Transmission-blocking vaccines: uses and current status of development.

Malaria continues to cause incomprehensible human suffering throughout most of the tropics and subtropics: in sub-Saharan Africa it is estimated that 2 million children die each year as a direct cause of infection with Plasmodium. Vector control and malaria chemotherapy that were previously effective in controlling and treating malaria are now largely ineffective due to insecticide-resistant mosquitoes and drug-resistant parasites. As alternatives to these mainstays of control, an intensive effort to develop subunit vaccines targeted at various stages of the life has been undertaken. One such vaccine, directed against the sexual and sporogonic stages and referred to as a transmission-blocking vaccine, offers the hope of controlling malaria in geographically isolated areas, preventing re-introduction of the parasite in malaria-free zones, blocking the spread of drug-resistant or vaccine escape mutants, and reducing exposure to "virulent" strains of parasites. A series of potential transmission-blocking vaccine candidates have identified and the genes encoding these surface proteins have now been isolated and sequenced. One such vaccine candidate, Pfs25, is now being tested in human Phase I safety and immunogenicity studies. Here the use and status of transmission-blocking vaccines are reviewed.