Clinical Microbiology HW#15

Concept Map: Viral Hepatitis

1. Which of the following NOT true for both hepatitis B and hepatitis C infection?

The disease is prevented by vaccination.

**There is a vaccine for hepatitis B.

***TRUE:

The virus can cause a chronic disease.

The infection is transmitted through blood and body fluids.

Diagnosis can be achieved through testing the blood for antibodies.

2. What do hepatitis A and hepatitis B have in common?

Both can be prevented by a vaccine.

3. What organ is most affected by hepatitis B virus?

Liver

Chapter 25 Reading Questions

1. John went to a picnic. He took some leftover chicken and rice home, heated it on the stove, ate it, and got sick two hours later. John thought the heating made his food safe because it would have killed any bacteria present. He didn't know that __________ produces a heat-stable toxin.

Staphylococcus aureus

2. Which is the correct sequence of events regarding the stages of tooth decay? 1. Dentin decay 2. Enamel decay 3. Plaque 4. Pulp decay

3-2-1-4

3. Ergot poisoning __________.

may cause hallucinogenic symptoms

Diseases in Focus Chapter 25 – Male, age 49

Medical History (Hx)

The patient is a male, age 49. He was admitted to the clinic with a high fever, muscle pains (myalgias), and facial swelling around his eyes (periorbital edema). The patient works as a pharmaceutical sales representative based in Hawai'i. He lives in Honolulu, on the island of Oahu. He is married, monogamous, and sexually active, with a 16-year old son. He does not report using drugs of abuse, and rarely drinks alcohol, but does smoke cigarettes (estimates 8 per day). His son has a pet iguana, which he has fed once or twice since his son got it (roughly two years ago). He is allergic to drugs containing sulfonamides. He has a family history of cancer. Within the last year (6 months ago), he and his wife traveled to Thailand to visit extended family. He reports feeling fine during and after his travel. A month ago, he and his family traveled to Maui to attend a street fair celebrating the Thai New Year. While at the fair, he ate several food items from vendors. He felt fine that night; however the following evening he experienced a sudden onset of diarrhea, accompanied by abdominal cramps and heartburn. After a few days, his symptoms faded, and he did not think anything more of the episode. Five days ago, he again rapidly developed frequent, watery diarrhea, myalgias, and a severe headache. Over the next few days, the tissue around his eyes began to swell, and small hemorrhages appeared under his fingernails (splinter hemorrhages). Initial examination shows that he is dehydrated and feverish, with large swollen bags under and around his eyes. No one else in his family is sick, despite the fact that his wife and son were also present and ate food at the street fair.

Differential Diagnoses

Differential diagnosis is the process of identifying a disease from a list of possible diseases that fit the information derived from examining a patient. Your job will be to synthesize information from a patient whose main presenting symptoms are consistent with a microbial disease of the digestive system. Use the "Diseases in Focus" 25.2, 25.3 and 25.4, and 25.5 tables and your knowledge about microbial diseases of the digestive system to identify the patient's risk factors and symptoms, evaluate diagnostic evidence, formulate and test a diagnosis about the pathogen responsible for the patient's woes, and suggest a course of treatment.

1. Identify relevant information

Review the patient's medical history, and then identify risks and concerns that are relevant to your diagnosis (and the patient's treatment).

Relevant:

Risk of vector-borne disease

Risk of travel-related disease exposure

Special concerns for treatment

Not Relevant:

Age-related risk of disease

Occupational risk of disease

Risk of sexually transmitted infection (STI)

Risk of drug-related disease exposure

Risk of genetic/familial disease

Risk of immunocompromised

**Your patient's medical history reveals that he has recently traveled, and that he is in contact with a vector animal associated with the transmission of certain types of infectious disease. Potentially, these factors could help you identify diseases your patient may have come into contact with.

2. Focus your hypothesis

Before you can focus your hypothesis further, you'd like to know more about the diarrheal symptoms your patient has been experiencing. You ask him to describe his bowel movements. He replies that he has been having roughly 10 watery bowel movements a day. You ask him to clarify "watery," and he adds that his movements have been loose with some fluid, but he would not describe them as extremely watery. He has not noticed any blood in his stool.

Based upon your patient's description of his bowel movements, you feel it is LESS likely that your patient has:

dysentery, or a disease with dysentery-like symptoms

cholera, or a disease with cholera-like symptoms

**It does not seem that your patient has a form of cholera, dysentery, or a disease of similar diarrheal symptoms. He could have a form of gastroenteritis, however. You will need to gather more information to solidify a hypothesis.

3. Gather more information

You take a blood sample from your patient, and record his vital signs. As you do this, you decide to ask your patient some details about situations where you believe it is most likely that he acquired his illness. You begin by asking him:

What did he and his family eat at the street fair?

**You ask your patient about what he ate the night of the street fair, and he recalls having eaten a fresh spring roll (spring roll wrapper, cooked rice noodles, sprouts, cabbage, onion, herbs, lime), a plate of pad thai (noodles, cooked chicken, cooked shrimp, cooked egg, fresh sprouts, chopped peanuts), a side of larb salad (ground pork, toasted rice, fish sauce, basil, mint, lime, chilies), and chicken satay (chicken on a skewer with peanut sauce). At the time, he had noted that his chicken skewer had seemed a little pink, but it "tasted fine," and he had eaten the entire thing.

You suspect that your patient may have acquired a foodborne illness. Many diseases of the digestive system are the result of ingesting food that is not properly prepared, stored, or fully-cooked. Since your patient ate several items that could explain the symptoms and timing of his illness, it is possible that he acquired his condition via ingestion of contaminated foods.

Refine your hypothesis

To further refine your hypothesis, you'd like to know what your patient's family ate the night of the street fair.

	Fresh Spring Roll (each person had their own)	Pad Thai	Larb Salad	Chicken Satay (each person had their own)	Mango with Sticky Rice
Your Patient	x	x	x	x	-
Wife	x	x	-	x	x
Son	x	x	-	-	x

The table above summarizes what each family member ate.

4. Considering the food items each family member ate, which dish do you think is the most likely source of infection?

The larb salad

**Since your patient is the only family member to have eaten the larb salad, you are suspicious that this item is responsible for his illness. Larb is a meat salad consisting primarily of a ground meat (in this case pork), as well as fish sauce, toasted rice, herbs, spices, lime, and chilies.

You know that contaminated pork can transmit a number of infectious diseases. After a quick review of the literature, you decide to highlight following the pork-related pathogens as potential causes for your patient's illness:

Pathogens Associated with Pork
Bacteria	Escherichia coli, Listeria monocytogenes, Salmonella sp., Staphylococcus aureus, Yersinia enterocolitica
Viruses	Hepatitis E virus
Helminths	Taenia solium, Trichinella spiralis

5. Interpret results

Your patient's blood test returns from the lab. Many of his levels are within a normal range; however his complete blood count (CBC) shows an elevation in the number of eosinophils (eosinophilia) in his blood, as well as an overall elevation in total white blood cell numbers (leukocytosis). He also has higher than normal levels of creatine kinase and lactic dehydrogenase, indicating some sort of tissue damage. Which of the following hypotheses does this evidence best support?

a multicellular parasite

**Elevated numbers of eosinophils could be indicative of an active infection by a multicellular parasite.

6. Refine your hypothesis

Considering the bloodwork, time-course, and symptoms of your patient's disease, which pathogen do you suspect he has contracted?

Trichinella spiralis

**The symptoms of Trichinella spiralis infection are the best fit for what your patient has been experiencing.

Select a course of action.

Now that you have a good idea about what pathogen your patient might be harboring, you would like to run some diagnostics that will allow you to confirm the presence of Trichinella spiralis. You collect a blood and a stool sample.

7. What diagnostics would you like to perform on one or both of these samples?

serology (ELISA)

**You order serology for Trichinella antibodies to be performed on your patient's samples, as well as a quantitative immunoglobulin test.

8. Predict your results

During an infection, the levels of more than one class of immunoglobulins may increase, or sometimes decrease. An increase in which of the following classes would best support the hypothesis that your patient has a helminth infection?

IgE

** IgE can be greatly increased during T. spiralis infection. This characteristic can be very useful for a diagnosis of trichinellosis, especially when combined with positive serology, muscle biopsy, and/or a combination of other classic trichinellosis symptoms (facial and/or eyelid edema, hemorrhages under the nails (subungual hemorrhage), myalgia, and diarrhea).

9. Treat the disease

The results of your patient's ELISA return positive for T. spiralis. Your hypothesis is confirmed: your patient has trichinellosis!
Now that you've identified your patient's disease, fill out his prescription for treatment:

Mebendazole and corticosteroids

** You prescribe your patient mebendazole and a course of corticosteroids. You also notify the health authorities of your diagnosis, and subsequently call several of the hospitals on Maui where you believe your patient contracted the disease. The staff of one of the largest hospitals tells you that they have had 28 other cases of trichinellosis. The outbreak was eventually traced to the larb dish your patient ate at the street fair. The pork was ground in a meat grinder that had also been used to make sausage from at least one infected wild hog. Traditionally, the meat in larb salad can be served raw with lime juice, or lightly cooked. In this case, the infected meat was not cooked long enough to kill the encysted worms, and thus several people contracted the parasites. Trichinellosis in wild hogs can be difficult to eradicate as rodents can also serve as a reservoir for the disease. The parasite is passed when hogs or other animals eat the meat of infected animals (rats, pork, etc.). This sort of transmission cycle means that omnivorous and carnivorous animals have a high incidence of infection. Trichinellosis is frequently found in animals such as bears, mountain lions, foxes, and seals. This has been a particular problem for Inuit and Native American cultures that traditionally consume these animals. Trichinellosis is also a common problem in Southeast Asia, where raw or lightly cooked pork dishes are part of many traditional celebrations.

Chapter 25

1. Clostridium difficile-associated diarrhea is usually preceded by

extended use of antibiotics

2. Which of the following diseases of the gastrointestinal system is transmitted by the respiratory route?

Mumps

3. Which of the following statements about staphylococcal food poisoning is FALSE?

It can be prevented by heating foods to 50°C for 15 minutes.

**TRUE:

It is treated by replacing water and electrolytes.

It can be prevented by adequate refrigeration of food.

It is characterized by rapid onset and short duration of symptoms.

It is caused by ingesting an enterotoxin.

4. Which of the following organisms is likely to be transmitted via contaminated shrimp?

Vibrio parahaemolyticus

5. Aflatoxin is a(n) ________ associated with ingestion of contaminated ________.

mycotoxin; peanuts

6. "Rice water stools" are characteristic of

Cholera

7. Epidemics related to bacterial infection of the digestive system are typically caused by

contaminated food and water.

8. Many bacterial infections of the lower digestive tract are treated with

water and electrolytes.

9. Bacterial intoxications differ from bacterial infections of the digestive system in that intoxications

have shorter incubation times

10. Helicobacter pylori can grow in the stomach because it

possesses an enzyme that neutralizes HCl.

11. Following a county fair, 160 persons complained of gastrointestinal symptoms. Symptoms included diarrhea (84 percent), abdominal cramps (96 percent), nausea (84 percent), vomiting (82 percent), body aches (50 percent), fever (60 percent; median body temperature = 38.3°C); median duration of illness 6 days (range 10 hr to 13 days).
In the situation, fecal samples were found to be negative when cultured. The next step in diagnosing the cause of illness would be

microscopic examination of fecess for oocysts.

12.

Food	Relative Risk
Black beans	0.58
Corn soup	0.75
Jalapeño peppers	34.13
Roma tomatoes	5.40

The relative risks shown in the table were calculated for foods suspected of transmitting Salmonella. Which food is the most likely source of infection?

jalapeño peppers

The Case of the Hidden Souvenir

Michael was excited when his boss sent him to work on a 6-month project with the Vice President of International Affairs at their corporation in Beijing, China. Before leaving the United States, he visited his family doctor for a complete physical and to receive his immunizations. The physician reviewed Michael’s medical history and current lab results and declared that he was a healthy 32-year-old. Michael adjusted well to the move and made many new friends. They would often get together on the weekends to go swimming at a nearby lake, to play volleyball at the local park, or to watch movies and cook dinner. He quickly found that his favorite meal was a stir-fry containing a mixture of pork, fresh raw vegetables, and noodles. He would eat this combination of foods three to four times a week.

To his surprise, within 3 months of moving to China, Michael started losing weight. He was not trying to lose weight and when asked about his diet, Michael would say that he ate all the time. At first, he thought the weight loss was just a result of his metabolism adjusting to his new Asian diet and was not a cause for concern. However, after 2 months of continuous weight loss, the non-stop eating was replaced by nausea and slight abdominal pain. At this time, Michael began to think something might be wrong.

Michael scheduled an appointment with Dr. Clark at the local medical center. During his appointment, the two of them discussed where Michael had traveled since he had been in China, the types of foods he had eaten, the specifics of his exercise regimen, and his extracurricular activities. They also discussed the lack of symptoms other than the weight loss and recent bouts of nausea. After talking with Michael, Dr. Clark requested that multiple stool specimen be sent to the laboratory for examination. He also ordered serological testing of Michael’s blood to determine his antibody titer levels. He was concerned that Michael may have an intestinal parasite infection, even though many are asymptomatic.

1. Why does Dr. Clark request stool samples for examination?

He will have the laboratory prepare the samples for an ova and parasite (O&P) exam. Fresh or preserved stool samples can be observed microscopically for the presence of parasites or their eggs/cysts.

Tapeworms are pathogens of the gastrointestinal tract; as a natural progression of digestion some of the tapeworm pieces will be expelled along with fecal matter.

** Investigation of stool samples is an important diagnostic tool for physicians and other medical personnel. The stool is prepared in such a way that any parasite eggs or proglottids remain in the sample. After processing, the sample is placed on a microscope slide for observation. Staining can be performed, but is not always necessary. Morphological examination of any specimen found in the stool will help with identification.

Preliminary laboratory results rule out bacterial, viral, and protozoan infections and indicate that Michael is most likely infected with a helminthic parasite.

2. Which of the following represents the MOST LIKELY route of transmission for Michael’s infection?

Foodborne - Eating undercooked, unwashed, or otherwise contaminated food that contained parasitic propagules

** The most likely mode of transmission in Michael’s case was through the undercooked pork that he ate in his stir-fry. Humans are a definitive host for the pork tapeworm and are infected when they ingest larval cysts embedded in the muscle tissue of the pig. This transmission cycle is common in Africa, Asia, and Latin America. Interestingly, pigs in the United States are virtually parasite-free, and pork tapeworm infections are transmitted person-to-person via the fecal-oral route. Eggs from infected people with poor hygiene can be ingested by others, which allows the life cycle to continue without the pigs as an intermediate host.

3. Which of the following organisms is most likely the causative agent of Michael’s tapeworm infection?

Taenia solium

** T. solium is the tapeworm associated with eating undercooked pork. Eggs and proglottids from the adult tapeworm are released in the intestines and can be observed in fecal samples with a light microscope. Diagnosis is based on these findings.

Microscopic analysis of Michael’s stool sample confirmed the presence of tapeworm eggs and proglottids in the genus, Taenia. Image A is the microscopic view of tapeworm eggs from a fecal sample. Image B is the microscopic view of a proglottid from a fecal sample. Dr. Clark informed Michael that given his diet history, he is most likely infected with the pork tapeworm, T. solium. A related species, T. saginata, is associated with eating raw beef and its scolex differs from that of T. solium. Image C is T. solium, the pork tapeworm. Notice how T. solium has a row of hooks. These structures are not found in T. saginata. Image D is Enterobius vermicularis, a roundworm.

4. Compare the anatomy of the tapeworm (Image C) to the anatomy of the roundworm (Image D). Given that both are parasitic worms, which of the following reasons best explains why the tapeworm is flat?

Tapeworms utilize diffusion to absorb nutrients from the host’s digestive system.

** The tapeworm’s high surface-area-to-volume ratio is an adaptation to utilize diffusion in the nutrient-rich environment of the host’s intestine. These worms lack digestive structures and must rely on the host to completely digest food before it is absorbed by the worm via its outer layer called a cuticle. Roundworms have a more complex digestive system and are capable of digesting food that has only been partially digested by the host. This decreases the need for a high surface-area-to-volume ratio because diffusion of nutrients is no longer an issue.

5. What is the correct sequence of events for the life cycle of the pork tapeworm, T. solium?

Eggs are produced by adult tapeworms living in the definitive host.

Eggs are released to the environment in the feces.

Pig eats grass contaminated, or fertilized, with human feces.

Inside the intermediate host, the eggs mature into larvae and encyst in the hosts muscles.

The definitive host ingests the larvae and becomes infected.

** The adult worm produces thousands of eggs in the human host. These eggs leave the digestive tract via the feces. When pigs eat grass contaminated with, or fertilized by, human feces they become infected with T. solium. The tapeworm eggs mature into larvae that encyst themselves in the muscle tissue of the pig. When humans eat pork that has not been cooked to high enough temperatures, they become infected with the tapeworm.

Michael’s blood work reveals an increase in eosinophils, which are granular white blood cells, and his IgE antibodies. Along with the microscopic analysis of the stool specimen, these lab results confirm the diagnosis of a tapeworm infection

6. Why do we see an increase in the levels of IgE antibody in Michael’s serum?

IgE is the class of antibodies involved in hypersensitivities such as allergies and parasitic infections.

**IgE is typically found in very low amounts in the blood serum. It increases in response to allergic reactions and parasitic infections. There is also a correlation with an increase in IgE amounts and the increase of eosinophils in a blood smear. Eosinophils are white blood cells that release peroxide ions to destroy the parasite from the outside.

7. What is the treatment that Dr. Clark will most likely recommend?

Praziquantel or albendazole, drugs that target eukaryotic parasites with minimal side effects in the host.

** Praziquantel and albendazole are both anti-helminthic drugs. Praziquantel is effective against tapeworms because it changes the permeability of the cuticle and blocks nutrient uptake. During this process the drug also uncovers surface antigens that stimulate an immune response. Albendazole is a broad-spectrum anti-helminthic drug that also blocks nutrient uptake by inhibiting microtubule formation in the cytoplasm. It is used commonly to treat livestock as well.

After treatment, Dr. Clark wanted to monitor Michael’s progress to make sure the tapeworm infection was completely cleared. He also ordered Michael to get a computed tomography (CT) scan and a magnetic resonance imaging (MRI) scan. These scans confirmed that Michael’s infection was localized to the digestive tract and the tapeworms had not spread beyond that point.

8. Why was Dr. Clark worried about tapeworm infection in other body sites?

When tapeworm larvae escape the stomach, they can travel to other parts of the body such as muscles, the liver, the eye, and even the brain to form cysticerci.

The presence of T. solium in the brain can result in neurocysticercosis, a serious condition which has symptoms resembling those of brain tumors or epilepsy.

** Tapeworms in the intestinal tract are usually asymptomatic. Humans are the definitive host and support the growth of adult tapeworms. Pigs are intermediate hosts that continue the life cycle of T. solium. Occasionally, the human host can become an intermediate host. Larvae escape the stomach and migrate to other tissues in the body. Once in other tissues, the larvae form cysts called cysticerci. These cysts can cause problems, especially in the eye and in the brain.

Chapter 25

1. Bacterial infections, but not intoxications, can cause diarrhea.

FALSE

2. An outbreak of viral gastroenteritis occurs in a pediatrics ward. Rotavirus is the most likely causative agent.

TRUE

Big Picture Coaching Activity: Cholera after natural disasters

Cody is an epidemiologist working for the Centers for Disease Control and Prevention (CDC) in Atlanta. He is on his way to a local college to give a presentation on cholera to the members of the Microbiology Club. The focus of his talk is a cholera epidemic in Haiti that followed an earthquake in 2010.

1. Causative agent of cholera

Cholera is a waterborne pathogen that causes severe gastrointestinal disease. The organism is a slightly curved, gram-negative rod that likes to grow in the small intestine and causes watery stools and violent vomiting. Complete the following statement: Cholera is caused by the bacterium, __________ and produces __________ that result in severe diarrhea.

Vibrio cholera; exotoxins

** The causative agent of cholera is Vibrio cholerae. This organism is a curve-shaped, gram-negative rod. It produces cholera toxin, which is an exotoxin that causes infected individuals to experience extreme diarrhea and vomiting.

2. Effect of natural disasters

During his presentation to the Microbiology Club, Cody mentions that the cholera epidemic in 2010 came shortly after an earthquake. He also mentions that other cholera epidemics had occurred following natural disasters such as flooding. Which of the following has the greatest impact on the number of cholera cases after a natural disaster?

sewage contamination in drinking water

** In the Big Picture activity, it mentions that the displacement of people and a loss of clean drinking water is the biggest contributor to cholera outbreaks. Given that cholera is caused by a bacterium found in the gastrointestinal tract, it makes sense that the feces of infected individuals would contain the pathogen. If the feces contaminate the water and then the people drink the water, this can lead to an epidemic. It is important to maintain water purification, especially following a natural disaster.

3. Mechanism of the cholera toxin

The pathogenesis of Vibrio cholerae is due to the organism’s ability to produce cholera toxin. This is an A-B toxin that affects host cells in the small intestine. Which of the following correctly describes the mechanism of the toxin?

The cholera toxin causes the host cells to secrete large amounts of fluids and electrolytes.

** The production of a superantigen and toxic shock syndrome is the mechanism used by staphylococcal enterotoxin.

4. Treatment

In untreated individuals, the mortality rate of cholera can be as high as 50%, but in individuals that are given oral rehydration therapy, fatalities are rare. Oral rehydration therapy involves treating the patients with an oral suspension of salt, sugar, and water. Which of the following choices explains why this suspension is used instead of pure water to treat cholera infections?

The salt and sugar in the rehydration solution will replace lost electrolytes and the water replaces the lost water.

** The oral rehydration solution is used over pure water because the salt and sugar compounds have ions that will replace the lost electrolytes. In the case of cholera, fatalities occur because a patient can lose between 12 and 20 liters of fluids in a day, and the large loss can lead to shock, collapse, and even death. It is very important in this situation to replace the electrolytes and the water that has been lost.

5. Bacterial infection versus intoxication

In this case study, the main focus has been on the organism Vibrio cholerae and the toxin it produces. Many organisms are capable of producing toxins that allow for pathogenesis, while others are able to infect the host directly and cause disease. In this activity, you will place the organism in a bin based on its ability to cause an infection, an intoxication, or both.

Infection: Shigella sonnei; Vibrio cholerae; Escherichia coli; Salmonella enterica

Intoxication: Staphylococcus aureus

Clinical Microbiology HW#14

Chapter 24

1. The patient is suffocating because of an inflamed epiglottis. What is the etiology of the symptoms?

Haemophilus

2. The patient has a sore throat. What is the etiology of the symptoms?

The answer cannot be determined based on the information provided

3. It is common for a normal, healthy individual to carry potentially pathogenic organisms in their upper respiratory tract.

TRUE

4. Which of the following diseases has a cutaneous form, especially in individuals over 30 years of age?

Diphtheria

5. The patient is suffocating because of the accumulation of dead tissue and fibrin in her throat. What is the etiology of the symptoms?

Corynebacterium

6. A patient has a paroxysmal cough and mucus accumulation. What is the etiology of the symptoms?

Bordetella

7. All of the following are true of the common cold EXCEPT

early treatment will drastically reduce the disease symptoms

Concept Map: Tuberculosis

1. Tuberculosis is the name of the ___________ caused by the _________ Mycobacterium tuberculosis.

Disease; bacterium

2. What can you deduce from the treatment strategy for M. tuberculosis infection?

The organism has some innate resistance to antibiotics.

**It is rare that you have to treat an infection with multiple antibiotics for such a long period of time.

3. Which of the following could be true of tuberculosis of the kidney?

All of the above could be true

**TRUE:

The disease could be subsequent to a normal primary infection.

The disease could be subsequent to a reactivated latent infection.

The patient would likely be infected with MDR TB or XDR TB.

The patient would likely have a positive skin test.

Chapter 24

1. Which of the following is mismatched?

Mycoplasma – gram-positive pleomorphic rod

2. Which of the following statements regarding tuberculosis is FALSE?

Nearly 1/3 of the worlds population shows symptoms of tuberculosis

3. A patient has fever, difficulty breathing, chest pains, fluid in the alveoli, and a positive tuberculin skin test. Gram-positive cocci are isolated from the sputum. The patient most likely has

pneumococcal pneumonia

4. Which one of the following produces small "fried-egg" colonies on medium containing horse serum and yeast extract?

Mycoplasma

5. The most common causative agent of bacterial pneumonia is Streptococcus pneumoniae.

TRUE

6. A positive tuberculosis skin test indicates that the patient has active tuberculosis.

FALSE

7. The primary victims of the influenza pandemic of 1918-1919 were

young adults

8. Vaccination with the influenza vaccine confers lifelong immunity to influenza virus.

FALSE

9. Microscopic examination of a lung biopsy shows thick-walled cysts. What is the etiology of the symptoms?

Pneumocystis

10. Which statement regarding influenza (flu) is true?

Antigenic shift can occur because the genome is in several pieces.

Diseases in Focus Chapter 24 – Male, age 78

MEDICAL HISTORY (Hx)

The patient is a male, age 78. He was admitted to the hospital for fever, chills, chest pain, and a productive cough. He lives in Houston, Texas, and is an aspiring author and retired investment banker. He spends much of his retired life golfing, or working on his novel. He is sexually active, and in a non-monogamous relationship. He and his partners are consistent with their use of birth control. He lives in a loft apartment by himself, and owns a dog. He is allergic to peanuts, but does not have any special concerns that would affect your ability to treat him. His family history does not suggest any factors associated with genetic disease. He smokes regularly (1 pack/day), and reports drinking alcohol (5+ drinks) 3 times a week, on average. He does not use drugs of abuse. Two weeks ago, he traveled to Seattle for two days to meet with his editors. Within the last five days he began to feel unusually tired with a persistent dry cough. As time passed, his cough worsened, and he developed a fever and chest pains. He also had several bouts of loose, watery diarrhea. Upon admission to the hospital, he seems clumsy and uncoordinated, with a fever of 40.8∘C.

Differential Diagnoses

Differential diagnosis is the process of identifying a disease from a list of possible diseases that fit the information derived from examining a patient. Your job will be to synthesize information from a patient whose main presenting symptoms are consistent with a microbial disease of the respiratory system. Use the "Diseases in Focus" 24.1, 24.2, and 24.3 tables and your knowledge about microbial diseases of the respiratory system to identify the patient's risk factors and symptoms, evaluate diagnostic evidence, formulate and test a diagnosis about the pathogen responsible for the patient's woes, and suggest a course of treatment.

1. Identify relevant information

Review the patient's medical history, and then identify risks and concerns that could be relevant to your diagnosis (and the patient's treatment).

Relevant:

Age-related risk of disease

Risk of sexually transmitted infection

Risk of vector-borne disease

Risk of travel-related disease exposure

Not Relevant:

Occupational risk of disease

Risk of drug-related disease exposure

Risk of genetic/familial disease

Special concerns for treatment

Risk of immunocompromised

**You have reviewed your patient's medical history, and you recognize several factors that could be relevant to your diagnostic process. His age, sexual habits, travel history, and pet dog all could increase his exposure to diseases, pathogens, or vector organisms.

Your first concern however, is that your patient's symptoms seem to include changes in his mental state. He is clumsy and uncoordinated, which could potentially signal a serious or life-threatening condition. He also has a high fever, a productive cough, and occasional diarrhea. These latter symptoms are general enough that they could apply to several different types of respiratory disease, but your patient's fever and possible cerebral involvement up the ante enough that you would like to begin treating him as soon as possible. You take a blood sample and a nasal swab from your patient, and order smear preps from the samples for Gram-staining and other diagnostics. While you wait for your results, you order a chest x-ray for your patient.

X-ray results

Your patient's x-ray is shown here. You observe bilateral (both sides of the body) basal (lower) pulmonary congestion, as well as pleural effusion, indicating excess fluid between the two pleural layers. These results are compatible with a diagnosis of pneumonia.

 

2. Interpret your results

Now that you have considered the evidence at hand, you should start to build a hypothesis about what disease your patient has. In the beginning of your diagnostic process you should try and think broadly to help you consider any and all reasonable possibilities. You can then narrow down these possibilities by performing diagnostics that can support or refute your hypothesis.

A form of bacterial pneumonia

Melioidosis

Viral pneumonia, RSV

Coccidioidomycosis

**You have narrowed down the diseases you suspect are responsible for your patient's condition to a form of bacterial or viral pneumonia, melioidosis, influenza, or coccidioidomycosis. Now you must wait for your initial diagnostics to return from the lab.

3. Interpret your results

After a day, you receive the following results:

What does this tell you?

Your patient's samples show the presence of a Gram-negative bacteria.

**Your initial results are positive for the presence of a Gram-negative bacterium. You believe your patient has a form of bacterial pneumonia!

4. Refine your hypothesis

Based upon these results, which of the following could your patient have?

Haemophilus influenzae pneumonia

Legionellosis

Melioidosis

**Your patient's Gram-stained sample does not show clear evidence for a Gram-positive pathogen, or for one with an obligate intracellular habit. Thus, you suspect your patient has Haemophilus influenzae pneumonia, legionellosis, or meliodosis.

5. Select a diagnostic

You would now like to try and culture your pathogen. Shown are three different types of media: A. Blood agar with gentamicin
B. Buffered charcoal-yeast extract agar
C. Chocolate agar with X and V factors

            Blood agar with gentamicin – Burkholderia pseudomallei

            Buffered charcoal-yeast extract agar – Legionella pneumophila

            Chocolate agar with X and V factors – Haemophilus influenza

After a five days, you observe the following:

 

6. Diagnose the disease

What diseases could result from the organism you cultured?

legionellosis

Pontiac fever

** Legionella pneumophila can cause both Pontiac fever and legionellosis

7. Fill in the disease that best fits your patient's symptoms.

Of the two diseases caused by the pathogen you isolated,  legionellosis fits your patient's symptoms the best.

8. Treat the disease

How will you treat this disease?

Erythromycin

** You start your patient on a course of erythromycin

9. Legionelllosis is a nationally reportable disease, and you must notify the authorities of your finding. Before you call in your diagnosis however, you want to try and identify how your patient first contracted it. You decide to question your patient about his possible exposure history in the ten days before his illness. You ask him if he has been in, around, or used:

a decorative fountain

any form of respiratory therapy equipment (e.g. sleep apnea, asthma devices)

a mall or other large enclosed shopping venue

long-term care, senior, or assisted living facility (e.g. nursing home, rehab facility)

a hospital (besides his current stay)

a shower (away from home)

construction or projects affecting, plumbing and/or water lines

a hotel

a pool, hot tub, jacuzzi or whirlpool spa

a doctor's or dentist's office

a steam room or sauna

grocery stores with misters for fruit and vegetables

recreational misters

a humidifier

** Legionellosis can be transmitted by almost any situation involving water conditions where the bacteria can grow, particularly if they are able to form a highly resistant biofilm. Legionella already exists in most water systems; however the frequency of outbreaks still remains relatively low.

10. As you read off the above questions to your patient, you start to get a feeling for the ubiquity of Legionella pneumophila in water sources. If Legionella is so common, then why doesn't everyone get sick? Generally, the risk of contracting legionellosis is low for an immunocompetent person; however there are some factors that seem to increase the likelihood of contracting the disease. Which of the following factors specific to your patient do you think played a role in whether or not he got sick once exposed to the bacterium?

His age

His cigarette and alcohol consumption

His travel history

** Men over the age of 50 are the most likely to contract legionellosis, especially if they are heavy smokers or drinkers.

Conclusion

Your patient answers your questions one by one. In Seattle, he stayed at a hotel with a decorative fountain in the lobby. He swam in the hotel's pool once, and spent roughly thirty minutes each night (for two nights) in the hotel's jacuzzi. He also took a shower in his room's bathroom. Subsequent analysis of the water sources throughout the hotel and his room were negative for Legionella.
Once back at home, your patient recalls going shopping at a local grocery store that uses misters to keep vegetables fresh. He also brought his dog to a grooming salon, where he opted to bathe the animal himself. He spent an hour bathing the dog, and was often splashed by the water from the grooming sink. Lastly, he visited the dentist for to get a filling replaced shortly before he took ill.
Water sources and lines were analyzed at every location he visited. The water at the grocery store and the dentist's was negative for Legionella; however the water at the dog grooming salon tested positive! The salon was immediately shut down, and all recent clients were contacted regarding a possible outbreak.
Your patient makes a full recovery on your course of erythromycin, and further spread of the disease was prevented by your speedy diagnosis!

Influenza: From the Great War to Today

It was the spring of 1918, and the world was at war. In Haskell County, Kansas, an epidemic of influenza was underway. Public health officials in Washington, D.C. were notified; however, no investigators were sent. Meanwhile, soldiers from all across Kansas were reporting to Camp Funston in training for the war. In hindsight, it appears that a soldier from Haskell County brought influenza with him to Camp Funston. By the middle of March, there was an epidemic in the camp. Ultimately, about 1100 soldiers were infected and 38 died during the outbreak. Unfortunately, the reporting methods at that time were not particularly good. The epidemic at Camp Funston essentially went unnoticed by public health officials. Within only a few months, the country would be caught in an epidemic that no one could ignore.

During the initial epidemic at Camp Funston, the infection was characterized by several of the typical symptoms of influenza infection.

1. Which of the following are symptoms of influenza infection?

Headache; fever; muscle pain

** After the person is exposed to the flu virus, there is a short incubation period—only about one day—before symptoms of infection appear. Influenza infection commonly causes muscle aches and headache. These are most likely due to the fever that is part of the normal immune response to infection. As fever raises the body temperature, cellular demand for water will increase. At the same time, the person’s appetite and thirst are typically depressed, leading to decreased consumption of water. These two factors contribute to dehydration and an electrolyte balance, which typically manifest as general malaise and headache.

The structure of the influenza virus is central to its ability to cause disease in susceptible hosts. The structure of the virus is relatively simple (compared to that of a prokaryotic or eukaryotic cell); however, each component has an important role to play in the infectious cycle of influenza.

2. Drag each one of the labels onto the figure to identify the function of each structure.

 

** During infection, the structure of influenza plays a vital role. Hemagglutinin (HA) mediates attachment to the host cells, after which the lipid envelope fuses with the host cell membrane. This allows the virus to be internalized, followed by release of the RNA genome from the capsid. Viral proteins will be produced, assembled, and released from the host cell. Release is mediated by neuraminidase (NA), and as the viral particles leave, they take part of the host membrane, thereby creating their envelope.

During the spring and summer of 1918, cases of influenza began to emerge throughout Europe. Soldiers on both sides of the front were struck down by this invisible pathogen. In contrast to the cases seen at Camp Funston, these infections were much more severe, with symptoms resembling those of pneumonia. As the months went on, the death toll continued to rise.

3. The successful infection of a host, and subsequent spread to another, results from a specific sequence of events known as the replication cycle. Each of the statements below describes an important step in the replication cycle of influenza.

Arrange the following statements in the order that best describes the sequence of events involved in the replication of influenza.

1. Hemagglutinin (HA) spikes attach to host cells.

2. Influenza enters the host cell.

3. Nucleic acid enters the host cytoplasm.

4. Influenza proteins are synthesized.

5. Influenza nucleic acid is packaged in capsid.

6. Influenza particles bud from the cell, releasing the virus into the surrounding environment.

** After gaining entry to the host respiratory system, influenza adheres to host cells. The virus then enters the cells and begins the process of hijacking host machinery in order to produce new viral particles. After all the components are synthesized, they are assembled, and the virus leaves via budding. The newly released particles then infect neighboring cells, perpetuating the infection.

It is thought that in Europe, the influenza virus changed in such a way to make it more virulent in the human population, resulting in increased severity of disease and increased mortality. What changes could have led to the differences in pathology observed in Camp Funston and in Europe? Research in recent years has led to our understanding that these changes were due to the process known as antigenic shift.

4. Which of the following statements regarding antigenic shift are true?

Viral strains resulting from antigenic shift contain RNA segments from different species.

Little immunity to virus strains resulting from antigenic shift exists in the population.

Antigenic shift results in a major change in the genetic composition of the virus.

** Genetic analysis of the 1918 flu revealed that it contained genetic material that was both avian and mammalian in origin. This reassortment led to a deadly combination—a virus that was both highly virulent and transmissible. These factors, coupled with the lack of immunity in any population, led to the pandemic that impacted the entire world.

Research conducted in recent years on the 1918 flu indicated that the high mortality rate and the severe pathology associated with the disease were likely due to a cytokine storm that was stimulated during infection. Recall that when they are released, cytokines stimulate the production of more cytokines (positive feedback). Sometimes, this feedback spins out of control, leading to an overproduction of cytokines known as a cytokine storm.

5. Predict which of the following are reasonable outcomes of the cytokine storm during the 1918 flu pandemic.

an excessive inflammatory response leading to extensive tissue damage

increased fluid in the lungs and labored breathing

** The cytokine storm during infection with the 1918 influenza was extremely destructive. The massive release of cytokines in the lungs led to an uncontrolled inflammatory response. As cells moved into the lung tissue, the tissue was destroyed. Fluid entered the lungs, and patients struggled to breathe. Furthermore, the ability to deliver oxygen to the body was severely compromised, giving many patients a blue appearance.

As soldiers returned home to the United States in the fall of 1918, they brought the deadly flu with them. The first cases were noted in August of 1918. By September of that year, influenza epidemics were reported in California, Texas, North Dakota, and Florida. The disease would continue to spread throughout the fall and winter of 1918 and into the spring of 1919. It is estimated that the 1918–1919 influenza pandemic resulted in approximately 675,000 deaths in the United States and more than 20 million worldwide. Today, approximately 30,000 to 50,000 people die each year from influenza infection. Several factors play a role in this relatively low mortality rate. One factor is the availability of an influenza vaccine. But although the vaccine does offer protection, its design and production are not without their challenges.

6. What are some of the current challenges to production of the influenza vaccine?

In order to yield a vaccine, the virus must be produced in eggs.

The virus undergoes antigenic changes on a regular basis.

** A vaccine for influenza has been available since about 1945. The current vaccine generates protection against the three strains most likely to cause infection during the flu season. The vaccine is currently available in two forms: a nasal spray (made from live, attenuated virus) and an injection (made from inactivated virus). Although both offer protection, the effect is relatively short-lived and is specific only for the three strains contained in the vaccine.

In addition to the vaccine, several antiviral drugs are available to treat influenza infection. One of the most prescribed treatments for influenza is Tamiflu (osteltamivir). Tamiflu works by inhibiting the action of neuraminidase (NA).

7. Predict which of the following would be outcomes of treatment with Tamiflu.

overall decrease in the replication rate of influenza

an increase in the ability of the immune system to combat the infection

a decrease in the release of viral particles from the cell

** If taken within 30 hours of the appearance of symptoms, Tamiflu is quite effective at inhibiting viral replication. Because NA has been inhibited, the viral particles are unable to bud from the infected cells. As a result, the infection isn’t perpetuated. This slowing in the replication cycle gives the body enough time to mount an effective immune response and eventually eliminate the infection.

Big Picture Coaching Activity: Pertussis

Megan woke up this morning with a feeling of dread. School was about to start, and Megan was due for her fifth DTaP, her second MMR, and her second Varicella vaccinations. Her physician explained that the DTaP vaccine would give her protection against diphtheria, tetanus, and whooping cough. He also said that the MMR would protect her against measles, mumps, and rubella, while the varicella shot would help protect against the chicken pox.

1. Causative Agent of Whooping Cough

Bordetella pertussis

** Whooping cough is caused by Bordetella pertussis, a small, obligately aerobic, gram-negative coccobacillus.

2. Pathogens of the Bacterium

Lower respiratory system infections, such as whooping cough, can lead to bronchitis or pneumonia due to the inhibition of normal protective responses. Which of the following explains how the pathogen overcomes normal protective responses of the respiratory system?

The bacteria attach to the ciliated cells of the trachea, thus preventing mucus from being cleared.

** Bordetella pertussis attaches to the ciliated epithelial cells of the trachea, which impedes the movement of the cilia. Without being able to move, the cilia cannot clear the mucus from the respiratory system and excess amounts accumulate.

While Megan was waiting for the administration of her vaccines, she was looking at all of the posters on the wall in the exam room. One of the posters was an information sheet on whooping cough. This poster listed the characteristics of the organism, signs and symptoms, the progression of infection, and finally the various vaccine options for this organism.

3. Progression of infection

Megan learned from the poster that there were three main stages of whooping cough. Place the following in order of how they would occur during progression of the infection.

Catarrhal; Paroxysmal; Convalescence

** Catarrhal refers to the initial stage of whooping cough that closely resembles a common cold. This may lead to misdiagnosis or delay in treatment. Paroxysmal refers to the second stage of disease progression when the patient, usually a child, suffers prolonged sieges of coughing. This excessive coughing is a result of the body trying to clear the mucus that has accumulated after the cilia were destroyed in the trachea. The final stage of whooping cough is the convalescence stage and can last several months.

4. Vaccine Effectiveness

The exam room poster for whooping cough also listed the various vaccines that could be given. The three possible vaccines were the DTP, the DTaP, and the Tdap. The DTP was made with heat-killed whole cells of the bacterium B. pertussis, while the DTaP and the Tdap were made with acellular pertussis components. Which of the following statements regarding the vaccines explains why the DTP vaccine is no longer used?

Bordetella pertussis was not killed during the heating process used on the DTP vaccine and could cause an active infection

** Bordetella pertussis whole cells used in the vaccine were heat-killed before being included in the vaccine. If the heating process was not done properly, the cells were not killed. When this happened to an entire batch of the vaccine, an epidemic of whooping cough resulted. It was determined that the bacteria in the vaccines were living and capable of causing infection. This led the health officials to determine that a safer vaccine was necessary.

The DTaP vaccine mentioned in the previous question was created as a safer vaccine than the DTP. After this vaccine was transitioned into use, epidemiologists were surprised to find that whooping cough infection rates were still increasing, rather than decreasing.

5. Immune Response

Many possible explanations were given as to why the numbers of pertussis infections were increasing, but the most likely explanation was that the DTaP vaccine was not as effective as the DTP at protecting children long-term. Which of the following best describes why this is the case??

The DTaP vaccine is not made with cellular components that would stimulate the immune system as effectively as the DTP vaccine.

** Cellular components are more effective at stimulating the immune response than non-cellular or acellular components. The reason that the number of cases most likely rose after the switch to the DTaP is that it did not offer the same long-term effectiveness because it lacked cellular components. As a result, an additional booster called the Tdap vaccine helps to provide protection after the memory has worn off from the DTaP vaccine, but it is not recommended for teenagers and expectant moms.