Comparison of Major Human Herpesvirus Infections
| Feature | HSV-1 | HSV-2 | VZV (HHV-3) | CMV (HHV-5) | EBV (HHV-4) |
|---|---|---|---|---|---|
| Typical Diseases/Manifestations | – Orofacial herpes (cold sores) – Herpetic whitlow – HSV encephalitis – Keratoconjunctivitis |
– Genital herpes – Neonatal herpes – Aseptic meningitis |
– Varicella (chickenpox) – Herpes zoster (shingles) – Zoster ophthalmicus |
– Congenital infection – CMV mononucleosis-like illness – Retinitis (AIDS), colitis, esophagitis – Transplant CMV disease |
– Infectious mononucleosis – Burkitt lymphoma, nasopharyngeal carcinoma (associations) – Oral hairy leukoplakia (HIV) |
| Key Symptoms | – Painful vesicles on lips/face – Fever, malaise – Tingling/burning prodrome |
– Painful genital/anal vesicles – Dysuria, discharge – Prodrome of tingling |
Varicella: pruritic vesicular rash, fever Zoster: dermatomal rash, pain/postherpetic neuralgia |
– Fever, malaise, lymphocytosis – Retinitis: floaters, vision loss – GI: abdominal pain, diarrhea |
– Fever, pharyngitis, lymphadenopathy, fatigue – Splenomegaly |
| Transmission | Contact with infected secretions/lesions; autoinoculation | Sexual contact; perinatal | Varicella: respiratory droplets Zoster: reactivation, contact with lesions |
Body fluids (saliva, urine, breast milk), blood, transplant organs | Saliva (“kissing disease”) |
| Risk Factors | – Close contact – Immunosuppression |
– Unprotected sex – Multiple partners – HIV |
– Unvaccinated – Older age (zoster) |
– Immunocompromised – Pregnancy (congenital risk) – Transplant recipients |
– Adolescents/young adults – Immunosuppression |
| First-Line Antiviral Treatment | Mild disease: oral acyclovir/valacyclovir/famciclovir Severe (encephalitis): IV acyclovir |
Similar to HSV-1; consider chronic suppressive therapy | Varicella: acyclovir/valacyclovir Zoster: high-dose acyclovir/valacyclovir/famciclovir; pain management |
Severe/CMV disease: IV ganciclovir or oral valganciclovir Foscarnet/cidofovir for resistance |
Supportive; corticosteroids for severe tonsillar swelling; antivirals generally not used |
| Treatment Notes | – Early therapy shortens duration – Suppressive therapy reduces recurrences/transmission |
– Suppressive reduces shedding & transmission – Neonatal disease requires IV therapy |
– Start within 72 hrs of rash onset for best effect – Postherpetic neuralgia requires multimodal pain control |
– Preemptive therapy in transplant based on viral load – Monitor counts & renal function |
– Mostly supportive – Corticosteroids in airway compromise |
| Vaccine Availability | None licensed specifically for HSV | None licensed specifically for HSV | Varicella vaccines: live attenuated (varicella) Zoster vaccines: recombinant (Shingrix), live (Zostavax) depending on age |
None licensed for general use (in development) | None |
| Special Clinical Tips | – Avoid steroids during active lesion without antivirals – HSV keratitis: refer to ophthalmology |
– Screen partners; pregnancy counseling to reduce neonatal risk | – Adults with zoster at high pain risk: consider early pain referral – Immunocompromised may have disseminated zoster |
– CMV in pregnancy: counsel on exposure reduction – In transplant: prophylaxis or preemptive monitoring reduces disease |
– Avoid contact sports with splenomegaly – EBV is oncogenic in specific settings |
Clinical Pearls
HSV-1 and HSV-2
- Prodrome matters: tingling/itching often precedes lesions; start antivirals early.
- Suppressive therapy (e.g., valacyclovir daily) reduces outbreaks and transmission, especially in HSV-2 genital infection.
- Neonatal herpes is high-mortality; maternal primary infection near delivery is highest risk.
VZV
- Shingles pain can precede rash by days; postherpetic neuralgia is common in older adults.
- Recombinant zoster vaccine (e.g., Shingrix) is preferred in adults ≥50 regardless of previous zoster history.
- Immunocompromised individuals may have atypical or disseminated disease.
CMV
- Preemptive therapy strategy in transplant: monitor viral load and treat before end-organ disease.
- Congenital CMV is leading infectious cause of neurodevelopmental disability—targeted screening and counseling matter.
EBV
- Heterophile antibody tests (Monospot) can help diagnosis but may be negative early.
- Do not prescribe ampicillin/amoxicillin in suspected EBV mononucleosis (rash often results).
Vaccine Summary
| Virus | Vaccine | Type | Indications / Notes |
|---|---|---|---|
| VZV | Varicella vaccine | Live attenuated / recombinant | Routine childhood immunization; catch-up in adults without immunity |
| VZV | Zoster vaccine (Recombinant) | Recombinant | Adults ≥50; high efficacy; safe in many immunocompromised (~guideline specific) |
| HSV-1/2 | — | — | No licensed vaccine at present |
| CMV | — | — | Several candidates in trials; none licensed |
| EBV | — | — | Vaccines under development; none licensed |
Evidence & Guidelines (General)
- HSV & VZV antivirals: Early initiation (≤72 hrs) correlates with improved outcomes (frequency and duration of lesions; reduced complications).
- Shingles vaccination: Recombinant zoster vaccine (RZV) shows higher efficacy than live vaccine in older adults.
- CMV in transplant: Preemptive monitoring with PCR guides therapy; valganciclovir/ganciclovir are mainstays.
- EBV mononucleosis: Supportive care; avoid certain antibiotics that cause rash.