The Power of Plagues. Irwin W. Sherman

pharaohs,” the hosts are humans and snails; and in sleeping sickness the hosts are tsetse flies, game animals, and humans. All parasites—whether they are large or small—cause harm to their host, though not all kill their host outright. This is because resistance may develop in any population of hosts and not every potential host will be infected—some individuals may be immune or not susceptible due to a genetic abnormality or the absence of some critical dietary factor (vitamin deficiency).

      To succeed in a hostile world where individual hosts are distinct and separate from one another, parasites need to disperse their offspring or infective stages to reach new hosts. To meet this requirement they produce lots of offspring, thereby increasing the odds that some of these will reach new hosts. It is a matter of numbers: more offspring will have a greater probability of reaching a host and setting up an infection. In this way the parasite enhances its chances for survival. Three cases will illustrate this: the red blood cell-destroying hookworms, malaria, and the white blood cell killer HIV.

      When a malaria-infected mosquito feeds, it injects with its saliva perhaps a dozen of the thousands of parasites that are present in its salivary glands. Each malaria parasite invades a liver cell, and after a week each produces up to 10,000 offspring; in turn, every one of these infects a red blood cell. Within the infected red blood cell, a malaria parasite produces 10 to 20 additional infective forms to continue the destructive process. In little more than 2 weeks a person infected by a single malaria parasite will have produced >100,000 parasites, and 2 days later the blood will contain millions of malaria parasites.

      Hookworms live attached to the lining of the small intestine, which they pierce with their razor-sharp teeth, allowing them to suck blood, as would a leech. Each female hookworm—no bigger than an eyelash—can live within the intestine for >10 years, producing each day >10,000 eggs. In her lifetime, this “Countess Dracula” can produce >36 million microscopic eggs.

      The AIDS-causing virus, HIV, is a spherical particle so small that if 250,000 were lined up they would hardly be 1 in. in length. Each virus, however, has an incredible capacity to reproduce itself. After it invades a specific kind of white blood cell (the T-helper lymphocyte), where it replicates, a million viruses will be produced in a few short days. To gain some appreciation of the high reproductive capacity of this virus, we might think of the infecting HIV as a person standing on a barren stretch of beach; if we were to return to this beach a few days later, we would find it jammed and overcrowded with millions—a population explosion.

      Any environment other than a living host is inimical to the health and welfare of the parasite. Some parasites have gotten around this with resistant stages such as spores, eggs, or cysts that enable them to move from one host to another in a fashion akin to “island hopping.” Hookworms, tapeworms, blood flukes, and pinworms have eggs that are able to survive outside the body; the microscopic cysts of the roundworm Trichinella are able to resist the ordinarily lethal effects of the acids in our stomach to cause trichinosis, and now we are all too familiar with the possibility of a bioterrorist attack from anthrax (p. 416), which has resistant spores that allow it to spread by inhalation of “anthrax dust.” The movement of a parasite from host to host—whether by direct or indirect means—is called transmission. When the transmission of parasites involves a living organism such as a fly, mosquito, tick, flea, louse, or snail, these “animate intermediaries” are called vectors. Transmission by a vector may be mechanical (e.g., the bite wound of a mosquito or fly) or developmental (e.g., parasites that grow and reproduce in snails in blood fluke disease, or in mosquitoes, as in malaria and yellow fever). Transmission of a parasite may also occur through contamination of eating utensils, drinking cups, food, needles, bedclothes, towels, or clothing, or in droplet secretions. In the 1976 outbreak of Legionnaires’ disease in Philadelphia, transmission was not from person to person but through a fine mist of water in the air conditioning system, whereas in the case of SARS (and influenza), transmission is from person to person via droplet secretions from the nose and mouth.

Parasites and their free-living relatives come in a variety of sizes, shapes, and kinds (species). Bacteria, 1 to 5 micrometers (µm) in size, are prokaryotes* that can be free-living or parasitic. They may assume several body forms: rods (bacilli), spheres (cocci), or spiral. Protozoa, 5 to 15 µm in size, are one-celled eukaryotes* that can lead an independent existence (such as the freshwater Amoeba sp.) or be parasitic (such as the Entamoeba sp. that causes amebic dysentery or the corkscrew-shaped trypanosomes that cause African sleeping sickness). Bacteria and protozoa are too small to be seen with the unaided eye. The technological advance—the microscope—perfected in the 1600s allowed for their discovery, and so they are called microparasites. The ultimate microparasite is a virus—a small piece of nucleic acid (RNA or DNA) enclosed within a protein coat. A virus has no cell membrane, no cytoplasm, and no organelles; and because it has no metabolic machinery of its own, it requires a living cell to make more virus. Viruses are <0.1 µm in size; they cannot be seen even with the light microscope, but only with the electron microscope, which can magnify objects >10,000 times. Viruses, such as the agents of SARS, AIDS, Zika, Ebola, yellow fever, and the flu, are neither cells nor organisms.

      Microparasites reproduce within their hosts and are sometimes referred to as infectious microbes, or, more commonly, “germs.” Larger parasites, ones that can be seen without the use of a microscope, are referred to as macroparasites; they are composed of many cells. Those that most often cause diseases of humans or domestic animals are roundworms, such as the hookworm; flatworms, such as the blood fluke; blood-sucking insects, such as mosquitoes, flies, and lice; or arachnids, such as ticks. Macroparasites do not multiply within an infected individual (except in the case of larval stages in the intermediate hosts) but instead produce infective stages that usually pass out of the body of one host before transmission to another host.

      “What’s in a name? That which we call a rose by any other name would smell as sweet.” When William Shakespeare penned these lines in Romeo and Juliet, he gave value to substance over name-calling. But being able to tell one microbe from another is more than having a proper name for a germ—it can have practical value. Imagine you have just returned from a trip and now suffer with a fever, headache, and joint pains, and worst of all you have a severe case of diarrhea. What a mess you are! When you see your physician, she tells you that the cause of your distress could be due to an infection with Salmonella or Giardia or Entamoeba or the influenza or SARS virus. Prescribing an antibiotic for diseases caused by a virus would do you no good, but for “food poisoning” caused by Salmonella, a bacterium, a course of antibiotic therapy might restore you to health. On the other hand, if your clinical symptoms were due to the presence of protozoan parasites such as Giardia or Entamoeba, they would not respond to antibiotics either, and other drugs would have to be prescribed to cure you. Determining the kind of parasite (or parasites) you harbor, therefore, will do more than provide the name of the offender; it will allow for the selective treatment of your illness.

      Plagues and Parasites

      In antiquity, all disease outbreaks, irrespective of their cause, were called plagues; the word “plague” comes from the Latin plaga, meaning “to strike a blow that wounds.” When a parasite invades a host, it establishes an infection and wounds the body (Fig. 1.2). Individuals who are infected and can spread the disease to others (such as SARS patient 4) are said to be contagious or infectious. Initially, Legionnaires’ disease and TSS were thought to be contagious. Despite the obvious clinical signs of coughing, nausea, vomiting, and diarrhea, however, a person-to-person-transmissible agent was not found. In short, the victims of TSS and Legionnaires’ disease were not infectious, in contrast to what we know in cases of influenza, SARS, and the common cold with a similar array of symptoms. Influenza and SARS are different kinds of diseases of the upper respiratory system: the flu is contagious 24 h before symptoms appear, has a short (2-to-4-day) incubation period, and requires hospitalization infrequently; whereas