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Cell‐mediated immunity and cytokines are probably involved in the pathogenesis of malaria. To investigate the role and the activity of different immune cells, we measured levels of tumour necrosis factor‐(TNF‐α), gamma interferon (IFN‐γ) and several interleukins (IL‐2, IL‐4, IL‐6 and IL‐10) in children with mild (MM) and cerebral (CM) Plasmodium falciparum malaria and compared them with those of healthy children from Guadalupe – Lobata District, St. Tomé Island, where malaria is mesoendemic. Both groups of patients had significantly higher levels of IL‐6, IL‐10 and TNF‐α than controls. For IL‐2, IL‐4 and IFN‐γ we found no difference between the groups. However, 24 h after admission the levels of IL‐10 and IL‐6 were significantly higher in CM than in MM patients, although 7 days after treatment they returned to normal levels, similar to those found in control children. Therefore, TNF‐α IL‐6 and IL‐10 increase during Plasmodium falciparum attacks in all children, not only in those with cerebral malaria. This finding suggests the activation of the monocyte/macrophage system during the early stage of clinical malaria.

Minutes after injection into the circulation, malaria sporozoites enter hepatocytes. The speed and specificity of the invasion process suggest that it is receptor mediated. The region II sequence of Plasmodium falciparum circumsporozoite (CS) protein includes a nonapeptide (WSPCSVTCG) which is highly conserved in all of the CS proteins sequenced to data, including the one from Plasmodium berghei. We have found that two peptides based on the P. falciparum region II sequence, P18 (EWSPCSVTCGNGIQVRIK) and P32 (IEQYLKKIKNS ISTEWSPCSVTCGNGIQVRIK), significantly inhibited P. berghei sporozoite invasion into Hep-G2 cells in vitro. This inhibition was enhanced if either peptide was preincubated with Hep-G2 cells prior to sporozoite invasion. We confirm that region II is a sporozoite ligand for the hepatocyte receptor; moreover, despite the few differences between P. falciparum and P. berghei region II sequences around the nonapeptide sequence (66% homology), the functional characteristics of the motif sequences are not affected. Since the conserved motifs represent a crucial sequence involved in Plasmodium sporozoite invasion of hepatocytes, antibodies to region II should inhibit sporozoite invasion into hepatocytes. Indeed, we found that polyclonal antibodies generated to the P. falciparum-based peptide P32 inhibited P. berghei sporozoite invasion of Hep-G2 cells. Furthermore, inbred mice (C57BL/6) immunized with P32 were protected against a lethal challenge of P. berghei sporozoites. Our results suggest that the conserved region II of the CS protein contains crucial Band T-cell epitopes, that such peptide sequences from the human malaria parasite P. falciparum can be screened in the P. berghei rodent model, and, finally, that region II can be considered useful as one of the components of a malaria vaccine.

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