A Complex Life

Malaria. Malaria infection occurs in over 30% of the world s population and almost exclusively in developing countries. Approximately 150 X 10 cases occur each year, with one million deaths occurring in African children (87). The majority of the disease in humans is caused by four different species of the malarial parasite. Vaccine development is problematic for several reasons. First, the parasites have a complex life cycle. They are spread by insect vectors and go through different stages and forms (intercellular and extracellular sexual and asexual) as they grow in the blood and tissues (primarily fiver) of their human hosts. In addition, malaria is difficult to grow in large quantities outside the natural host (88). Despite these difficulties, vaccine development has been pursued for many years. An overview of the state of the art is available (89). 

Trichinellosis is caused by the parasitic nematode Trichinella spiralis. This parasite has a complex life cycle that alternates between intestinal and muscle cell compartments of the host. This nematode infection is unusual because 7. spiralis is an intracellular parasite of mammalian cells. In addition, the broad host range of this parasite includes most mammals. The disease in humans has intrigued parasitologists, other biologists and public health workers for over a century (Cambell, 1983). The attraction to trichinellosis pardy stems from the debilitating and sometimes fatal effects that characterize this disease. 

To date, no effective vaccine has been developed for many parasites, notably the malaria-causing parasitic protozoa Plasmodium. One of the major difficulties in such instances is that parasites go through a complex life cycle, often spanning at least two different hosts. 

Figure 9.5 Malaria parasites have a complex life cycle, existing in many different forms between humans and mosquitoes. This offers a number of targets for drug design.

Plasmodia. Malaria parasites. These have a complex life cycle both in the mosquito and in the vertebrate host. Parasites in different stages of development, e.g. in the liver, in the red blood cell and the gametocytes which infect mosquitos, respond differently to drugs. 

The malaria parasite Plasmodium has a complex life cycle with several forms and spends much of its life hiding within red blood cells.1 It may also suppress the immune system. The unicellular sporozoites, which are injected into the bloodstream by mosquitos, are protected by an external coat protein that is unusual in containing many short repeated sequences. For example, that of P. falciparum, which causes the most deadly form of malaria, contains the sequence Asn-Ala-Asn-Pro repeated 37 times.q These coat proteins undergo unusually rapid evolution, which makes the preparation of vaccines difficult.1... 

Schistosomiasis (bilharziasis) (see also p. 292). The causative organisms are trema-todes with a complex life cycle that need (aquatic) snails as intermediate hosts. Free-swimming larval cercariae penetrate the intact skin of humans. The adult worms (Schistosoma mansoni, D) live in the venous vasculature. Occurrence tropical countries rich in aquatic habitats. About 200 million humans are af icted. Therapy praziquantel, 10-40 mg/kg, single dose, is highly effective with minimal adverse effects. Substances released from decaying worms may cause problems. 

A companion element to carbon, directly below it in the periodic table, is silicon. Silicon (Si) can also form long chains of linked silicon nuclei, and it also assumes a tetrahedral shape like carbon. But silicon does not readily form the double and triple bonds of carbon, so it does not appear to possess the versatility necessary for a complex life form, though some science fiction writers would have it otherwise. Still, silicon forms the basis for quartz, gemstones, and glass, which contribute to the beauty of life. 

Like salamanders, newts have a complex life cycle, the stages of which are egg, larva, and adult. Some species of newts can be distinguished from salamanders in that the newts have two distinct adult stages. 

Malaria parasites have a complex life cycle that permits drug action at several points. Plasmodium species that infect humans P falciparum, P malariae, P ovale, P vivax) tire spread by the female Anopheles mosquito and, after inoculation into the human host, undergo a primary developmental stage in the liver (primary tissue phase). They then enter the blood and parasitize erythrocytes (erythrocytic phase). P falciparum and P malariae have only one cycle of liver cell invasion thereafter, multiplication is confined to erythrocytes. The other species have a dormant hepatic stage (in which they become bypnozoites) that is responsible for recurrent infections and relapses after apparent recovery of the host from the initial infection. 

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