Epidemiology (March 2001)

Table of Contents

Introduction

Definition of Terms

HIV

A Riddle to Be Solved

Some History

John Snow

Typhoid Mary

Objectives

Footnotes are enclosed within square brackets and colored green. Words in blue are defined and/or part of your class objectives.

Introduction

Epidemiology is the scientific study of the occurrence, distribution, and control of diseases and unusual health states in populations and subpopulations for the purpose of prevention or influencing health care policy. Unlike physicians, who are primarily concerned with diagnosis and treatment of disease states in the individual patient, epidemiologists focus almost exclusively on populations. They may, at times, diagnose disease in an individual as part of their need to develop data on the population.

The prevalence of a disease is the number of diseased individuals at any one time (point prevalence) or over a given period (period prevalence). The incidence is the number of new cases of a disease that occur within a defined population over an established period of time. Frequently either prevalence or incidence, or both, are given as a rate, meaning the number of cases in a fixed number of people, e.g., cases per 100,000. Individual cases of disease in widely separated geographic areas or otherwise independent cases are said to be sporadic. Any excessive and related incidence of a particular disease above what is normally expected in a population is defined to be an epidemic. When an epidemic extends beyond the confines of a continent and becomes a more widespread problem, it is a pandemic. AIDS today is a pandemic disease, insofar as cases have been diagnosed on every continent, save Antarctica. Any disease with a low to moderate normal base level incidence rate in the population, but not necessarily constant, is said to be endemic.

Individuals who are infected and show either no or only mild symptoms are said to have a subclinical infection. Subclinically infected individuals with no symptoms are identified as well-carriers of the disease because they are carrying and frequently shedding the pathogen. The following table gives the incubation period (time between exposure and the first detectable symptom), latency period (time when the disease is concealed, hidden, or inactive), and infectious period (time during which the disease can be transmitted with or without contact) for several common diseases.

 Time Course of Common Infections (all in days)

Disease

Incubation period

Latency period

Infectious period

Measles

8-13

6-9

6-7

Mumps

12-26

12-18

4-8

Pertussis

6-10

21-23

7-10

Rubella

14-21

7-14

11-12

Diphtheria

2-5

14-21

2-5

Varicella

13-17

8-12

10-11

Hepatitis B

50-110

13-17

19-22

Poliomyelitis

7-12

1-3

14-20

Influenza

1-3

1-3

2-3

 

Epidemiologists monitor morbidity (state of being diseased) and mortality (death) in a population in an effort to identify unusual trends and patterns. The control of the great epidemic diseases of the twentieth century, such as cholera, Plague, smallpox, yellow fever, and typhoid came about, in large part, through the efforts of epidemiologists. These diseases devastated human populations until epidemiological principles were applied to identify the factors that influenced their spread. Contaminated water supplies were found to be the problem in the spread of cholera, mosquitoes can carry yellow fever, and rodents can harbor fleas that transmit the Plague-all epidemiological discoveries. The total eradication of smallpox as a naturally occurring disease agent was also due primarily to epidemiological intervention, continuous surveillance, and an aggressive immunization program. Through careful investigative study, epidemiologists were able to elucidate critical factors and, when these factors were controlled, were able to halt the progress of epidemics.

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Germ Theory

Finding the causative agent of disease was no small feat. Historically, the notion of germs is of relatively recent origin. The Romans believed disease resulted from the imbalance of the four bodily humors: blood, phlegm, choler, and black bile. If you had a fever and rosy cheeks (rubor), it was clear that you suffered from an excess of blood. The obvious solution was to withdraw blood by attaching leaches to your body or making an incision for the purpose of bleeding you.

Convincing medical science of the validity of the germ theory was no small task. Unsuccessful attempts were made (at least indirectly) by John Snow, Ignaz Semmelweiss, Florence Nightingale, and many others.

Early in his career Robert Koch had the good fortune to be in India to study an outbreak of anthrax, a bacterial disease usually infecting cattle and sometimes humans (as we now well know). Koch sought to establish a chain of experiments that closed on themselves so that it would be unequivocal and irrefutable that a certain agent was responsible for a certain disease. In an 1876 paper he published the following short list of requirements, appropriately called Koch's Postulates (unfortunately for him, because they are not extendable to some other germs).

  1. The microbe must be present in every case of the disease;
  2. The microbe must be capable of being isolated from a diseased host and grown in pure culture;
  3. The disease must be reproduced when the cultured microbe is introduced into a nondiseased susceptible host;
  4. The microbe must be recoverable from an experimentally infected host.

Proving that an outbreak of disease had a specific cause required extracting the causative agent from every infected individual tested. That common agent then has to be grown in "pure culture," which is usually sterilized agar (seaweed extract), beef broth, milk protein, soybeans, or other "nutritious" (to the agent) stuff. Then either someone or some animal must volunteer to be infected with the agent. Currently, the Centers for Disease Control and Prevention (www.cdc.gov) (CDC) is the federal agency responsible for overseeing such research.

While this chain sufficed for many of the bacterial diseases of the nineteenth century, modifications had to be made in order to include diseases caused by viruses, viroids, and/or prions. For instance, few (if any) viruses, viroids, or prions can be isolated in "pure culture." On some rare occasions, disease symptoms don't arise until after the body has expelled the causative agent. Some disease agents are so mutable that precisely the same organism cannot be recovered from different experimentally infected hosts, e.g., HIV. Even for bacterial diseases, there are dose/response curves that are a function of the characteristics of the state of the individual. Such curves predict the extent of symptoms in terms of the number of germs introduced into the individual. For some people, extremely large numbers are needed to cause disease, while others will develop symptoms from a much smaller dose. Since all individual characteristics have neither been isolated nor thoroughly studied, this forces a random character on infection and disease causation. Thus, it is reasonable to add the following requirements to make a set of Extended Koch's Postulates:

  1. Statistical association: the relation between exposure to the causative agent and the appearance of disease symptoms should have a highly statistically significant positive correlation; the greater the exposure, the more likely the disease.
  2. Biological plausibility: there should be some (correctly) explainable mechanism by which the body experiences disease symptoms as a result of exposure and infection.
  3. Temporal sequence: symptoms should follow risk/exposure within a reasonable and broadly predictable period of time.
  4. Dose/response: higher exposure doses should result in an increased probability of developing symptoms.
  5. Specificity: exposure to specific microbes should result in the development of appropriate symptoms.
  6. Consistency: the exposure/symptoms cycle should be repeatably consistent.

The following table shows the extent of variability in the symptoms as various diseases arise. It is not common for a microbe to produce exactly the same disease in all infected hosts. Many other factors must be considered, e.g., infecting dose, route of entry, presence or absence of other microbes, age, sex, genetic makeup, nutritional status, general health of the host, and others. From the table below, you see that many diseases need not present themselves in all their classical glory. Thus isolating a patient or enforcing quarantine may have little effect when there are many asymptomatic individuals walking around and generously sharing their infectious cargo.

  Frequency of Clinically Apparent Symptoms

Infection

Approximate % with clinically apparent disease

Pneumocystis carinii pneumonia

0.6

Poliomyelitis (child)

0.1-1.0

EB virus (1-5 yr old child)

(young adults)

1.0

30-75

Rubella

50

Influenza (young adult)

60

Pertussis

Typhoid

Malaria

Anthrax

> 90

Gonorrhea (adult male)

Measles

99

Rabies

HIV (?)

100

 

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Definition of Terms

A host is any organism capable of supporting the nutritional and physical requirements of another.

A microbe is a microscopic organism.

The presence and multiplication of an organism on or within a host is called colonization or infection.

We refer to the colonization of one organism by another as symbiosis. If the symbiotic relationship benefits both organisms, it is called mutualism. Commensalism is a symbiotic relation in which one organism benefits and the other is not harmed. Parasitism occurs when the infecting organism benefits and the host is harmed. If the host sustains injury or pathological changes in response to the parasite, the process is an infectious disease.

Anything causing a disease is termed a pathogen.

There are many agents of infectious diseases: prions, viroids, viruses, bacteria, spirochetes, mycoplasmas, rickettsiae, chlamydiae, fungi, protozoa, helminths, and arthropods. More about these creatures later.

A portal of entry is the process by which a pathogen enters the body, gains access to susceptible tissue, and causes disease.

  1. It can do this by penetration of the skin or mucous membranes. This route is taken by: rabies, warts, staphylococci (boils), typhus, leptospirosis (contact with water containing infected animal urine), streptococci (impetigo, erysipelas), cutaneous anthrax, syphilis, yaws, Plague, ringworm, athlete's foot, hookworm, filariasis, and schistosomiasis and the arboviruses (viruses that are arthropod borne): malaria, yellow fever, dengue fever, sleeping sickness, Lyme disease, and many others.
  2. Disease can also be caused by direct contact, such as physical or sexual contact (horizontal transmission, no pun intended) or by vertical transmission (inheritance as is the case in childbirth). Sexually transmitted diseases (STDs), rubella, toxoplamosis, cytomegalovirus, herpes simplex virus (HSV), and varicella (chickenpox) are all spread by direct contact.
  3. Pathogens can be ingested, passing through the oral cavity into the gastrointestinal tract, e.g., cholera, typhoid fever, dysentery, food poisoning by Salmonella or other microbes, traveler's diarrhea, hepatitis A, enteric fever, hookworm, and polio.
  4. The easiest and most efficient form of transmission is inhalation, whereby the microbes are deposited on the respiratory mucosa, e.g., influenza, common cold, measles, mumps, chickenpox, hantavirus, bacterial pneumonias, pneumonic Plague, tuberculosis, Legionnaire's disease, and meningitis.
  5. Disease can also be spread by the deposit of pathogens on inanimate objects, called fomites, from which they may be conveyed to the next organism coming in contact with the object before the organism dies.
  6. Lastly, we have the unfortunate case of accidental injection of a pathogen; a deep needle stick of a health care worker, transfusion of tainted blood, etc.

Once a disease has been introduced into a population, there is a need to find the process by which the causative organism leaves the body of a carrier and is transmitted to another host, called the portal of exit. Clearly this is different for common source and host-to-host epidemics.

Diseases acquired while hospitalized are said to be nosocomial. Such hospital-acquired infections are not as rare as one might think. Complete data are currently available only up to the year 2000. The Chicago Tribune analyzed these data to arrive at a figure of 103,000 hospital deaths of which 75,000 could have been prevented by such simple measures as hand-washing, adequate sterilization of surgical instruments, and proper cleaning of hospital facilities. Just implementation of a strict hand washing policy alone could save 20,000 lives every year! Current CDC policies carry no penalties, are strictly advisory, and are more honored in the breach than the observance.

Any diseases or conditions induced by word or action of a physician or health care worker are said to be iatrogenic. One common medical problem is inadequate or incorrect patient teaching. It is more than a little difficult for most patients to self-administer complex drug regimens and change dressings even with excellent teaching.

Here's a list of some of the most common diseases that you could come away from a health care facility with.

Most Common Nosocomial Pathogens

Bacteremia

Coagulase-negative staphylococci

Staphylococcus aureus

Enterococci

Candida and other fungi

Enterobacter species

Pseudomonas aeruginosa

Lower Respiratory Tract Infection

P. aeruginosa

S. aureus

Enterobacter species

Acinetobacter species

Klebsiella pneumoniae

Surgical Wounds

Enterococci

Coagulase-negative staphylococci

S. aureus

Enterobacter species

P. aeruginosa

Escherichia coli

Urinary Tract Infection

Candida species

E. coli

Enterococci

P. aeruginosa

Enterobacter species

 

Diseases that arise over a very short period of time are said to be fulminant, whereas those that are slow to develop are said to be insidious. Plague is fulminant and cancer tends to be insidious.

Once a pathogen has found its way into an organism (called causation), its development proceeds in several phases:

A host that does not reach the convalescent stage may continue in the acute stage until death or be maintained in a chronic disease state.

There is more to an epidemic than the biology of the infectious agent. We need to consider the ecological triad of host-agent-environment. Changes in any one of the three can break or enhance the chain of infection. Certainly, there are organisms that are more contagious than others, but factors other than the infectiveness of a diseases-causing agent often determine whether an epidemic occurs or not.

The virulence of a disease is due to many factors. For the microbe, there are:

 pH susceptibility of the organism,

  interaction of the organism with food menstrum and the environment,

  immunological "uniqueness" of the organism, potential for damage and/or stress of the microbe,

  interactions with other organisms (especially normal flora), and

  variability of gene expression of multiple pathogenic mechanism(s).

For the host, we need to consider

 age,

 general health,

 nutritional status and amount and type of food consumed,

 gastric acidity,

 immune competence,

 occupation,

 medications being taken,

 surgical history,

 metabolic and organ disorders (e.g., alcoholism, drug addiction, etc.), and

 genetic makeup (including anomalies).

The environment frequently determines which pathogens survive and which do not. Tropical diseases, such as malaria and dengue fever, are rarely found in temperate or cold climates. Arid regions can cause desiccation of animal feces so that they can become airborne, e.g., hantavirus in mouse excrement. Whereas moist and humid regions can allow easy transmission by liquids, e.g., Bolivian hemorrhagic fever from mouse urine.

Generally, a disease that can be transmitted from an animal to a human is a zoonosis. There are more than 250 organisms known to cause zoonotic infections, some of which are resident on common household pets.

Looking at the agent, pathogens produce toxins, which are substances that alter or destroy the normal function of the host's cells:

 Exotoxins are proteins released from bacteria during growth;

 Endotoxins are potent activators of some regulatory systems and can induce clotting, bleeding, inflammation, etc.

 Adhesion factors allow the pathogen to gain a foothold in the host:

 Receptors are the sites to which a parasite can adhere and the substance to which it binds is called a ligand or adhesin;

 Pili or fimbriae are hairlike structures to which a microbe can adhere.

 Once colonization has begun, the pathogen can employ evasive factors to prevent or slow natural immune responses put forth by the host:

 Extracellular polysaccharides are produced by the microbe to discourage engulfment and killing by phagocytes (neutrophils and macrophages);

 Leukocidins are toxins that deplete the host of phagocytes (more about this later);

 Some microbes even reproduce within phagocytes, while others employ

 Surface disguises or surface coverings.

Other parts of a microbe's arsenal are its invasive factors that facilitate the penetration of anatomical barriers and host tissue:

 Phospholipases destroy cellular membranes;

 Elastases and collagenases destroy connective tissue;

 Hyaluronidase destroys intracellular matrices; and

 Proteases destroy structural protein complexes.

Analytical epidemiology employs two basic approaches to the interpretation of data, case control and cohort studies. Case control studies compare a group in which infection is present to a matching control group in which it is absent, hence, such a study is retrospective, or after-the-fact. Most cohort studies are prospective, or before-the-fact, insofar as they monitor the appearance of infection in carefully predefined groups over a period of time by comparing subjects exposed to the risk factors to those not exposed. Beyond the medical aspects of such studies are the statistical analyses from which we can infer causation. Some cases are easier than others. Establishing smoking as one of the main causative agents of cardiovascular disease and lung cancer required very extensive research over a several decades before the inferences were well established.

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HIV

In 1981 the CDC used a case control study of AIDS, then called GRID for gay-related immunodeficiency, sufferers for both gay and straight subpopulations to provide convincing (to most) evidence that the disease was sexually transmitted. In fact, the first reference in this country was published in the CDC's Morbidity and Mortality Weekly Report (MMWR) for June 5, 1981. (You may access a copy of the original article at www.cdc.gov/mmwr/) In Los Angeles five cases of Pneumocystis carinii pneumonia were found in "active (male) homosexuals." The diagnosis was verified ante-mortem, i.e., after their deaths. "The patients did not know each other and had no common contacts or knowledge of sexual partners who had had similar illnesses. The 5 did not have comparable histories of sexually transmitted diseases." The treatment of choice was aerosolized pentamidine, a drug distributed exclusively by the Food and Drug Administration (FDA) at that time. Scrutiny of the records showed that in the interval from 1967 to 1979 there were only two requests for the drug, but within a few months in 1981 there were five such requests. Less than a month later the July 3, 1981 issue of the MMWR carried a report of 26 gay men (20 from New York City and 6 from California) diagnosed with a rare vascular cancer, Kaposi's sarcoma. This was most unusual because the disease heretofore had affected mostly elderly men of Mediterranean origin, primarily Ashkenazi Jews. In the past the disease manifested itself as small blue-purple lesions on the legs and was rarely either disseminated or fatal, little more than a minor nuisance.

Often an epidemiological investigation must be carried out, whereby all relevant (and some irrelevant) data are collected with an eye to identifying the infectious agent, the mode(s) of transmission, and the possible measures for control. An epidemiologist must be a good (and possibly brave) detective.

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A Riddle to Be Solved

The following tables, drawn from a single retrospective observational study, illustrate an incidence of excess mortality at a period in history. Deaths for this population are categorized by economic status and gender, and then by economic status and age.

 By Economic Status and Gender

 

Population Exposed to Risk

Number of Deaths

Deaths per 100 Exposed to Risk

Economic Status

Male

Female

Both

Male

Female

Both

Male

Female

Both

I (high)

180

145

325

118

4

122

66

3

38

II

179

106

285

154

13

167

86

12

59

III (low)

510

196

706

422

106

528

83

54

75

Other

862

23

885

670

3

673

78

13

76

Total

1731

470

2201

1364

126

1490

79

27

68

                     

 

By Economic Status and Age

 

Population Exposed to Risk

Number of Deaths

Deaths per 100 Exposed to Risk

Economic Status

Adult

Child

Both

Adult

Child

Both

Adult

Child

Both

I (high)

319

6

325

122

0

122

38

0

37

II

261

24

285

167

0

167

64

0

59

III (low)

627

79

706

476

52

528

76

66

73

Other

885

0

885

673

0

673

76

-

76

Total

2092

109

2201

1438

52

1490

69

48

68

                   

 

This case of excess mortality is quite unusual insofar as it affected males at a far higher rate than females. Additionally, there seems to be a relation between economic status and survival rates, e.g., the highest economic status had the lowest mortality rate. Only children in the lowest economic status category III died.

What was the risk to which people were exposed? What was the cause of death? Over what period of time do you think this happened? Clearly the mortality rate (which is given per hundred, so that it is a percentage) is very high and the total number that died is also high.

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Some History

At the end of the 1400s, after the major global attack of Plague, the intelligentsia of the time arrived at a full (though incorrect, but containing some glimmer of truth) causation of epidemics as follows:

1.      Such a disease as the Plague was highly contagious, spreading from sick to well by contact (according to some authorities by the glance of the eye); and infection was associated with objects and places used or occupied by the sick.

2.      The infection consisted in a corruption of the air (of what we should call a chemical nature).

3.      This corruption of the air arose from decomposing organic matter, unburied bodies of the dead, marshy and putrid waters and the like; and was favored by certain meteorological conditions, such as heat, dampness and southerly winds.

4.      The basic factor that made possible the generation of particularly virulent corruption (such as characterized a great and unusual pandemic) was a malign conjunction of the planets and fixed stars.

5.      Such a conjunction was apt to be associated with other unusual earthly and heavenly phenomena such as unseasonable weather, earthquakes, falling stars, thunderstorms, and the like; but these were "signs" of an epidemic constitution of the atmosphere rather than "causes" of such a condition.

6.      Individual predisposition played a considerable part in determining which particular persons were stricken in the course of an epidemic.

Far though it may be far from the truth of the matter, it was a start. Besides, medicine advanced little beyond the Greek "physician" Galen until Lister, Koch, and Pasteur did their pioneering work in the mid-to-late 1800s.

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John Snow

Others made progress toward understanding the causes of infectious disease without knowing the underlying responsible mechanisms. Prior to the discovery of the germ theory of disease, an English physician (in fact anesthetist to Queen Victoria during childbirth), John Snow, spent many years studying the incidence of cholera. He plotted the locations of cholera deaths on a map of London and, in 1854, found an unusually high mortality rate (500 fatal cases within ten days in August and all within a circle of radius 250 yards) on Broad Street, Golden Square, near Soho. A brewery within this circle had no deaths; it had its own well and workers could drink either well water or free beer (Some choice! But then again, how many people lived at the brewery?). His earlier theories were that something in the water was, somehow, associated with the disease. Snow asked the local officials to remove the pump handle from the local well, which was done on September 7. Within the week the cholera epidemic, although already slowing, all but disappeared from this area.

Additional follow-up showed that a workhouse in the area was more than three-fourths surrounded by houses in which cholera deaths occurred, but only 5 cases had appeared amongst the 535 inmates; no doubt due to the fact that the house, like the brewery, had its own private well. Also, a gentleman from Brighton visited his brother who had died of cholera, drank the local water, and came down with cholera in his distant home the next evening. Even more remote was the case of a woman who had not visited the district in months but who had once lived there and had a special taste for the Broad Street water. Daily a carter brought a supply, filled at the Broad Street pump, to her house in Hampstead. On August 31, she too was stricken. A niece who happened to visit the woman also drank from the supplied water and returned to her home in Islington to die of cholera. Neither of these two communities had any other cases of cholera. After the epidemic, others opened the Broad Street well, and found the main drain from No. 40 Broad Street was only 2'6" from the well and 9'2" above the water level. Discolored soil and a washed appearance of the surrounding gravel indicated a high level of pollution, no doubt containing infected fecal matter from one (or more) well carrier(s).

In the following year, Snow analyzed a much larger area south of the Thames River, across from Westminster Abbey and the Parliament Building, where water was supplied by competing companies, the Southwark & Vauxhall Company and the Lambeth Company. In parts of this area, each company enjoyed a monopoly, but for a majority of the customers, the companies competed head-to-head, each having installed pipes along the same streets. In this totally unregulated free market, residents enjoyed the option of connecting to either supplier and the distribution of houses between the companies appeared to be random. Customers of the Southwark & Vauxhall Company credited their water with having a "full bodied flavor," possibly due to the high salt content of 38 grains per gallon [The water was so "full-bodied" that it had a brown color with a bit of a head whenever the Thames was low and the ocean pushed saltwater as far as London. Water left in a pot took on a slimy coating and had a rather unpleasant odor. When a tap was covered with cloth to filter water for a pot of tea, it was not unusual to extract a tablespoon of "foreign materials." Yummy!]. The results of Snow's detailed survey of all cholera deaths in the area showed that in one four week period the Southwark & Vauxhall customers had 71 deaths per 10,000 houses and the Lambeth customers 4, while the overall rate for the rest of London was 9. In total, there were 315 deaths per 10,000 houses supplied by Southwark & Vauxhall, and 37 per 10,000 houses supplied by Lambeth. The death rate for the rest of London was 59 per 10,000 houses. These figures persisted across the areas of monopoly and the areas of competition. Snow concluded that the water Southwark & Vauxhall withdrew from the heart of London (Battersea Fields), containing the excrement and emissions of cholera victims, was the source of infection. The Lambeth Company withdrew its water considerably upstream of the city at Thames Ditton, which, at that time, was fairly pristine. Snow's reportage of this is worth repeating:

The experiment, too, was on a grand scale. No fewer than three hundred thousand people of both sexes, of every age and occupation, and of every rank and station, from gentlefolk down to the very poor, were divided into two groups, without their choice, and, in most cases, without their knowledge; one group being supplied with water containing the sewage of London, and, amongst it, whatever might have come from cholera patients, the other group having water quite free from such impurity.

Despite this quite convincing numerical display, evangelical reformers like Edwin Chadwick who had preached the so-called Sanitation Doctrine, wherein disease was thought to arise from dirt (and dirt alone), held sway. Their solution was to scour and scrub the great unwashed of London, while giving no consideration to their, possibly infected, innards. In a similar vein, William Farr preached the miasma theory, whereby clouds of diseased effluvia were thought to arise from the city's sewers and cesspools to infect any and all that came in contact with these menacing, but invisible, nebulosities. Although the sanitation movement was in full swing when the 1854 epidemic struck, little effect was felt, other than by the removal of the Broad Street pump handle. Nevertheless, Snow's work was disregarded; the main criticism being that he was unable to identify the causative agent in the water. This remained a mystery until the publication of the germ theory of disease and the isolation of Vibrio cholerae by Koch 29 years later in 1883.

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Strangely, in the twentieth century, as the germ theory of disease took hold, some officials embraced the new explanation with such vigor that they rejected any connection between dirt and disease. This relegated the collection of garbage and street cleaning to the newly formed public works departments, outside the venues of the health officials.

Moving ahead in time, we come to the twentieth century and the classic first case in North America of an identified well-carrier (an asymptomatic infected person), so-called Typhoid Mary.

Mary Mallon served as a cook (reputedly a very good one) to several households and institutions in New York City and Long Island. After a typhoid outbreak in a rented summer home in Oyster Bay, New York, the owner, Mr. George Thompson, in the interests of removing any stigma attached to his rental property, hired Dr. George Soper in 1906 to investigate. Soper earned his doctorate in sanitary engineering and had extensive experience in the epidemiological analyses of typhoid outbreaks. After sifting through all available evidence, he hit upon the fact that the family had changed cooks just prior to the outbreak. One of the cook's specialties was an ice cream dessert served with sliced fresh peaches, an ideal medium for the growth of the causative microbes. Further investigation led to the employment agency that placed her. Of the eight families that had previously employed Mary, seven had instances of typhoid fever [Between 1900 and 1907 Soper tracked a total of 22 cases (fourteen servants and eight family members) of the fever to Mary. More interestingly, every one of these cases had been previously investigated and explained to be the result of other sources of infection. As a comparison, from 300 to 4500 cases were reported each year in New York City.]. In the last instance, the daughter of Henry Warren of Park Avenue contracted typhoid and died, the first death to be attributed to Mary. To Soper, this indicated that Mary Mallon was the likely source of contamination. Soper confronted her at the Warren household and asked, as diplomatically as he could, considering the intensely personal nature of the request, for samples of her blood, urine, and feces. Claiming not to ever have had typhoid, Mary, menacingly displaying a carving fork and using rough language to the effect that she never had typhoid fever, promptly showed Soper the door. Undeterred, he and a colleague went to her home [At that time Mary although single, was living with Mr. A. Breihof (or Breshof)a sure sign, in those days, of not very high moral fiber.]. Both were physically ejected by the suspect, this time using even coarser language and another carving fork. Since Soper was independently employed, he had no authority to compel Mary to provide the requested samples. He turned to the city health department and the official health inspector, Dr. S. Josephine Parker. With police assistance in the five-hour search of the Warren residence, Dr. Parker took Mary into custody (going so far as restraining her by sitting on her in the police car) and obtained the requested samples. In the interests of "protecting the public health," Mary was imprisoned in a cottage on North Brother Island. At this time a similar case arose in upstate New York where an Adirondack mountain guide was identified as the source of an outbreak among 38 tourists, two of whom died (a higher rate than that attributed to Mallon). The state health department, claiming no legal authority to do so, did not detain him. This left Mary as a singular prisoner of the public health system.

Bacteriological analysis by the health department of Mary's feces revealed a high titer of Salmonella typhi, the bacterium causing typhoid, although of 163 samples taken between March 20, 1907 and June 16, 1909, fully 43 were negative [Mary had arranged for an outside lab, the well-known Ferguson Laboratories, to test her urine and feces. Of the ten specimens, not one tested positive. This contradicted eight of the city's results. The specimens were secreted off the island by Breihof.]. Her urine never tested positive. Public health authorities postulated that she had remained a carrier for several years because her gallbladder was infected. (Remember, at this time typhoid could not be cured with certainty.) The drugs hexamethylenamin and utropin were given, but with no change in her infective status. They offered to remove her gallbladder [At no time was Mary informed of the danger of this surgery nor of its poor record for altering the typhoid well-carrier state.], but she refused and was in most ways totally uncooperative. In June of 1909 she sued for release but the writ of habeus corpus was denied. The following year, upon the arrival of a new commissioner of health, after having served nearly three years, in February of 1910 she was released on the condition that she not cook or handle food for others and that she report to the health department every three months. Three months later she complained to the New York City Board of Health that she had been unjustly deprived of her means of earning a living. For a few years she worked as a laundress but then departed for parts unknown. Under the assumed name of Mrs. Brown, she returned to her vocation of choice and left a swath of typhoid behind her. As a result of an investigation of an outbreak of twenty-five cases (including two deaths) at the Sloan Hospital for Women in Manhattan, after five years of freedom, Mary was rearrested and reimprisoned in 1915. She remained in custody on North Brother Island for 23 years and died in 1938, 32 years after first being identified as a chronic typhoid carrier. A total of forty-seven cases, including four deaths, were attributed to her. Bacteriologic analysis of her feces between 1915 and 1936 yielded 207 positives and 23 negatives.

By comparison, Alphonse Cotils was a baker, restaurant owner, and well-carrier of typhoid who had been prohibited from preparing food in either of his establishments. Nevertheless, he continued to work in his bakery and was brought up on charges. The judge refused to imprison him since that would have been illegal, because he was not ill. Besides Alphonse, there were several hundred other well-carriers who were not singled out for isolation. In 1922 one Tony Labella, a well-carrier as diagnosed by the New York authorities, was found in New Jersey and an outbreak of 87 cases and two deaths were laid at his doorstep. A further 35 cases and three deaths were also attributed to him. The inconsistency of having Mary Mallon isolated on North Brother Island for a first offense and then permanently put away for a second offense, while Cotils and Labella, who were also repeat offenders, remained free did not seem untoward to any of the officials concerned.

How was all this viewed by the public? The July 7, 1909 issue of the British humor magazine Punch carried this bit of doggerel:

The Germ Carrier by O.S.

In the U.S.A. (across the brook)

There lives, unless the papers err,

A very curious Irish cook

In whom the strangest things occur:

Beneath her outside's healthy gloze

Masses of microbes seethe and wallow

An everywhere that MARY goes

Infernal epidemics follow.

And it continues with the usual English disparagement of the Irish.

1910 saw the publication of a work of fiction, The Silent Bullet, by Arthur Reeve wherein a villainous lawyer arranges the death of rich man by inserting the Irish cook Bridget Fallon [The similarity in the last names is unlikely to have been coincidental because Reeve was meticulous with details.], who is a well-carrier, into the household so as to infect all and sundry with typhoid.

The May 18, 1915 issue of the august publication Scientific American carried the following less than compassionate statement:

The great trouble with Typhoid Mary has been her perversity, exceeding even that which obtains in her most temperamental of callings. She has never conceded herself a menace; she has not obeyed the sanitary directions given her; she would not wash and disinfect her hands as required; she will not change her occupation for one that in which she will not endanger others; under an assumed name she had competed with the Wandering Jew in scattering destruction in her path.

Neither Alphonse Cotils nor Tony Labella received such censure in the popular press of the time, even though they were responsible for similar, or worse, acts and outcomes. Whenever the New York Times referred to Labella it was as an "alleged" well-carrier, despite the certainty of that diagnosis in the eyes of health department officials. Oh, but for some equity and justice!

 

What was mankind's greatest (and first) achievement that significantly reduced disease? The easiest problem to attack was the common source epidemic and the most efficient first tool was the development of adequate sewer systems. This led to the establishment of trustworthy sources of clean (but not necessarily pure) water. Once adequate sewers were in place the notions of sepsis, such as handwashing, lead to even more improvement in the health of the population. The introduction of sepsis into surgery, as argued by Semmelweiss and Nightingale, caused a steep decline in iatrogenic deaths at the (biologically dirty) hands of surgeons.

 

As a final word on the tabular mortality data: the unusual excessive mortality was due to the sinking of the Titanic on April 15, 1912. Economic status I and II were cabin classes, and III was steerage. The Other category refers to the crew, hence there were no children in this group. Remember: "Women and children to the lifeboats first."

Objectives: Know: Koch's Postulates and the extended Koch's Postulates, be able to tell why they are important. Host, naive host, microbe. What is epidemiology and what do epidemiologists do? Prevalence and incidence, how are they different? Epidemic, pandemic, endemic, epizootic. Well-carriers and subclinical infections. Incubation period, latency period, and infectious period of a disease. Morbidity and mortality. Infection, symbiosis, mutualism, commensalism, parasitism, and be able to give examples of each. What is an infectious disease? What are portals of entry and exit; give examples. What is the difference between horizontal and vertical transmission of disease? What are vectors and fomites. What are nosocomial and iatrogenic diseases? What are the stages of disease? What are the differences between an insidious, chronic, and a fulminant disease? Explain the host-agent-environment triad. What are case-control studies and cohort studies and how do they differ? Explain how John Snow studied and explained the cause of cholera. What methodology did the CDC use to determine that HIV/AIDS is sexually transmitted?

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