Lecture 23: CV and Lymph infections

(CV and Lymph infections) Lecture 23 Cardiovascular Infections · infections of the blood (blood borne) · infections of the heart valves and heart muscle · infections of the vessel walls (artery walls usually) Systemic Infections (disseminated infections) · Bacteremia (bacteria in blood) ↳ can lead to septicemia and then bacteria replicate in your blood · Septicemia/Sepsis → evidence of infection + systemic response · Septic Shock: caused by both G-/+, but more serious with G- due to LPS endotoxin ↳ can be called endotoxic shock Bacteremia · enters the body through broken skin, like trauma and burns · leads to infection and inflammation of tissues · bacteremia is tested by blood cultures · common causes of bacteremia: ↳ perforation/penetration of intestine, appendicitis, invasion (eg. Salmonella), oral surgery, Kidney infection, pneumonia, catheters · Bacteremia can lead to different scenarios: 1. bacteremia that clears spontaneously 2. bacteremia that seeds other areas of the body and causes local infections 3. Sepsis 4. septic shock Common Organisms in Positive Blood Cultures: · Staphylococcus aureus and epidermidis (usually a contaminant tho) · Streptococcus pneumoniae · Enterococci (VRE or non-VRE) · alpha-streptococci · G- (eg. E. coli, Klebsiella pneumoniae) ↳ G- usually means something REALLY bad Sub-acute Bacterial Endocarditis · long, chronic disease · bacteria (usually from teeth/mouth) go through the bloodstream and to the heart valves ↳ worse if you had rheumatic fever or artificial heart valves ↳ forms "vegetations" or clumps of biofilms on the valves · symptoms: fever, weakness, heart murmur, develops slowly · alpha-hemolytic Streptococci, S. epidermidis or enterococci from GI tract · antibiotics don't work for biofilms → must replace valves A big difference between sub-acute and acute endocarditis is the virulence factors. Sub-acute is often caused by bacteria with less severe virulence factors Acute Bacterial Endocarditis · RAPIDLY progressive damage to heart valves · often occurs when open heart surgery has been done and wound contaminated · usually S. aureus and other pyogenic bacteria Pericarditis · inflammation of the pericardium ↳ membrane hardens, pus builds up · often caused by Streptococcus pyogenes · also caused by Coxsackievirus, an RNA virus that causes "Bornholm disease" ↳ self limiting, common in long distance runners · treatment: remove pericardium then treat with antibiotics Atheroscerosis · cardiovascular disease that causes the arteries to harden and occlude ↳ proliferation of smooth muscle cells (grows inwards) Normal artery · most likely caused by a multi-pathogen load ↳ C. pneumoniae is most suspected b/c it can be found in the plaque Occluded artery Lymphangitis · inflammation of the lymphatic channels, can be caused by spread of infectious agent up the channels which eventually drains into the bloodstream ↳ microorganisms are spread easily through the lymphatic and cardiovascular systems · dangers: ↳ G- sepsis can lead to shock ↳ endocarditis/pericarditis ↳ asplenic: increased risk for infection with organisms that have a capsule Spleen · functions to remove contaminants and cells, is a major site of production for opsonizing antibodies (for encapsulated organisms) · Splenectomy: removing the spleen b/c of trauma, damage, or thrombocytopenia (spleen hoards the platelets) · patients without a spleen are VERY susceptible to infection by encapsulated organisms (cannot produce opsonizing antibodies) ↳ need to vaccinate before splenectomy if possible ↳ need for antibiotic prophylaxis (for prevention) Some Causes of Bacterial Systemic Infections (from bites/scratches) · Anthrax: caused by Bacillus anthracis · Lyme disease: caused by Borrelia burgdorferi · Black death: caused by Yersinia pestis · Pasteurella multocida (cat or dog bite/scratches) Lyme Disease (Borrelia burgdorferi) · microaerophilic spirochaete · "erythema migrans", typical bullseye rash · transmission: ticks (ixodes) which must be attached for 24 hours before the bacterium is transferred ↳ ticks live on mice and jump onto deer (so beware when hunting) · Borrelia can survive for years in untreated patients within joints, nervous system, and skin Black death /Bubonic plague (Yersinia pestis) · facultatively anaerobic G- small bacillus that can live in phagocytes · two syndromes: pneumonic and bubonic (bubo: infected lymph gland) · transmission: ↳ bubonic: rat fleas vector ↳ pneumonic: human-human · mortality: untreated bubonic 50-80%, pneumonic 100% · treatment: antibiotics tetracycline and streptomycin if caught in time Pasteurella multocida · small facultatively anaerobic G- bacillus · found in mouths of dogs and cats ↳ most infections caused by cat bites · untreated can rapidly result in sepsis and septic shock · immediate acute treatment with antibiotic even before results of culture Viral Hemorrhagic Fevers · most are zoonotic diseases · first symptoms: fever, chills, headache, nausea, vomiting ↳ followed by jaundice (liver damage) - yellow fever, dengue, WNV, ebola Yellow Fever · RNA virus (flaviviridae) transmitted by aedes mosquitoes · hemorrhagic fever syndrome characterized by: hepatic, renal, myocardial injury, hemorrhage, and high death rate (20%) · occurs only in tropical South America and sub-Saharan Africa · monkeys natural reservoir in wild · diagnosis by serology (blood test looks for antibodies) · no antiviral treatment, live attenuated vaccine available Dengue Fever · RNA virus (flaviviridae), transmitted by aedes mosquito (day biters) ↳ milder than yellow fever, similar symptoms ↳ four different subtypes (antigenically) · endemic in tropics and subtropics · symptoms: fever, muscle pain, joint pain and rash "breakbone fever", rarely fatal · treatment: supportive care Dengue Hemorrhagic Fever · caused by having two subtypes · more severe than normal DF, causes shock within hours · first infection: immune response, antibodies can be used on different types · second infection: amplified infection b/c of antibodies Zika Virus · RNA, enveloped, flaviviridae family · first identified in a rhesus monkey in Zika forest Uganda, mosquito borne · only 20% of infected get symptoms, typically mild non-pregnant individuals · linked with Guillan-Barre syndrome and microcephaly in infants · no vaccine or antiviral Ebola Virus · enveloped RNA virus (filovirus), zoonosis (Africa), likely bat related · transmission: direct contact with bodily fluids ↳ spread due to lack of education, lack of good health facilities, movement of people in West Africa, traditions for caring for the dead · treatment: aggressive supportive treatment (IV fluids) ↳ Use BSL 4 highest level of security (suit + breathing system) · symptoms: ↳ 1-2 week incubation ↳ primarily GI infection - gastroenteritis ↳ abrupt onset of fever, headache, myalgia, sore throat, red eyes, followed by nausea, vomiting, diarrhea, rash, chest pain · problem: With these symptoms it could also be malaria, typhoid fever, lassa fever, leptospirosis, Shigella, yellow fever, sepsis, measles (HIV and Complications of Immunodeficiency) HIV (human immunodeficiency virus) Lecture 23 · progresses to AIDS (acquired immune deficiency syndrome) · no vaccine · originates from SIV (Simian immunodeficiency virus) ↳ HIV-1: monkey (chimpanzee/gorilla) → human [Pandemic] ↳ HIV-2: monkey → human · "Skinny disease" · epidemiology: 40 million+ people have the virus, only 5% are diagnosed · transmission: by body fluids, sexually (heterosexual > homosexual) · diagnosis: ↳ repetitive screening for HIV antibodies (ELISA) ↳ virus PCR: virus load from blood (looks at genetic sequences for gene resistance) ↳ virus culture (not usually done, takes long time, not useful) ↳ antigen tests: p24 HIV Virus · RNA retrovirus with reverse transcriptase to make DNA copies, which is then incorporated into chromosome with integrase ↳ DNA either produces more virus or lays dormant as a provirus (invisible) · enveloped, glycolipid envelope has spikes called gp120 · infects CD4+ T cells, macrophages, and dendritic cells ↳ MUST attach to CD4+ AND chemokine receptors in order for infection to occur (CCR4, CXCR5) · virulence factors: latent as a provirus that immune system cannot detect, antigenic variation (+ drug resistance b/c of RNA variation) Monitoring Progression: ① Viral load (number of HIV particles in blood) ↳ blood tests ② Number of CD4+ cells ↳ below 200/mm3 indicative of clinical AIDS ↳ normal CD4+ cells live for several years, and infected cells only survive two days ↳ virus inhibits new production of T-cells Stages of HIV Stage A: · infection is asymptomatic or causes chronic swollen lymph nodes Stage B: · persistent infections by opportunists like C. albicans, VZV, cryptosporidia, hairy leukoplakia Stage C: Clinical AIDS · defined by "indicator conditions" like C. albicans infections of respiratory mucosa, CMV eye infections, TB, pneumocystis pneumonia, toxoplasmosis of the brain, and Kaposi's sarcoma Initial Symptoms of HIV · mild flu-like symptoms, may go unnoticed (could take up to 10 years) · symptoms are only characteristic of a viral infection · symptoms: fever, adenopathy (swollen lymph glands), pharyngitis, rash, myalgia/arthralgia, thrombocytopenia, leukopenia, diarrhea, nausea Primary HIV maculopapular rash Oral HIV Diseases: Oral hairy leukoplakia · oral candidiasis: usually C. albicans (most common is thrush) · oral leukoplakia: white lesions (EBV) on tongue usually ↳ usually asymptomatic, no treatment needed · gingivitis and peridontitis: severe pain, bleeding gums, loosening of teeth · oral ulcers: HSV 1 and HSV 2, CMV Ocular HIV infections · very common, ranges from benign retinopathy to blindness Herpes from viral infections · CMV retinitis: inflammation of the retina (most common) · Varicella-zoster retinitis: severe necrotizing retinitis · ocular toxoplasmosis: infection of eye from a parasite Pulmonary Disease · leading cause of mortality and morbidity · pneumocystis jiroveci pneumonia (PJP) (opportunistic) ↳ yeast found in dust, common in respiratory tract but only affects immunocompromised ↳ insidious onset (slow start) ↳ early diagnosis and treatment important ↳ dry cough (not productive), no purulent sputum, no pus in lungs like normal pneumonia ↳ trimethoprim-sulfa "Septra" for treatment (must be taken for rest of life, inhibits yeast) · bacterial pneumonia · viral pneumonia · fungal pneumonia Mycobacterial Diseases · usually first infectious complication · HIV increased risk for reactivation of latent infections (like Shingles or TB) · HIV increased risk of symptomatic disease after infection ↳ can't hold bacteria in granuloma ↳ b/c of failed granuloma, increased risk of disseminated infections (TB, MDR-TB, and XDR-TB) · HIV patients have 5%-10% annual risk of developing active disease (25% more likely to get TB) Kaposi's Sarcoma · associated with HHV8, treated by radiotherapy · well-known AIDS defining illness · appears as cutaneous red purple nodules or plaques ↳ usually on: legs, feet, mucous membranes, hard palate, nose, trunk, scalp · vascular neoplastic disorder: usually seen in late stage HIV infection (AIDS) ↳ cancer Transmission of HIV · direct contact with body fluids, intimate sexual contact ↳ blood has highest viral load ↳ Semen also has a lot · blood contamination with needles, organ transplants, blood transfusion · transmission most effective if sores are present (like if you have an STD) · vertical transmission (mother → fetus) ↳ to the fetus: not infected during pregnancy, just after birth after contact with the mothers blood ↳ artificial insemination: if the donor semen has HIV · HIV survives 1.5 days inside cells, but only 6 hours outside of cells (cannot eliminate, infected for life) You are already infected in your genome, this just stops new ones Treatment of HIV (works on HIV life cycle) · Nucleoside reverse transcriptase inhibitors (NRTI's) → cannot make RNA · Non-nucleoside reverse transcriptase inhibitors (NNRTI's) → doesn't require · Protease inhibitors (PI's) → cannot make proteins · Integrase inhibitors (INST's) → stops integrase from putting DNA into genome · Fusion inhibitors (FI's) · Chemokine receptor antagonists (CCR5 antagonists) Problem: rapid development of resistance HAART: (highly active anti-retroviral therapy): combination of several anti-HIV medicines Treat as soon as they are found to be infected with HIV, irregardless of CD4+ count DRUG: Truvada ① PrEP (pre-exposure) to prevent infection the specific HIV is done to check for mutations for ② Treatment of HIV disease ↳ Usually triple therapy, but genome sequencing of resistance to drugs Risks for Health Care Workers · HIV = .003%, HBV = 37-62%, HCV = 23-37% · with mucosal membrane exposure, risk is 0.09% · Risks: ↳ deep injury ↳ up to 75% protection ↳ in combination with other drugs Prevention · barriers (gloves/goggles etc.) · immediately scrub hands after contact w/bodily fluids · carefully handle and dispose of sharp instruments ↳ visible blood on the device PEP (post exposure prophylaxis) ↳ source with late-stage HIV infection and high viral load with person who has HIV ↳ needle placement in artery or vein ↳ low vs. high risk after contact