Endocarditis

Endocarditis is an inflammation of the endocardium, the lining of the heart or the heart valves (Figure 14.3). The condition can be classified as infective if a microorganism is involved, or as noninfective. Noninfective endocarditis involves the formation of platelet and fibrin thrombi on heart valves and the surrounding endocardium, in response to trauma, circulating immune complexes, vasculitis, or a hypercoagulated state. Infective endocarditis symptoms may develop slowly (subacute) or suddenly and they include the following:

The most common cause of infectious endocarditis is bacterial, but it also can be caused by fungi. In some cases, no causative organism can be identified.

Myocarditis

Myocarditis is the inflammation of the myocardium, the muscular portion of the heart, and is generally caused by viral or parasitic infections. However, it also can be caused by bacterial infections, as well as by exposure to chemicals, or allergic reactions. The cardiac muscle becomes weakened and this can result in heart failure. The symptoms of myocarditis are vague, making the diagnosis difficult. They can include the following:

Pericarditis

Pericarditis is the term used to describe inflammation of the pericardium, the saclike membrane surrounding the heart (see Figure 14.3). The condition is usually a result of complications of a viral infection, but can also be caused by bacteria and fungi. The symptoms include the following:

Blood-borne Infectious Diseases

Blood-borne disease is spread by contaminated blood or bodily fluids. Any exposure to blood or other bodily fluids can transmit infectious disease. Although blood-borne diseases can affect anyone exposed to infected blood or bodily fluids, the risk of exposure is greater with certain occupations such as healthcare, emergency response, public safety, teaching, and many others (see Chapter 5, Safety Issues). Pathogens of primary concern for these professions, according to the Centers for Disease Control and Prevention (CDC, Atlanta, GA), are HIV, hepatitis B virus, hepatitis C virus, and those causing viral hemorrhagic fever. These viruses are discussed in detail in Chapter 17 (Sexually Transmitted Infections/Diseases). Diseases that are not transmitted directly by blood or by contact with bodily fluids, but by an insect or other vector, are classified as vector-borne diseases.

Microbemia

Microbemia is the term used to describe infections caused by microorganisms that enter the circulatory system through the lymphatic drainage. This entry occurs from areas of localized infections, and from diseased skin or mucous membranes that are colonized by members of the normal flora. Depending on the number and type of the microorganisms, microbemias may be asymptomatic, symptomatic, transient, continuous, or intermittent. Large numbers of organisms, including pathogens, may produce systemic signs and symptoms, such as:

Treatment usually involves intravenous application of a broad-spectrum antibiotic (see Chapter 22, Antimicrobial Drugs).

Bacteremia

Blood is normally sterile, but microorganisms can enter the blood under a variety of conditions. Bacteremia is the term used when bacteria are present in the bloodstream (see Chapter 9, Infection and Disease). Bacteremia has various possible causes including infection during dental procedures, catheterization and the placement of other indwelling devices, surgical procedures, wound infection, and many more. In general, the presence of bacteria in the blood elicits a strong immune response by circulating macrophages, the complement system, and lymphocytes (see Chapter 20, The Immune System), thus preventing bacteria from multiplying. In addition, the blood is relatively low on iron, a requirement for most bacterial growth. If the defenses of the immune and circulatory systems fail microbes can undergo uncontrolled proliferation in the blood, causing a condition called septicemia.

Septicemia

Sepsis is a toxic condition caused by the spread of bacteria or bacterial toxins from the site of infection (see Chapter 9, Infection and Disease). Septicemia is sepsis that occurs when bacteria multiply in the bloodstream. Septicemia is a medical emergency that requires immediate medical treatment. If the condition progresses to septic shock the death rate is as high as 50%, depending on the type of organism involved. Septic shock is the result of hypotension (low blood pressure) despite adequate fluid substitution. Septicemia develops quickly and the patient becomes extremely ill. Although each individual may experience symptoms differently the most common symptoms include the following:

Rheumatic Fever

Rheumatic fever is an inflammatory disease that can develop as a rare complication after a group A streptococcal infection such as strep throat or scarlet fever (see Chapter 11, Medical Highlights: Complications of “Strep Throat”). The condition commonly involves the heart, joints, brain, spinal cord, and skin. In general, rheumatic fever occurs in children between the ages of 4 and 18 years. Symptoms normally begin several weeks after the disappearance of localized throat symptoms and vary greatly between individuals, depending on the parts of the body inflamed. The most common symptoms include the following:

In some children carditis may not be evident, and the inflammation of the heart is recognized only years later, when heart damage is discovered. Treatment involves long-term antibiotic administration to eliminate any residual streptococcal infection, antiinflammatory medication to reduce inflammation, and also the limiting of physical activity that might aggravate the inflamed structures. People who do not take low-dose antibiotics continually, especially during the first 3 to 5 years after the first episodes of the disease, will likely experience recurrence of the condition, resulting in severe heart complications.

Gangrene

Gangrene is a complication of necrosis, the decay and death of tissue, that is often related to wounds. If the blood supply to a tissue is interrupted by an infection or ischemia (restriction of blood supply) gangrene can occur. Gangrene most commonly affects the extremities (Figure 14.4); however, it can also occur in muscle tissue and organs. Enzymes released from the dying cells and tissue will further destroy the surrounding tissues and thus provide a perfect nutrient environment for many bacterial species. Tissues devoid of blood supply become ischemic and provide an environment for anaerobic bacteria. Several species of the genus Clostridium, gram-positive, endospore-forming anaerobes, grow easily under these conditions. Clostridium is commonly found in soil as well as in the intestinal tracts of humans and domestic animals. The most frequent species involved in gangrene is C. perfringens, but other species and several other genera of bacteria can also grow under the conditions mentioned.

Treatment of gangrene usually entails the removal of necrotic tissue, and in many cases amputation may be necessary. Because antibiotics cannot reach the ischemic tissue, antibiotics alone are not effective. In addition to surgery and antibiotics, hyperbaric oxygen therapy can be used to kill the anaerobic Clostridium causing the condition.

There are different types of gangrene, including the following:

Zoonotic Diseases

Any disease and/or infection that can be transmitted from vertebrate animals to humans is classified as a zoonosis. More than 200 zoonoses have been described, but not all affect the circulatory system (Table 14.2). Zoonoses may be caused by bacteria, viruses, parasites, and unconventional agents such as prions. The emerging field of conservation medicine integrates human medicine, veterinary medicine, and environmental services and is largely concerned with zoonoses.

Vector-transmitted Diseases

Vectors are animals that are capable of transmitting infectious diseases. These vectors include, but are not limited to, flies, mites, fleas, ticks, and rats. Insects are a major cause of human mortality and morbidity due to the transmission of infectious pathogens by blood-feeding species. The transmission of vector-borne diseases is based on a complex relationship between a parasite, the vector, and humans. Vectors are mobile and add an additional dimension to the range of transmission of infectious diseases. This particular section addresses bacterial vector-borne diseases (Table 14.3).

Plague

The plague is an infectious disease caused by Yersinia pestis, a gram-negative, rod-shaped bacterium. People usually become infected when bitten by a flea that carries the bacteria from an infected rodent or by handling an infected animal. After the flea bite, the bacteria enter the bloodstream and proliferate in the lymph and blood. Y. pestis can reproduce within cells; therefore even if phagocytosed, they still survive. Once the organism enters the lymph it causes swelling of the lymph nodes, especially in the groin and armpits. These swellings are referred to as buboes, and the term buboes led to the disease’s name, bubonic plague (Figure 14.5). Because the lymph is delivered to the subclavian veins via the right lymphatic duct and the thoracic duct, it ultimately enters the bloodstream and the bacteria within the lymph are now capable of multiplying in the blood, causing septicemic plague, which is followed by septic shock. Septicemic plague can occur when the bacteria enter the bloodstream directly through a flea bite, or as a complication of the bubonic or pneumonic plague. All forms of the plague can be treated with antibiotics in the early stages, but if untreated, septicemic plague is universally fatal.

The least common form of the plague is the pneumonic plague, which occurs if the bacteria are carried to the lungs. The disease can then be spread from human to human by air droplets. Epidemics can be started this way, as happened in the Middle Ages. Even now the mortality rate for this particular type of the plague is nearly 100% if not diagnosed and treated within the first 12 hours of the onset of fever.

Recovery from the plague provides reliable immunity. Vaccines are available for persons who are likely to come in contact with infected fleas, either during field experiments or operations, or for laboratory workers who may have contact with the pathogen. Elimination of the plague is not realistic because it would require the elimination of its reservoir, namely rodents and other wild animals. As a preventive measure, periodic application of rodenticides is advised for ships, airplanes, and buildings or other places with a high population of rodents.

HEALTHCARE APPLICATION
Types of the Plague

Type	Site of Infection	Symptoms	Transmission	Treatment
Bubonic	Lymph nodes	Appears suddenly, usually 2–5 d after exposure; high fever, smooth painful lymph nodes—buboes; chills, malaise, muscle pain, severe headache, seizures	Rodent to rodent; rodent to fleas; fleas to humans	Antibiotics if diagnosed in a timely manner
Pneumonic	Lungs	Symptoms occur 1–4 d after exposure and include severe cough, bloody sputum, difficulty in breathing	Inhalation of the organism by face-to-face contact, coughs, or sneezes	Isolation from other patients; early treatment with appropriate antibiotics is essential—the pneumonic form is almost always fatal
Septicemic	Blood	Abdominal pain, blood-clotting problems, diarrhea, fever, low blood pressure, nausea, vomiting, organ failure	Bacteria enter the bloodstream	Early antibiotic treatment, respiratory support, intravenous fluids; usually fatal

Rocky Mountain Spotted Fever

Rocky Mountain spotted fever is caused by Rickettsia rickettsii, an obligate intracellular pleomorphic gram-negative bacterium, and is transmitted to humans by ticks. In contrast to its name it occurs throughout the United States; it is a severe disease and the most frequently reported of the rickettsial illnesses. The incubation period varies from 5 to 10 days after the tick bite, with nonspecific symptoms that may resemble a variety of other infectious diseases. These initial symptoms may include the following:

• Fever

• Nausea

• Vomiting

• Severe headache

• Muscle pain

• Lack of appetite

• Rash developing 2 to 5 days after the onset of the fever

Later signs include the following:

• Rash (Figure 14.6)

• Abdominal pain

• Joint pain

• Diarrhea

The characteristic rash of the illness is usually not seen until day 6 or later after the onset of the initial symptoms. Only 35% to 60% of patients with the condition develop the characteristic rash, and 50% to 80% of these show the rash on the palms or soles.

Diagnosis of Rocky Mountain spotted fever is based on a combination of clinical signs, symptoms, and laboratory tests. Antibiotic treatment should be given immediately if there is a suspicion of Rocky Mountain spotted fever, even before laboratory confirmation is obtained. At present the most commonly used antibiotics are tetracycline and chloramphenicol. Despite treatment, about 3% to 5% of persons developing the fever still die from the condition.

Lyme Disease

Lyme disease is caused by Borrelia burgdorferi, a gram-negative, motile spirochete that is transmitted to humans by the bite of an infected blacklegged tick (Figure 14.7). The infection in humans presents itself in three stages. Typical early symptoms include the following:

• Skin rash, often resembling a bull’s-eye (Figure 14.8)

• Fever and fatigue

• Headache and stiff neck

• Muscle pain

In most cases the early stages of Lyme disease can be successfully treated by administration of antibiotics for a few weeks. The second stage may occur weeks to months later if the condition is untreated. The infection then can spread to the joints, heart, and nervous system causing symptoms including severe fatigue, myalgia, skin lesions, heart failure, meningitis and encephalitis. The third stage results in repeated and severe attacks of arthritis over years. Borrelia burgdorferi can cross the placenta and cause damage to the fetus. Once diagnosed, the disease is a reportable disease for the purpose of surveillance.

Infectious Mononucleosis

Mononucleosis (mono) or glandular fever is usually caused by Epstein-Barr virus (EBV). EBV, also called human herpesvirus 4, is a member of the herpesvirus family, one of the most common human viruses occurring worldwide. The virus infects B lymphocytes and the disease name refers to the lymphocytes with unusual lobed nuclei that proliferate during the acute infection. Many children become infected with the virus and the symptoms are indistinguishable from those of other mild illnesses of childhood. When an infection with EBV occurs during adolescence it causes infectious mononucleosis 35% to 50% of the time. Symptoms include the following:

On occasion, a swollen spleen or liver problems may develop.

Although most patients recover within 2 to 4 weeks, some will experience fatigue for up to 2 months, and EBV remains dormant or latent in a few cells in the throat and blood for the rest of the person’s life. It is essential to avoid sports during the time of the illness, because complications due to exhaustion may lead to rupture of the spleen. Although no specific treatment is available, symptoms may be treated, and bed rest and adequate fluids are recommended. Transmission of infectious mononucleosis requires contact with the saliva of an infected person. From the time of infection to the appearance of symptoms ranges from 4 to 6 weeks in adults and around 10 days in children. The virus is often found in the saliva of healthy people, and therefore transmission of the virus cannot be prevented.

Cytomegalovirus Infections

Cytomegalovirus (CMV), also known as human herpesvirus 5, is a large herpesvirus that remains mostly latent in leukocytes, such as monocytes, neutrophils, and T lymphocytes, and replicates very slowly. CMV is spread from person to person by direct contact. The infection is usually harmless but can cause severe disease in people with a compromised immune system. The virus can be present in several bodily fluids including urine, blood, saliva, semen, cervical secretions, and breast milk. Most people have been exposed to the virus, but a healthy immune system keeps the virus in check. Active infections are often associated with salivary glands, but also may be found throughout the body. Symptoms include the following:

Most people infected with the virus do not develop symptoms; in those who do, the symptoms will appear 3 to 12 weeks after exposure. CMV is common worldwide and an estimated 80% of adults in the United States are infected with the organism. There is no specific cure or treatment for CMV.

Viral Hemorrhagic Fevers

Viral hemorrhagic fevers (VHFs) are a group of febrile illnesses that range in severity from relatively mild to life-threatening, and can result in severe multisystem problems. They are caused by four distinct families: the Arenaviridae, Filoviridae, Bunyaviridae, and Flaviviridae. These viruses share a number of features, including the following:

All types of VHFs are characterized by:

The viruses that cause VHFs are scattered over much of the world. Each virus is associated with one or more specific host species, and therefore the virus and the associated disease are limited to the area where the host species live. Many of these viruses are present in geographically limited areas and the risk of infection by them is restricted to those areas. Transmission to humans occurs by contact with a host, that is, by handling infected animals, their remains, fecal material, urine, or secretions. Viruses associated with arthropod vectors are generally spread by mosquito or tick bites.

An infected person may transmit the disease to other persons either by person-to-person contact, through bodily fluids, or by contact with contaminated objects, contaminated syringes, and needles. Infected people who travel to other areas of the country or world can then infect people outside of the original geographical area (also see Chapter 18, Emerging Infectious Diseases).

Systemic Mycoses

Systemic mycoses are fungal infections capable of affecting all internal organs and are becoming more and more common in the hospital environment. The clinical features of systemic mycoses depend on the specific organism causing the illness and the organs affected. Whereas persons with a competent immune system will show only minor or no symptoms at all, immune-compromised patients are at high risk of systemic mycoses. These include people infected with HIV, patients with cancer, people with neutropenia (a low neutrophil cell count), organ transplant recipients, patients after surgery for pancreatitis or splenectomy, persons with poorly controlled diabetes mellitus, patients in intensive care, and the very young or very old. Treatment of systemic mycosis may include reducing or discontinuing immune-suppressing medications or systemic antifungal medications. The prognosis depends on the patient’s immune function and unfortunately, despite treatment, the infection may be fatal for many of these patients.

Malaria

Malaria is one of the most common vector-borne infectious diseases; it is widespread in tropical and subtropical regions including parts of tropical Asia, Africa, and Central and South America. Most cases reported in the United States are related to exposure through travel or military duty in areas with endemic malaria. The disease is caused by protozoans of the genus Plasmodium. Four types of the parasite can infect humans: Plasmodium vivax, Plasmodium falciparum, Plasmodium ovale, and Plasmodium malariae. All the species are transmitted by female Anopheles mosquitoes, but also need to have a human host. The most common form of transmission is through a bite by the mosquito; however, the parasite can also be transmitted by blood transfusion from an infected donor, or by sharing needles.

All species of the malaria parasite have similar life cycles, comprising three distinct stages, and characterized by alternating extracellular and intracellular forms (Figure 14.9). Malaria parasites are ingested by mosquitoes feeding on an infected human carrier; the mosquitoes then carry Plasmodium sporozoites in their salivary glands. In humans Plasmodium grows and multiplies originally in the liver and then in erythrocytes. Once in the blood the parasites grow inside the erythrocytes and destroy them, releasing daughter parasites referred to as merozoites, all of which continue the cycle, invading other red blood cells. It is the blood stage of the parasites that causes the symptoms of malaria. Once the gametocytes, a form of the blood stage, are picked up by the mosquito during a blood meal, the parasites start another, different cycle of growth and multiplication in the insect.

Humans infected with the parasite can develop a wide range of symptoms depending on the age and immune status of the patient, and also on the type of the Plasmodium species. Malaria can occur as uncomplicated malaria or severe malaria.

Babesiosis

Babesiosis is a vector-borne, malaria-like illness caused by the protozoan Babesia, and is usually transmitted by ticks. Infections may be asymptomatic or cause a mild nonspecific illness, and cases might go unnoticed. However, the infection can cause severe illness especially in the very young, the very old, or people with immunodeficiency. The symptoms of severe illness include the following:

Babesia parasites reproduce in red blood cells and can be easily misdiagnosed as Plasmodium. The life cycle involves two hosts: a rodent, usually the white-footed mouse, and the definitive host, the deer tick. Deer are the hosts that the adult ticks feed on and therefore are indirectly part of the cycle. If a deer population increases, the tick population increases, and the potential for transmission is heightened. Humans enter the cycle when bitten by an infected tick. Humans are generally considered the dead-end host, and human-to-human transmission can occur only through blood transfusions. The most common treatment is a combination of quinine and clindamycin for 7 to 10 days.

Toxoplasmosis

Toxoplasmosis is a disease caused by the protozoan Toxoplasma gondii (Figure 14.10), a single-celled, spore-forming parasite found throughout the world. The organisms carry out their reproductive cycle within the members of the cat family only. The cat is the definitive host. Transmission of toxoplasmosis to humans can occur in the following ways:

It is estimated that more than 60 million people in the United States carry the Toxoplasma parasite, but because of an intact immune system very few ever show symptoms. Newly infected pregnant women and people with a compromised immune system should be aware that toxoplasmosis can have severe consequences for the unborn fetus including brain damage and damage to the eyes and other organs. Toxoplasmosis can be acquired by contact with wastes from an infected cat, consumption of contaminated meat (raw or undercooked), contact with utensils or cutting boards that have been in contact with raw meat, consumption of contaminated drinking water, or by receiving an organ transplant or blood transfusion from an infected individual. Most people with toxoplasmosis do not require treatment, but it is available for pregnant women and persons with a compromised immune system.

Chagas’ Disease

Chagas’ disease, also referred to as American trypanosomiasis, is caused by Trypanosoma cruzi, a flagellated protozoa, and is transmitted to humans and other mammals by insect vectors that are currently found only in the Americas, primarily in the areas of Latin America with widespread poverty. It is estimated that 8 to 11 million people in Mexico, Central America, and South America are infected, with most of them not even knowing that they are infected. The infection is lifelong and if not treated can be life-threatening. There are two phases of the disease: an acute phase and a chronic phase.

The acute phase of the disease lasts for the first few weeks or months after infection and is often unnoticed because the symptoms are mild and not necessarily unique to Chagas’ disease. These symptoms may include the following:

There also may be a mild enlargement of the spleen or liver and swollen glands at the site of parasite entry.

The chronic phase may remain silent for decades or even for life. Some people develop cardiac complications including an enlarged heart, heart failure, altered heart rate or rhythm, and cardiac arrest. Furthermore, intestinal complications can occur, including an enlarged esophagus or colon, and also can lead to difficulties with eating and/or defecation. Treatment of the condition includes antiparasitic and symptomatic treatment; no vaccines are currently available to prevent the infection.

Leishmaniasis

Leishmaniasis is a widespread complex disease caused by protozoan parasites of the genus Leishmania, with about 20 different species involved. The disease exhibits several clinical forms including the following:

The infection is transmitted by female sandflies found in the tropical world and around the Mediterranean. Although most forms of the disease are transmitted only by insects to humans, some can be spread between humans. The illness is commonly found in Mexico, Central America, and South America. Cases also have been reported in southern Texas, southern Europe, Asia, the Middle East, and Africa. Although treatment is available, some species have developed drug resistance.