Viral Infections PDF - Medical Practice I - Spring 2025

Viral Infections Medical Practice I Spring 2025 Dr. Tom Hatten, DO  To Be Covered Today Herpes Simplex 1&2 Ebola Virus Varicella Zoster Virus HIV/AIDS Epstein-Barr Virus HPV Infections Cytomegalovirus...

Viral Infections Medical Practice I Spring 2025 Dr. Tom Hatten, DO  To Be Covered Today Herpes Simplex 1&2 Ebola Virus Varicella Zoster Virus HIV/AIDS Epstein-Barr Virus HPV Infections Cytomegalovirus SIRS/Sepsis Influenza Coronavirus (COVID-19) Rabies Zika Virus  HHV-1 Herpes Simplex Type 1 HSV-1 HHV-2 Herpes Simplex Type 2 HSV-2 HHV-3 Varicella-Zoster Virus VZV Human HHV-4 Epstein-Barr Virus EBV Herpes HHV-5 Cytomegalo Virus CMV Viruses HHV-6 Roseola HHV-7 Can also cause Roseola HHV-8 Kaposi Sarcoma-associated KSV Herpes Virus Herpes Simplex Type 1 (usually oral but…) Herpetic whitlow and ocular lesion Oral HSV 1 caused by HSV 1 Both HЅV-1 and НSV-2 can cause genital herpes  Virus transmittable via contact with lesions or secretions Clinical manifestations: Prodrome of pain, burning, tingling, fever Then multiple vesicular lesions on an erythematous base Herpes Simplex Dx: Virus 1 & 2 Clinical Can confirm with PCR, viral culture, or type-specific serologic tests Tzanck smear (from lesion scraping) - nonspecific Tx: Antivirals (Acyclovir, Valacyclovir) Acute flair (start during prodrome phase) or Chronic suppressive therapy  Primary infection = “chickenpox” Epidemiology: Common, transmitted by resp. droplets or contact with vesicular fluid Clinical manifestations: Prodrome – fever, malaise, Varicella Zoster pharyngitis Vesicular rash on an Virus (HHV-3) erythematous base; presents in “crops” – will be in various stages of development Dx: clinical Tx: Supportive; maybe acyclovir or valacyclovir in complicated cases Prevention: Vaccinate! Varicella Zoster Virus Reactivation of infection = ”Shingles” Clinical Manifestations: May have preceding neuritis Unilateral vesicular eruption (dermatomal distribution) Painful (often pain precedes the rash) Dx: Clinical Tx: Antivirals within 72 hrs of symptom onset Prevention: Vaccinate!!!! Varicella Zoster Virus (HHV-3) “Chickenpox” Herpes Zoster Vesicular lesions on an erythematous base Grouped vesicles on an erythematous base are characteristic of chickenpox. in the S2 dermatome on the buttock. Epstein-Barr Virus Herpesvirus (HHV-4) Primary agent of infectious mononucleosis  Widely disseminated 90-95% of adults are seropositive Peak incidence = 15 to 24 yrs Epidemiology If infection acquired in childhood: Most are subclinical 10% develop clinical infection  Spread by intimate contact between susceptible persons and asymptomatic EBV shedders Via passage of saliva Transmission Sexual transmission also occurs Virus can shed for 18 months after clinical recovery from infection  Incubation period = 4-8 weeks Prodrome: Clinical Manifestations Malaise Headache Low grade fever Classic Infectious mononucleosis: Fever (98%) Cervical lymph node enlargement and tenderness (100%) Fatigue – can be persistent and severe Tonsillitis and/or pharyngitis (85%) Splenomegaly (50-60%) Rash Maculopapular, urticarial, or petechial Can occur after the administration of antibiotics or without antibiotics Laboratory and Diagnostic Studies CBC & peripheral smear: Leukocytosis WBC 12-18k (normal 4-11k) Lymphocytosis > 4500/microL Differential > 50% Atypical lymphocytes > 10% Laboratory and Diagnostic Studies CMP – elevated LFT’s “Monospot” test Heterophile ab test Relatively quick results Test of choice in many settings High false negative rate in early infections and young children EBV specific antibodies If heterophile ab test negative Differential Diagnoses CMV Group A strep Acute HIV Toxoplasma gondii (rare) Drug induced (anticonvulsants & antibiotics) HHV-6 rare in adults  Supportive Care Good hydration, antipyretics, analgesics Clinical Intervention Stop antibiotics Corticosteroids only if there is significant tonsillar swelling to the point that the airway may become obstructed Patient Education Refrain from strenuous physical activity and contact sports due to the potential for splenic rupture Acyclovir suppresses viral shedding but has NO clinical benefit Complications of EBV Oral Hairy Leukoplakia Splenic rupture 1 to 2 cases per 1,000 70% are in males, usually under 30 yrs of age Lymphoproliferative disorders Malignancy Infection Lymphomas and head/neck cancer Copyrights apply  Infectious mononucleosis Epstein-Barr Virus: Epidemiology: 15-24 yr olds Symptoms: Fever, cervical lymph node enlargement, fatigue, pharyngitis Dx: Lymphocytosis + positive Summary heterophile antibodies (Monospot) Tx: Supportive care; avoid contact sports  Beta-herpes virus that infects the majority of humans Seroprevalence rates in adults worldwide 40-100% Higher rates in underdeveloped countries Incidence increases with age Cytomegalovirus Primary infection in (CMV) immunocompetent adults: Asymptomatic usually HHV-5 Or a Mononucleosis type presentation Reactivation (or primary infection) in immunocompromised: Uncontrolled CMV replication ensues Transmission of CMV Person to person Vertical transmission (mom to baby) Most common congenital infectious cause of sensorineural hearing loss and developmental delay. Blood transfusion Organ or hematopoietic stem cell transplantation Clinical Manifestations of CMV: Mononucleosis-like syndrome Protracted fever Lassitude Absolute lymphocytosis & atypical lymphocytosis BUT NEGATIVE heterophile antibody More common in EBV than CMV: Cervical lymphadenopathy Exudative tonsillitis Splenomegaly Younger age Clinical Manifestations of CMV (that are more common in immunocompromised patients) GI Colitis – diarrhea, abdominal pain Nausea and vomiting Hepatitis Neurologic Encephalitis Guillain-Barre Ocular Retinitis - Visual floaters and blindness  CBC – lymphocytosis CMP – elevated LFT’s Laboratory & Serology – ELISA CMV IgM titer Diagnostic (antibodies) Acute infection Studies CMV IgG titer Suggests previous infection PCR Blood and tissue specimens Detects viral DNA CMV pp65 antigenemia test Viral Culture CD4 count CXR  Patient Education Acquired self-limited illness (Immunocompetent) Reassurance Clinical Intervention Immunocompromised Intravenous ganciclovir or oral valganciclovir HAART therapy  Congenital CMV infection: Developmental delay/Low IQ Sensorineural deafness Visual impairment Complications Developmental abnormalities Ganciclovir- and valganciclovir-induced bone marrow suppression  CMV: Summary HHV-5 Symptoms: Immunocompetent patient = usually asymptomatic Immunocompromised patient = Mono-like syndrome Diagnosis: Lymphocytosis, elevated LFT’s, antibodies/PCR/CMV pp65 antigenemia Treatment: Supportive OR IV antivirals for immunocompromised patients  Acute respiratory illness caused by Influenza A or B viruses Occur in outbreaks and epidemics worldwide, mainly during the winter season Influenza Transmitted in respiratory secretions of infected persons (i.e.- sneezing, coughing) Self-limited infection Associated with increased morbidity and mortality in certain high-risk populations (i.e.-children, elderly, patients with chronic illnesses, immunocompromised) Microbiology 4 types of influenza virus (A, B, C, and D) Human influenza A & B cause seasonal epidemics Influenza A cause pandemics Surface proteins of the virus: Hemagglutinin (H) – 18 subtypes 3 major (H1, H2, and H3) Neuraminidase (N) – 11 subtypes 2 major (N1 and N2)  Host of origin - if not human - is included after the virus type If a pandemic is caused by a strain, it is indicated last (pdm09 for example for the 2009 pandemic virus) Antigenic Drifts vs. Shifts Influenza A viruses tend to undergo periodic changes in their surface proteins Minor changes = Antigenic drifts Responsible for local outbreaks of varying extent Major changes = Antigenic shifts Responsible for epidemics & pandemics Influenza B viruses generally only show antigenic drifts, with minor changes in hemagglutinin  Vaccination history? Risk reduction between 40 and 60% Comorbidities? Likelihood of being an uncomplicated self resolving infection vs. complicated influenza Patient History Season? Less likely in warmer months, but not impossible Known exposure? Incubation period 1-4 days; avg 2 days Clinical Manifestations - Symptoms Abrupt onset of: Children: Fever Often have higher fever than Headache adults Myalgia GI sx (vomiting/diarrhea) present in 10-20% Malaise Respiratory tract illness sx: Cough Rhinorrhea/Nasal Congestion Sore throat  Generally few Clinical Fever Manifestations - Hyperemia of the oropharynx Signs (uncommon) Mild cervical lymphadenopathy (more so in younger patients) Laboratory and Diagnostic Studies Clinical Diagnosis Rapid Diagnostic Tests Positive for influenza A and/or B Should be performed within 24-48 hours of symptoms due to peak in viral shedding Chest x-ray Usually not necessary but may need to be performed to exclude primary viral or secondary pneumonia  Who should get the annual influenza vaccine? Everyone 6 months and older!!! But especially: Chronic pulmonary or cardiac conditions Diabetes Renal disease Prevention via Liver disease Chronic neurologic conditions Vaccination! Immunosuppression Older adults (>65 years old) Infants 6 – 59 months Pregnant women Healthcare workers Caregivers to members of an at-risk population  The vaccine each year is an educated guess as to what strains will circulate in the upcoming year Influenza Vaccines Some are designed specifically for people over age 65 to induce a stronger immune response Quadrivalent vaccines: 1 Influenza A H1N1 virus 1 influenza A H3N2 virus 2 influenza B viruses (One from each lineage) Trivalent vaccines: Both of the above A’s + 1 B  Antiviral Therapy: (benefits of treatment are greatest when medications are initiated in the first 24 to 48 hours after symptom onset) Oseltamivir (Tamiflu) 75mg PO BID x 5 days Zanamivir 10mg (two inhalations) twice daily Clinical Intervention Peramivir 600mg IM as a single dose Symptomatic Treatment Antipyretics/analgesics Complications Pneumonia Aseptic (viral) The major meningitis complication GB Can be primary viral Cardiac complications pneumonia or secondary bacterial Acute MI Myocarditis ARDS Pericarditis CNS complications Encephalopathy/ encephalitis  Viral infection common in winter Influenza: Summary Transmitted via respiratory secretions Sx: Abrupt onset of headache, fever, fatigue, malaise + respiratory symptoms Dx: Clinical + Rapid flu test Tx: Antivirals if within 48 hrs of symptom onset Antivirals for ALL patients hospitalized with influenza Supportive care Prevent with vaccination Coronavirus (COVID-19) Coronaviruses are a large family of viruses common in many species SARS-CoV (Severe acute respiratory syndrome) MERS-CoV (Middle East respiratory syndrome) A novel coronavirus was identified at the end of 2019 (COVID- 19) Caused a cluster of pneumonia cases in Wuhan (Hubei Province of China) Spread rapidly in China (epidemic) and then around the world (pandemic) The disease is now called COVID-19 The virus that causes the disease has been designated SARS-CoV-2 (previously 2019-nCoV) COVID-19 Transmission via respiratory droplets Incubation period = within 14 days (most cases at 5 days) Spectrum of disease: Asymptomatic Mild respiratory illness (no or mild pneumonia) Pneumonia Fever, cough, dyspnea, mylagias Bilateral infiltrates on imaging 20% have critical illness – respiratory failure/septic shock/MSOF  Cough (50%) Fever (43%) Myalgia (36%) HA (34%) Dyspnea (29%) Sore throat (20%) Symptoms Diarrhea (19%) N/V (12%) Loss of smell/taste, abdominal pain, rhinorrhea (< 10%) COVID-19: Risk factors for severe illness Advanced age > 65, especially > 80 yrs Comorbid conditions CVD, DM, chronic lung disease, cancer, CKD, obesity, smoking, liver disease Diagnosis *NAAT with RT-PCR: Samples from naso/oropharyngeal & sputum can be used Detects SARS-CoV-2 RNA Preferred initial test Rapid tests may be less sensitive WBC = variable but lymphopenia is most common Elevated aminotransferases Elevated procalcitonin (in severe cases)  Don’t forget to consider other COMMON causes of their symptoms! Viral Upper Respiratory Infection (common DiaViragnoses cold!) Differential Influenza Strep, mycoplasma, legionella pneumonia Strep pharyngitis if sore throat is the main complaint Chest Imaging Outpatient Treatment Depending on vaccination status – can qualify for monoclonal antibodies Currently in use - nirmatrelvir-ritonavir (Paxlovid) Outpatient Treatment Inpatient Flowchart  Respiratory failure – ARDS * Cardiac COMPLICATIONS Arrhythmia, MI, shock, cardiomyopathy Thromboembolic Pulmonary embolism, stroke (even in patients < 50 without risk factors) Neurologic COVID-19 Encephalopathy, cognitive deficits Inflammatory “Exuberant inflammatory response”; GBS, Kawasaki, Toxic shock syndrome Secondary infections – not as common  One of the oldest and most feared human infections Highest case fatality rate of any infectious disease Caused by viruses in the Rhabdoviridae Family and other members of the Lyssavirus genus Lyssaviruses like neural tissue Rabies Spread via peripheral nerves to the CNS Transmitted by animal bites (exposure to saliva) Average incubation period 1-3 months, but can range from several days to many years post exposure Epidemiology WHO estimates that 59,000 people die of rabies each year 127 human cases from 1960 to 2018 in the US Avg 1-3 cases per year in the US Animal reservoirs in the US: Canine rabies was the largest source prior to the 1950’s Now: bats, racoons, skunks, and foxes are the major reservoirs 70% of infections in the US were attributed to bat exposures Patient History History of animal bite or known exposure Immunization status  Non-specific sx: Low grade fever, chills, malaise, myalgias, weakness, fatigue, anorexia, sore throat, N/V, HA, occ. photophobia Clinical Lasts few days to 1 week Manifestations - Paresthesias radiating proximally from a Prodrome bite wound = suggestive of rabies infection Once the patient has exhibited clinical signs of Emphasizes the disease, rаbieѕ usually leads to progressive importance of early post- encephalopathy and death, with rare exception exposure treatment!!! Encephalitic rabies (most common) Clinical Manifestations: Hydrophobia (most common; 33-50% of patients) (fear of water) Aerophobia (9%) (fear of drafts of fresh air) Fever Pharyngeal spasms & dysphagia Opisthotonos (neck and back become hyperextended with muscle spasticity) Hyperactivity subsiding to paralysis Autonomic instability 25% Agitation and Combativeness 50% Coma Death  Less common type (20%) Paralytic rabies: Ascending paralysis Flaccid paralysis Fasciculation Clinical Deep tendon and plantar reflexes are lost Manifestations – Death Hydrophobia is unusual  Routine laboratory tests are non-specific Diagnostic Studies Lumbar Puncture CT brain Laboratory and Normal early in the course; later stages show cerebral edema MRI Isolation of virus from saliva PCR Detection of anti-rabies antibodies in serum or CSF Virus-specific immunofluorescent staining of skin biopsy specimens  Not every patient will be aware of their exposure Differential Diagnoses Prodrome: Mononucleosis, bacteremia, or any other infectious process Encephalitic Rabies: Meningitis Encephalitis from other cause – HSV, West Nile Toxic or metabolic encephalopathy Tetanus Paralytic Rabies: Guillain-Barre Poliomyelitis Acute transverse myelitis West Nile virus  No proven effective treatment for rabies Clinical Interventions Symptomatic Rabies Supportive/palliative care: Focus on comfort, pain control, and sedation  Persons NOT previously immunized with Rabies Vaccine Clinical Interventions Non-bite exposure with no infection risk Reassurance Bite exposure – see algorithm (next slide) Wound cleansing/ debridement Human rabies immunoglobulin As much as possible of the full dose should be infiltrated around the wound, with any remaining injected intramuscularly (opposite from where vaccine given) Multiple-dose immunization protocol with rabies vaccine 5 doses (1 mL each) on days 0, 3, 7, 14, 28; administer rabies immune globulin Copyrights apply Clinical Interventions Persons who have previously received pre-exposure Rabies Vaccine Any exposure with infection risk Wound cleansing 2-dose immunization protocol 1mL each on days 0 and 3; do not administer immune globulin  Rhabdoviridae family – spreads via peripheral nerves to the CNS Transmitted from animal bites (especially bats) Sx: Nonspecific prodrome Encephalitic rabies Rabies: Summary Paralytic rabies Dx: Good history/physical, LP, CT/MRI brain, isolation of virus Tx: No proven effective treatment Human rabies immunoglobulin & vaccine Zika Virus A flavivirus First (confirmed) human case was in Uganda and Tanzania in 1952 – now widespread Spread primarily via Aedes aegypti mosquito Found in Southeastern US However, a certain type of mosquito can be seen as far north as Pennsylvania Can also be spread via sexual transmission in humans and from mother to fetus Incubation period about 10 days  25% of patients experience symptoms Clinical Manifestations Acute onset fever (low grade) Pruritic maculopapular rash - Face, trunk, extremities, palms and soles Non-purulent conjunctivitis Arthralgia - Small joints Generally a mild illness that resolves in 2- 7 days Most patients (75%) are asymptomatic!  CDC recommends testing in: Persons with symptoms if they live or have traveled recently to an area with active transmission Labs and Pregnant women who lived in or have visited affected Diagnostics regions Viral RNA or neutralizing antibody, IgM detected 4 days or more after sx onset If Zika (+) mom, check serial fetal ultrasounds Complications *Guillain-Barre syndrome *Ventriculomegaly, Microcephaly in developing fetus. Other neuro complications – Encephalitis, CIDP, transverse myelitis, neuropsych and cognitive symptoms Decreased sperm counts for 4 months Spontaneous abortions Clinical Intervention No treatments available/No vaccine available Avoid ASA and NSAIDs Propensity to cause hemorrhage Prevention is best Mosquito control efforts Test pregnant women via CDC recommendations No unprotected sex (of ANY type) Men for 6 months Women for 8 weeks Ebola Virus Disease From the family Filoviridae Amongst the most virulent pathogens of humans Epidemics start when an individual becomes infected through contact with the body fluids of an infected animal Transmission through direct contact with blood or body fluids Outbreak from 2014 – 2016 in West Africa - >11,000 deaths Mortality often 80-90% in certain regions; overall 50% Can be transmitted during convalescent period Persists in other body fluids longer than in blood Patient History TRAVEL LATELY? CONTACT WITH WILDLIFE LATELY? (CHIMPANZEES OR BATS)  Abrupt onset of symptoms 6-12 days after exposure Clinical Presentation Includes F/C, malaise, HA, vomiting, diarrhea, loss of appetite Rash – diffuse erythematous, maculopapular rash day 5-7 Face, neck, trunk, arms Can desquamate GI – up to 10 L of watery diarrhea per day! Hemorrhage – less common – more in terminal phase Neurologic – AMS, hyperreflexia, stiff neck, gait issues, seizures Cardiac – bradycardia Respiratory – tachypnea and SOB due to muscle fatigue Ocular – Conjunctival injection, uveitis  Malaria Differential Diagnoses Typhoid Marburg Lassa fever Meningococcal disease (Neisseria meningitidis) Measles Traveler’s diarrhea  CBC Leukopenia Thrombocytopenia Elevated AST and ALT Diagnostics Prolonged PT and PTT In severe cases Proteinuria Elevated BUN/Cr Significant electrolyte abnormalities related to GI manifestations Diagnostics Clinically based: Risk of exposure + Symptoms High risk Moderate Low but not zero risk Need to test RT- PCR (of blood) in any risk within 3 days of symptom Testing to be done in conjunction with onset state health departments Can also do rapid immunoassay *MUSC is South Carolina’s only state- (ReEBOV) that detects Ebola virus designated Ebola Treatment Center antigen within 15 minutes (July 2020)  If you are to survive, improve during second week of illness Fatal disease is characterized by more severe clinical signs and symptoms early in course Convalescence – can persist for more than 2 years Weakness, fatigue, insomnia, HA, unable to gain weight, arthralgias, hearing loss, uveitis, extensive sloughing of skin and hair loss Course Treatment Use mega PPE Supportive care is mainstay Rapid volume replacement Antiemetics, antidiarrheals Replete electrolytes If needing respiratory support, go to intubation to prevent aerosolizing of virus Blood products TPN Consider empiric antibiotics Experimental therapies Remdesivir, favipiravir, convalescent plasma/whole blood -> poor efficacy Monoclonal antibodies (Inmazeb & Ebanga) Prognosis Dependent on early diagnosis and prompt initiation of care Mortality increases with age Diarrheal disease carries poor prognosis Higher viral load = higher mortality  More than 40 million people in the world affected Immunodeficiency Highest prevalence: Central and East sub-Saharan Africa About 1.1 million individuals in the US Affects all cells containing the T4 antigen – primarily CD4 helper inducer lymphocytes Immunodeficiency caused by continuing viral replication Human Transmission via body fluids – sexual contact, blood or blood products, injection drug use and perinatal exposure Virus  10-60% of individuals with early HIV infection will be ASYMPTOMATIC Acute symptoms occur 2-4 weeks after initial Acute HIV Clinical infection and resolve spontaneously “Acute retroviral syndrome” Fever, fatigue, myalgias features Lymphadenopathy – axillary, cervical, & occipital Sore throat, mucocutaneous ulcerations Diarrhea/nausea/anorexia/weight loss Generalized rash Headache Laboratory profile of HIV infection over time.  The CDC, USPSTF, AAFP, and ACP recommend routine HIV screening in ages 15-65 years. Opt-out approach HIV Screening CDC has tasked all PCP’s to: Screen ALL individuals between ages 13-64 at least 1 time Conduct more frequent screening for higher risk patients (annual) Link all patients who test positive to medical treatment, care, and prevention services  Informed Consent WHO “5 C’s” of HIV Confidentiality Counseling Correct test results testing Connection (linkage to care, treatment, and other services)  ELISA for antibodies to HIV antigens Sensitive (>99.5%) but not highly specific. Positive 3–7 weeks after infection Used as screening “3rd generation” tests if detecting IgM & IgG Screening Tests Can be lab based or rapid tests (results in 20 min) Rapid tests for antibodies may miss acute HIV infections Combination HIV antigen + antibody tests “4th generation” HIV tests S/S 100% for chronic infection; 80% in acute HIV that would be missed with antibody only test Not as sensitive as HIV RNA tests  HIV-1/HIV-2 differentiation immunoassay Confirmatory Tests Rapid lab-based test (results in 20 min) Used after a positive 4th gen combo assay Preferred over the Western blot Western blot for antibodies to HIV antigens Highly specific Positive 4–6 weeks after infection Previously was the preferred confirmatory test after a positive ELISA screening test Longer turn around time/some sent to a reference lab  Direct detection of virus (Plasma HIV RNA) Positive 10 – 15 days after infection Can be used to dx acute HIV Qualitative (NAT) Viral Detection Primarily used as screening (ex: blood donation) Quantitative (Viral load) Primarily used for monitoring/management of known HIV HIV antigen detection Positive 1-2 weeks after infection Most often used now as part of the combo antibody/antigen test  Stage 1 Stage 2 Stage 3 CDC Staging of HIV Acute HIV Clinical AIDS infection latency CD4 cell count CD4 cell count CD4 cell count 500 cells/micr 200 to 499 oL oL HIV active but Or the producing at presence of a lower levels stage 3 (ie, AIDS)-defining Can last 10 opportunistic years or illness longer; much faster in some  If CD4 count is 1 month); bronchitis, pneumonitis or esophagitis AIDS? CMV disease And more…  Opportunistic Infection Prophylaxis Prophylaxis for P. jirovecci when CD4 < 200 (TMP/SMX) Prophylaxis for MAC when CD4 < 50 (Azithromycin) Relationship of CD4 count to development of opportunistic infections. MAC, Mycobacterium avium complex; CMV, cytomegalovirus; CNS, central nervous system.  Reduces mortality as well as Anti-Retroviral Therapy serious AIDS- and non-AIDS- related complications Prevents transmission of HIV to others Recommended to start on any HIV positive patients regardless of CD4 count  Four classes of antiretroviral drugs typically used in initial regimens Nucleoside (and nucleotide) reverse transcriptase inhibitors (NRTIs) Non-nucleoside reverse transcriptase inhibitors (NNRTIs) Anti-Retroviral Protease inhibitors (PIs) Integrase strand transfer inhibitors (INSTIs) Most effective antiretroviral therapy (ART) regimens Regimens contain two different NRTIs and an integrase strand transfer inhibitor (INSTI) Infectious Disease referral Metabolic Complications of HIV Lipodystrophy Lipohypertrophy Bone Mineral Density Loss Renal Disease Hypogonadism Insulin Resistance/Diabetes Lipoatrophy Mellitus Heart Disease Dyslipidemia Atherosclerotic cardiovascular disease  Retrovirus transmitted via body fluids Screen everyone between ages 13 and 64 at least once Clinical Manifestations: Acute retroviral syndrome 2-4 weeks after infection Nonspecific, flu-like illness HIV/AIDS Review Dx: Rapid antibody test (or antigen/antibody combo test) followed by HIV-1/HIV-2 antibody differentiation assay Monitor treatment response with CD4 & HIV viral load Tx: Start anti-retroviral therapy on ALL patients dx with HIV; consider PrEP & PEP Prophylaxis once CD4 < 200 for PJP & < 50 for MAC Monitor and treat for metabolic complications Be aware of increased risk for malignancy – CNS lymphoma, Kaposi sarcoma, cervical cancer, etc.  Double-stranded DNA virus > 200 types of HPV Causes anogenital or Human Papilloma oropharyngeal disease Virus Epidemiology: Transmitted from one epithelial source to another Most common STI globally Most infections resolve within 12 months Persistent infection with high-risk HPV types increase the risk of precancerous & cancerous lesions  Condyloma or common warts: Diagnosis & Treatment Clinical diagnosis Warts may resolve on their own Otherwise topical Podofilox, Imiquimod, or Sinecatechins ointments Cervical dysplasia: Dx by reflex HPV testing in setting of abnormal cervical cytology on PAP (or can be ordered simultaneously) No curative treatment for HPV  For females aged 9-10 or 11-12 with “catch-up” vaccines up to age 26 Prevention of HPV AND for MALES age 11-12 with catch-up to age 26 Quadrivalent (Gardasil) – 6, 11, 16, and 18 Bivalent (Cervarix) – 16 & 18 Nine-valent (Gardasil 9) – 6, 11, 16, 18, 31, 33, 45, 52, 58 Only available choice in the US Sepsis Systemic Inflammatory Response Syndrome (SIRS) A systemic response to a nonspecific infectious or noninfectious insult  Body temp > 100.4 F (38 C) or < 96.8 F (36 C) HR > 90 bpm SIRS Criteria = 2 or RR > 20 or hyperventilation with PaCO2 < 32 mmHg more WBC > 12 k or < 4 k; or > 10% bands Sepsis: is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. Early sepsis — Ιnfеϲtiоn and bасterеmia may be early forms of infеctiοn that can progress to ѕepsiѕ. However, there is no formal definition of early sерѕiѕ. Nonetheless, despite the lack of definition, monitoring those suspected of having ѕepѕis is critical for its prevention. Septic shock: is defined as sepsis with circulatory, cellular, and metabolic dysfunction that is associated with a higher risk of mortality Previously, septic shock was identified by the presence of hypotension. It is now recognized that hypotension can be a late manifestation, and tissue hypoperfusion precedes hypotension. Lactate level, an indirect marker of tissue perfusion, has been incorporated in the diagnosis of septic shock in addition to the need for vasopressor therapy required to maintain mean arterial pressure of greater than 65 mm Hg (hypotension). Multiple organ dysfunction syndrome(ΜODЅ) Refers to progressive organ dysfunction in an acutely ill patient, such that homeostasis cannot be maintained without intervention. It is at the severe end of the severity of illness spectrum of both iոfеϲtiοuѕ (ѕерѕiѕ, seрtiϲ shock) and noninfectious conditions (eg, ЅІRЅ from pancreatitis). Sepsis: The leading cause of death among adults in intensive care units (ICU’s) Affects more than 900,000 people annually in the United States. Medical advances over the past decade, standardized protocols and physician awareness have significantly improved survival. However mortality rates remain between 20% and 36% with approximately 270,000 deaths annually in the United States.  ICU admission Bacteremia Advanced age (65+ years) Immunosuppression (comorbidities that depress host defense) Neoplasms, renal failure, hepatic failure, AIDS, asplenism Risk Factors Diabetes and obesity Cancer Community Acquired pneumonia Previous hospitalization Genetic factors Defining Sepsis A life-threatening organ dysfunction caused by a dysregulated host response to infection Organ dysfunction is defined as an increase of two or more points in the quick sequential (sepsis-related) organ failure assessment (qSOFA) score Sepsis occurs when the release of proinflammatory mediators in response to an infection exceeds the boundaries of the local environment, leading to a more generalized response  Early sepsis – no formal definition – still should monitor! Calculators: quickSOFA (qSOFA) score, SOFA score and NEWS Identifying qSOFA is to be used outside of ED and ICU to “Sepsis” help identify patients at risk SOFA = Sequential (sepsis-related) Organ Failure Assessment – slightly more extensive A score >/= to 2 is associated with poor outcomes NEWS2= National Early Warning Score qSOFA Respiratory rate >/= 22 per minute Altered mentation Systolic blood pressure 20 breaths/minute. Signs of end-organ perfusion: Warm, flushed skin may be present in the early phases of sepsis Altered mental status, obtundation or restlessness, and oliguria or anuria. Labs to Check CBC with diff CMP Lactic Acid Procalcitonin CRP Coags Urinalysis Cultures Imaging Chest X-ray Additional studies as indicated (Echocardiography for suspected endocarditis) (CT of the Chest for empyema or parapneumonic effusions) (CT of the abdomen/pelvis for renal or abdominal abscess) Management Give supplemental oxygen Make sure they have IV access FLUIDS! Antibiotics! AKA early goal-directed therapy  The goal is to maintain tissue perfusion! Fluid Resuscitation Give aggressive intravenous fluid (IVF) administration Recommended 30ml/kg within the first three hours of presentation Infusing an initial 1-L bolus over the first 30 minutes is an accepted approach. IV crystalloids (e.g., normal saline, Ringer lactate) Administer in well-defined, rapidly infused boluses Re-evaluate the patient in between each bolus.  Current recommendation is to give appropriate antibiotics within one hour of presentation AFTER getting cultures! ☺ Generally, empiric antibiotics based on suspected source Antibiotic therapy of infection Most common isolated pathogens: Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, and Streptococcus pneumoniae Take into consideration Patient’s history (have they had recent antibiotics? What have they been infected with before?) Comorbidities – things like immunosuppression can affect causative organism Clinical context – community vs healthcare acquired Local prevalence and resistance patterns  Norepinephrine is the first-line vasopressor agent for patients with septic shock… Vasopressor therapy …if initial fluid resuscitation fails to restore the mean arterial pressure to 65mm Hg or greater. Vasopressor therapy clearly improves survival in these patients and should be started within the first hour following initial fluid resuscitation. Vasopressor therapy should be titrated to maintain adequate hemodynamic status and should be used for the shortest duration possible.  Monitor response Most patients will respond to fluids within 6 to 24 hours Ok, so now what? Do they need invasive lines? Indicated if BP is labile, or on/will need vasopressors Follow clinically Mean arterial pressure -> MAP = DBP + 1/3 (SBP – DBP) Urine output Heart rate Respiratory rate Skin color and temperature Pulse oximetry Mental status  Host-related Failure to develop a fever, leukopenia, thrombocytopenia, hyperchloremia, comorbidities, age, hyperglycemia, hypo Prognostic Factors coagulability and failure of procalcitonin to fall = poor outcomes Site of infection UTI source = lower mortality rates Unknown/GI/respiratory source = higher mortality Type of infection Nosocomial pathogens = higher mortality Antimicrobial therapy Early therapy = better outcome Restoration of Fluid Failure of aggressive reperfusion = higher mortality  During hospital admission Prognosis with sepsis Increased risk of developing another infection while in hospital Long term After discharge – increased risk of death (up to 20%) and increased risk of recurrent sepsis with subsequent hospital admission Most deaths associated with having sepsis occur within the first 6 months – but risk can last for two years! More likely to have persistent decrease in quality of life Increased risk of major cardiovascular events and stroke  Your patient improves! Scale back those fluids! They might even need diuretics Next Steps De-escalate those antibiotics! Once you know the pathogen you’re dealing with, tailor to that pathogen! Typically, antibiotics given for 7-10 days total  Sources for todays lecture included: UpToDate Questions? CMDT CDC.gov WHO.int American Family Physician