Immune Response to Infectious Diseases CHAPTER 17 after treatment begins. To avoid the side effects associated with PLASMODIUM LIFE CYCLE AND PATHOGENESIS the usual antibiotic therapy, many patients, once they feel OF MALARIA better,stop taking the medications long before the recom- Plasmodium progresses through a remarkable series of devel- mended treatment period is completed. Because briefer treat- opmental and maturational stages in its extremely complex ment may not eradicate organisms that are somewhat resistant life cycle. Female Anopheles mosquitoes, which feed on blood to the antibiotics, a multidrug-resistant strain can emerge. meals. serve as the vector for Plasmodium, and part of the Noncompliance with required treatment regimes, one of the parasite's life cycle takes place within the mosquito. (Because most troubling aspects of the large number of current tuber- male Anopheles mosquitoes feed on plant juices, they do not culosis cases, clearly compromises efforts to contain the spread transmit Plasmodium of the disease Human infection begins when sporozoites, one of the ated strain of M. bovis called BCG(Bacillus Calmette-Guerin). stream as an infected mosquito takes a blood meal(Figure The vaccine appears to provide fairly effective protectior 17-11). Within 30 min, the sporozoites disappear from the against extrapulmonary tuberculosis but has been inconsis tent against pulmonary tuberculosis In different studies, BCG has provided protection in anywhere from 0% to 80% of vac cinated individuals. in some cases. BCG vaccination has even increased the risk of infection moreover after bcg vaccina- tion the tuberculin skin test cannot be used as an effective monitor of exposure to M. tuberculosis. Because of the variable effectiveness of the BCG vaccine and the inability to monitor for exposure with the skin test after vaccination, this vaccine is not used in the United States. However, the alarming increase in multidrug-resistant strains has stimulated renewed efforts to develop a more effective tuberculosis vaccine. Liver Protozoan diseases Merozoites Protozoans are unicellular eukaryotic organisms. They are responsible for several serious diseases in humans, includ g amoebiasis, Chagas disease, African sleeping sickness, malaria, leishmaniasis, and toxoplasmosis. The type of im mune response that develops to protozoan infection and the effectiveness of the response depend in part on the location of the parasite within the host. Many protozoans have life-cycle stages in which they are free within the bloodstream, and it is during these stages that humoral antibody is most effective Many of these same pathogens are also capable of intracellular growth; during these stages, cell-mediated immune reactions effective in host defense. In the development of vaccines ft protozoan diseases, the branch of the immune system that is Gametocytes most likely to confer protection must be carefully considered. Malaria(Plasmodium Species)Infects 600 Million People Worldwide FIGURE 17-11 The life cycle of Plasmodium Sporozoites enter the Malaria is one of the most devastating diseases in the world bloodstream when an infected mosquito takes a blood meal. The today, infecting nearly 10% of the world population and sporozoites migrate to the liver, where they multiply, transforming causing 1-2 million deaths every year. Malaria is caused by liver hepatocytes into giant multinucleate schizonts, which release various species of the genus Plasmodium, of which P. falci- thousands of merozoites into the bloodstream. The merozoites in- parum is the most virulent and prevalent. The alarming fect red blood cells, which eventually rupture, releasing more mero development of multiple-drug resistance in Plasmodium and zoites. Eventually some of the merozoites differentiate into male and the increased resistance of its vector, the Anopheles mosquito, female gametocytes, which are ingested by a mosquito and differen- to ddt underscore the importance of developing new stra- tiate into gametes. The gametes fuse to form a zygote that differenti tegies to hinder the spread of malaria ates to the sporozoite stage within the salivary gland of the mosquitoafter treatment begins. To avoid the side effects associated with the usual antibiotic therapy, many patients, once they feel better, stop taking the medications long before the recom￾mended treatment period is completed. Because briefer treat￾ment may not eradicate organisms that are somewhat resistant to the antibiotics, a multidrug-resistant strain can emerge. Noncompliance with required treatment regimes, one of the most troubling aspects of the large number of current tuber￾culosis cases, clearly compromises efforts to contain the spread of the disease. Presently, the only vaccine for M. tuberculosis is an attenu￾ated strain of M. bovis called BCG (Bacillus Calmette-Guerin). The vaccine appears to provide fairly effective protection against extrapulmonary tuberculosis but has been inconsis￾tent against pulmonary tuberculosis. In different studies, BCG has provided protection in anywhere from 0% to 80% of vac￾cinated individuals; in some cases, BCG vaccination has even increased the risk of infection. Moreover, after BCG vaccina￾tion, the tuberculin skin test cannot be used as an effective monitor of exposure to M. tuberculosis. Because of the variable effectiveness of the BCG vaccine and the inability to monitor for exposure with the skin test after vaccination, this vaccine is not used in the United States. However, the alarming increase in multidrug-resistant strains has stimulated renewed efforts to develop a more effective tuberculosis vaccine. Protozoan Diseases Protozoans are unicellular eukaryotic organisms. They are responsible for several serious diseases in humans, includ￾ing amoebiasis, Chagas’ disease, African sleeping sickness, malaria, leishmaniasis, and toxoplasmosis. The type of im￾mune response that develops to protozoan infection and the effectiveness of the response depend in part on the location of the parasite within the host. Many protozoans have life-cycle stages in which they are free within the bloodstream, and it is during these stages that humoral antibody is most effective. Many of these same pathogens are also capable of intracellular growth; during these stages, cell-mediated immune reactions are effective in host defense. In the development of vaccines for protozoan diseases, the branch of the immune system that is most likely to confer protection must be carefully considered. Malaria (Plasmodium Species) Infects 600 Million People Worldwide Malaria is one of the most devastating diseases in the world today, infecting nearly 10% of the world population and causing 1–2 million deaths every year. Malaria is caused by various species of the genus Plasmodium, of which P. falci￾parum is the most virulent and prevalent. The alarming development of multiple-drug resistance in Plasmodium and the increased resistance of its vector, the Anopheles mosquito, to DDT underscore the importance of developing new stra￾tegies to hinder the spread of malaria. PLASMODIUM LIFE CYCLE AND PATHOGENESIS OF MALARIA Plasmodium progresses through a remarkable series of devel￾opmental and maturational stages in its extremely complex life cycle. Female Anopheles mosquitoes, which feed on blood meals, serve as the vector for Plasmodium, and part of the parasite’s life cycle takes place within the mosquito. (Because male Anopheles mosquitoes feed on plant juices, they do not transmit Plasmodium.) Human infection begins when sporozoites, one of the Plasmodium stages, are introduced into an individual’s blood￾stream as an infected mosquito takes a blood meal (Figure 17-11). Within 30 min, the sporozoites disappear from the Immune Response to Infectious Diseases CHAPTER 17 401 Sporozoites Liver Merozoites Gametocytes In mosquito gut RBC FIGURE 17-11 The life cycle of Plasmodium. Sporozoites enter the bloodstream when an infected mosquito takes a blood meal. The sporozoites migrate to the liver, where they multiply, transforming liver hepatocytes into giant multinucleate schizonts, which release thousands of merozoites into the bloodstream. The merozoites in￾fect red blood cells, which eventually rupture, releasing more mero￾zoites. Eventually some of the merozoites differentiate into male and female gametocytes, which are ingested by a mosquito and differen￾tiate into gametes. The gametes fuse to form a zygote that differenti￾ates to the sporozoite stage within the salivary gland of the mosquito