๐ฆ Welcome to Viral Diseases Comprehensive Guide
This interactive tool provides evidence-based information on viral diseases, following current medical guidelines and scientific evidence. Designed for healthcare professionals to enhance clinical decision-making and patient care.
๐ What's Included:
- Viral Classification: Comprehensive taxonomy and characteristics
- DNA & RNA Viruses: Detailed pathogen profiles
- Clinical Syndromes: System-based presentations
- Diagnostic Approaches: Evidence-based testing strategies
- Treatment Guidelines: Current antiviral therapies
- Prevention Strategies: Vaccination and prophylaxis
๐งฌ DNA Viruses
Herpesviruses, Adenovirus, Papillomaviruses, Poxviruses, Parvoviruses, Hepadnaviruses
๐งฌ RNA Viruses
Influenza, Coronavirus, Paramyxoviruses, Flaviviruses, Togaviruses, Picornaviruses
๐ Retroviruses
HIV, HTLV - Unique reverse transcription mechanism
โ ๏ธ Clinical Importance:
Viral infections remain a leading cause of morbidity and mortality worldwide. Accurate diagnosis and evidence-based management are essential for optimal patient outcomes. This tool synthesizes current guidelines from CDC, WHO, and major medical societies.
๐ Viral Classification
Baltimore Classification System
The Baltimore classification categorizes viruses based on their genome type and replication strategy:
| Class | Genome Type | Examples |
|---|---|---|
| Class I | Double-stranded DNA (dsDNA) | Herpesviruses, Adenoviruses, Poxviruses |
| Class II | Single-stranded DNA (ssDNA) | Parvoviruses |
| Class III | Double-stranded RNA (dsRNA) | Reoviruses, Rotavirus |
| Class IV | Positive-sense ssRNA (+ssRNA) | Picornaviruses, Flaviviruses, Coronaviruses |
| Class V | Negative-sense ssRNA (-ssRNA) | Orthomyxoviruses, Paramyxoviruses, Filoviruses |
| Class VI | ssRNA-RT (Retroviruses) | HIV, HTLV |
| Class VII | dsDNA-RT | Hepadnaviruses (Hepatitis B) |
Structural Classification
๐ฌ Enveloped vs Non-Enveloped Viruses
Enveloped Viruses:
- Possess lipid bilayer membrane
- More susceptible to disinfectants, heat, drying
- Examples: Influenza, HIV, HSV, SARS-CoV-2, Measles
Non-Enveloped (Naked) Viruses:
- Protein capsid only
- More resistant to environmental conditions
- Examples: Adenovirus, Norovirus, Poliovirus, Papillomavirus
Clinical Classification by System
๐ซ Respiratory Viruses
- Influenza A & B: Seasonal epidemics, pandemics
- SARS-CoV-2: COVID-19 pandemic agent
- RSV: Major cause in infants/elderly
- Rhinovirus: Common cold (50% of cases)
- Adenovirus: URI, pneumonia, conjunctivitis
- Parainfluenza: Croup in children
- MERS-CoV: Middle East respiratory syndrome
๐ด Hepatotropic Viruses
- Hepatitis A (HAV): RNA, fecal-oral, acute only
- Hepatitis B (HBV): DNA, parenteral/sexual, chronic
- Hepatitis C (HCV): RNA, parenteral, chronic (70-85%)
- Hepatitis D (HDV): Requires HBV coinfection
- Hepatitis E (HEV): RNA, fecal-oral, severe in pregnancy
๐ง Neurotropic Viruses
- Herpes Simplex (HSV-1/2): Encephalitis, meningitis
- Varicella-Zoster (VZV): Chickenpox, shingles, encephalitis
- Rabies: Fatal encephalitis (99% mortality)
- West Nile Virus: Meningitis, encephalitis, AFP
- Enteroviruses: Aseptic meningitis, AFP
- JC Virus: PML in immunocompromised
- Cytomegalovirus (CMV): Encephalitis in HIV/AIDS
๐ฆ Arthropod-Borne Viruses (Arboviruses)
- Dengue: 4 serotypes, hemorrhagic fever risk
- Zika: Congenital abnormalities, Guillain-Barrรฉ
- Chikungunya: Severe arthralgia
- Yellow Fever: Hemorrhagic fever, hepatitis
- Japanese Encephalitis: Leading cause viral encephalitis Asia
- West Nile: Most common arbovirus in US
๐งฌ DNA Viruses
Herpesviridae Family
Large, enveloped, dsDNA viruses. All establish latency with potential for reactivation.
| Virus | Subfamily | Primary Disease | Latency Site |
|---|---|---|---|
| HSV-1 | ฮฑ-herpesvirus | Orolabial herpes, encephalitis | Trigeminal ganglia |
| HSV-2 | ฮฑ-herpesvirus | Genital herpes, neonatal | Sacral ganglia |
| VZV | ฮฑ-herpesvirus | Chickenpox, shingles | Dorsal root ganglia |
| EBV | ฮณ-herpesvirus | Infectious mononucleosis, lymphomas | B lymphocytes |
| CMV | ฮฒ-herpesvirus | Congenital, retinitis, colitis | Monocytes, lymphocytes |
| HHV-6 | ฮฒ-herpesvirus | Roseola infantum | Monocytes, T cells |
| HHV-8 | ฮณ-herpesvirus | Kaposi sarcoma | B lymphocytes |
๐ด HSV Encephalitis - Medical Emergency
- Presentation: Fever, altered mental status, seizures, focal neurologic deficits
- MRI: Temporal lobe involvement (classical finding)
- CSF: Lymphocytic pleocytosis, elevated protein, RBCs
- Diagnosis: CSF PCR for HSV (sensitivity 96-98%)
- Treatment: IV Acyclovir 10 mg/kg q8h ร 14-21 days
- Prognosis: 70% mortality untreated, 30% with treatment
Adenoviridae
Structure: Non-enveloped, dsDNA, icosahedral
Transmission: Respiratory droplets, fecal-oral, contact
Clinical Manifestations:
- Respiratory: Pharyngitis, bronchitis, pneumonia (can be severe in military recruits)
- Ocular: Epidemic keratoconjunctivitis, pharyngoconjunctival fever
- Gastrointestinal: Gastroenteritis (types 40, 41)
- Genitourinary: Hemorrhagic cystitis
Treatment: Supportive (most cases). Cidofovir in severe immunocompromised patients
Papillomaviridae (HPV)
๐ HPV Classification & Clinical Significance
Structure: Non-enveloped, dsDNA, circular genome
Types: >200 genotypes identified
Low-Risk Types (6, 11):
- Anogenital warts (condyloma acuminatum)
- Respiratory papillomatosis
- Not associated with cancer
High-Risk Types (16, 18, 31, 33, 45, others):
- Cervical cancer: 99.7% associated with HPV
- Oropharyngeal cancer: 70% associated (mostly HPV-16)
- Anal, vulvar, vaginal, penile cancers
๐ HPV Vaccination (ACIP Guidelines 2023):
- Routine: Age 11-12 years (can start at 9)
- Catch-up: Through age 26 years
- Shared decision: Ages 27-45 years
- 9-valent vaccine (Gardasil-9): Covers types 6, 11, 16, 18, 31, 33, 45, 52, 58
- Schedule: 2 doses (ages 9-14) or 3 doses (โฅ15 years, immunocompromised)
Poxviridae
Variola (Smallpox) - Eradicated 1980
Historical significance: Caused 300-500 million deaths in 20th century
Bioterrorism concern: Category A agent
Monkeypox (Mpox)
- Transmission: Animal-to-human, human-to-human (close contact, respiratory, sexual)
- Incubation: 3-17 days (mean 7 days)
- Presentation: Fever, lymphadenopathy, characteristic rash (maculesโpapulesโvesiclesโpustulesโscabs)
- 2022-2023 Outbreak: Global spread, primarily among MSM
- Treatment: Tecovirimat (TPOXX) for severe disease
- Vaccination: JYNNEOS vaccine (modified vaccinia Ankara-Bavarian Nordic)
Molluscum Contagiosum
- Presentation: Umbilicated papules, 2-5mm
- Common in: Children, immunocompromised, sexually active adults
- Treatment: Often self-limited; curettage, cryotherapy if needed
Parvoviridae
Parvovirus B19
Unique feature: Smallest DNA virus infecting humans
Target cells: Erythroid progenitor cells
Clinical Manifestations:
- Fifth Disease (Erythema infectiosum): "Slapped cheek" rash in children
- Arthropathy: Symmetric polyarthritis (adults, especially women)
- Transient Aplastic Crisis: In patients with hemolytic anemias (sickle cell, spherocytosis)
- Pure Red Cell Aplasia: Chronic infection in immunocompromised
- Hydrops Fetalis: Fetal infection (5-10% if infected in 1st/2nd trimester)
Diagnosis: IgM antibody, PCR in immunocompromised or fetus
Treatment: Supportive; IVIG for chronic cases in immunocompromised
Hepadnaviridae - Hepatitis B Virus (HBV)
Structure: Partially dsDNA, enveloped, reverse transcriptase
Epidemiology: 296 million chronically infected worldwide (WHO 2023)
Transmission: Parenteral, sexual, perinatal
| Marker | Interpretation |
|---|---|
| HBsAg+ | Active infection (acute or chronic) |
| Anti-HBs+ | Immunity (vaccination or resolved infection) |
| Anti-HBc IgM+ | Acute infection |
| Anti-HBc IgG+ | Past or chronic infection |
| HBeAg+ | High viral replication, high infectivity |
| Anti-HBe+ | Lower viral replication |
Treatment Indications (AASLD 2023):
- HBV DNA >2,000 IU/mL + elevated ALT + significant fibrosis
- Cirrhosis with detectable HBV DNA
- First-line agents: Entecavir, Tenofovir (TDF or TAF)
- Interferon-ฮฑ: Limited use (finite duration option)
๐งฌ RNA Viruses
Orthomyxoviridae - Influenza Viruses
Structure: Enveloped, segmented (8 segments) negative-sense ssRNA
Key Surface Proteins:
- Hemagglutinin (HA): Viral attachment, 18 subtypes (H1-H18)
- Neuraminidase (NA): Release of virions, 11 subtypes (N1-N11)
Antigenic Variation:
- Antigenic Drift: Point mutations, minor changes โ seasonal epidemics
- Antigenic Shift: Reassortment of segments, major changes โ pandemics
| Type | Hosts | Clinical Impact |
|---|---|---|
| Influenza A | Humans, birds, pigs, others | Epidemics, pandemics (drift & shift) |
| Influenza B | Primarily humans | Epidemics (drift only) |
| Influenza C | Humans, pigs | Mild illness |
| Influenza D | Cattle, pigs | Not known to infect humans |
โ ๏ธ Clinical Management (CDC 2024-2025):
- High-risk for complications: Age <2 or >65, pregnancy, chronic conditions, immunocompromised
- Antivirals: Most effective within 48h of symptom onset
- Oseltamivir (Tamiflu): 75mg PO BID ร 5 days
- Zanamivir (Relenza): 10mg inhaled BID ร 5 days
- Baloxavir (Xofluza): Single dose (40-80mg based on weight)
- Peramivir: Single IV dose 600mg
- Vaccination: Annual, quadrivalent preferred
Coronaviridae
๐ฆ SARS-CoV-2 (COVID-19)
Emergence: December 2019, Wuhan, China โ Global pandemic
Structure: Enveloped, positive-sense ssRNA, crown-like spikes
Transmission: Respiratory droplets, aerosols, fomites
Incubation: 2-14 days (median 5 days)
Clinical Spectrum:
- Asymptomatic: ~40% of infections
- Mild-Moderate: Fever, cough, fatigue, myalgia, anosmia, ageusia
- Severe: Dyspnea, hypoxia, pneumonia (>50% lung involvement)
- Critical: ARDS, septic shock, multiorgan failure
- Long COVID: Persistent symptoms >4 weeks (fatigue, brain fog, dyspnea)
Risk Factors for Severe Disease:
- Age >65 years
- Cardiovascular disease, diabetes, obesity (BMI >30)
- Chronic lung disease, immunosuppression
- Pregnancy (especially 3rd trimester)
๐ Treatment Guidelines (NIH 2024):
Mild-Moderate (Outpatient, High-Risk):
- Nirmatrelvir/Ritonavir (Paxlovid): 300/100mg PO BID ร 5 days (within 5 days of symptoms)
- Remdesivir: IV option for high-risk outpatients
- Molnupiravir: Alternative if others contraindicated
Hospitalized (Requiring Oxygen):
- Remdesivir: 200mg IV day 1, then 100mg daily ร 5 days (or until discharge)
- Dexamethasone: 6mg daily ร 10 days or until discharge
- Baricitinib: Consider in combination with remdesivir
- Tocilizumab: Consider for rapidly deteriorating patients
Variants of Concern:
- Alpha (B.1.1.7): Increased transmissibility
- Delta (B.1.617.2): Higher severity, immune escape
- Omicron (B.1.1.529): Multiple subvariants, significant immune escape, generally less severe
๐ฆ Other Human Coronaviruses
Common Cold Coronaviruses:
- HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU1
- Account for 15-30% of common colds
- Mild upper respiratory symptoms
SARS-CoV (2003):
- Severe Acute Respiratory Syndrome
- Case fatality rate: ~10%
- Controlled through public health measures
MERS-CoV (2012-present):
- Middle East Respiratory Syndrome
- Zoonotic (dromedary camels)
- Case fatality rate: ~35%
- Limited human-to-human transmission
Paramyxoviridae
Measles (Rubeola)
Structure: Enveloped, negative-sense ssRNA
Transmission: Highly contagious (R0: 12-18), airborne
Incubation: 10-14 days
Clinical Phases:
- Prodrome (3-5 days): 3 C's - Cough, Coryza, Conjunctivitis + fever
- Koplik spots: Pathognomonic, blue-white spots on buccal mucosa
- Exanthem: Maculopapular rash, starts face/hairline, spreads cephalocaudally
Complications:
- Pneumonia (most common cause of death)
- Encephalitis (1:1,000 cases)
- Subacute sclerosing panencephalitis (SSPE) - rare, delayed, fatal
- Immunosuppression lasting weeks to months
๐ Prevention:
MMR Vaccine: 2 doses (12-15 months, 4-6 years)
Post-exposure prophylaxis:
- MMR within 72 hours (if no contraindication)
- IVIG within 6 days (immunocompromised, infants, pregnant)
Mumps
- Classic presentation: Bilateral parotitis
- Complications: Orchitis (20-30% post-pubertal males), meningitis, pancreatitis, deafness
- Prevention: MMR vaccine
Respiratory Syncytial Virus (RSV)
- Leading cause: Bronchiolitis and pneumonia in infants
- High-risk: Premature infants, congenital heart disease, chronic lung disease
- Seasonality: Fall-winter in temperate climates
- Treatment: Supportive care, oxygen, hydration
- Prophylaxis (high-risk infants):
- Nirsevimab (Beyfortus): Monoclonal antibody, single dose
- Palivizumab (Synagis): Monthly during RSV season
- Maternal vaccine (RSVPreF3): FDA approved 2023, protects infants via transplacental antibodies
Parainfluenza Viruses
- Types 1-4: Cause 30-40% of respiratory infections in children
- Croup (Laryngotracheobronchitis): Classic "barking cough," stridor
- Treatment: Dexamethasone, nebulized epinephrine for severe cases
Flaviviridae
๐ฆ Dengue Virus
Epidemiology: 400 million infections/year, endemic in 100+ countries
Serotypes: DENV-1, DENV-2, DENV-3, DENV-4
Vector: Aedes aegypti, Ae. albopictus mosquitoes
Clinical Classification (WHO 2009):
1. Dengue Without Warning Signs:
- Fever + 2 of: nausea/vomiting, rash, myalgia, arthralgia, headache, retro-orbital pain, petechiae, leukopenia
2. Dengue With Warning Signs:
- Abdominal pain, persistent vomiting
- Clinical fluid accumulation (ascites, pleural effusion)
- Mucosal bleeding, lethargy
- Liver enlargement >2cm, rising hematocrit with falling platelets
3. Severe Dengue:
- Severe plasma leakage โ shock, respiratory distress
- Severe bleeding
- Organ impairment (AST/ALT >1,000, severe CNS involvement)
โ ๏ธ Management:
- Supportive care: Fluid management crucial
- Avoid: NSAIDs, aspirin (bleeding risk), IM injections
- Monitor: Hematocrit, platelets, vital signs
- Severe dengue: ICU admission, crystalloid resuscitation, blood products if needed
Prevention:
- Dengvaxia vaccine: For endemic areas, ages 9-45, with previous dengue infection
- Vector control, protective clothing, repellents
๐ฆ Zika Virus
Vector: Aedes mosquitoes
Transmission: Mosquito-borne, sexual, perinatal, blood transfusion
Incubation: 3-14 days
Clinical Features:
- 80% asymptomatic or mild
- Symptomatic: Fever, rash, arthralgia, conjunctivitis
- Usually self-limited (2-7 days)
โ ๏ธ Severe Complications:
- Congenital Zika Syndrome:
- Microcephaly
- Brain abnormalities (ventriculomegaly, cortical malformations)
- Ocular abnormalities
- Congenital contractures
- Guillain-Barrรฉ Syndrome: Risk increased post-infection
Pregnancy Considerations:
- Test all pregnant women with possible exposure
- Serial ultrasounds for fetal monitoring
- Contraception counseling in endemic areas
- Defer conception 2-3 months after exposure/recovery
๐ฆ Yellow Fever & Other Flaviviruses
Yellow Fever:
- Endemic: Tropical Africa, South America
- Clinical phases:
- Infection: Fever, myalgia, headache
- Remission: 24-48 hours
- Intoxication (15%): Jaundice, hemorrhage, organ failure (50% mortality)
- Vaccination: Live-attenuated (YF-Vax), required for travel to endemic areas
West Nile Virus:
- Most common arbovirus in US
- 80% asymptomatic
- 20% West Nile fever: Fever, headache, myalgia, rash
- <1% Neuroinvasive disease: Meningitis, encephalitis, acute flaccid paralysis
- Risk factors for severe disease: Age >60, immunosuppression
Japanese Encephalitis:
- Leading cause viral encephalitis in Asia
- Case fatality: 20-30%
- Vaccine available for travelers
Hepatitis C Virus (HCV)
Family: Flaviviridae (unique genus Hepacivirus)
Structure: Enveloped, positive-sense ssRNA
Genotypes: 6 major (1-6), with subtypes. Genotype 1 most common in US
Transmission: Primarily parenteral (IVDU, blood transfusion pre-1992, needlestick)
Natural History:
- Acute HCV: Often asymptomatic (70-80%)
- Chronic HCV: 70-85% develop chronic infection
- Cirrhosis: 15-30% within 20 years
- Hepatocellular carcinoma: 1-4% per year with cirrhosis
๐ฏ Direct-Acting Antivirals (DAAs) - Curative! (AASLD/IDSA 2023):
Recommended Regimens (Treatment-Naive, No Cirrhosis):
- Glecaprevir/Pibrentasvir (Mavyret): 8-16 weeks
- Pangenotypic (all genotypes)
- High barrier to resistance
- 98-100% SVR rates
- Sofosbuvir/Velpatasvir (Epclusa): 12 weeks
- Pangenotypic
- 97-100% SVR rates
- Ledipasvir/Sofosbuvir (Harvoni): 8-12 weeks (genotypes 1, 4, 5, 6)
SVR (Sustained Virologic Response) = Cure: Undetectable HCV RNA 12 weeks post-treatment
Screening Recommendations (CDC 2024):
- One-time screening for all adults โฅ18 years
- Pregnant women during each pregnancy
- Ongoing risk: PWID, HIV+, hemodialysis, incarceration
Picornaviridae
Poliovirus
Structure: Non-enveloped, positive-sense ssRNA
Transmission: Fecal-oral
Serotypes: 1, 2 (eradicated 2015), 3
Clinical Forms:
- Asymptomatic: ~95% of infections
- Abortive poliomyelitis: Minor illness, self-limited
- Non-paralytic (aseptic meningitis): 1-5%
- Paralytic poliomyelitis: <1%, acute flaccid paralysis
๐ Eradication Efforts:
- Wild poliovirus type 1: Endemic in only 2 countries (Afghanistan, Pakistan) as of 2024
- Vaccines:
- IPV (Inactivated): Used in US, 4 doses
- OPV (Oral): Used in eradication efforts (risk of vaccine-derived poliovirus)
- WHO target: Global eradication
Enteroviruses (Non-Polio)
- Coxsackievirus A: Hand-foot-mouth disease, herpangina
- Coxsackievirus B: Myocarditis, pericarditis, pleurodynia
- Echovirus: Aseptic meningitis, rash
- Enterovirus D68: Severe respiratory illness, acute flaccid myelitis
Rhinovirus
- Most common cause of common cold (30-50%)
- >100 serotypes
- Peak seasons: Fall and spring
- Treatment: Supportive only
Hepatitis A Virus (HAV)
- Transmission: Fecal-oral, contaminated food/water
- Incubation: 15-50 days (mean 28)
- Clinical: Acute hepatitis, jaundice, no chronic form
- Prevention: HAV vaccine (2 doses), immune globulin for post-exposure
Togaviridae
Rubella (German Measles)
Structure: Enveloped, positive-sense ssRNA
Transmission: Respiratory droplets
Incubation: 14-21 days
Clinical (Postnatal):
- Mild fever, lymphadenopathy (post-auricular, suboccipital, posterior cervical)
- Maculopapular rash (face โ trunk โ extremities)
- Arthralgia/arthritis (common in adults, especially women)
โ ๏ธ Congenital Rubella Syndrome (CRS):
Risk highest in 1st trimester (up to 90% if infected <11 weeks)
Classic Triad:
- Cardiac defects (PDA, pulmonary stenosis)
- Ocular defects (cataracts, glaucoma, retinopathy)
- Sensorineural deafness
Other manifestations: Microcephaly, intellectual disability, hepatosplenomegaly, thrombocytopenia
Prevention:
- MMR vaccine
- Pre-conception immunity confirmation in women
- Contraception for 4 weeks post-vaccination
Chikungunya
- Vector: Aedes mosquitoes
- Name: Swahili for "that which bends up" (severe arthralgia)
- Clinical: Acute fever, severe polyarthralgia (can persist months-years)
- Rash: Maculopapular
- Treatment: Supportive, NSAIDs for arthralgia
Reoviridae - Rotavirus
Structure: Non-enveloped, dsRNA (11 segments), triple-layered
Leading cause of severe diarrhea in infants/young children worldwide
Transmission: Fecal-oral
Clinical:
- Incubation: 1-3 days
- Watery diarrhea, vomiting, fever
- Dehydration risk (severe cases)
- Duration: 3-8 days
๐ Vaccination (ACIP):
- RotaTeq (RV5): 3 doses at 2, 4, 6 months
- Rotarix (RV1): 2 doses at 2, 4 months
- First dose: 6 weeks to 14 weeks 6 days
- Series completion: By age 8 months
- Impact: >85% reduction in rotavirus hospitalizations in vaccinated populations
Retroviridae - HIV
Structure: Enveloped, diploid positive-sense ssRNA, reverse transcriptase
Types: HIV-1 (pandemic), HIV-2 (West Africa, less pathogenic)
Target: CD4+ T lymphocytes (also macrophages, dendritic cells)
Transmission:
- Sexual contact (highest risk: receptive anal intercourse)
- Parenteral (needle sharing, needlestick, blood transfusion)
- Perinatal (in utero, delivery, breastfeeding)
Natural History (Untreated):
- Acute HIV Syndrome (2-4 weeks post-infection): Fever, lymphadenopathy, pharyngitis, rash, myalgia (mononucleosis-like)
- Asymptomatic/Chronic phase: Years to decades
- AIDS: CD4 <200 cells/ฮผL or AIDS-defining illness
| CD4 Count | Opportunistic Infections |
|---|---|
| <200 | PCP, Candida esophagitis, Toxoplasmosis |
| <100 | Cryptococcal meningitis, CNS lymphoma |
| <50 | MAC, CMV retinitis |
๐ฏ Antiretroviral Therapy (ART) - DHHS Guidelines 2024:
Initiation: All persons with HIV, regardless of CD4 count
Goal: Undetectable viral load (<50 copies/mL) = Untransmittable (U=U)
Preferred Initial Regimens:
- Bictegravir/TAF/FTC (Biktarvy): INSTI-based, single tablet daily
- Dolutegravir/Abacavir/3TC (Triumeq): If HLA-B*5701 negative
- Dolutegravir + (TAF or TDF)/FTC: 2-drug combinations also effective
Drug Classes:
- NRTIs: Backbone (TDF, TAF, FTC, 3TC, ABC)
- INSTIs: First-line (bictegravir, dolutegravir, raltegravir)
- NNRTIs: Alternative (efavirenz, rilpivirine, doravirine)
- PIs: Boosted with ritonavir/cobicistat (darunavir, atazanavir)
Prevention:
- PrEP (Pre-Exposure Prophylaxis):
- TDF/FTC (Truvada) or TAF/FTC (Descovy) daily
- Cabotegravir LA (Apretude) injection q2 months
- >99% effective if adherent
- PEP (Post-Exposure Prophylaxis): Within 72 hours, 28-day course
- PMTCT: ART during pregnancy, delivery, neonatal prophylaxis
- Treatment as Prevention: U=U (Undetectable = Untransmittable)
Filoviridae - Ebola & Marburg
Ebola Virus Disease (EVD)
Structure: Enveloped, negative-sense ssRNA, filamentous
Species: 6 (Zaire ebolavirus most deadly)
Natural reservoir: Fruit bats (suspected)
Case fatality: 25-90% (varies by outbreak, species, supportive care)
Transmission:
- Direct contact with blood/body fluids
- Contaminated objects (needles, clothing)
- Infected animals (bushmeat)
- High infectivity in late stages/post-mortem
Clinical Phases:
- Incubation: 2-21 days (mean 8-10)
- Early (3-10 days): Fever, severe headache, myalgia, fatigue
- Gastrointestinal phase: Diarrhea, vomiting, abdominal pain
- Late/severe: Hemorrhagic manifestations, shock, multiorgan failure
Management:
- Isolation: Strict infection control, PPE
- Supportive care: Aggressive fluid/electrolyte management
- Investigational treatments:
- Monoclonal antibodies (Inmazeb, Ebanga)
- Remdesivir (emergency use)
- Vaccine: rVSV-ZEBOV (Ervebo) - highly effective, ring vaccination strategy
Marburg Virus Disease
- Similar to Ebola (same family)
- Case fatality: 23-90%
- Sporadic outbreaks Africa
- No approved vaccine/treatment
Rhabdoviridae - Rabies
Structure: Enveloped, negative-sense ssRNA, bullet-shaped
Transmission: Saliva of infected animals (bites, scratches, mucous membrane exposure)
Reservoirs: Bats, dogs (worldwide), raccoons, skunks, foxes (US)
Case fatality: ~100% once clinical symptoms develop
Pathophysiology:
- Virus travels via peripheral nerves to CNS
- Incubation: 20-90 days (can be years)
- Replicates in brain (encephalitis), spreads to salivary glands
Clinical Phases:
- Prodrome (2-10 days): Fever, headache, malaise, paresthesia at bite site
- Acute neurologic phase:
- Furious rabies (80%): Hyperactivity, hydrophobia, aerophobia, agitation
- Paralytic rabies (20%): Ascending paralysis
- Coma and death: Usually within 7-10 days of symptom onset
๐จ Post-Exposure Prophylaxis (PEP) - Lifesaving!
Initiate IMMEDIATELY after high-risk exposure
- Wound care: Thorough washing with soap and water (15 minutes)
- Previously unvaccinated:
- HRIG (Human Rabies Immune Globulin): 20 IU/kg, infiltrate wound + IM
- Rabies vaccine: Days 0, 3, 7, 14
- Previously vaccinated: Vaccine only (days 0, 3)
Pre-Exposure Prophylaxis (high-risk individuals):
- Veterinarians, animal handlers, lab workers, travelers to high-risk areas
- 3-dose series (days 0, 7, 21-28)
- Serologic testing for antibody titers (risk-based)
๐ฉบ Clinical Syndromes by System
๐ซ Viral Pneumonia
Common Viral Pathogens:
- Influenza A/B: Most common cause of viral pneumonia in adults
- RSV: Infants, elderly, immunocompromised
- SARS-CoV-2: COVID-19 pneumonia, varying severity
- Adenovirus: Military recruits, children
- Parainfluenza: Children
- HMPV (Human Metapneumovirus): Similar to RSV
- Varicella (VZV): Adults with chickenpox
- Measles: Complication in unvaccinated
Clinical Features:
- Fever, cough (often nonproductive), dyspnea
- Chest X-ray: Bilateral interstitial infiltrates (more common than lobar consolidation)
- Labs: Normal or low WBC, elevated procalcitonin suggests bacterial superinfection
๐ด Bacterial Superinfection:
Common post-influenza: S. pneumoniae, S. aureus (including MRSA), H. influenzae
Suspect if: Clinical deterioration, new fever, leukocytosis, lobar infiltrate
๐ง Viral Meningitis & Encephalitis
Viral (Aseptic) Meningitis
Most Common Causes:
- Enteroviruses: 85-95% of cases (Coxsackie, Echovirus)
- HSV-2: Recurrent benign lymphocytic meningitis (Mollaret's)
- VZV, EBV, CMV: Immunocompromised
- HIV: Acute retroviral syndrome
- Arboviruses: West Nile, La Crosse
CSF Findings (Typical):
| Parameter | Viral Meningitis |
|---|---|
| WBC count | 10-1,000 cells/ฮผL (usually <500) |
| Cell type | Lymphocytic predominance (may be PMN early) |
| Protein | Normal to mildly elevated (50-100 mg/dL) |
| Glucose | Normal (>50% serum) |
| Gram stain/Culture | Negative |
Viral Encephalitis
Most Common Causes:
- HSV-1: Most common sporadic (10-20% of cases)
- VZV: Second most common
- Arboviruses: West Nile (most common in US), La Crosse, St. Louis, Eastern Equine
- Rabies: Always consider with animal exposure
- Enteroviruses: EV-A71, EV-D68
- Measles, mumps: Post-infectious encephalitis
๐จ Clinical Approach:
Red Flags for Encephalitis:
- Altered mental status, seizures
- Focal neurologic deficits
- Personality changes, behavioral abnormalities
Diagnostic Workup:
- MRI brain (temporal lobe involvement suggests HSV)
- CSF: PCR for HSV-1, HSV-2, VZV, enteroviruses, West Nile IgM
- EEG: Temporal lobe periodic lateralizing discharges (PLEDs) in HSV
Empiric Treatment:
- Start immediately: IV Acyclovir 10 mg/kg q8h (don't wait for results!)
- Add antibiotics if bacterial not excluded
๐คฎ Viral Gastroenteritis
| Virus | Age Group | Seasonality | Features |
|---|---|---|---|
| Norovirus | All ages | Year-round (winter peak) | Leading cause outbreaks (cruise ships, restaurants). Vomiting prominent. 12-48h duration. |
| Rotavirus | Infants, young children | Winter-spring | Watery diarrhea, dehydration risk. Vaccine available. |
| Adenovirus 40/41 | Young children | Year-round | Prolonged diarrhea (8-12 days) |
| Astrovirus | Children, elderly, immunocompromised | Winter | Milder than rotavirus |
| Sapovirus | Children | Year-round | Similar to norovirus, less common |
๐ง Management:
- Mainstay: Oral rehydration therapy
- Severe dehydration: IV fluids
- Antiemetics: Ondansetron (can reduce vomiting, ER visits)
- Probiotics: Some evidence for reducing duration
- No role for antibiotics or antivirals
โค๏ธ Viral Myocarditis & Pericarditis
Viral Myocarditis
Common Viral Causes:
- Coxsackievirus B: Most common in children/young adults
- Adenovirus, Parvovirus B19: Children
- HHV-6, EBV, CMV: Immunocompromised
- HIV: Direct effect or opportunistic infections
- Influenza, SARS-CoV-2: Adults
Clinical Presentation:
- Chest pain (may mimic MI)
- Heart failure symptoms (dyspnea, fatigue, edema)
- Arrhythmias, sudden cardiac death (rare)
- Preceding viral illness (50-60%)
Diagnostic Criteria (ESC 2013):
- ECG: ST-segment changes, arrhythmias
- Cardiac biomarkers: Elevated troponin, BNP/NT-proBNP
- Echocardiography: Regional/global wall motion abnormalities
- Cardiac MRI: Gold standard - myocardial edema, late gadolinium enhancement
- Endomyocardial biopsy: Definitive (rarely needed)
โ ๏ธ Management:
- Supportive care: Heart failure management (ACE-I, beta-blockers, diuretics)
- Activity restriction: 3-6 months from diagnosis
- Avoid NSAIDs: May worsen outcomes
- Immunosuppression: Controversial, only in specific cases (giant cell myocarditis, cardiac sarcoidosis)
- Antivirals: No proven benefit for most viral causes
Viral Pericarditis
Common causes: Coxsackievirus, Echovirus, Adenovirus, EBV, CMV, HIV
Clinical: Sharp chest pain (pleuritic, positional), pericardial friction rub
Diagnosis: ECG (diffuse ST elevation, PR depression), echocardiography (pericardial effusion)
Treatment: NSAIDs + colchicine (reduces recurrence), corticosteroids for refractory cases
๐๏ธ Viral Conjunctivitis
Most Common Causes:
- Adenovirus: 65-90% of viral conjunctivitis
- Epidemic keratoconjunctivitis (EKC): Types 8, 19, 37 - severe, highly contagious
- Pharyngoconjunctival fever: Types 3, 4, 7 - with pharyngitis, fever
- Herpes Simplex: Unilateral, dendritic keratitis on fluorescein staining
- Varicella-Zoster: Associated with zoster ophthalmicus
- Enterovirus 70: Acute hemorrhagic conjunctivitis
Clinical Features:
- Watery discharge (vs purulent in bacterial)
- Follicular conjunctivitis
- Preauricular lymphadenopathy
- Often bilateral (may start unilateral)
Management:
- Supportive: Cool compresses, artificial tears
- Adenoviral: Self-limited (1-3 weeks), no specific treatment
- HSV: Topical antivirals (ganciclovir 0.15% gel, trifluridine 1% drops)
- Infection control: Highly contagious for 10-14 days
- Red flags: Vision changes, severe pain, photophobia โ ophthalmology referral
๐ฆด Viral Exanthems
| Disease | Virus | Rash Description | Other Features |
|---|---|---|---|
| Measles (1st disease) | Measles virus | Maculopapular, starts face โ cephalocaudal spread | 3 C's, Koplik spots, conjunctivitis |
| Scarlet Fever (2nd disease) | Strep pyogenes (bacterial) | Sandpaper-like, circumoral pallor | Strawberry tongue, pharyngitis |
| Rubella (3rd disease) | Rubella virus | Pink maculopapular, face โ body | Post-auricular lymphadenopathy, mild |
| Filatov-Dukes (4th disease) | Historical, not distinct entity | - | - |
| Erythema infectiosum (5th disease) | Parvovirus B19 | "Slapped cheek," lacy reticular on extremities | Arthralgia in adults |
| Roseola (6th disease) | HHV-6 (HHV-7) | Rose-pink macules, trunk โ extremities | High fever 3-5 days, then rash as fever resolves |
Other Important Viral Exanthems:
- Chickenpox (Varicella): "Dew drop on rose petal," vesicles, crops, pruritic
- Hand-Foot-Mouth Disease: Coxsackievirus A16, EV-A71 - vesicles on hands, feet, mouth
- Herpangina: Coxsackievirus - vesicles/ulcers on posterior pharynx
- Molluscum Contagiosum: Poxvirus - umbilicated papules
๐ฌ Viral Diagnostics
Diagnostic Modalities
| Method | Principle | Advantages | Limitations |
|---|---|---|---|
| Viral Culture | Growth in cell culture | Gold standard, allows phenotypic testing | Slow (days-weeks), requires viable virus, labor-intensive |
| PCR (Polymerase Chain Reaction) | Amplifies viral nucleic acid | Rapid, high sensitivity/specificity, detects non-viable virus | Cannot distinguish active vs latent, contamination risk |
| Rapid Antigen Tests | Detects viral proteins | Point-of-care, results in minutes | Lower sensitivity than PCR, timing-dependent |
| Serology (Antibody Testing) | Detects IgM/IgG antibodies | Determines immune status, useful for epidemiology | Retrospective, window period, doesn't detect acute infection early |
| Direct Fluorescent Antibody (DFA) | Fluorescent-labeled antibodies | Rapid (2-4 hours), detects viral antigens | Requires skilled technician, lower sensitivity than PCR |
| Electron Microscopy | Direct visualization | Can identify unknown viruses, morphology | Requires high viral load, expensive, specialized |
Common Diagnostic Tests by Virus
๐ซ Respiratory Viruses
Influenza:
- Rapid Antigen Detection Tests (RADTs): 50-70% sensitivity, results <30 min
- RT-PCR: Gold standard, >95% sensitivity, 1-6 hours
- Multiplex PCR panels: Detect multiple respiratory viruses simultaneously
- Timing: Ideally within 3-4 days of symptom onset
SARS-CoV-2:
- RT-PCR (nasopharyngeal): Gold standard
- Rapid Antigen Tests: Lower sensitivity (60-85%), best when symptomatic
- Antibody Testing: Not for acute diagnosis, measures prior exposure
- Home tests: Widely available, repeat testing if negative with symptoms
RSV:
- Rapid antigen tests: 80-90% sensitivity in infants
- RT-PCR: More sensitive, especially in adults
- DFA: Nasopharyngeal aspirate
Respiratory Multiplex PCR Panels:
Detect 15-20+ pathogens: Influenza A/B, RSV, SARS-CoV-2, adenovirus, parainfluenza, rhinovirus/enterovirus, HMPV, coronaviruses, Mycoplasma, Chlamydophila
Clinical utility: Immunocompromised, severe illness, outbreak investigation
๐ง CNS Infections
CSF PCR Testing:
Standard Panel:
- HSV-1/2: 96-98% sensitivity, 99% specificity
- VZV: >95% sensitivity
- Enterovirus: 90-100% sensitivity
- West Nile Virus: IgM antibody (CSF/serum)
Meningitis/Encephalitis Multiplex PCR:
BioFire FilmArray ME panel: Detects 14 pathogens simultaneously
- Viruses: HSV-1, HSV-2, VZV, CMV, HHV-6, enterovirus, human parechovirus
- Bacteria: E. coli K1, H. influenzae, L. monocytogenes, N. meningitidis, S. agalactiae, S. pneumoniae
- Yeast: C. neoformans/gattii
- Results: ~1 hour
- Sensitivity: 95-100% for most pathogens
โ ๏ธ Important Notes:
- Don't delay empiric acyclovir while awaiting results
- Negative PCR doesn't rule out if symptoms >1 week (viral load may decrease)
- Consider repeat LP or brain biopsy if high suspicion with negative results
๐ด Hepatitis Viruses
Hepatitis A (HAV):
- Anti-HAV IgM: Acute infection
- Anti-HAV IgG (Total): Past infection or vaccination
Hepatitis B (HBV):
| Test | Interpretation |
|---|---|
| HBsAg | Active infection (acute or chronic) |
| Anti-HBs | Immunity (recovery or vaccination) |
| Anti-HBc IgM | Acute infection |
| Anti-HBc Total | Current or past infection |
| HBeAg | High replication, high infectivity |
| Anti-HBe | Lower replication (may have precore mutant) |
| HBV DNA (Quantitative) | Viral load, monitor treatment |
Hepatitis C (HCV):
- Anti-HCV (Antibody): Screening test
- Positive: Current or resolved infection
- False negatives in early infection, immunocompromised
- HCV RNA (Quantitative): Confirms active infection, viral load
- HCV Genotype: Guides treatment (less important with pangenotypic DAAs)
Diagnostic Algorithm for HCV:
- Screen with Anti-HCV antibody
- If positive โ HCV RNA to confirm active infection
- If HCV RNA positive โ Genotype, assess fibrosis (FibroScan, FIB-4)
- Initiate treatment
Hepatitis D (HDV):
- Test if HBsAg positive and severe/fulminant hepatitis
- Anti-HDV IgM/IgG: Screening
- HDV RNA: Active replication
Hepatitis E (HEV):
- Anti-HEV IgM: Acute infection
- HEV RNA: Confirmatory, monitor chronic infection
๐ฆ HIV Testing
Current Testing Algorithm (CDC 2024):
Step 1: 4th Generation Antigen/Antibody Combo Test
- Detects HIV-1/2 antibodies + p24 antigen
- Can detect infection ~2-3 weeks post-exposure (window period)
- Sensitivity >99%, Specificity >99%
Step 2: If positive โ HIV-1/HIV-2 Antibody Differentiation
- Distinguishes HIV-1 from HIV-2
Step 3: If discordant/indeterminate โ HIV-1 RNA (Viral Load)
- Resolves acute infection vs false positive
- Acute HIV: Positive RNA, antibodies may be negative/indeterminate
Special Considerations:
- Acute HIV Syndrome: Consider HIV RNA if high suspicion with negative/indeterminate antibody
- Screening Recommendations:
- All persons ages 13-64 at least once
- Annual testing if high risk (MSM, PWID, multiple partners)
- All pregnant women
- Point-of-Care Rapid Tests: Available, results in 20 minutes, requires confirmatory testing if positive
Monitoring Tests:
- CD4 count: Immune status, OI prophylaxis decisions
- HIV-1 RNA (Viral Load): Treatment efficacy, goal <50 copies/mL
- Resistance testing: Genotype at diagnosis, treatment failure
๐ฌ Herpesvirus Diagnostics
HSV-1/2:
- PCR (Gold Standard): Lesion swab, CSF (encephalitis)
- Viral culture: Less sensitive than PCR, takes longer
- DFA: Lesion scraping, rapid
- Type-specific serology (IgG): Determines prior infection, HSV-1 vs HSV-2
VZV:
- PCR: Vesicle fluid, CSF
- DFA: Vesicle scraping (Tzanck smear historical)
- Clinical diagnosis: Often sufficient (dermatomal vesicular rash)
CMV:
- PCR (Quantitative): Blood, monitor viremia in transplant/HIV
- pp65 Antigenemia: Rapid, blood leukocytes
- Tissue biopsy: Owl's eye inclusions, immunohistochemistry
- Serology: IgG for immunity status (pre-transplant)
EBV:
- Heterophile antibody (Monospot): 70-90% sensitive in acute IM, false negatives in children <4 years
- EBV-specific antibodies:
- VCA IgM: Acute infection
- VCA IgG: Past or current infection
- EBNA IgG: Appears later, confirms past infection
- EBV DNA (PCR): Monitor PTLD, CNS involvement
๐ Prevention & Vaccination
Vaccine-Preventable Viral Diseases
| Vaccine | Type | Schedule (Routine) | Efficacy |
|---|---|---|---|
| MMR (Measles, Mumps, Rubella) | Live attenuated | 2 doses: 12-15 mo, 4-6 years | Measles: 97% (2 doses), Mumps: 88%, Rubella: >95% |
| Varicella (Chickenpox) | Live attenuated | 2 doses: 12-15 mo, 4-6 years | 90% prevention disease, >95% severe disease |
| Zoster (Shingrix) | Recombinant (gE protein) | 2 doses (2-6 mo apart), age โฅ50 | >90% prevention shingles, >85% PHN |
| Influenza | Inactivated or recombinant | Annual (โฅ6 months) | 40-60% (varies by season, match) |
| COVID-19 | mRNA (Pfizer, Moderna) or protein (Novavax) | Updated annually | Variable vs infection, high vs severe disease/death |
| HPV (Gardasil-9) | Recombinant (VLP) | 2-3 doses (age 9-14: 2 doses; โฅ15: 3 doses) | >90% prevention targeted HPV types |
| Hepatitis A | Inactivated | 2 doses (12-23 mo, 6-18 mo apart) | >95% |
| Hepatitis B | Recombinant (HBsAg) | 3 doses: birth, 1-2 mo, 6-18 mo | 90-95% |
| Polio (IPV) | Inactivated | 4 doses: 2 mo, 4 mo, 6-18 mo, 4-6 years | 99% (3 doses) |
| Rotavirus | Live attenuated | 2-3 doses: 2, 4, (6 mo) | 85-98% prevention severe disease |
| RSV (Maternal) | Recombinant (prefusion F) | Single dose, weeks 32-36 gestation | ~70% prevention severe infant RSV |
| Yellow Fever | Live attenuated | Single dose (travelers), booster q10y if ongoing risk | >95% |
| Rabies (Pre-exposure) | Inactivated | 3 doses: days 0, 7, 21-28 (high-risk occupations) | 100% with post-exposure booster |
| Japanese Encephalitis | Inactivated | 2 doses: days 0, 28 (travelers to endemic areas) | ~90% |
โ ๏ธ Contraindications to Live Vaccines:
- Pregnancy (defer until postpartum)
- Severe immunodeficiency (HIV with CD4 <200, immunosuppressive therapy, primary immunodeficiency)
- Recent receipt of antibody-containing products (timing varies, 3-11 months)
- Severe allergic reaction to prior dose or vaccine component
Note: HIV with CD4 โฅ200 can receive MMR, Varicella (individualized)
Passive Immunization
๐ Immunoglobulin Products
| Product | Indication | Dosing |
|---|---|---|
| Hepatitis B Immune Globulin (HBIG) | Post-exposure prophylaxis (needlestick, sexual, perinatal) | 0.06 mL/kg IM (within 24h exposure) + HBV vaccine series |
| Rabies Immune Globulin (RIG) | Post-exposure prophylaxis (unvaccinated) | 20 IU/kg (infiltrate wound, remainder IM) + vaccine series |
| Varicella-Zoster Immune Globulin (VariZIG) | Post-exposure in high-risk (immunocompromised, pregnant, newborn) | 125 IU per 10 kg IM (within 10 days exposure) |
| RSV Monoclonal Antibody (Nirsevimab) | Prevention in infants | Single dose: 50 mg (<5 kg) or 100 mg (โฅ5 kg) IM |
| Palivizumab (Synagis) | RSV prophylaxis high-risk infants | 15 mg/kg IM monthly during RSV season |
| Intravenous Immunoglobulin (IVIG) | Measles post-exposure (immunocompromised), Parvovirus B19 (chronic) | Measles: 400 mg/kg IV (within 6 days). Parvovirus: Variable |
Non-Vaccine Prevention Strategies
๐งผ Hygiene Measures
- โ Hand hygiene (soap 20s or alcohol-based)
- โ Respiratory etiquette (masks, cover cough)
- โ Avoid touching face (eyes, nose, mouth)
- โ Safe food handling (HAV, HEV, norovirus)
๐ฆ Vector Control
- โ Mosquito nets, repellents (DEET, picaridin)
- โ Eliminate standing water
- โ Protective clothing in endemic areas
- โ Indoor residual spraying
๐ฉบ Blood/Body Fluid Precautions
- โ Universal precautions (HBV, HCV, HIV)
- โ Safe injection practices
- โ Screening blood products
- โ Harm reduction (needle exchange, safe sex)
๐ฌ Antiviral Prophylaxis
- โ HIV PrEP/PEP
- โ Influenza antivirals (post-exposure)
- โ Acyclovir (HSV recurrence suppression)
- โ Hepatitis B treatment as prevention
๐ Public Health Measures:
- Surveillance: Early detection of outbreaks
- Quarantine & Isolation: Prevent transmission
- Contact tracing: Identify exposed individuals
- Travel advisories: Emerging threats (Ebola, MERS, mpox)
- Education: Community awareness campaigns
- Vaccination programs: High coverage essential (herd immunity)