Suspected infectious mononucleosis (febrile sore throat, fatigue, lymphadenopathy)
BioMG follows French guidelines. Adapt it to the guidelines and the tests available where you practise.
First-line tests
Laboratory tests
- FBC with differential count (film: activated lymphocytes)
- Monospot test (heterophile antibodies); if negative, the laboratory does EBV serology
- EBV serology straight away (VCA IgM and IgG, EBNA IgG) in children under 5 yearsif neededThe mononucleosis spot test is often falsely negative before age 5 [1] (sensitivity below 50% before age 6 [2]); specific serology is prescribed if primary EBV infection is suspected, but cannot be combined with the spot test [3].
- EBV serology straight away (if pregnancy, immunosuppression or age over 50 years)if needednon-French guidelineNew Zealand (bpac, 2012) goes straight to specific serology and FBC in pregnant women, immunocompromised people, children and older people, the spot test being less reliable outside the 12-25 age range and the causes to be excluded having heavier consequences [4]; its sensitivity falls below 50% after age 50 [2]. The French laboratory fee schedule (NABM) has the spot test done first when the picture suggests mononucleosis, serology being prescribed if primary infection is suspected, without being combined with it [3].
- ASTif needednon-French guidelineRaised transaminases in 58 to 100% of outpatients; they strengthen suspicion when the spot test is negative [1].
- ALTif needednon-French guidelineRaised transaminases in 58 to 100% of outpatients; they strengthen suspicion when the spot test is negative [1].
- HIV serology (combined test)if needednon-French guidelineAt-risk exposure, or signs pointing to primary infection (mucocutaneous lesions, rash, diarrhoea, weight loss): differential diagnosis of mononucleosis [5].
Do not order
Negative monospot test and EBV serology: other causes
Laboratory tests
- CMV serology (IgG and IgM)
- HIV serology (combined test)
- HIV viral load (if primary infection suspected: recent exposure)if neededAcute infectious syndrome compatible with primary HIV infection: NABM indication for viral load (HIV-1 first) [3].
- Toxoplasmosis serology (IgG and IgM)if needednon-French guidelineRecent undercooked meat or contact with cat litter; lymphadenopathy [5].
Sources (9)
- Sylvester JE, Buchanan BK, Silva TW. Infectious Mononucleosis: Rapid Evidence Review. Am Fam Physician. 2023;107(1):71-78.
- Lupo J, Truffot A, Andreani J, Habib M, Epaulard O, Morand P, Germi R. Virological markers in Epstein-Barr virus-associated diseases. Viruses. 2023;15(3):656.
- Caisse nationale de l’assurance maladie. Nomenclature des actes de biologie médicale (NABM), version 105 : actes 3786, 1009, 1010, 1008 (virus d’Epstein-Barr), 1260 (CMV), 4122 (charge virale VIH).
- bpacnz (Nouvelle-Zélande). Sick and tired of being tired and sick: laboratory investigation of glandular fever. Best Tests, octobre 2012.
- Womack J, Jimenez M. Common questions about infectious mononucleosis. Am Fam Physician. 2015;91(6):372-6.
- Centers for Disease Control and Prevention (États-Unis). Epstein-Barr Virus and Infectious Mononucleosis: Laboratory Testing. Page revue le 28 septembre 2020.
- National Institute for Health and Care Excellence. Sore throat (acute): antimicrobial prescribing. NICE guideline NG84, 26 janvier 2018 : recommandation 1.1.5.
- NHS Borders (Écosse). Referral help toolkit : Glandular fever. Right Decisions (outil local de soins primaires), révisé le 18 septembre 2025.
- Haut Conseil de la santé publique. Prévention de l'infection à cytomégalovirus chez la femme enceinte et chez le nouveau-né. Rapport, 18 mai 2018.