PART I. Identifying a Problem
This morning (June 21) the local health department (large town health department) received a telephone call from the infection control practitioner (ICP) from a nearby hospital reporting that 2 patients were seen in the emergency department (ED) late yesterday with complaints of fatigue, fever, night sweats, and cough. As part of their work-up, the ED physician ordered chest x-rays for both patients. The health department was informed that, in both cases, the radiology report indicated abnormal findings consistent with TB. As a result, both patients were admitted to the hospital with a diagnosis of suspected pulmonary TB. Once admitted, sputum samples collected from both patients were read as positive on microscopic smear with final culture identification pending.
You know that tuberculosis (TB) is an infectious disease caused by bacteria called Mycobacterium tuberculosis. The bacteria usually affect the lungs (pulmonary TB) but also can affect any part of the body outside the lungs (extrapulmonary TB) with the most common sites being the lymph nodes, bone, kidney, and pleura. While TB disease was once the leading cause of death in the United States, it can now be treated successfully with appropriate antibiotics. However, if not diagnosed early or not treated appropriately, TB disease can be fatal.
You also know that according to the CDC the “presence of acid-fast-bacilli (AFB) on a sputum smear or other specimen often indicates TB disease. Acid-fast microscopy is easy and quick, but it does not confirm a diagnosis of TB because some acid-fast-bacilli are not M. tuberculosis. Therefore, a culture is done on all initial samples to confirm the diagnosis. (However, a positive culture is not always necessary to begin or continue treatment for TB.) A positive culture for M. tuberculosis confirms the diagnosis of TB disease. Culture examinations should be completed on all specimens, regardless of AFB smear results. Laboratories should report positive results on smears and cultures within 24 hours by telephone or fax to the primary health care provider and to the state or local TB control program, as required by law.”2 While some microbiology laboratories have access to advanced technology and have the ability to identify TB in a specimen in just a few days, your laboratory requires 4 to 8 weeks for growth and final identification. Therefore, you will need to wait for the results on these 2 suspected cases.
Your health department (large town health department) receives calls of suspected TB cases several times a week. At total of 40% of these reports turn out to be negative for TB.
What questions should you ask and what information should you collect from the ICP while he/she is on the telephone with you? At this early juncture, should you consider initiating an investigation about these 2 cases?
The CDC classifies TB as a notifiable disease. “A notifiable disease is one for which regular, frequent, and timely information regarding individual cases is considered necessary for the prevention and control of the disease.”3
At this point, would you consider this an outbreak?
You decide that the next step you should take is to visit the patients in the hospital, collect information from their medical records, and interview them.
Question 3: What should you have as goals in your interviews with these suspected TB cases?
Question 4: What types of questions should you ask the suspected cases?
According to the CDC… “The period of infectiousness is the time period during which a person with TB disease is capable of transmitting M. tuberculosis. Determining the period of infectiousness can help focus the contact investigation efforts on those persons who were exposed while the patient was infectious.”4
The following guidelines may be used to estimate the beginning of the infectious period.5
The CDC guidelines also state that the period of infectiousness ends when all the following criteria are met4:
· Symptoms have improved
· The patient has been receiving adequate treatment for at least 2 to 3 weeks
· The patient has had 3 consecutive negative sputum smears from sputum collected on different days
From your interview you are able to learn the following:
· Jack Gold, a 62-year-old male who lives at 87 Jefferson Street in Large Town, NJ, has not been feeling well for 2 weeks and for the past 7 days he has been feeling weak, has also had some unexpected weight loss, fever, and cough. Mr. Gold has a history of bladder cancer. He works at Large Company X in Large Town, NJ. His home phone number is 973-555-2233, and he could not remember his work number. Mr. Gold also does not know anyone with similar symptoms, including anyone hospitalized with similar symptoms. Mr. Gold lives with his wife and his 85-year-old father. Mr. Gold was born in the United States and he has never traveled outside North America.
· Marla Smith is a 47-year-old female who lives at 33 Madison Avenue in Large Town, NJ, and has been sick for 3 weeks. She has been feeling weak, has had some unexpected weight loss, fever, night sweats, and cough. She works at Large Company Y in Large Town, NJ. Her cell phone number is 973-555-1290 and work number is 973-555-1212. Ms. Smith has a history of hypertension, diabetes, and obesity and also indicates that she does not know anyone with similar symptoms, including anyone hospitalized with similar symptoms. Ms. Smith lives with her husband and 2 children, 13 and 17 years of age. Ms. Smith was born in the United States. Ms. Smith has not traveled outside the United States since her children were born. Previously, she had traveled to South America and Europe.
You decide to test the families of these 2 individuals for TB infection. The families of these suspected cases were given tuberculin skin tests (TST), and results of all were negative (0 mm). After 4 weeks, you receive the culture results from Mr. Gold and Ms. Smith. As was suspected, you learn from the hospital microbiology department that M. tuberculosis was identified on final culture from both patients. You also learn that genotyping, or DNA fingerprinting results will be available within the next 2 weeks. You know that DNA results represent a valuable piece of information that could potentially link, or not link, these cases to other known cases.
Meanwhile a colleague of yours in the TB Control Program happens to tell you about a case that he has been following: a 38-year-old homeless non-U.S. born male who emigrated from Somalia (a high-incidence country) to the United States 1 year ago, named Ali Yusef. Since his arrival, Mr. Yusef has worked as a church custodian. The patient complained of having a productive cough for 1 month prior to his being hospitalized on May 3 and reported a history of pneumonia and malnutrition. A cavitary chest x-ray coupled with a positive sputum smear raised suspicions of TB and, as a result, appropriate TB treatment was prescribed. The diagnosis of TB was confirmed when M. tuberculosis was identified on final culture. Upon discharge from the hospital with 3 negative sputum smears, Mr. Yusef was placed in a homeless shelter and provided directly observed therapy (DOT) by health department staff. Outpatient care is currently being provided by the local health department clinic.
When the DNA results become available, you are informed that not only do the 2 culture isolates (from Mr. Gold and Ms. Smith) possess the same banding pattern (see Figure 1 below), but they also match a third person (Mr. Yusef) who was previously identified in Large Town in early June as a confirmed TB case. In addition, according to a search through a national DNA database, the strain profile of all 3 cases indicates that they are most commonly found in Africa.
The IS6110 RFLP analysis is one technique used to explore the molecular epidemiology of M. tuberculosis complex. IS6110 RFLP analysis is done by inserting an IS6110 probe into the DNA, which then attaches to a specific enzyme, called a restrictive enzyme, whose location is unique to each strain of TB. The size of each fragment depends on its distance from this site to the next restrictive enzyme and the location of each of these restrictive enzymes can be measured to see if the samples taken from each patient have the same or similar strains.6
Figure 1. IS6110 RFLP analysis of cases 1, 2, and 3
2 and 3
|Index/Source Case 1*|
|*” the first case or instance of a patient coming to the attention of health authorities” 7|
Since Mr. Yusef emigrated from Somalia (remember neither Mr. Gold nor Ms. Smith have traveled outside the country recently), the DNA strain that they all share is most commonly found in Africa and Mr. Yusef was diagnosed with TB much earlier than the other 2 cases, we can assume that Mr. Yusef is the index case (the first case of the disease in an outbreak). We will refer to Mr. Yusef as Case 1 for the remainder of this investigation.
This new information provides molecular evidence that Case 1 appears to be the source or index to Cases 2 and 3. With this new information, it has been decided that follow-up interviews with all 3 cases should be initiated to not only review previously collected information but to focus in-depth on establishing a common link (person, place, and time) between the cases that may not only provide an exposure site but could potentially lead to the identity of additional contacts and cases. Follow-up interviews reveal that the common link shared among all 3 cases was that they are all congregants of the same church and that all 3 cases are members of the church choir.
You now decide to combine and organize into a line listing information collected on all three cases starting with the first confirmed case, Mr. Yusef. You organize the information that you have collected into a line list.
Question 5: Complete the line list below for the confirmed cases.
Table 2. Line list for confirmed cases
|ID||TB Status||Name||Age/ Sex||Smear/Culture||Phone #s||Address||Place of
|Symptoms/ Chest X-Ray||Date Onset||Med Hx||Social Environment|
|1||Confirmed||Ali Yusef||38/M||+/+||None||Homeless/ from Somalia||Church||
||Pneumonia, malnutrition||Church choir|
Is this an outbreak? Provide your reasons.
What are the steps you should take in investigating this outbreak?
Your supervisor suggests that you use a concentric circle analysis in your investigation.4 The concentric circle approach (Figure 2) is a method of testing contacts by their exposure time and risk, with those at highest risk of infection or disease tested first. In this approach, the original TB patient (the index case) is at the center. The circle is divided into 3 concentric rings to represent the 3 levels of risk: high, medium, and low. The circle is also divided, like a pie, into segments that represent the 3 types of environment where the exposure may have taken place: household or residential, work or school, leisure or recreation environments.
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