Many of these drugs have side effects, referred to by physicians as adverse drug reactions, ADRs for short. The ADRs of most drugs are well known and well defined, based on the experience of thousands of people who took the drug during its clinical trials, and on the experience of everyone who took the drug once it was on the market. Although anyone can develop ADRs, for some reason ADRs are more common in people with HIV infection. For instance, trimethoprim-sulfamethoxazole (Bactrim or Septra) causes ADRs in 10 percent of the people without HIV infection and 50 percent of those with HIV infection.     ADRs are classified as either allergic or toxic. Allergic reactions mean that the cells of the immune system have recognized the drug as foreign and have responded by causing a rash, a fever, or both—like the rashes that penicillin causes in some people. In allergic reactions, the dose of the drug is unimportant: the immune system will respond similarly regardless of the dose. Serious allergic reactions often imply that neither that drug nor any related drugs should be taken again.     Toxic reactions are caused, not by the immune system, but directly by the drug itself. An example is the drowsiness caused by Dramamine or other antihistamines or the kidney damage and anemia caused by amphotericin B. Toxic reactions are usually dose-related; lowering the dose will relieve the symptoms.     People usually develop ADRs after they have been taking the drug for one or two weeks. Some people, however, will have a serious ADR after one dose; others will have no ADRs until after they have taken the drug for months or years; some develop ADRs after repeated courses of the same drug. Therefore, ADRs are unpredictable: because a drug was taken once and tolerated does not mean that it can be taken later and cause no ADR.     Sorting out and controlling ADRs will be done by a physician. The physician will either give the person with a suspected ADR what is called a drug holiday—discontinuation of all drugs—or will stop drugs one at a time, starting with those that are most likely to cause ADRs and those that are most dispensable.*180\191\2*

Alan Madison: I’m scared as hell at different periods. I have little sores on my skin, and my leg tingles. I’m going to be crazy until I see the doctor. I wake up at night and cry a little.     People fear what they do not understand and cannot control. Like Alan, they worry about symptoms that may or may not be serious. They fear being a patient in a hospital, or undergoing painful medical tests and procedures. They fear dependency: “My husband had a tremendous fear of being bedridden and me caring for him,” said Lisa. They fear rejection: Alan was afraid that people would treat him as though he had leprosy; Helen said she was fearful of telling her sons. People with HIV infection are afraid they will give someone else the virus. Caregivers fear contagion.     People with HIV fear what the infection might do to them: they fear becoming blind, or losing their cognitive abilities. They fear dying. They say they fear not death, but the way death comes. “I could handle dying,” said Alan, “if I knew how I might die. My biggest fear is what the end will be like.” When June goes with her son to the hospital, she feels fear: “It is hard for me to see his friends who are also in the hospital. I think, what’s the last time going to be like for him? It’s so frightening. You can drive yourself crazy thinking these things. And you’re also crazy if you don’t think these things. You are faced with that ultimate fear all the time.” People fear the future. All these fears are realistic responses to a situation that in fact includes the possibility of sickness, pain, dependency, rejection, and death.     Sometimes, however, people feel not fear, but anxiety. That is, they have feelings of fear that are unrealistic. People who are anxious say they feel as if something terrible were about to happen. They cannot say what exactly they fear, only that they have a sense of underlying uneasiness. They feel restless and uncomfortable wherever they are. They are irritable, tense, and preoccupied with their bodies. They have trouble breathing, are nauseated, break out into cold sweats, have racing pulses. Some have periods of feeling panicky.     People whose feelings of anxiety persist too long or are too severe should see a mental health professional or a doctor who might in turn recommend a visit to a psychiatrist. Persistent anxiety takes a tremendous amount of energy, and it is often curable. Psychiatrists can prescribe medication to relieve anxiety. Mental health professionals can teach techniques that help you relax. Physical relaxation usually makes people feel calmer and more themselves again.
*74\191\2*

Infectious causation of some acute diseases was recognized early in the 1800s as a result of conspicuous chains of transmission. The infectious nature of smallpox, measles, and chicken pox was recognized by medical experts and the general public decades before the microscope led Koch, Pasteur, and other early microbe hunters to the first cause-and-effect linkage of bacteria with disease during the 1870s and 1880s. Before the identification of microbes, the concept of infection was less tangible, and the distinction between infection (the invasion and growth of a disease-causing entity in the body) and contagion (the spread from one body to another) was often blurred. But infection was invoked to refer to diseases caused by something that grew inside people and could be transmitted to others to continue the process.
No special training was needed to witness the chains of transmission of many respiratory tract diseases, only a moderately observant eye. Parents noticing chicken pox in their child’s playmate would see chicken pox in their own child within a couple of weeks, and then chicken pox in another playmate within a couple of weeks after that. They wouldn’t have to be a Pasteur to realize that something was growing inside the bodies of their kids and being transferred from child to child. Though the viruses that caused these diseases were not seen with a microscope until the middle of the twentieth century, a half century after Pasteur, the medical texts before Pasteur’s time already had the causation and transmission right for these diseases. These texts had it wrong, however, for every other category of infectious disease.
At the end of the nineteenth century, after the microbe hunters of Pasteur’s time had observed some of the bacteria that cause diarrheal diseases, the writers of medical texts were still arguing about whether the bacteria caused the diarrheal diseases or were just innocent bystanders. The confusion can be seen in the standard American medical text of the 1880s, A Dictionary of Medicine. “Asiatic cholera” to be infectious, but transmission rather than infection was emphasized. “Simple cholera” was considered nontransmissible. This distinction probably arose because Snow’s work left little doubt that epidemic cholera—which could be traced to south Asia and was therefore termed Asiatic cholera—was waterborne. Snow deduced that the cause of the disease must be some organism that could multiply inside people, be shed in the feces, and be transmitted in fecally contaminated water and food. No one had done similar work on “simple cholera,” which probably included what are now recognized as several different diseases characterized by watery diarrhea. So those who favored noninfectious explanations for diarrheal disease could justify relinquishing only the epidemic cholera. The Dictionary noted the presence of the typhoid bacterium in typhoid patients but attributed typhoid fever to transmissible “typhoid poison” rather than transmission of the organisms themselves.
Why were acute diarrheal diseases recognized so much later than the acute diseases of the respiratory tract? A simple exercise can reveal part of the answer. When you go to work, school, or wherever you mingle, study the people next to you. Look and listen for signs of respiratory tract infection. If someone is infected with, say, one of the rhinoviruses that cause the common cold, you will have a good chance of detecting it. You may see or hear them sneeze. If they talk, you may hear the telltale muffling of nasal congestion. Then look and listen for signs of diarrheal disease. It’s not so easy. Other avenues of information are also restricted. Say you see a
not-so-close acquaintance who looks a little peaked and ask, “Feeling all right?” You might get the response, “Oh, I’ve got a cold.” But how many times have you heard “Oh, I’ve got diarrhea”? People prefer not to broadcast information about such matters. It tends to be reserved to very close friends and family. It is not surprising that infectious causation of diarrheal diseases, being reinforced by less evidence from common experience, was generally accepted later than infectious causation of acute respiratory tract diseases.
Infectious causation of diarrhea was probably also more difficult to recognize than infectious causation of respiratory tract diseases like chicken pox because many people who are infected with diarrheal pathogens show no symptoms at all. Diarrheal diseases also can be transmitted over long distances—for example, by fecally contaminated water. So if one is assessing whether diarrheal diseases are a result of something growing in a person and being transmitted to other people, one will often find seemingly contradictory information. If one chooses as a study subject someone who acquired an infection from an asymptomatic person or through the water supply, no direct contact with diarrhea may be apparent, no matter how careful and thorough the study.
Acceptance of infectious causation of vector-borne diseases was delayed for similar reasons. If a disease is transmitted by a mosquito, an observer might track down every contact of a sick person without turning up another person who has the disease. That is just what happened in a study of yellow fever in Barcelona. In 1822 the French government was still trying to learn the lessons of the Haitian revolution that had occurred two decades before. The Haitians were successful in large part because yellow fever killed thousands of French soldiers while leaving Haitians relatively unscathed. Wanting to figure out the problem before their next clash with yellow fever, the French government sent Nicholas Chervin to Barcelona to determine whether yellow fever was contagious. Chervin’s careful studies documented that many people who came down with yellow fever had no contact with anyone else who had yellow fever. He concluded, logically enough, that yellow fever was not transmissible between people. He did not consider other possibilities for long-distance transmission. If one does not entertain the full range of possibilities, one may miss the right answer. Infectious causation of vector-borne diseases remains obscure if one does not consider the possibility of vector-borne transmission. The Cuban epidemiologist Carlos Finlay did so six decades later, correctly implicating Aedes mosquitoes as the vector for yellow fever. Still, the idea of infectious causation of yellow fever was often rejected out of hand. In 1898, for example, an official bulletin of the U.S. Marine Hospital Service stated that “one has not to contend with an organism or germ which may be taken into the body with food or drinks but with an almost inexplicable poison so insidious in its approach and entrance that no trace is left behind.” When one isn’t on the right track, problems do seem inexplicable. Acceptance of yellow fever’s infectious cause finally occurred a few years later, after Walter Reed’s commission published the results of its experimental transmission of yellow fever to humans.
“Oh, I’ve got diarrhea” would be an unusual response to a casual “How are you?” but “Oh, I’ve got a venereal disease” may never have been given. That kind of information is withheld even from close friends and family—sometimes especially from close friends and family. One might try looking and listening for evidence of sexually transmitted infections among casual acquaintances, but as with diarrheal diseases, telltale signs are lacking. Sexual transmission also introduces a novel source of crypticity. Because few people have sex in public and most do not go around broadcasting their sexual activities, knowledge about who has had potentially transmissible contact with whom is lacking.
Not surprisingly, the infectious causation of sexually transmitted diseases was also recognized later than that of respiratory diseases. The Dictionary of Medicine attributed gonorrhea to causes such as too much physical disturbance of the genitalia by too much sex or masturbation. The presence of Neisseria gonorrheal which had been discovered five years earlier, was mentioned but was interpreted as possibly being that of an innocent bystander. Syphilis was referred to as “a specific contagious, noninfectious disease; communicable by contact of the poison with a breach of surface, or by hereditary transmission.”
*18\225\2*

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