of anti-P. falciparum antibodies in plasma samples obtained from children with severe malaria, children with mild malaria and from children with other illnesses. Mean antibody levels in patients with malaria were higher than those in patients with other conditions but, with only one exception, there were no significant differences in antibody titres between cases of severe or mild malaria. A parasitized-erythrocyte agglutination assay was used to estimate the diversity of parasite isolates to which children had been exposed; plasma samples obtained from children with cerebral malaria recognized as many isolates as did samples obtained from children with mild disease. Our findings do not provide any support for the view that the development of severe malaria in a small proportion of African children infected with P. falciparum is due to lack of previous exposure to the infection. Keywords malaria African children
INTRODUCTION Plasmodiumfalciparum malaria remains a major cause of death among children in Africa. However, although malaria causes many deaths, severe disease or death is an unusual outcome of malaria infection in African children; perhaps only 2% of infections progress to severe disease. The reasons why some children, but not others, develop severe disease are not fully understood [1] but are important in regard to the development of rational strategies for reducing mortality from malaria. It is likely that the genetic characteristics of both the parasite and the host are important [2-4]. Another possibility is that children who develop severe malaria have had less previous exposure to the infection, and are thus less immune, than children who develop mild disease. We have investigated this possibility by comparing levels of antibodies to a variety of malaria antigens in Gambian children with severe or mild malaria infections. PATIENTS AND METHODS clnica maari whoattnde theMedcal Mostchidrenwit Research Council Hospital, Fajara, or the Royal Victoria Correspondence: Dr B. M. Greenwood, Medical Research Council Laboratories, P.O. Box 273, Banjul, The Gambia.
Hospital, Banjul, The Gambia, between the months of August and November 1988 were recruited into a study of risk factors for severe malaria [1]. Malaria was defined as a febrile illness accompanied by P. falciparum asexual stage parasitaemia for which no other cause could be found. Severe malaria was defined according to the criteria set out by the World Health Organization [5]. Nearly all patients with severe malaria had either cerebral malaria and/or severe anaemia. Cerebral malaria was defined as a coma score of less than 3 on a modified Glasgow a haemoglobin coma scale [6] and severe anaemia was defined an level of
Severe malaria in Gambian children is not due to lack of previous exposure to malaria 0. A. ERUNKULU*, A. V. S. HILLt, D. P. KWIATKOWSKI*t, J. E. TODD*, J. IQBALt, K. BERZINSt, E. M. RILEY* & B. M. GREENWOOD* *Medical Research Council Laboratories, Banjul, The Gambia, tInstitute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK, and +Department of Immunology, University of Stockholm, Stockholm, Sweden (A ccepted for publication 23 March 1992)
SUMMARY The reasons why only a small proportion of African children infected with Plasmodiumfalciparum develop severe or fatal malaria are not known. One possible reason is that children who develop severe disease have had less previous exposure to malaria infection, and hence have less acquired immunity, than children who develop a mild clinical attack. To investigate this possibility we have measured titres of a wide range of anti-P. falciparum antibodies in plasma samples obtained from children with severe malaria, children with mild malaria and from children with other illnesses. Mean antibody levels in patients with malaria were higher than those in patients with other conditions but, with only one exception, there were no significant differences in antibody titres between cases of severe or mild malaria. A parasitized-erythrocyte agglutination assay was used to estimate the diversity of parasite isolates to which children had been exposed; plasma samples obtained from children with cerebral malaria recognized as many isolates as did samples obtained from children with mild disease. Our findings do not provide any support for the view that the development of severe malaria in a small proportion of African children infected with P. falciparum is due to lack of previous exposure to the infection. Keywords malaria African children
INTRODUCTION Plasmodiumfalciparum malaria remains a major cause of death among children in Africa. However, although malaria causes many deaths, severe disease or death is an unusual outcome of malaria infection in African children; perhaps only 2% of infections progress to severe disease. The reasons why some children, but not others, develop severe disease are not fully understood [1] but are important in regard to the development of rational strategies for reducing mortality from malaria. It is likely that the genetic characteristics of both the parasite and the host are important [2-4]. Another possibility is that children who develop severe malaria have had less previous exposure to the infection, and are thus less immune, than children who develop mild disease. We have investigated this possibility by comparing levels of antibodies to a variety of malaria antigens in Gambian children with severe or mild malaria infections. PATIENTS AND METHODS clnica maari whoattnde theMedcal Mostchidrenwit Research Council Hospital, Fajara, or the Royal Victoria Correspondence: Dr B. M. Greenwood, Medical Research Council Laboratories, P.O. Box 273, Banjul, The Gambia.
Hospital, Banjul, The Gambia, between the months of August and November 1988 were recruited into a study of risk factors for severe malaria [1]. Malaria was defined as a febrile illness accompanied by P. falciparum asexual stage parasitaemia for which no other cause could be found. Severe malaria was defined according to the criteria set out by the World Health Organization [5]. Nearly all patients with severe malaria had either cerebral malaria and/or severe anaemia. Cerebral malaria was defined as a coma score of less than 3 on a modified Glasgow a haemoglobin coma scale [6] and severe anaemia was defined an level of
