To date, the only reported human trials of asexual-stage malaria vaccines have been performed by Dr. Patarroyo and his colleagues in Colombia (Patarroyo et al., 1988). The vaccines were synthetic peptides based on studies in aotus monkeys (Patarroyo et al., 1987). All immunized subjects became clinically ill, but the infection in three of five volunteers receiving one of the vaccines was controlled without treatment, while all nonimmunized control subjects required treatment. This trial called for treatment only for individuals with more than 0.5 percent of their erythrocytes infected with parasites. No efficacy would have been demonstrated in this trial if a more conservative threshold for starting treatment had been used (see below). The mechanism of immunity, and the role of immune responses against the different antigens included in the vaccine, have not been established. Results of more recent clinical trials with this vaccine are not available for analysis.
Many of the same obstacles to the development of pre-erythrocytic vaccines are relevant to asexual blood-stage vaccines. Several additional impediments are worth mentioning.
Animal Models Animal models for vaccine challenge with P. falciparum and P. vivax are not optimal. Parasites often require extensive adaptation before they will grow in aotus monkeys, and splenectomy is required to get reproducible infections in saimiri monkeys. Further, there are only a few parasite isolates adapted to monkeys, making testing of antigenically diverse vaccine antigens difficult. Variation in the course of infection in control-group monkeys has made interpreting results difficult for vaccines that produce only partial protection. Despite its shortcomings, the aotus monkey model system remains the best available for simulating human P. falciparum infection.
Clinical Trials The outcome of a sporozoite vaccine trial is relatively simple to measure, since any appearance of parasites in the bloodstream signals failure. In contrast, an asexual-stage vaccine that controls parasite multiplication and protects against morbidity and mortality would be considered useful, even if it allowed moderate levels of parasitemia. Because the clinical effects of parasitemia vary with the immune status of the individual, determining when such a vaccine is effective is problematic. Trials performed in nonimmune volunteers, for example, may have to be terminated when only 0.05 percent of erythrocytes are infected. Parasitemia