COM 1802 Hematology and Oncology TBL 4 PDF

COM 1802 Hematology and Oncology TBL 4 – Infections of the Blood and Lymphatics Spring 2025 Krista Edmiston, PhD Session Learning Outcomes...

COM 1802 Hematology and Oncology TBL 4 – Infections of the Blood and Lymphatics Spring 2025 Krista Edmiston, PhD Session Learning Outcomes Dr. Edmiston 1. Describe the pathogenesis of sepsis and septic shock and identify common pathogens involved. 2. Describe the structure, classification, transmission (including common sources), and mechanism of pathogenesis of the following pathogens: –Viral Hemorrhagic fever: Yellow Fever Virus, Dengue Virus, Chikungunya Virus, Lassa virus, Ebola virus, and Marburg virus –Malaria and Babesiosis: Plasmodium spp. and Babesia spp. –African Trypanosomiasis: Trypanosoma brucei –Lymphatic Filariasis (Elephantiasis): Wuchereria bancrofti 3. Identify the clinical presentation, identification, treatment (if available), prevention, and control of the diseases caused by the above pathogens. 2  Bloodstream Infection Terminology Dr. Edmiston Bloodstream infection (BSI) is a frequent presentation of infection. –Bacteremia is detectable bacteria in the blood. –Viremia is detectable virus in the blood. –Fungemia is detectable fungi in the blood. –Parasitemia is detectable parasites in the blood. The various “-emias” can be with symptoms = acute or without symptoms (asymptomatic) = transient. If the “-emia” lasts for ≥ 3 days = persistent BSIs (most commonly bacteremia) can lead to sepsis by triggering the host immune response either by a portion of the microbe itself or by the production of a toxin. The subsequent inflammatory response includes vascular, cellular, and chemical responses designed to stop injury. 3  Sepsis and Septic Shock Dr. Edmiston Sepsis (“putrefaction” or “decay of organic matter”) is not always well defined, but, in general, it is a life-threatening organ dysfunction caused by dysregulated host response to infection (septicemia). – Infections leading to sepsis are among the most frequent conditions that promote disseminated intravascular coagulation (DIC) (TBL 6). Septic shock occurs during sepsis in which underlying circulatory and cellular/metabolic abnormalities are profound enough to substantially increase mortality. – Specifically, the Lipid A portion of LPS/LOS (endotoxin) of Gram-negative bacteria and lipoteichoic acid (LTA) of Gram-positive bacteria can induce a severe systemic Most Common Types of Organ Failure in Sepsis response leading to septic shock. The manifestations of sepsis depend on the source of infection and the pathogen, type, and extent of organ dysfunction, drug use and comorbidity of the patient, and if there was a delay before the start of treatment. – Generally, the presentation includes fever, tachycardia, tachypnea, altered mental status, significant edema or positive fluid balance. 4  Common Causative Agents of Sepsis Dr. Edmiston Incidence of Sepsis by Causative Organism There is no gold standard for diagnosing sepsis. – A clinical pattern based on the patient's history and physical examination combined with laboratory, radiology, and microbiology testing (cultures and Gram-staining) is typically required for the diagnosis. A causative microorganism can be identified in up to 2/3 of patients admitted to an ICU for sepsis, with positive blood cultures on ~1/3. Septic shock is most frequently triggered by Gram-positive bacterial infections, followed by Gram-negative bacteria and fungi. Common Causes of Bloodstream Infections – The most common isolated Gram-positive bacterial pathogens are Staphylococcus aureus, Streptococcus pneumoniae, and Enterococcus spp. – The most common Gram-negative pathogens are Escherichia coli, Klebsiella spp., Pseudomonas spp., and Acinetobacter spp. Microbes that have a high rate of antibiotic resistance are of particular concern, including: – Methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Staphylococcus aureus (VRSA), cephalosporin-resistant Gram-negatives via enzyme- 5 extended spectrum β-lactamases (ESBL).  Viral Hemorrhagic Fever Dr. Edmiston Viral hemorrhagic fever (VHF) is an acute systemic febrile syndrome caused by over 30 viruses from four different virus families – Flaviviridae, Arenaviridae, Filoviridae, and Bunyaviridae. Most of the viruses that cause hemorrhagic fever are zoonotic (except dengue) – endemic areas are limited to the distribution of their mammalian reservoirs and/or arthropod vectors (arboviruses). The incubation period is usually short (~1–2 weeks), followed by a rapidly progressive illness usually lasting no longer than 2 weeks. VHF is characterized by microvascular instability with capillary leak and impaired hemostasis. – Initial signs and symptoms are usually very non-specific and include fever, headache, and myalgia, followed rapidly by gastrointestinal symptoms and, in some cases, rash and Oral bleeding in Ebola hemorrhagic fever. neurologic involvement. – Severe cases develop hemodynamic instability, bleeding, shock, and multi-organ system failure. – Death occurs in 1-80% of cases depending on the infecting virus. Typical laboratory findings in VHF at presentation include lymphopenia, thrombocytopenia, and elevated hepatic transaminases, with AST>ALT. – Lymphocytosis and thrombocytosis may be seen in late stages. Rectal bleeding in Ebola hemorrhagic fever. 6  Arboviruses Dr. Edmiston Arboviruses are a group of viruses that are spread by insect vectors. Include members of the Togaviridae, Flaviviridae, Bunyaviridae, Rhabdoviridae, Orthomyxoviridae, and Reoviridae. To be an arbovirus, the virus must be able to: 1. Infect both vertebrates and invertebrates 2. Initiate a sufficient viremia in a vertebrate host for a sufficient time to allow acquisition of the virus by the invertebrate vector 3. Initiate a persistent productive infection of the salivary gland of the invertebrate to provide for the infection of other host animals. 7 Arboviruses Dr. Edmiston Arboviruses ss (+) RNA ss (-) RNA dsRNA Family: Togaviridae EEEV Family: Reoviridae WEEV Colorado tick fever Genus: Alphavirus Chikungunya Order: Bunyavirales California encephalitis Genus: Orbivirus Genus: Orthobunyavirus La Crosse encephalitis Rift Valley fever Coltivirus Nairovirus Dengue Phlebovirus Family: Flaviviridae Yellow fever Tospovirus Genus: Flavivirus Zika Japanese Encephalitis West Nile St Louis Family: Rhabdoviridae Genus: Vesiculovirus Family: Orthomyxoviridae Genus: Thogotovirus 8  Important Arboviruses and Other Related Viruses Dr. Edmiston Virus Family Genus Distribution Host Vector Case Fatality Rate Aedes aegypti Dengue+ Tropics worldwide, some cases in the US Humans 1–5% Aedes albopictus Aedes spp. Yellow Fever+ Sub-Saharan Africa, Central and South America Primates 15–30% Haemagogus spp. Flaviviridae Aedes aegypti Zika Worldwide, especially tropics Humans