Glandular fever (EBV mononucleosis): what to expect and when to worry

What glandular fever actually is

Glandular fever — the common name for infectious mononucleosis (IM) — is a clinical syndrome characterised by fever, severe sore throat, enlarged lymph nodes, and profound fatigue. Epstein-Barr virus (EBV) causes about 90% of cases. The remaining 10% are caused by CMV (cytomegalovirus), HHV-6, toxoplasmosis, or acute HIV — all of which can produce an almost identical picture.

EBV infects B lymphocytes (a type of white blood cell) and spreads through saliva — explaining why it earned the nickname “kissing disease”. The virus remains latent in the body for life after the first infection. Over 90% of Australian adults carry EBV and most acquired it in childhood without knowing, because childhood infection is usually asymptomatic. When primary infection is delayed until adolescence or early adulthood — as happens more commonly in high-income countries — the immune response is far more vigorous and the clinical illness much more pronounced.

Peak age of glandular fever in Australia is 15–25 years.

A. Core clinical — the AU general practice framework

Who gets it and how it spreads

EBV spreads via infected saliva — direct kissing, sharing drinks and utensils, or close respiratory contact. The incubation period is 4–6 weeks, which means you may not link the illness to any specific exposure. Viral shedding in saliva can persist for months after recovery, though the risk of transmission falls sharply once acute symptoms settle.

There is no formal isolation requirement. Returning to school or work once symptoms allow is appropriate — the virus is too ubiquitous and the shedding window too long for exclusion to have any population benefit.

Recognising the illness

The classic triad is fever, severe pharyngitis, and lymphadenopathy — but the full picture includes more:

Typical features:

• Fever — often high and prolonged
• Sore throat — frequently severe, with a whitish-grey exudate on the tonsils; can be worse than typical streptococcal tonsillitis
• Posterior cervical lymphadenopathy — nodes at the back of the neck are the hallmark; submandibular and generalised lymphadenopathy also common
• Fatigue — often the most disabling feature; can be profound and outlast all other symptoms
• Headache and myalgia
• Splenomegaly — detected in about 50% by ultrasound; palpable in only 10–15%
• Hepatomegaly in about 20%; mild liver enzyme elevation in up to 80%
• Palatal petechiae (small blood-spot-like lesions on the palate) in about 30%
• Periorbital (eye area) swelling
• Rash — appears spontaneously in about 10% of cases; appears in 80–100% of cases when amoxicillin or ampicillin is given — this is a non-allergic drug reaction, not a true penicillin allergy

Investigations in general practice

eTG recommends a standard bundle for suspected IM:

Full blood count and film: lymphocytosis with greater than 50% lymphocytes is typical; atypical lymphocytes (Downey cells) making up more than 10% of the white cell count are the haematological hallmark. Mild thrombocytopenia and mild neutropenia are common.

Liver function tests: transaminase elevation — typically AST more than ALT — occurs in up to 80% of cases. Clinical jaundice is rare.

Heterophile antibody test (Monospot / Paul-Bunnell): a rapid, cost-effective bedside test. It is positive in about 70% of cases in the first week, rising to 85–90% by weeks 2–3. In children under 12, sensitivity is only about 50%.

EBV-specific serology (VCA IgM, VCA IgG, EBNA-1 IgG): used when the Monospot is negative but suspicion remains high, or in children. VCA IgM indicates acute primary infection. EBNA-1 IgG — if already positive at presentation — indicates past rather than current infection.

HIV test: recommended in anyone with atypical features or risk factors. Acute HIV seroconversion illness closely mimics glandular fever and must not be missed.

Splenic ultrasound: not required routinely for all cases, but useful in elite athletes before return to contact sport, or when splenomegaly is suspected clinically.

Treatment: what works and what doesn’t

Supportive therapy is the foundation of treatment:

• Paracetamol (up to 1 g four times daily in adults) or ibuprofen (400 mg three times daily with food in adults) for fever, sore throat, headache, and myalgia. In children, avoid aspirin — there is a risk of Reye syndrome.
• Adequate hydration — oral fluids encouraged; intravenous fluid is occasionally needed when severe pharyngitis limits swallowing
• Rest as needed, but excessive bed rest is counterproductive and can prolong fatigue
• Cool or soft foods for throat comfort; saline gargles, throat lozenges
• Avoid alcohol during the acute illness and until liver enzymes normalise

Antibiotics: antibiotics are not indicated for EBV mononucleosis. Amoxicillin and ampicillin must be avoided — they trigger a widespread morbilliform rash in up to 100% of cases. This rash is not a true penicillin allergy and does not contraindicate future use of other penicillins — but patients must understand this to avoid incorrect future labelling. If Group A streptococcus is confirmed on throat swab, treat with penicillin V or, if a penicillin is truly contraindicated, azithromycin.

Corticosteroids: Cochrane review evidence does not support routine steroid use for symptom relief in glandular fever — limited benefit, potential harm. Corticosteroids are reserved for specific severe complications:

• Severe airway compromise from massive tonsillar enlargement (impending obstruction)
• Severe autoimmune haematological complications — autoimmune haemolytic anaemia, severe thrombocytopenia

Antivirals (acyclovir, valaciclovir): have no role in immunocompetent individuals with glandular fever. Antiviral trials have shown no clinical benefit in healthy adults and adolescents.

B. The single most important safety rule — contact sport restriction

The enlarged spleen that accompanies glandular fever is fragile. Splenic rupture is the most feared acute complication, occurring in less than 1% of cases but often within the first 3 weeks of illness. Rupture can be spontaneous or triggered by surprisingly minor trauma — a bump, a tackle, or vigorous coughing.

RACGP guidelines, NICE CKS, and specialist consensus all recommend:

• No contact or collision sport for at least 3–4 weeks from the onset of illness — some authorities extend this to 4–6 weeks for elite athletes or those with confirmed significant splenomegaly
• Non-contact activities (walking, gentle swimming, cycling) can resume once symptoms allow, with caution if splenomegaly is present
• Splenic ultrasound is recommended before return to contact sport in elite athletes

Warning signs of splenic rupture requiring immediate emergency department attendance:

• Sudden severe left upper abdominal pain or left shoulder tip pain
• Dizziness or near-fainting
• Rapid heart rate or feeling of collapse

C. Post-viral fatigue and the ME/CFS risk

Fatigue is the most persistent feature of glandular fever. The majority of people feel significantly better within 4–6 weeks. However:

• Persistent fatigue beyond 2–3 months is not uncommon and does not indicate ongoing viral activity — it reflects how the immune system is recalibrating
• 10–15% of people develop a prolonged fatigue syndrome with post-exertional malaise — symptoms that worsen significantly after physical or mental exertion and require a recovery period — that meets criteria for ME/CFS
• Pushing through severe fatigue during the recovery phase appears to worsen outcomes in this group; pacing — matching activity level to available energy — is the recommended approach per current ME/CFS guidelines
• If fatigue is severe and persistent (beyond 3 months), causes functional limitation, or includes post-exertional worsening, discuss referral to a chronic fatigue clinic or specialist

Mood changes, anxiety, and reactive depression are also common during a prolonged illness course. If these are affecting your wellbeing or function, a Mental Health Treatment Plan via your GP can provide access to subsidised psychology sessions.

D. Australian operations — MBS, PBS, and referral pathways

MBS items

Standard general practice consultations (items 23, 36, 44) apply. A longer Level C or Level D consultation (items 36 or 44) is appropriate for the first visit where history-taking, examination, investigation ordering, diagnosis communication, and sport-restriction counselling need to occur. MBS Online item 73807 covers the standard blood panel (FBC, LFTs, Monospot); item 73881 covers EBV-specific serology and HIV testing.

Splenic ultrasound (item 55028 or 55036 for abdominal USS) is appropriate when splenomegaly is clinically suspected or when clearing an athlete for return to sport.

PBS

Paracetamol and ibuprofen are on the general schedule. Prednisolone (general schedule) is available for the specific severe complications described above.

Referral

Most cases are managed entirely in general practice. Refer to hospital emergency or a specialist when:

• Suspected splenic rupture — emergency
• Severe airway compromise from tonsillar swelling — emergency
• Immunocompromised patient with severe or atypical disease — infectious diseases or haematology
• Prolonged atypical course suggesting an alternative diagnosis (lymphoma, leukaemia, HIV)
• Post-EBV fatigue progressing to ME/CFS — chronic fatigue clinic or specialist rehabilitation service

Aboriginal and Torres Strait Islander patients benefit from care coordination through an Aboriginal Community Controlled Health Service (ACCHS) where available.

E. Special populations

Children under 12: glandular fever is milder and often has fewer classic features. The Monospot test is less reliable; EBV-specific serology is preferred. Children recover faster than adolescents or adults.

Older adults (40+): EBV mononucleosis is less common but tends to be more severe. Jaundice is more frequent. The presentation may be dominated by fatigue, fever, and hepatitis rather than the classic sore-throat picture. Lymphoma should be considered if the course is atypical.

Immunocompromised patients: EBV can cause severe or atypical disease, including EBV-associated lymphoproliferative disorders. Specialist infectious disease or haematology input is essential.

Students and young workers: school or work return when symptoms allow is appropriate. Academic or workplace accommodation for prolonged fatigue is reasonable — a medical certificate from your GP can support this.

Athletes: the sport-restriction rule applies to all athletes, from recreational weekend sport to elite competition. For elite athletes, return-to-sport clearance should be guided by clinical assessment and, where appropriate, splenic ultrasound. Gradual return (light activity → moderate → full contact) is recommended rather than an abrupt return to full competition.

When to escalate

Seek medical attention urgently if you develop:

• Sudden severe left-sided abdominal pain, left shoulder tip pain, or signs of collapse — possible splenic rupture
• Difficulty breathing or speaking due to severe throat swelling — possible airway compromise
• Rash with penicillin-class antibiotics — confirm not an allergy, document in records
• Symptoms suggesting an alternative diagnosis: persistent drenching night sweats, unexplained weight loss, progressive lymphadenopathy that fails to resolve by 6 weeks

Review with your GP within 2–3 weeks if symptoms are not improving, or sooner if you have specific concerns.

What this article is and is not

This is general health information drawn from current Australian general practice resources — Therapeutic Guidelines, RACGP, Royal Children’s Hospital Melbourne guidelines, and AMH. It is not personal medical advice and does not create a doctor–patient relationship. Your own GP will assess your individual circumstances and make decisions about your management.

Australian consumer resources: HealthDirect — Glandular fever, Better Health Channel — Glandular fever.

For crisis support: Lifeline 13 11 14, Beyond Blue 1300 22 4636.

---

Sources cited

1. eTG complete — Infectious mononucleosis
2. RACGP — Infectious mononucleosis in general practice
3. Royal Children’s Hospital Melbourne — Infectious mononucleosis guidelines
4. Australian Medicines Handbook
5. Cochrane — Corticosteroids for infectious mononucleosis
6. NICE CKS — Glandular fever
7. BMJ Best Practice — Infectious mononucleosis
8. HealthDirect — Glandular fever
9. Better Health Channel — Glandular fever
10. Bjornevik et al. — EBV and multiple sclerosis (Science 2022)
11. Australasian Society for Infectious Diseases (ASID)