Lecture 20: Systemic Infections PDF

CHAPTER 21 Systemic Infections Copyright © 2021 W. W. Norton & Company Systemic Infections Chapter Objectives § Correlate the anatomy and physiology of the circulatory system with the infectious processes affecting them. § Describe symptoms that can help differentiate circulatory system infection...

CHAPTER 21 Systemic Infections Copyright © 2021 W. W. Norton & Company Systemic Infections Chapter Objectives § Correlate the anatomy and physiology of the circulatory system with the infectious processes affecting them. § Describe symptoms that can help differentiate circulatory system infections caused by viruses from those caused by bacteria and parasites. § Relate prevention strategies based on transmission routes for microbes that cause systemic infections. § Choose appropriate treatment and prevention modalities for microbes that cause systemic infections. 2 Too Tired for Soccer – 1 Scenario § Mira, a 16-year-old soccer player, complained of a sore throat and woke up in a cold sweat two days in a row. § She felt very tired but wanted to go to soccer practice anyway. § Her mother was reluctant to give permission unless Mira went to her pediatrician first. 3 Too Tired for Soccer – 2 Labs § Mira was not feeling well when they got to the clinic. The nurse practitioner (NP) examined her and found that Mira had a mild fever, pharyngitis, swollen tonsils, and some swollen lymph nodes in her neck. She swabbed Mira’s throat to check for infectious mononucleosis (mono) and strep throat. § The mono test was positive. It was at this point that Mira recalled her boyfriend complaining of a sore throat a couple of weeks back. 4 Too Tired for Soccer – 3 Treatment § Mira was instructed to rest, take ibuprofen for pain, and call the office if any of her symptoms got worse. § She was told not to take aspirin because it could cause a severe reaction. § The NP emphasized that Mira should not play soccer or engage in any other strenuous physical activity for 4 weeks because her spleen could be enlarged as a result of infection. An enlarged spleen could burst (rupture) if she were hit or fell onto the left side of her body. § The NP further explained that a ruptured spleen causes internal bleeding, a life-threatening condition. 5 Too Tired for Soccer – 4 Follow-Up § By week 4 Mira called the clinic to see whether she could start playing soccer again. § She was asked to come to the clinic for a follow-up visit first. The NP examined Mira and told her she could return to playing soccer because her spleen was not enlarged. § Mira was happy to go back to her soccer practice that afternoon and resume her normal life. 6 21.1 Anatomy of the Cardiovascular and Lymphatic Systems – 1 Section Objectives § List the structural components of the cardiovascular and lymphatic systems and their relationship to one another. § Compare and contrast the systemic and pulmonary circulations. § Explain the relationship between the circulatory systems and systemic infections. 7 21.1 Anatomy of the Cardiovascular and Lymphatic Systems – 2 § Systemic infection: starts in one part of the body and then spreads to other sites § Example: S. Typhi 8 21.1 Anatomy of the Cardiovascular and Lymphatic Systems – 2 Cardiovascular system: § responsible for the transportation of blood, nutrients, oxygen, and waste products throughout the body § consists of the heart, blood vessels (arteries, veins, and capillaries), and blood Cardiovascular System Lymphatic System 9 21.1 Anatomy of the Cardiovascular and Lymphatic Systems – 2 Lymphatic system: § Lymph Nodes: small, bean-shaped structures located throughout the body. Filter lymph fluid and contain immune cells that help fight infections § Lymphatic Vessels: network of thin tubes that carry lymph fluid throughout the body; Collect excess fluid from tissues and return it to the bloodstream. § Lymphatic Organs: spleen, thymus, and tonsils; Produce and store immune cells and help in the immune response . Cardiovascular System Lymphatic System 10 21.1 Anatomy of the Cardiovascular and Lymphatic Systems – 2 § Heart, arteries, and veins form the pulmonary and systemic circulatory circuits § Pulmonary circuit: takes the oxygen-poor blood from the heart to the lungs and returns oxygen-rich blood from the lungs to the heart. § Systemic circuit: delivers oxygen-rich blood from the heart to the entire body and brings back oxygen-poor blood from all over the body back to the heart 11 21.1 Anatomy of the Cardiovascular and Lymphatic Systems – 3 Structure of Arteries, Veins, and Capillaries Lymphatic capillary beds 12 21.1 Anatomy of the Cardiovascular and Lymphatic Systems – 3 § Inflammation of • The endocardium = endocarditis • The pericardium = pericarditis • The myocardium = myocarditis 13 21.1 Anatomy of the Cardiovascular and Lymphatic Systems – 4 § Lymphadenopathy: swelling of the lymph nodes § Lymphadenitis: inflammation of the lymph nodes § Lymphangitis: inflammation of the lymph vessels Lymphangitis Lymphadenitis 14 21.2 Systemic Viral Infections Section Objectives § Explain the pathogenesis of each systemic viral infection discussed. § Relate the diagnoses of systemic viral infections to the pathogenesis of the specific virus causing disease. § Relate the signs and symptoms of each systemic viral infection to the effect of the respective virus on different organ systems. § List the treatment and prevention options for different systemic viral infections. 15 Infectious Mononucleosis: “The Kissing Disease” § Epstein-Barr virus (EBV) • Herpes virus family, human herpesvirus 4 (HHV4) • Causative agent of Infectious mononucleosis • Shed in saliva • Fever, sore throat, enlarged lymph nodes, fatigue • Also can cause menigintis, Guillian-Barre syndrome, splenomegaly, and kidney failure • Virus infects and replicates – B cells, oropharyngeal epithelium, tonsils, salivary glands – B-cells have atypical appearance 16 Cancers Associated with Epstein-Barr Virus § Burkitt’s lymphoma • Cancer of B lymphocytes • Tumors form in upper/lower jaw and orbits of the eye • Grows rapidly • Treatment is chemotherapy 17 Cytomegalovirus Infections § Cytomegalovirus (CMV) • Herpes virus family, human herpesvirus 5 (HHV-5) • dsDNA virus, integrates into chromosome à latency • Asymptomatic – Shed virus in body fluids (saliva and urine) • Cell-mediated immunity • Reinfection – Infections with a second strain of CMV • Immunocompromised individuals face higher risk of reactivation – Fever, pneumonia, hepatitis, encephalitis • Vertical transmission – Transplacental A hematoxylin- and eosin-stained tissue sample from a lung infected with CMV shows the resulting enlargement of an infected cell and two large inclusion bodies that have the appearance of an owl’s eyes 18 Other Systemic Viral Diseases § Dengue virus – – – – – 400M/year infected worldwide Endemic in the tropics Causes intense joint and muscle pain 22K die/year of dengue hemorrhagic fever (severe dengue) Transmitted by mosquitoes § Ebola virus – Acute rapid onset of fever, muscle pains, and bleeding from multiple orifices – Transmitted through contact with body fluids § Chikungunya virus – Causes debilitating muscle and joint pain – Prevalent in the area around the Indian Ocean, Europe, and recently the United States 19 Clicker Question 1 Which viral infection can cause a wide range of symptoms and diseases, from asymptomatic infections to mononucleosis to Burkitt’s lymphoma? a. dengue virus b. ebola virus c. Epstein-Barr virus d. cytomegalovirus 20 21.3 Systemic Bacterial Infections Section Objectives § Compare the systemic signs and symptoms of different bacterial circulatory infections. § Generate a list of organ malfunctions according to the pathogenesis of each bacterial pathogen discussed. § Relate the pathogenesis of the systemic bacterial infections discussed with the symptoms and progression of each disease. § Summarize the treatment and prevention plans for the various systemic bacterial infections discussed. 21 Sepsis and Septic Shock – 1 § Bacteremia: bacteria in the bloodstream Figure 21.11 Overlap of Infection, Sepsis, and Systemic Inflammatory Response Syndrome (SIRS) § Sepsis: immune response due to bacteria in Not all infections result in sepsis, and not all SIRS patients the bloodstream have sepsis. § Septicemia: pathogen replicates to high numbers, overcomes the innate immune system § Systemic inflammatory response syndrome (SIRS): medical emergency characterized by rapid heart rate, breathing rate, and abnormal white blood cell count § Septic shock: catastrophic drop in blood pressure due to severe sepsis • Superantigens or PAMPs 22 Case History: Prairie Dogs Are Not Good Companions ‒ 1 § A 25-year-old New Mexico rancher was admitted to an El Paso hospital because of a 2-day history of headache, chills, and fever (40°C, 104°F). § The day before, he began vomiting. The day of admission, an orange-sized, painful swelling in the right groin area was noted. A lymph node aspirate and a smear of peripheral blood were reported to contain Gram-negative rods that exhibited bipolar staining (the ends of the bacilli stained more densely than the middle). § white blood cell count was 24,700/μl (normal is 4,300–10,800/μl), and platelet count was 72,000/μl (expected is 130,000–400,000/μl). 23 Case History: Prairie Dogs Are Not Good Companions – 2 § In the 2 weeks prior to becoming ill, the patient had trapped, killed, and skinned two prairie dogs, four coyotes, and one bobcat. § The patient had cut his left hand shortly before skinning a prairie dog. § PCR and typical biochemical testing of a Gram-negative rod isolated from blood cultures identified the organism as Yersinia pestis, the organism that causes plague. § The patient received an antibiotic cocktail of gentamicin and tetracycline. He eventually recovered after 6 weeks in intensive care. 24 Systemic Infections Involving Multiple Organs – 1 § Plague: Yersinia pestis • Bubonic plague – Organisms move from site to lymph nodes, forming buboes (inflamed, swollen LNs) – Not transmissible • Septicemic plague – Pathogen enters bloodstream – Not transmissible • Pneumonic plague – Pathogen infects lungs – Transmissible, easily spread through populations 25 Systemic Infections Involving Multiple Organs – 2 § Virulence factors of Yersinia pestis • Lipoproteins – Inhibit phagocytosis • F1 protein capsule – Blocks phagocytosis • Biofilm formation – Attachment – Aids in transmission from flea • Type III secretion system – Injects virulence proteins into host cells 26 Systemic Infections Involving Multiple Organs – 3 27 Case History: Bull’s Eye Rash § Brad, an otherwise healthy 9-year-old from Connecticut, developed a fever and a large (8 cm) reddish rash with a clear center (erythema migrans) on his arm. § also had some left facial nerve palsy (paralysis). § A week before, Brad had returned from a Boy Scout camping trip to the local woods, where he did a lot of hiking. § Brad admitted finding a tick on his stomach while in the woods but thought little of it. § The doctor ordered serological tests for Borrelia burgdorferi (the organism that causes Lyme disease), Rickettsia rickettsii (which produces Rocky Mountain spotted fever), and Ehrlichia chaffeensis (which causes ehrlichiosis). § The ELISA for B. burgdorferi came back positive, confirming a diagnosis of Lyme disease. § The boy was given a 3-week regimen of doxycycline (a tetracycline derivative), which led to resolution of the rash and palsy. 28 Systemic Infections Involving Multiple Organs – 4 § Lyme disease • The most common vector-borne illness • B. burgdorferi – Spirochete – Linear chromosome – Transmitted by tick bite (ixodid tick) – Complex life cycle § Lyme disease treatment • Antibiotic treatment is most effective in earlier stages. • Doxycycline 29 Systemic Infections Involving Multiple Organs – 5 § Stage 1 • 3–30 days • Bull’s eye rash (erythema migrans), fever, muscle pain, joint pain, headache § Stage 2 • Weeks to months • Spreads from blood to organs • Neurological and cardiac involvement • Inflammation causing joint pain thought to be an autoimmune reaction § Stage 3 • Months to years • Neuropathy and encephalopathy • Affects memory, mood, and sleep 30 Systemic Infections Caused by Intracellular Pathogens – 1 § Typhoid fever • Salmonella enterica serovar Typhi (S. Typhi) • Lives inside macrophages in the gastrointestinal tract • Infects a variety of organ systems • Bacteria are continuously shed during infection; can be transmitted via fecal–oral route. Rose Spots of Typhoid Fever 31 Systemic Infections Caused by Intracellular Pathogens – 2 § Rocky mountain spotted fever • Caused by Rickettsia rickettsia • Transmitted by ticks and lice • Rash begins on the wrist and ankles and spreads to the center of the body. 32 Clicker Question 2 Which form of plague is easily transmitted from person to person? a. septicemic plague b. pneumonic plague c. bubonic plague d. sylvatic plague 33 Clicker Question 3 Which of the following diseases is caused by Borrelia burgdorferi, is transmitted by the deer tick, and causes a bull’s-eye rash? a. Rocky Mountain spotted fever b. typhoid fever c. Lyme disease d. malaria e. leishmaniasis 34 21.4 Bacterial Infections of the Heart – 1 Section Objectives § Name and define the different manifestations of bacterial infections of the heart. § Compare and contrast different types of endocarditis. § Discuss the possible links between bacterial infections and atherosclerosis. 35 Case History: Dental Procedure Leads to “Heartache” § Elizabeth was 58 years old and had a history of mitral valve prolapse (a common congenital condition in which a heart valve does not close properly). § She was on immunosuppressive therapy following a kidney transplant. § She had recently been admitted to the hospital complaining of fatigue, intermittent fevers for 5 weeks, and headaches for 3 weeks—symptoms the physician recognized as possible indications of endocarditis. § Reported having a dental procedure a few weeks prior to the onset of symptoms; forgot to take the recommended prophylactic antibiotic beforehand. § A sample of her blood placed in a liquid bacteriological medium grew Gram-positive cocci, which turned out to be Streptococcus mutans, a bacterial species associated with dental caries. § the diagnosis of bacterial endocarditis was confirmed. Elizabeth began a 1-month course of intravenous penicillin G and gentamicin therapy and eventually recovered to normal health. 36 21.4 Bacterial Infections of the Heart – 2 § § § § § Pericarditis: infection of the sac surrounding the heart Myocarditis: infection of the heart Endocarditis: inflammation of the inner layer of the heart • Symptoms can be vague and intermittent. Subacute bacterial endocarditis (SBE) • S. mutans • Gradual, symptoms extended over longer period of time • fatigue, low-grade fever, weight loss, night sweats, joint pain, and mild anemia Acute bacterial endocarditis (ABE) • S. aureus • Sudden, rapidly progressive, potentially fatal within days • high fever, chills, severe fatigue, rapid heart rate, and signs of systemic infection 37 21.4 Bacterial Infections of the Heart – 2 Pathogenesis of Infective endocarditis § a. Pathogens gain access to the bloodstream, e.g., via an intravenous catheter, injection drug use or from a dental source. § b. Pathogens adhere to an area of abnormal cardiac valve surface. § c. Some pathogens, such as Staphylococcus aureus, obtain intracellular access to the valve endothelium. § d. The infected vegetation is created by burying of the proliferating organism within a protective matrix of serum molecules. § e. Vegetation particles can detach and disseminate to form emboli. § may lead to complications, such as ischaemic stroke, mycotic aneurysms and infarcts or abscesses at remote sites. Infective endocarditis Holland TL, Baddour LM, Bayer AS, Hoen B, Miro JM, Fowler VG Jr. Infective endocarditis. Nat Rev Dis Primers. 2016 Sep 1;2:16059. doi: 10.1038/nrdp.2016.59. PMID: 27582414; PMCID: PMC5240923. 38 21.4 Bacterial Infections of the Heart – 3 § An open normal mitral valve shows the cords that tether it to the heart wall. § Close-up of native mitral valve endocarditis, showing vegetation, a microbial biofilm encased in a thick glycocalyx coating. § An infected prosthetic heart valve showing bacterial endocarditis (granulated tissue at center, shown by arrow). 39 21.5 Systemic Parasitic Infections Section Objectives § Construct a list of systemic parasitic infections according to the type and mode of transmission of each parasite. § Relate the different stages of systemic parasitic diseases to the growth cycle of the infecting agent. § List the organ systems affected by each systemic parasitic infection discussed. § Devise a plan for preventing infection by each systemic parasite discussed. 40 Malaria and Mosquitoes – 1 § Malaria • 219 Million infected worlwide (2017) – 435, 000 died (mostly children) • Transmitted by four species of Plasmodium – P. falciparum – P. vivax – P. ovale – P. malariae • Complex life cycle – Asexual erythrocytic cycle – Sexual cycle • Treatment includes chloroquine 41 Areas of the world where malaria transmissio Malaria and Mosquitoes – 2 Plasmodium life cycle: Key Players § Sporozoites • the form of the parasite that is transmitted from the mosquito vector to the human host during a mosquito bite § Merozoites • the form of the parasite that infects and replicates within red blood cells § Ring stage. • Developmental stage within RBC where merozoites transform in trophozoites to give rise ultimately to merozoite-filled Schizonts • Hemoglobin consumption § Schizont • cluster of merozoites surrounded by a mass of coarse, darkbrown pigment • Marks stage of parasite replication in bloodstream • Upon the rupture of the infected red blood cells, the mature merozoites are released and can go on to invade new red blood cells § Gametocytes: • Male and female products of some merozoites involved in sexual reproduction in the mosquito gut § Definitive Host: Mosquito • Host where sexual reproduction occurs § Intermediate Host: Human • Transient host where asexual reproduction and multiplication occurs. 42 Malaria and Mosquitoes – 2 Plasmodium life cycle: Key Players § Blood stage gives rise to symptoms • Chills, high fever, sweating • Erythrocytic cycle repeats 48 – 72 hrs. § Immune evasion via modification of PfEMP1 • Produced by Plasmodium and key for immune recognition • Leads to cyclic infection • Hinders vaccine development § Treatment: Chloroquine • Prevents Plasmodium-dependent hemoglobin polymerization, key for its detoxification • Iron from free heme kills the parasite 43 Babesiosis and Ticks § Babesiosis is caused by Babesia microti – Protozoan • Similar to malaria, except it is transmitted by ticks that have fed on white-footed mice. • Characteristic cell arrangement – Maltese cross formation • Immunocompetent patients have a mild flu-like illness. • Patients with immunosuppression can have a prolonged illness. 44 Chagas Disease and the Reduviid Bug – 1 § Chagas disease • Trypanosoma cruzi – Protozoan • Vector = Reduviid bug – Parasite released in bug feces, enter host through nearby bug bites. • Acute Systemic symptoms include – Enlarged spleen, liver, fever, eyelid swelling • Chronic symptoms (10 – 20 yrs after infection!) – Heart failure, enlarged esophagus and colon Trypanosoma cruzi (arrow), the cause of Chagas disease Reduviid bug Romaña sign. • Treatment (works best in acute phase) – Nifurtimox (ROS generator à damages parasite DNA) – or benznidazole (Inhibits parasite DNA synthesis 45 Toxoplasmosis and Cats – 2 § Toxoplasmosis • Toxoplasma gondii – Protozoan • Transmitted to humans via cats • Two stages: feline and mammal stage • Symptoms – Immunocompetent individuals = no/mild symptoms – Immunocompromised individuals = more serious – Congenital disease = organism crosses placenta 46 Toxoplasmosis and Cats – 2 § Toxoplasmosis § Infected cats can release up to 100 million gametes (unsporulated oocytes) every day for 7–21 days. • Oocytes – – – – • Sporocysts (aka sporozoites) – – • – Rapidly dividing form typically found in the bloodstream Invade host cells (immune, muscle, nerve) and cause damage and trigger immune response Responsible for acute phase of infection Bradyzoites – – – § Contained with oocytes and released during sporulation Develop in to tachyzoites Tachyzoites – – • environmentally resistant stage of the parasite's life cycle Shed in feces (major source) Contaminates other food and water sources Contains sporocysts semidormant, slowly dividing cellular stage; turn into tissue cysts (eyes, brain, muscle) Cysts form in response to immune pressure Responsible for chronic infection Sexual reproduction of T. gondii occurs exclusively in cat gut epithelium 47 Leishmaniasis and the Sand Fly § Leishmaniasis • Cutaneous – Leishmania tropica and L. braziliensis The female sand fly, the insect vector for the disease. • Visceral – Spleen, liver, bone marrow – L. donovani – Patients may die within months. o Hemorrhage, severe anemia, bacterial pneumonia • Treatment via antimony compounds (sodium stibogluconate, or Pentostam) – Disrupt enzymes needed for survival and metabolism – Disrupt membrane integrity Promastigote form of Leishmania donovani. Hepatosplenomegaly in a patient with visceral leishmaniasis. Tape lines mark the areas of the infected liver (top left) and spleen (bottom right 48 Leishmaniasis and the Sand Fly Leishmaniasis § § § § Motile, dividing, non infective Leishmania non-infective dividing procyclic promastigotes differentiate in sandflies into infective, non-dividing metacyclic promastigotes, which are located ready for transmission at the stomodeal valve (an invagination of the foregut into the midgut). During blood feeding, the sandfly regurgitates metacyclic promastigotes, together with immunomodulatory parasitederived proteophosphoglycans and various salivary components. The metacyclic promastigotes are then phagocytosed by one of several possible cell types that are found in the local environment After establishing an intracellular residence, metacyclic promastigotes transform into aflagellate amastigotes. § Amastigotes undergo replication within host cells, which rupture when too many amastigotes are present, allowing reinfection of local phagocytes. § The transmission cycle is complete when infected phagocytes are taken up by another sandfly with the blood meal, and amastigotes then convert into promastigotes in the sandfly midgut. Non-dividing, infective intracellular stage à clinical symptoms 49 Lymphatic Filariasis and Filarial Worms – 1 § Filariasis describes a group of diseases caused by nematodes in the family Filarioidea. • Adult worms in the lymphatic system can produce lymphatic obstruction. – Swelling of limb (elephantiasis) – Swelling of scrotum (hydrocele) 50 Lymphatic Filariasis and Filarial Worms – 1 Filariasis § Larvae • L1 – L3 § Microfilariae • early stage in the life cycle • Produced by adult worms • Ingested by mosquitos § Humans: definitive host § Mosquitoes: intermediate host 51 When Fungi go Systemic Candida albicans: If the number or function of neutrophils is decreased or the gastrointestinal mucosa is damaged, yeast may invade beyond the mucosal surface, disseminate, and infect virtually any organ system 52 Clicker Question 4 Which of the following diseases affects the lymphatic system? a. endocarditis b. lymphatic filariasis c. dengue fever d. malaria e. Lyme disease 53