2 Seeking the Cause | Infectious Diseases

Activity 1

Identifying the Causative Agent

Introduction

The purpose of this activity is to have students model the second big idea of epidemiology, identifying the cause. Working in teams, students analyze epidemiological, medical, and laboratory data and use information about various causes of respiratory distress to narrow down the candidates and identify the causative agent.

Materials

For each team of 4 students:

One copy of each report (epidemiological data, medical data, and laboratory data)
One copy of Respiratory Distress Table
Poster board and markers (optional)

Procedure

Divide the class into teams of 4. Distribute one copy of each report and the Respiratory Distress table to each team
Have students read the introduction to the activity in the student materials
Inform the students that in order to determine the cause of the disease, they must use each report and the table. You may allow access to the Internet (except for Googling the answer. If they do, they are still required to develop a reasonable and logical explanation of why this solution is the most likely one. Just knowing the answer is not sufficient.)
Remind students that they must keep track of why they eliminated some information and deemed other information important. They need to record the rationale behind each decision and be responsible for justifying every decision. Their conclusions must be based on analysis of the data in relation to symptoms, method of detection, immune response, characteristics of the causative agents of lung disease, treatment, and target population.
You may want to have students prepare a poster and present their findings to the class. The poster should contain the following information:
- The nature of the epidemic; is it an infectious or noninfectious disease?
- The probable causative agent of the epidemic, if infectious.
- The process by which you came to the decision about the causative agent.
- The rationale for each decision.
- Recommendations for preventing further spread of the disease.

Sample Responses

The following is an example of reasoning students might use based on the information in the data reports. Each tab represents the type data on which conclusions are based. The combination of these reports should lead to the conclusion that the hantavirus is the causative agent of the epidemic.

Epidemiological
Medical
Laboratory

Conclusions based on Epidemiological Data

(using Report 1 and Table):

Relationships between individuals and their living and working conditions suggest that direct contact is not necessarily a requirement for the transmission of the causative agent.
Cases occurred in rural areas.
Environmental conditions indicate an increase in the rodent population.
Disease candidates would include plague, hantavirus, or chemical toxin.
These data must be connected to medical and laboratory data.

Conclusions based on Medical Data

(using Report 2 and Table):

Victims show respiratory symptoms.
The disease is not antibiotic-sensitive or responsive to anti-protozoal drugs.
The disease, therefore, could be a virus, a chemical toxin, or antibiotic-resistant bacteria.
Data eliminates Toxoplasma, pneumocystis; age range eliminates
S. pneumoniae.
Remaining candidates include Legionnaires’ disease, viruses, and
chemical toxins.
These data must be connected to epidemiological data or laboratory data.

Conclusions based on Laboratory Data

(using Report 3 and Table):

The disease agent cannot be visualized by light microscopy; unlikely to be parasite or the larger bacteria. Probably viral in origin since it cannot be visualized.
Infectious agent unable to be grown in culture.
Immunological assay shows presence of white blood cells, indicative of intracellular pathogen.
Antibody detection suggests Ebola or hantavirus.
These data must be connected to medical data or epidemiological data.

Scientific Background

Hantavirus was first identified in Korea as a disease of the renal system. The virus was transmitted in the feces of rodents. Infected individuals suffered fatigue, fever, weakness, and kidney failure. Initial identification of the agent of infection in the Four Corners epidemic as hantavirus was met with skepticism by some scientists, as respiratory distress was the characteristic symptom.

All strains of hantavirus known then caused only kidney problems not respiratory distress. However, analysis by molecular biological techniques such as polymerase chain reaction (PCR) and DNA sequencing revealed that the Four Corners virus was a new strain of hantavirus. This virus had mutated and the change resulted in new tissue specificity for the virus; this particular strain now targeted and grew in cells of the respiratory system.

The Four Corners virus was officially named Muerto Canyon, referring to the valley inside the Navajo Nation—Muerto Canyon, meaning Valley of Death.

Report One
Report Two
Report Three

Report One: Epidemiological Data

Data about infected individuals (victims)

Geographical distribution—lived in New Mexico and other parts of the Southwest, South, and Northwest United States
Habits—worked in a variety of jobs; some held positions in maintenance or cleaning; no unusual hobbies
Living Conditions—lived in trailers, small homes; generally in rural areas
Relationships—in some cases victims were related; one instance of engaged couple as victims; primarily isolated cases of unrelated, uninvolved individuals
Travel—no pattern of foreign travel or association with anyone who has traveled

Data about the environment

Recent rains and good growing conditions for seeds, nuts, berries, and insects had resulted in increase in rodent population.

Report Two: Medical Data

Symptoms—respiratory distress, flu-like symptoms, fever, muscle aches, coughing, difficulty in obtaining oxygen
Victims—range of ages; many young adults
Treatment—antibiotics ineffective; no response to anti-protozoal drugs (drugs which eliminate parasitic, single-celled organisms or protozoans)

Autopsy report

death by suffocation
rapid occurrence of death after onset of symptoms
air sacs in lungs filled with fluid, presumably from blood plasma leaking from pulmonary (lung) veins

Report Three: Laboratory Data

Mass spectral analysis—negative for chemical toxins and heavy metals
Examination of lung tissue and blood smears by direct stain and light microscopic analysis—negative for visible pathogens
Growth in culture from blood and lung tissue—no growth demonstrated

Immunology Report

large increase in number of white blood cells
results of antibody detection assays:
negative for Toxoplasma gondii, Streptococcus pneumoniae, Mycoplasma, influenza virus
inconclusive for Ebola virus, hantavirus, pneumocystis, Legionella, Pasteurella pestis

Adapted from Insights in Biology: A Journey of Discovery. Kendall / Hunt, 2007.

Tracking the source and spread of a disease requires a strong knowledge of probability, statistics and scientific inquiry. It involves knowing what kind of data to collect and which data is relevant. Epidemiologists must have careful observation skills and the ability to determine whether their observations, such as the number of cases of a disease in certain area at a certain time, differs from what might be expected. It requires an understanding of human behavior because often it is human behaviors that facilitate outbreaks and epidemics. Data collection requires a lot of legwork, interviewing many individuals in a short amount of time, and the ability to talk with people and gain information they may or may not want to share.

John Snow’s data were largely observational. He talked with families of cholera victims about where they lived, habits they had, where they worked, whom they interacted with, what they ate and drank, and so forth. Epidemiologists today have access to other kinds of information such as medical, biochemical and molecular data.

In the following activity you will use data to determine what is causing an outbreak of respiratory distress syndrome that is killing young adults in Four Corners, New Mexico.

Long-distance runner Merrill Bahe was on his way to his girlfriend’s funeral on May 14, 1993, when he found himself gasping for air. Suddenly, and quite dramatically, Bahe was overcome with fever, headache, and respiratory distress. In the presence of his grief-stricken relatives, Bahe gulped desperately for air in their car, en route south to Gallup, New Mexico. Minutes later the nineteen-year-old Navajo athlete was dead.

His twenty-four-year old girlfriend had died in a small Indian Health Service clinic located sixty miles away from Gallup a few days earlier after an identical bout of sudden respiratory illness. And within the week her brother and his girlfriend, also young, athletic Navajos, who lived in trailers near Bahe’s, fell mysteriously ill; the young woman died.

Excerpted from The Coming Plague by Laurie Garrett, page 528. Copyright &capy; 1994. Permission pending from Farrar, Straus and Giroux, Inc.,

The disease started with flu-like symptoms of fever, muscle aches, and headaches. After a period of a few hours to two days, the victims suffered irritated lungs and began coughing up blood. Leakage of the capillary networks feeding the lungs with blood filled the air sacs of the lungs. As a result the victims were unable to absorb oxygen from the air they took into their lungs. Starving for oxygen, the heart would slow down and death could soon follow.

Your task is to determine what is causing the killer respiratory distress syndrome, how it is being transmitted, and then determine if anything can be done to stop the epidemic. Like epidemiologists from the Centers for Disease Control and Prevention (CDC), your team will sift through data and narrow down information in order to determine the cause of the respiratory distress syndrome in Four Corners, New Mexico.

You will find the following table helpful in your investigation.

Causes of Respiratory Distress

The online version is below. If you are on a computer, click the table and use the cursor keys to scroll. If you are on a tablet, swipe left or right to navigate.

Causes of Respiratory Distress	Type of Agent	Mode of Transmission	Geographic Location	Symptoms	Main Target Population	Treatment	Nature of Immune Response	Location in Body	Method of Detection	Prognosis
phosgene	chemical toxin; poison gas	aerosol as gas	worldwide	coughing; fluid filled lungs	all ages	NA*	NA*	blood; lungs; other tissues	mass spectral analysis**	damage to lungs
paraquat	chemical toxin; herbicide	ingestion of treated plants	South America; Central America	cough; congestion; fluid filled lungs	all ages	NA*	NA*	blood; lungs; renal and skeletal tissues	mass spectral analysis**	damage to lungs
influenza	virus	airborne; human to human	worldwide	fever; cough; muscle pain	all ages	bedrest; fluids	white blood cells; antibodies	inside a cell; lungs	antibody detection***	death in elderly and sickly; otherwise recovery
Ebola	virus	direct contact; human to human	Africa	internal bleeding; fluid loss	all ages	bedrest; fluids	white blood cells; antibodies	inside a cell; blood vessels	antibody detection***	80% death rate
hantavirus	virus	airborne; aerosol of mice feces	Asia; U.S.	congestion; fever; fluid filled lungs	all ages; especially adults between 20 and 60	bedrest; fluids	white blood cells; antibodies	inside a cell; blood vessels in lungs	antibody detection***	70% death rate
plague	bacteria (Pasteurella pestis)	fleas living in rodents	worldwide	fever; swollen lymphs; cough; pain	all ages	antibiotics	antibodies	lungs; blood; lymph glands	direct stain of blood smears; antibody detection*; culture**	generally fatal if untreated
Legionnaires' disease	bacteria (Legionella)	aerosol; "scum water" from appliances	U.S.	fever; muscle aches; congestion	all ages; older adults	antibiotics (often resistant)	antibodies	lungs; blood	direct stain of blood smears; antibody detection*; difficult to culture**	can be fatal if untreated
Mycoplasma Pneumonia	bacteria	airborne; human to human	worldwide	persistent cough; fever; congestion	all ages	antibiotics	white blood cells; antibodies	inside a cell; lungs	antibody detection*; difficult to culture**	generally complete recovery
bacterial pneumonia (Streptococcus pneumonia)	bacteria	airborne; human to human	worldwide	cough; fever; ear ache	children	antibiotics (often resistant)	antibodies	connective tissue; lungs; ear canals	antibody detection*; culture**;	generally complete recovery; may persist
Toxoplasma	parasitic protozoan	cat feces; undercooked meat	worldwide	congestion; convulsion paralysis; heart disease	newborns; generally asymptomatic in adults	anti-protozoal drugs	white blood cells; antibodies	inside a cell; lungs	antibody detection***	eventual recovery; may cause birth defects
Pneumocystic pneumonia	parasitic protozoan	believed to be airborne; human to human	Europe; U.S.	high fever in adults; air sacs filled with foam	malnourished children; weakened adults	anti-protozoal drugs	white blood cells; antibodies	inside a cell; lungs	direct stain of sputum; antibody detection***	often fatal

NA means that the information is not available.

Mass spectral analysis is an assay for detecting hemical substances and heavy metals in blood and tissue.

***

Antibody detection is an assay in which the blood of victims is mixed with purified infectious agents. If antibodies specific to those organisms are present in the blood of victims, clumping will be seen in the sample, indicating that the antibody has bound to the added microorganism and that the person is most likely infected with that microorganism.

****

Culture is the growth of the organism in agar.

Adapted from Insights in Biology: A Journey of Discovery. Kendall / Hunt, 2007.