Bacterial Diseases of the Cardiovascular and Lymphatic Systems

Sepsis and Septic Shock

Septic shock occurs when a body’s response to an infection (sepsis) leads to life-threatening low blood pressure.

Learning Objectives

Compare and contrast the symptoms of: sepsis, severe sepsis, septic shock

Key Takeaways

Key Points

  • Sepsis results from certain bacterial infections, often acquired in a hospital. Having certain conditions, such as a weakened immune system, certain chronic disorders, an artificial joint, or heart valve increases the risk.
  • Symptoms of sepsis include either fever or low body temperature, rapid breathing, chills and shaking, rapid heartbeat, decreased urine output, and confusion or delirium.
  • Severe sepsis often causes extremely low blood pressure, which limits blood flow to the body and can result in organ failure and death. This is known as septic shock.
  • Sepsis is treated with antibiotics, fluids, and medicines to support blood pressure and prevent organ damage.

Key Terms

  • septic shock: A life-threatening condition caused by infection and sepsis, often after surgery or trauma.
  • sepsis: A life-threatening medical condition caused by a severe inflammatory response of the human body triggered by the presence of an infectious agent.
  • mortality rate: the number of deaths per given unit of population over a given period of time

Sepsis is a potentially deadly medical condition characterized by a whole-body inflammatory state (called a systemic inflammatory response syndrome or SIRS) that is triggered by an infection. Septic shock is a medical condition as a result of severe infection and sepsis, though the microbe may be systemic or localized to a particular site. Its most common victims are children, immuno-compromised individuals, and the elderly, as their immune systems cannot deal with the infection as effectively as those of healthy adults. Frequently, patients suffering from septic shock are cared for in intensive care units. The mortality rate from septic shock is approximately 25–50%.

Sepsis

Sepsis is an illness in which the body has a severe response to bacteria or other germs. The body may develop this inflammatory response by the immune system to microbes in the blood, urine, lungs, skin, or other tissues. A popular term for sepsis is blood poisoning. Severe sepsis is the systemic inflammatory response, infection, and the presence of organ dysfunction.

A bacterial infection anywhere in the body may set off the response that leads to sepsis. Common places where an infection might start include:

  • the bloodstream
  • bones (common in children)
  • the bowel (usually seen with peritonitis)
  • the kidneys (upper urinary tract infection or pyelonephritis )
  • the lining of the brain ( meningitis )
  • the liver or gallbladder
  • the lungs (bacterial pneumonia )
  • the skin (cellulitis)

For patients in the hospital, common sites of infection include intravenous lines, surgical wounds, surgical drains, and sites of skin breakdown known as bedsores (decubitus ulcers).

The therapy of sepsis rests on intravenous fluids, antibiotics, surgical drainage of infected fluid collections, and appropriate support for organ dysfunction. This may include hemodialysis in kidney failure, mechanical ventilation in pulmonary dysfunction, transfusion of blood products, and drug and fluid therapy for circulatory failure. Ensuring adequate nutrition—preferably by enteral feeding, but if necessary by parenteral nutrition—is important during prolonged illness.

Septic Shock

In sepsis, blood pressure drops, resulting in septic shock. Major organs and body systems, including the kidneys, liver, lungs, and central nervous system, stop working properly because of poor blood flow.

Most cases of septic shock are caused by Gram-positive bacteria, followed by endotoxin-producing Gram-negative bacteria. Endotoxins are bacterial membrane lipopolysaccharides (LPS) consisting of a toxic fatty acid (lipid A) core common to all Gram-negative bacteria, and a complex polysaccharide coat (including O antigen) unique for each species. Analogous molecules in the walls of Gram-positive bacteria and fungi can also elicit septic shock. In Gram-negative sepsis, free LPS attaches to a circulating LPS-binding protein, and the complex then binds to a specific receptor (CD14) on monocytes, macrophages, and neutrophils.

If sepsis worsens to the point of end-organ dysfunction (renal failure, liver dysfunction, altered mental status, or heart damage) then the condition is called severe sepsis. Once severe sepsis worsens to the point where blood pressure can no longer be maintained with intravenous fluids alone, then the criteria have been met for septic shock. The precipitating infections which may lead to septic shock if severe enough include appendicitis, pneumonia, bacteremia, diverticulitis, pyelonephritis, meningitis, pancreatitis, and necrotizing fasciitis.

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Sepsis: Sepsis due to meningococcal disease.

Treatment primarily consists of the following:

  1. Volume resuscitation
  2. Early antibiotic administration
  3. Early goal directed thearpy
  4. Rapid source identification and control.
  5. Support of major organ dysfunction.

There are new drugs that act against the extreme inflammatory response seen in septic shock. These may help limit organ damage.

The mortality rate from sepsis is approximately 40% in adults, and 25% in children, and is significantly greater when left untreated for more than seven days.

Bacterial Infections of the Heart

Bacterial endocarditis is an infection of the inner surface of the heart or heart valves caused by the presence of bacteria in the blood.

Learning Objectives

Recognize the causes and treatments for endocarditis

Key Takeaways

Key Points

  • Endocarditis occurs when bacteria grow on the edges of a heart defect or on the surface of an abnormal valve after the bacteria enter the blood stream, most commonly from dental procedures but also from procedures involving the gastrointestinal or urinary tract.
  • The most important diagnostic test for endocarditis involves a positive blood culture. A blood culture is a small sample of blood drawn from the vein which is grown in a special solution so that bacteria can be detected.
  • Symptoms and signs of endocarditis vary but include prolonged fever poor appetite, feeling weak or tired, joint pains, skin rashes, and changes in the nature of a previously present heart murmur.
  • Treatment of bacterial endocarditis consists of a period of intravenous doses of appropriate antibiotics determined from blood tests under the supervision of an infectious disease specialist and cardiologist.

Key Terms

  • Endocarditis: An inflammation of the interior lining of the heart or the endocardium and possibly the heart valves (pathology, cardiology).
  • bacteremia: The medical condition of having bacteria in the bloodstream.

In a healthy individual, a bacteremia (where bacteria get into the blood stream through a minor cut or wound) would normally be cleared quickly with no adverse consequences. If a heart valve is damaged and covered with a piece of blood clot, the valve provides a place for the bacteria to attach themselves and an infection can be established. Endocarditis, or inflammation of the inner tissue of the heart, occurs as a result. The valves of the heart do not receive any dedicated blood supply. As a result, defensive immune mechanisms (such as white blood cells) cannot directly reach the valves via the bloodstream. When bacteria attaches to a valve surface and forms a vegetation, the host immune response is blunted. The lack of blood supply to the valves also has implications for treatment, since drugs also have difficulty reaching the infected valve. Normally, blood flows smoothly through these valves. If they have been damaged – from rheumatic fever, for example – the risk of bacterial attachment is increased.

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Endocarditis ultrasound: Vegetation on tricuspid valve by echocardiography. Arrow denotes the vegetation.

Bacteremia caused by dental procedures (in most cases due to streptococci viridans, which reside in oral cavity), such as a cleaning or extraction of a tooth and from procedures involving the gastrointestinal or urinary tract can cause bacterial endocarditis. Intravenous drug abuse may also cause bacterial endocarditis from the aseptic introduction of skin bacteria.

Symptoms and signs of endocarditis vary, but prolonged fever (more then 2-3 days) without an obvious cause is a most important sign and should always be investigated in a child with congenital heart disease. Other signs and symptoms include poor appetite, feeling weak or tired, joint pains, skin rashes, and changes in the nature of a previously present heart murmur. The chance that these signs and symptoms are caused by endocarditis is more likely if they occur soon after a dental cleaning or procedure involving the gastrointestinal or urinary tract.

High dose antibiotics are administered by the intravenous route to maximize diffusion of antibiotic molecules into vegetation(s) from the blood filling the chambers of the heart. This is necessary because neither the heart valves nor the vegetations adherent to them are supplied by blood vessels. Antibiotics are continued for a long time, typically two to six weeks depending on the characteristics of the infection and the causative microorganisms.

Rheumatic Fever

Rheumatic fever is an inflammatory disease that can develop as a complication of inadequately treated strep throat.

Learning Objectives

Outline the effect of infection by Steptococcus pyogenes on the immune system

Key Takeaways

Key Points

  • Rheumatic fever is a condition that is a complication of untreated strep throat. Strep throat is caused by a group A streptococcal infection found in the throat.
  • When the body senses the strep infection, it sends antibodies to fight it and sometimes these antibodies attack the tissues of your joints or heart instead. This is known as anitbody cross-reactivity which leads to rheumatic fever.
  • Symptoms of rheumatic fever occur several weeks after initial throat problems have disappeared; and include chest pain, fever, heart problems, joint pain, nosebleeds, and skin rash.
  • Rheumatic fever is treated using a combination of antibiotics and anti-inflammatory medications.

Key Terms

  • rheumatism: Any disorder of the muscles, tendons, joints, bones, nerves, characterized by pain, discomfort and disability.
  • Streptococcus: A spherical, gram-positive bacterium of the genus Streptococcus. Although commonly found benignly in the human mouth and gut, and though many species are non-pathogenic, other species can cause diseases including strep throat and more serious conditions.

Rheumatic fever is an inflammatory disease that occurs following a Streptococcus pyogenes infection, such as streptococcal pharyngitis (strep throat) or scarlet fever, that affects the peri-arteriolar connective tissue. Believed to be caused by antibody cross-reactivity that can involve the heart, joints, skin, and brain; the illness typically develops two to three weeks after a streptococcal infection.

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Streptococcus pyogenes bacteria: Photomicrograph of Streptococcus pyogenes bacteria, 900x Mag. A pus specimen, viewed using Pappenheim’s stain. Last century, infections by S. pyogenes claimed many lives especially since the organism was the most important cause of puerperal fever and scarlet fever.

Acute rheumatic fever commonly appears in children between the ages of six and 15, with only 20% of first-time attacks occurring in adults. The illness is so named because of its similarity in presentation to rheumatism.

This cross-reactivity is a Type II hypersensitivity reaction and is termed molecular mimicry. During a Streptococcus infection, mature antigen -presenting cells, such as B cells, present the bacterial antigen to CD4-T cells which differentiate into helper T2 cells. In turn, Helper T2 cells activate the B cells to become plasma cells and induce the production of antibodies against the cell wall of Streptococcus. However the antibodies may also react against the myocardium and joints, producing the symptoms of rheumatic fever.

Diagnosis of rheumatic fever can be made when two of the major criteria, or one major plus two minor criteria, are present along with evidence of streptococcal infection.

The major criteria for diagnosis include:

  • Arthritis in several large joints (polyarthritis)
  • Heart inflammation (carditis)
  • Nodules under the skin (subcutaneous skin nodules)
  • Rapid, jerky movements (chorea, Sydenham chorea)
  • Skin rash (erythema marginatum)

Minor Criteria:

  • Fever of 38.2–38.9 °C (101–102 F)
  • Arthralgia: Joint pain without swelling (Cannot be included if polyarthritis is present as a major symptom)
  • Raised erythrocyte sedimentation rate or C reactive protein
  • Leukocytosis
  • ECG showing features of heart block, such as a prolonged PR interval (Cannot be included if carditis is present as a major symptom)
  • Previous episode of rheumatic fever or inactive heart disease.

Acute rheumatic fever is treated with antibiotics and anti-inflammatory medications such as aspirin and corticosteroids.

Tularemia

Tularemia is an infection caused by the Gram-negative bacteria Francisella tularensis.

Learning Objectives

Recall the mode of transmission and symptoms associated with tularemia

Key Takeaways

Key Points

  • Tularemia is an infection common in wild rodents that is passed to humans through contact with infected animal tissues or by ticks, biting flies, and mosquitoes.
  • Symptoms vary depending upon the site of infection. The main clinical signs include fever, lethargy, anorexia, muscle pains and signs of septicemia.
  • Although tularemia can be life-threatening, most infections can be treated successfully with antibiotics.

Key Terms

  • Francisella tularensis: Francisella tularensis is a pathogenic species of gram-negative bacteria and the causative agent of tularemia or rabbit fever.
  • macrophage: A white blood cell that phagocytizes necrotic cell debris and foreign material, including viruses, bacteria, and tattoo ink. It presents foreign antigens on MHC II to lymphocytes. Part of the innate immune system.
  • tularemia: An infectious disease caused by the bacterium Francisella tularensis.

Tularemia (also known as Pahvant Valley plague, rabbit fever, deer fly fever, and Ohara’s fever) is a serious infectious disease caused by the bacterium Francisella tularensis. A Gram-negative, nonmotile coccobacillus, the bacterium has several subspecies with varying degrees of virulence.

The most important of these is F. tularensis tularensis (Type A), which is found in lagomorphs (rabbits and similar animals) in North America, and it is highly virulent in humans and domestic rabbits. F. tularensis palaearctica (Type B) occurs mainly in aquatic rodents (beavers, muskrats) in North America and in hares and small rodents in northern Eurasia. It is less virulent for humans and rabbits.

The primary vectors are ticks and deer flies, but the disease can also be spread through other arthropods. The disease is named after Tulare County, California and most commonly occurs in North America and parts of Europe and Asia. Although outbreaks can occur in the United States, they are rare.

Depending on the site of infection, tularemia has six characteristic clinical symptoms: ulceroglandular, glandular, oropharyngeal, pneumonic, oculoglandular, and typhoidal. The incubation period for tularemia is one to 14 days; most human infections become apparent after three to five days.

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Tularemia Lesion: A Tularemia lesion on the dorsal skin of right hand. Tularemia is caused by the bacterium, Francisella tularensis. Symptoms vary depending on how the person was exposed to the disease and, as is shown here, can include skin ulcers.

In most susceptible mammals, the clinical signs include fever, lethargy, anorexia, signs of septicemia, and possibly, death. Fever is moderate or very high. Tularemia bacilli can be isolated from blood cultures at this stage. The face and eyes redden and become inflamed. Inflammation spreads to the lymph nodes, which enlarge and may suppurate (mimicking bubonic plague), accompanied by a high fever. Death occurs in less than 1% if therapy is initiated promptly.

Francisella tularensis is an intracellular bacterium, meaning it is able to live as a parasite within host cells. It primarily infects macrophages and is able to evade the immune system. The course of disease involves the spread of the organism to multiple organ systems, including the lungs, liver, spleen, and lymphatic system; and differs according to the route of exposure.

Tularemia is primarily treated with streptomycin but can also be treated with gentamicin for ten days and tetracycline-class drugs such as doxycycline for two to three weeks, chloramphenicol, or fluoroquinolones. An attenuated, live vaccine is available, but its use is only for high-risk groups.

Brucellosis (Undulant Fever)

Brucellosis is an infectious disease that occurs from contact with animals carrying Brucella bacteria.

Learning Objectives

Recognize the causes and symptoms of brucellosis

Key Takeaways

Key Points

  • Brucella can infect cattle, goats, dogs, and pigs. The bacteria can spread to humans by ingesting unsterilized milk or meat from infected animals, or close contact with their secretions.
  • Brucellosis symptoms include fever, joint pain and fatigue. The infection can usually be treated successfully with antibiotics.
  • People working in jobs where they often come in contact with animals or meat such as slaughterhouse workers, farmers, and veterinarians are at higher risk for contracting Brucellosis.

Key Terms

  • brucellosis: Disease caused by the bacterium, Brucella, which is carried by ruminants. Symptoms include recurring fevers, sweating, weakness, anorexia, headaches, depression and generalized aches and pains.
  • Brucella: A genus of Gram-negative bacteria. They are small, non-motile, non-encapsulated coccobacilli, which function as facultative intracellular parasites.

Brucellosis, also called Bang’s disease, Crimean fever, Gibraltar fever, Malta fever, Maltese fever, Mediterranean fever, rock fever, or undulant fever, is a highly-contagious zoonosis caused by ingestion of unsterilized milk or meat from infected animals or close contact with their secretions. Transmission from human to human, through sexual contact or from mother to child, is rare but possible.

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Brucella bacteria: Brucella spp. are poorly staining, small gram-negative coccobacilli.

Brucella spp. are small, gram-negative, non-motile, non-spore-forming, rod-shaped (coccobacilli) bacteria. They function as facultative intracellular parasites causing chronic disease, which usually persists for life. Symptoms include profuse sweating, and joint and muscle pain.

Species infecting domestic livestock are B. melitensis (goats and sheep), B. suis (pigs), B. abortus (cattle), B. ovis (sheep), and B. canis (dogs). B. abortus also infects bison and elk in North America and B. suis is endemic in caribou. Brucella species have also been isolated from several marine mammal species (pinnipeds and cetaceans).

Brucellosis in humans is usually associated with the consumption of unpasteurized milk and soft cheeses made from the milk of infected animals, primarily goats, infected with Brucella melitensis, as well as with occupational exposure of laboratory workers, veterinarians, and slaughterhouse workers. Some vaccines used in livestock, most notably B. abortus strain 19, also cause disease in humans if accidentally injected.

Brucellosis induces inconstant fevers, sweating, weakness, anaemia, headaches, depression, and muscular and bodily pain. The symptoms are like those associated with many other febrile diseases, but with emphasis on muscular pain and sweating.

The duration of the disease can vary from a few weeks to many months or even years. In the first stage of the disease, septicemia occurs and leads to the classic triad of undulant fevers, sweating (often with characteristic smell, likened to wet hay), and migratory arthralgia and myalgia.

Antibiotics like tetracyclines, rifampicin, and the aminoglycosides streptomycin and gentamicin are effective against Brucella bacteria. However, the use of more than one antibiotic is needed for several weeks, because the bacteria incubate within cells.

Anthrax

Anthrax is a rare, infectious disease caused by Bacillus anthracis that can spread from animals to humans.

Learning Objectives

Discuss the causes and mode of transmission for anthrax including: inhalation, ingestion and direct entry through abrasions

Key Takeaways

Key Points

  • Bacillus anthracis exists in the soil as spores. Spores are inactive forms of the bacteria and can survive for decades in this form.
  • Humans can become infected through contact with the anthrax spores from infected animals. It is not conatgious and cannot be spread from one infected person to another person.
  • There are three ways one can become infected with anthrax: by inhalation of anthrax spores, entrance of spores through cuts in the skin, and by eating undercooked meat containing anthrax spores.
  • Anthrax can be successfully treated with early antibiotic treatment. An anthrax vaccine has been approved for use in humans and is effective in protecting against an anthrax infection.

Key Terms

  • Bacillus anthracis: Bacillus anthracis is the etiologic agent of anthrax and the only obligate pathogen within the genus Bacillus. B. anthrais a Gram-positive, endospore-forming, rod-shaped bacterium, with a width of 1-1.2µm and a length of 3-5µm.It can be grown in an ordinary nutrient medium under aerobic or anaerobic conditions.
  • anthrax: An infectious bacterial disease of herbivores than can also occur in humans through contact with infected animals, tissue from infected animals, or high concentrations of anthrax spores.

Anthrax is an acute disease caused by the bacterium Bacillus anthracis. Most forms of the disease are lethal, and it affects both humans and animals. Anthrax commonly infects wild and domesticated herbivorous mammals that ingest or inhale the spores while grazing. Carnivores living in the same environment may become infected by consuming infected animals. Humans become infected through contact with the anthrax spores from infected animals.

Bacillus anthracis is a rod-shaped, Gram-positive, aerobic bacterium about 1 by 9 micrometers in length. The bacterium normally rests in endospore form in the soil, and can survive for decades in this state. B.anthracis bacterial spores have been known to have reinfected animals over 70 years after burial sites of anthrax-infected animals were disturbed. Herbivores are often infected whilst grazing or browsing, especially when eating rough, irritant, or spiky vegetation. It has been hypothesized that the vegetation may cause wounds within the gastrointestinal tract, permitting entry of the bacterial endospores into the tissues. This has not been proven, however. Once ingested or placed in an open wound, the bacterium begins multiplying inside the animal or human and typically kills the host within a few days or weeks. The endospores germinate at the site of entry into the tissues and then spread via the circulation to the lymphatics, where the bacteria multiply.

There are three ways in which people can become infected by anthrax:

  1. By inhaling contaminated air containing anthrax spores. This is known as inhalation anthrax or pulmonary anthrax and can cause serious, sometimes lethal respiratory disease. Symptoms are flu-like, but soon develop into nausea and severe breathing problems. Inhalation anthrax has a 97% mortality rate.
  2. By handling infected animals and/or animal products, antrax spores can enter through cuts in the skin. This is known as cutaneous anthrax. It first appears as a boil-like lesion then eventually forms a painless ulcer with a black center. Death is rare when the appropriate antibiotics are used.
  3. By eating undercooked meat containing anthrax spores. This is known as gastrointestinal antrax. This is rare, with only 2 cases reported in the United States. Symptoms include intestinal inflammation, nausea, loss of appetite, vomiting of blood, abdominal pain and severe diarrhea.

Anthrax can be treated with anitbiotics. The earlier the anthrax is treated, the higher the chance of survival. Treatment for anthrax infection and other bacterial infections includes large doses of intravenous and oral antibiotics, such as fluoroquinolones (like ciprofloxacin), doxycycline, erythromycin, vancomycin, or penicillin. FDA-approved agents include ciprofloxacin, doxycycline, and penicillin. In possible cases of inhalation anthrax, early antibiotic prophylaxis treatment is crucial to prevent possible death.

In the United States, the human anthrax vaccine is required for most US military units and civilian contractors assigned to homeland bioterrorism defense or deployed in Iraq, Afghanistan or South Korea.

Gangrene

Gangrene is a serious and potentially life-threatening condition that arises when a considerable mass of body tissue dies.

Learning Objectives

Compare and contrast the different types of gangrene: dry, wet, gas, noma, fournier gangrene and necrotizing fasciitis

Key Takeaways

Key Points

  • Gangrene may be caused by an infection, injury, or a complication of a long-term condition that restricts blood circulation.
  • There are six main types of gangrene: dry gangrene, wet gangrene. gas gangrene, necrotizing fasciitis, Fournier’s gangrene, and noma.
  • Dead tissue cannot be saved, and amputation is necessary in most cases.

Key Terms

  • gangrene: The death of tissue due to reduced blood supply as a result of infection or a blocked blood vessel.
  • necrosis: The localized death of cells or tissues through injury, disease, or the interruption of blood supply.
  • debridement: The removal of dead, damaged, or infected tissue to improve the healing potential of the remaining healthy tissue.

Gangrene is a serious and potentially life-threatening condition that arises when a considerable mass of body tissue dies. This may occur after an injury or infection, or in people suffering from chronic health problems affecting blood circulation. The primary cause of gangrene is reduced blood supply to the affected tissues, which results in necrosis, or cell death. Diabetes and long-term smoking increase the risk of suffering from gangrene.

There are different types of gangrene with different symptoms, including:

  • Dry gangrene begins at the distal part of a limb due to ischemia (restriction of circulation), and often occurs in the toes and feet of elderly patients due to arteriosclerosis (hardening of the arteries). Dry gangrene spreads slowly until it reaches the point where the blood supply is adequate to keep tissue viable. The affected part is dry, shrunken, and dark reddish-black, resembling mummified flesh. The gangrenous tissue most often detaches spontaneously.
  • Wet gangrene occurs in naturally moist tissue and organs such as the mouth, bowel, lungs, cervix, and vulva. Bedsores occurring on body parts such as the sacrum, buttocks, and heels are also categorized as wet gangrene infections. In wet gangrene, the tissue is infected by microorganisms that cause decay, in turn causing tissue to swell and emit a fetid smell. Wet gangrene usually develops rapidly due to blockage of blood flow, most commonly in veins. The affected part is saturated with stagnant blood, which promotes the rapid growth of bacteria. The toxic products formed by bacteria are absorbed, causing systemic manifestation of septicemia and finally death.
  • Gas gangrene is a bacterial infection that produces gas within tissues. It is a deadly form of gangrene usually caused by Clostridium perfringens bacteria. Infection spreads rapidly as the gases produced by bacteria expand and infiltrate nearby healthy tissue. Because of its ability to quickly spread to surrounding tissues, gas gangrene should be treated as a medical emergency.
  • Necrotizing fasciitis affects the deeper layers of the skin.
  • Noma is a gangrene of the face.
  • Fournier gangrene usually affects the male genitals and groin.

Treatment of gangrene is usually surgical debridement, wound care, and antibiotic therapy, though amputation is necessary in many cases.

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Dry Gangrene: Gangrene of the 1st to 4th toes of the right foot of a person with diabetes.