Failure to respond to the surface of Plasmodium falciparum infected erythrocytes predicts susceptibility to clinical malaria amongst African children.

Following infection with Plasmodium falciparum malaria, children in endemic areas develop antibodies specific to antigens on the parasite-infected red cell surface of the infecting isolate, antibodies associated with protection against subsequent infection with that isolate. In some circumstances induction of antibodies to heterologous parasite isolates also occurs and this has been suggested as evidence for cross-reactivity of responses against the erythrocyte surface. The role of these relatively cross-reactive antibodies in protection from clinical malaria is currently unknown. We studied the incidence of clinical malaria amongst children living on the coast of Kenya through one high transmission season. By categorising individuals according to their pre-season parasite status and antibody response to the surface of erythrocytes infected with four parasite isolates we were able to identify a group of children, those who failed to make a concomitant antibody response in the presence of an asymptomatic parasitaemia, at increased susceptibility to clinical malaria in the subsequent 6 months. The fact that this susceptible group was identified regardless of the parasite isolate tested infers a cross-reactive or conserved target is present on the surface of infected erythrocytes. Identification of this target will significantly aid understanding of naturally acquired immunity to clinical malaria amongst children in endemic areas.

Simulation model for dental arch shapes.

OBJECTIVE: To develop a simulation model for dental arch shapes. DESIGN: Analysis of measurements of dental casts to determine a general second degree equation for the dental arches. SETTING: Department of Human Anatomy and School of Computing and Informatics, University of Nairobi. SUBJECTS: The measurement of dental casts, 30 (15M and 15F) each from three Kenyan ethnic groups (Maasai, Kalenjin, Kikuyu), aged 12 years. RESULTS: The arches change their shapes from a parabola to an ellipse, governed by the boundary conditions at the position of the canine tooth, based on the general second degree equation for the conic sections. CONCLUSION: The simulation model graphically confirms the change from parabolic to elliptic shapes of dental arches with boundary conditions at the canine. This could be used to show the changes in dental arches for other ethnic groups.

The antimalarial triazine WR99210 and the prodrug PS-15: folate reversal of in vitro activity against Plasmodium falciparum and a non-antifolate mode of action of the prodrug.

We have studied the reversal of activity against Plasmodium falciparum of WR99210, a triazine antimalarial drug, and of the pro-drug PS-15 by folic acid (FA) and folinic acid (FNA). Folic acid and FNA inhibit the growth of P. falciparum in vitro at concentrations > 10(-4.5) and 10(-3.5) mol/L, respectively. The activity of pyrimethamine against Kenyan strains M24 and K39 is reduced 10-12-fold by 10(-5) mol/L of FA, and virtually eliminated by 10(-5) mol/L of FNA. Folates do not antagonise the action of WR99210 against Kenyan strains, and only partially antagonize the action of WR99210 action against the Southeast Asian strains V1/S and W282. Similarly, FA and FNA exerted weak or no antagonism of the action of PS-15. The inability of folates to antagonize the action of WR99210 can be explained in terms of high drug-enzyme affinity, but this does not account for the inability of FA and FNA to antagonize PS-15. These results suggest that action of PS-15 against P. falciparum is primarily due to a non-folate mechanism.

Antimalarial activity in crude extracts of Malawian medicinal plants.

Aqueous and organic fractions from Cassia abbreviata, Senna petersiana (both Caesalpiniaceae) and Azanza garckeana (Malvaceae) were tested for in-vitro antimalarial activity against the multi-drug-resistant, Vietnam-Smith strain of Plasmodium falciparum; VI/S. Both roots and leaves from these Malawian medicinal plants were investigated. High activity, with a median inhibitory concentration < 3 micrograms/ml, was seen in the organic fractions of C. abbreviata and S. petersiana, the two species most commonly cited by traditional healers in an ethnobotanical investigation of Malawian antimalarials. Extracts of A. garckeana showed weaker activity. Biologically active compounds have thus been detected within species of the family Caesalpiniaceae. Ethnobotanical investigation appears to be useful in identifying plants with antimalarial activity.