Methods in Infectious Disease Epidemiology
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1 P A R T Methods in Infectious Disease Epidemiology 1 95337_CH01_001–018.indd 1 2/1/13 11:56 PM 95337_CH01_001–018.indd 2 2/1/13 11:56 PM CHAPTER 1 Early History of Infectious Disease: Epidemiology and Control of Infectious Diseases Kenrad E. Nelson and Carolyn Masters Williams INTRODUCTION wrong theories or knowledge has hindered advances in understanding, one can also cite examples of Epidemics of infectious diseases have been docu- great creativity when scientists have successfully mented throughout history. In ancient Greece and pursued their theories beyond the knowledge of Egypt, accounts describe epidemics of smallpox, the time. leprosy, tuberculosis, meningococcal infections, and diphtheria. 1 The morbidity and mortality of in- fectious diseases profoundly shaped politics, com- THE ERA OF PLAGUES merce, and culture. In epidemics, no one was spared. Smallpox likely disfigured and killed Ramses V in The sheer magnitude and mortality of early epidemics 1157 BCE, although his mummy has a significant are difficult to imagine. Medicine and religion both head wound as well. 2 At times, political upheavals strove to console the sick and dying. However, before exacerbated the spread of disease. The Spartan wars advances in the underlying science of health, medi- caused massive dislocation of Greeks into Athens, cine lacked effective tools, and religious explana tions triggering the epidemic of 430–427 BCE that killed for disease dominated. As early communities con- up to half of the population of ancient Athens. 3 solidated people more closely, severe epidemics of Thucydides’ vivid descriptions of this epidemic make plague, smallpox, and syphilis occurred. clear its political and cultural impact, and provide The bubonic plague and its coinfections, measles valuable clinical details of the epidemic. 4 Several and smallpox, were the most devastating of the modern epidemiologists have speculated about the epidemic diseases. In 160 CE plague contributed to causative agent. Langmuir et al. 5 favor an influenza the collapse of the Han Empire, 8 and six years later the and toxin-producing Staphylococcus epidemic, Roman Empire was ravaged by the Antonine Plague while Morrens and Chu suggest Rift Valley fever. 6 (165–180 CE), which likely killed both coemperors A third researcher, Holladay believes the causative Lucius Verus (130–169 CE) and Marcus Aurelius agent no longer exists. 7 (121–180 CE) along with 5 million others. 9,10 Plague From the earliest times, humans have sought and other communicable diseases flourished in the to understand the natural forces and risk factors cities of the Roman Empire and surely contributed affecting the patterns of illness and death in society. to its final demise. 11 The devastating Justinian These theories have evolved as our understanding plague (541 CE) was caused by a distinct strain of of the natural world has advanced—sometimes Yersinia pestis. This epidemic killed approximately slowly; sometimes, when there are profound 40% of Constantinople and heralded the end of the breakthroughs, with incredible speed. Remarkably, second plague era. From 700 CE until the massive advances in knowledge and changes in theory have epidemics of the 14th century, bubonic plague not always proceeded in synchrony. Although was much less common. However, the plague—or 3 95337_CH01_001–018.indd 3 2/1/13 11:56 PM 4 CHAPTER 1 EARLY HISTORY OF INFECTIOUS DISEASE: EPIDEMIOLOGY AND CONTROL OF INFECTIOUS DISEASES Black Death, as it was then called—struck again in the 1490s as a highly contagious venereal disease in 1345 and swept across Europe. Starting in the in Spain, Italy, and France. By the 1530s, the vene- lower Volga, it spread to Italy and Egypt in 1347 on real spread of this infection was widely recognized merchant ships carrying rats and fleas infected with the in Europe. 18 The name syphilis originated from the plague bacillus, Yersinia pestis .1 During the next five popular, and extremely long, poem by Girolamo years (1347–1351), the Black Death killed 3 Europeans Fracastoro “Syphilis sive morbus Gallicus.” Written out of 10, leaving 24 million Europeans dead and in 1546, the poem recounts the causes of disease and causing a total of 40 million deaths worldwide. 1,12–14 the origin and treatment of syphilis. 12,18 Fracastoro These waves of bubonic plague fundamentally describes the legend of a handsome young shepherd affected the development of civilizations as well as named Syphilis, who, because of an insult to the imposed a genetic bottleneck on those populations god Apollo, was punished with a terrible disease, exposed to the pathogen. In fact, Europeans may be “the French Disease”—or syphilis. The origins of able to attribute their lower susceptibility to leprosy venereal syphilis are debated. One theory proposes and human immunodeficiency virus (HIV) to the that it began as a tropical disease transmitted by selective pressure of bubonic plague. 15 To survive direct (nonsexual) contact. 18 In support of this theory, in an ancient city was no small immunologic feat— the causative organism, Treponema pallidum, was and populations that had the immunologic fortitude isolated from patients with endemic (nonvenereal) had an advantage over others when exploration syphilis (bejel) and yaws. After the first accounts of and colonization brought them and their pathogens syphilis appeared, it was reported to spread rapidly together. 11 through Europe and then North America. In keeping The first recorded epidemic of smallpox was with the hypothesis that syphilis was a recently in 1350 BCE, during the Egyptian–Hittite war. 1 emerged disease, mortality from syphilis was high in In addition to Ramses V, typical smallpox scars these early epidemics. 11 have been seen on the faces of mummies from the time of the 18th and 20th Egyptian dynasties (1570–1085 BCE). Smallpox was disseminated dur- EARLY EPIDEMIOLOGY ing the Arabian expansion, the Crusades, the dis- covery of the West Indies, and the colonization of In Western medicine, Hippocrates (460–377 BCE) the Americas. Mortality ranged from 10% to 50% was among the first to record his theories on the in many epidemics. The disease apparently was un- occurrence of disease. In his treatise Airs, Water known in the New World prior to the appearance and Places , Hippocrates dismissed supernatural of the Spanish and Portuguese conquistadors. Cortez explanations of disease and instead attributed illness was routed in battle in 1520 but ultimately proved to characteristics of the climate, soil, water, mode victorious as smallpox killed more than 25% of of life, and nutrition surrounding the patient. 2,19–21 the Aztecs over the next year. 8 Mortality rates of It is Hippocrates who coined the terms endemic and 60–90% were described by the Spanish priest Fray epidemic disease to differentiate those diseases that Toribio Motolinia. He reported that 1000 persons are always present in a population (endemic) from per day died in Tlaxcala, with ultimately 150,000 those that are not always present but sometimes total dead. 16 Smallpox then traveled north across occur in large numbers (epidemic). It was Claudius the Americas, devastating the previously unexposed Galen (131–201 CE), however, who codified the Native American populations. 11 Hippocratic theories in his writings. Galen combined At that time, there was a reasonable under- his practical experience caring for gladiators with standing of the epidemiology of smallpox trans- experiments, including vivisections of animals, to mission. At the least, it was appreciated that the study the anatomy and physiology of humans. 22 skin lesions and scabs could transmit the disease. His voluminous writings carried both his correct Survivors of the infection were recognized as be- and incorrect views into the Middle Ages. It was ing immune to reinfection after further exposure. more than 1000 years before Andreas Vesalius The practice of inoculation, or variolation, whereby (1514–1564), who based his work on dissections people were intentionally exposed to smallpox of humans, was able to correct Galen’s errors in was practiced in China, Africa, and India centuries anatomy. 22 before the practice would be adopted in Europe and That infectious diseases were contagious was the Americas. 17 recognized in early epidemics, but because knowl- Syphilis is another epidemic infectious disease of edge of the true epidemiology of diseases was lack- great historical importance. Syphilis became epidemic ing, efforts to control the spread of such diseases 95337_CH01_001–018.indd 4 2/1/13 11:56 PM EARLY EPIDEMIOLOGY 5 were flawed. Plague was recognized to be con- person to person by minute invisible particles. 12,24 tagious; however, the control measures focused Fracastoro conceived of the idea that infections primarily on quarantine and disposal of the bod- were spread from person to person by minute ies and the possessions (presumably contaminated) invisible seeds, or seminaria , that were specific of the victims. Although it was observed that large for individual diseases, were self-replicating, and numbers of rats appeared during an epidemic of acted on the humors of the body to create disease. plague, the role of rats and their fleas was not Although his theory was revolutionary, Fracastoro appreciated. did not realize that the seeds of a disease were As far back as biblical times, leprosy was microbes, and he held to ancient beliefs that believed to be highly contagious. Afflicted patients they were influenced by planetary conjugation were treated with fear and stigmatization. Given particularly “nostra trium superiorum, Saturni, that leprosy progresses slowly, quarantine of cases Iovis et Martis” (“our three most distant bodies: late in disease likely had little effect on the epidemic Saturn, Jupiter, and Mars”). He postulated that spread. In the Middle Ages, lepers were literally the environment became polluted with seminaria stricken from society as leprosy became increasingly and that epidemics occurred in association with equated with sin. Some even required lepers to stand certain atmospheric and astrologic conditions.