Abstract. We have developed a typing system using natural sequence variation in the thrombospondin-related adhesive protein (TRAP) gene of Plasmodium falciparum. This method permits a haplotype to be assigned to any particular TRAP gene. We have applied this method to a hospital-based, case control-study in Mali. Previous sequence variation and conservation in TRAP has been confirmed. Particular TRAP haplotypes can be used as geographic hallmarks. Because of the high level of conflict between characters, we have examined the phylogenetic relationships between parasites using a network approach. Having received patient samples from urban and periurban areas of Bamako, the majority of haplotypes were closely related and distinct from TRAP sequences present in other continents. This suggests that the structure of TRAP can only tolerate a limited number of sequence variations to preserve its function but that this is sufficient to allow the parasite to evade the host's immune system until a long-lived immune response can be maintained. It may also reflect host genetics in that certain variants may escape the host immune response more efficiently than others. For vaccine design, sequences from the major regional variants may need to be considered in the production of effective subunit vaccines.The thrombospondin-related adhesive protein (TRAP) gene of Plasmodium falciparum was first described in 1988. 1 The gene derives its name from the deduced protein sequence that contains two amino acid motifs found in the adhesive host glycoprotein thrombospondin. 2 One of these motifs is based on the amino acid sequence Glu-Trp-Ser-ProCys-Ser-Val-Thr-Cys-Gly-Lys-Gly-Thr-Arg-Ser-Arg-LysArg, which has been demonstrated to allow TRAP to bind to sulfatide. 3 The protein is present in sporozoites and erythrocytic-stage parasites. 4, 5 Antibodies against TRAP inhibit sporozoite invasion. 3 Recent data demonstrate that TRAP is expressed in mature, salivary gland sporozoites but not in hemocoel sporozoites, suggesting that TRAP may be one of the unidentified accessory molecules required for infection of the vertebrate host. 6 Data from a longitudinal and prospective study showed that the immune response to TRAP is long-lived in adults and older children but short-lived in young children. 7 There were seasonal fluctuations of the levels of specific antibodies, as well as age-dependent quantitative differences. 7 These data, together with that for the TRAP homolog sporozoite surface protein 2 (SSP2) from P. yoelii, suggesting that adoptive transfer of a CD8 ϩ cytotoxic T cell clone recognizing SSP2 gave complete protection against P. yoelii infection, suggest that TRAP would be an important component of a multi-subunit malaria vaccine. 8 Further evidence for this has been the identification of a cytotoxic T lymphocyte response to certain conserved epitopes in TRAP. 9,10 A major problem in the design of any malaria vaccine is which antigens to choose and which variants of these antigens are relevant. We have previously shown that TRAP is ...
Neonatal mortality remains very high in Mali. Health authorities should take measures to decentralize the care of sick newborns in order to reduce neonatal mortality in Mali.
Approximately one million newborn babies die every year as a result of birth asphyxia in developing countries. The objectives of this study are to develop the management of birth asphyxia and to establish a community-based surveillance system of vital events in rural areas of Oueléssébougou, Mali. Traditional birth attendants, female leaders of village associations and village health workers were trained to carry out communication activities designed to change behaviours in the management of birth asphyxia. The study has improved health facility-based delivery (from 80 to 93%) and the identification of birth asphyxia (11 to 12% new born babies have been resuscitated). As a result of training and supervising community actors, the quality of delivery is improved and neonatal mortality is reduced.
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