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THE COURSE OF INFECTIOUS MONONUCLEOSIS IN ADULTS AND CHILDREN
Kamoldinov Marufjon Murodzhon o’g’li
assistant department of infectious diseases
Andijan State Medical Institute
Uzbekistan, Andijan
Relevance:
Infectious mononucleosis (IM), commonly caused by the Epstein-Barr virus (EBV),
is a significant health condition worldwide due to its high prevalence and impact on various age
groups. Over 90% of the global population is infected with EBV by adulthood, making it one of
the most ubiquitous human viruses [1]. The clinical syndrome of IM (often called “glandular
fever”) typically manifests when EBV infection is acquired during adolescence or young
adulthood. In contrast, children often contract EBV at an earlier age, especially in lower-income
regions, but usually experience either mild illness or no recognizable symptoms [2]. This age-
dependent difference in disease expression makes IM particularly relevant: it is a leading cause
of prolonged fever and lymphadenopathy in teens and young adults, while frequently
underdiagnosed in younger children due to its subtle presentation in that group. From a global
perspective, socio-demographic factors influence the timing of EBV infection. In many
developing countries and densely populated areas, most children are infected in early childhood
(with seroprevalence exceeding 50% before age 3), reducing the incidence of adolescent IM [3].
Conversely, in developed countries with higher hygiene and living standards, primary EBV
infection is often delayed until the second decade of life, resulting in a higher proportion of
symptomatic IM cases in that age group [5].
Understanding the characteristics of IM across different ages is clinically important because the
disease can disrupt schooling or work during the acute illness and occasionally leads to serious
complications. Moreover, EBV’s impact extends beyond the acute infection: a symptomatic
primary EBV infection (IM) in adolescence has been associated with increased risks of certain
malignancies such as Hodgkin lymphoma later in life [4]. Therefore, a comprehensive, age-
stratified understanding of infectious mononucleosis has global public health relevance. This
article examines IM in children versus adults, highlighting epidemiological trends, clinical
course differences, immune response variations, and management strategies, to inform better
recognition and care of this disease in different populations.
Keywords:
Infectious mononucleosis, Epstein-Barr virus (EBV), Children, Adults,
Epidemiology, Clinical presentation, Immunological response, Complications
Актуальность:
Инфекционный мононуклеоз (ИМ), обычно вызываемый вирусом
Эпштейна-Барр (ВЭБ), является значимым заболеванием во всем мире из-за его высокой
распространенности и воздействия на различные возрастные группы. Более 90%
населения мира инфицированы ВЭБ во взрослом возрасте, что делает его одним из самых
распространенных вирусов человека [1]. Клинический синдром ИМ (часто называемый
«железистой лихорадкой») обычно проявляется, когда инфекция ВЭБ приобретается в
подростковом или молодом возрасте. Напротив, дети часто заражаются ВЭБ в более
раннем возрасте, особенно в регионах с низким уровнем дохода, но обычно испытывают
либо легкое заболевание, либо отсутствие распознаваемых симптомов [2]. Эта возрастная
разница в проявлении заболевания делает ИМ особенно актуальной: он является основной
причиной длительной лихорадки и лимфаденопатии у подростков и молодых людей, при
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этом часто не диагностируется у детей младшего возраста из-за его сдержанного
проявления в этой группе. С глобальной точки зрения социально-демографические
факторы влияют на сроки заражения ВЭБ. Во многих развивающихся странах и
густонаселенных районах большинство детей заражаются в раннем детстве
(серопревалентность превышает 50% до 3 лет), что снижает заболеваемость подростковым
ИМ [3]. Напротив, в развитых странах с более высоким уровнем гигиены и жизни
первичное заражение ВЭБ часто откладывается до второго десятилетия жизни, что
приводит к более высокой доле симптоматических случаев ИМ в этой возрастной группе
[5].
Понимание характеристик ИМ в разных возрастах имеет клиническое значение, поскольку
заболевание может нарушить учебу или работу во время острой болезни и иногда
приводит к серьезным осложнениям. Более того, воздействие ВЭБ выходит за рамки
острой инфекции: симптоматическая первичная инфекция ВЭБ (ИМ) в подростковом
возрасте связана с повышенным риском некоторых злокачественных новообразований,
таких как лимфома Ходжкина в более позднем возрасте [4]. Поэтому всестороннее,
стратифицированное по возрасту понимание инфекционного мононуклеоза имеет
глобальное значение для общественного здравоохранения. В этой статье рассматривается
ИМ у детей и взрослых, подчеркиваются эпидемиологические тенденции, различия в
клиническом течении, вариации иммунного ответа и стратегии лечения, чтобы обеспечить
лучшее распознавание и лечение этого заболевания в разных группах населения.
Ключевые слова:
Инфекционный мононуклеоз, вирус Эпштейна-Барр (ВЭБ), дети,
взрослые, эпидемиология, клиническая картина, иммунологический ответ, осложнения
Introduction
Infectious mononucleosis is classically defined as an acute viral syndrome characterized by fever,
pharyngitis (sore throat), lymphadenopathy (especially of the cervical lymph nodes), and fatigue,
accompanied by atypical lymphocytosis in the blood. EBV is the primary etiologic agent in
~90% of IM cases, with transmission typically through saliva (hence the nickname “kissing
disease”). Other pathogens (such as cytomegalovirus) can cause a similar “mononucleosis-like”
illness, but EBV is by far the most common cause of IM and will be the focus of this discussion.
EBV infection in early childhood is usually asymptomatic or indistinguishable from a mild
nonspecific viral illness, whereas infection in adolescents and adults often produces the full IM
syndrome [5]. This variance is thought to result from differences in host immune response by age:
young children’s immune systems tend to control the virus with minimal symptoms, while
adolescents mount vigorous cellular immune responses that contribute to the disease
manifestations (as discussed later). The global epidemiology reflects this pattern – in high-
income countries many individuals reach adolescence still EBV-naïve and thus at risk of IM,
whereas in low-income settings most are seropositive by childhood, blunting the incidence of IM
in the teenage years [6].
The significance of infectious mononucleosis lies not only in its acute clinical effects – which
can include prolonged illness, missed school or work, and occasionally hospitalization – but also
in its potential long-term consequences. Primary EBV infection triggers a lifelong latent
infection of B-lymphocytes. While most people recover uneventfully, the infection has been
linked to later development of certain cancers (e.g. Hodgkin lymphoma, endemic Burkitt
lymphoma, nasopharyngeal carcinoma) and autoimmune diseases (e.g. multiple sclerosis) in a
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subset of individuals [7]. These links underscore the importance of managing the primary
infection optimally and understanding how the clinical course might differ in children vs. adults.
The objective of this article is to compare the clinical characteristics of infectious mononucleosis
in children and in adults, taking a global and evidence-based perspective. We will review and
contrast the epidemiology, typical symptoms, laboratory findings, complications, and outcomes
in pediatric versus adult cases of IM. We also discuss the immunological factors that may
underlie age-related differences in disease expression [8]. By analyzing published studies and
clinical data from diverse populations, we aim to highlight how age influences the presentation
and progression of IM. Finally, we will offer recommendations for clinical practice (such as age-
appropriate diagnostic approaches and management considerations) and suggest priorities for
future research, including vaccine development and improved therapies.
Materials and Methods
Study Design: This work is structured as a comparative review of infectious mononucleosis in
children and adults. We conducted a comprehensive literature search focusing on studies and
reports from different regions to capture a global perspective [9]. Key sources included
epidemiological surveys, clinical cohort studies, and review articles that stratified data by patient
age. We also included relevant clinical guidelines and virology/immunology research to inform
our comparison. No new patient data were collected for this article; rather, we synthesized
published evidence to elucidate age-related differences in IM.
Patient Population: For the purposes of this review, “children” are defined as patients in the
pediatric age range (typically infancy up to about 12 years old, including early childhood and
school-age children), and “adults” are defined as older adolescents and adults (generally age 13
and above, with some considerations for young adults versus older adults). Many studies
specifically highlight adolescents/young adults (often ages 15–24) as the group with highest IM
incidence, so this group is considered within the “adult” category for our comparison, while
noting distinctions for older adults when data permit. We included studies from both pediatric
and adult medicine settings worldwide [10]. Inclusion criteria for considered studies typically
required that EBV-associated IM be confirmed by laboratory testing (serological or molecular) to
ensure we are comparing true EBV primary infection across ages. Both prospective and
retrospective analyses were reviewed to gather information on clinical presentation, course, and
outcomes.
Diagnostic Criteria and Methods: The diagnosis of EBV infectious mononucleosis in the
literature is generally based on a compatible clinical syndrome in combination with specific
laboratory tests. The heterophile antidiv test (Monospot test) is commonly used, especially in
older children and adults, as an initial diagnostic assay. It detects heterophile antibodies
produced in response to EBV; a positive heterophile test in the context of a compatible illness is
considered diagnostic of IM. However, this test is known to have limitations: during the first
week of illness it can be falsely negative in about 25% of cases, and it is often negative in young
children who may not produce heterophile antibodies robustly [1]. Therefore, we considered
studies that also used EBV-specific serologic testing (such as viral capsid antigen (VCA) IgM
and IgG, EBV nuclear antigen (EBNA) antibodies) or polymerase chain reaction (PCR) for EBV
DNA to confirm acute infection, particularly in pediatric cases. These more specific tests help
distinguish acute primary EBV infection from past infection or other causes of mononucleosis-
like illness. In our analysis, a case was regarded as EBV-positive IM if EBV IgM antibodies
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were present (with or without a positive Monospot) or if EBV DNA was detected in the acute
phase, along with consistent clinical features [11].
Data Extraction and Optimization: From each source, data on patient age, clinical symptoms,
physical findings, laboratory results, and complications were extracted and categorized by
“children” vs. “adults.” We paid special attention to how authors defined these groups, aligning
them as much as possible with our criteria. To optimize the comparison, we focused on key
clinical parameters (e.g., duration of fever, severity of pharyngitis, lymph node enlargement,
liver involvement) and outcomes (recovery time, complication rates) in each age group. When
synthesizing results, we cross-verified findings from multiple studies to ensure consistency. Any
conflicting data (for example, if one study reported a certain symptom frequency in children that
differed from another) are noted and interpreted in context. We also incorporated immunological
findings from laboratory research to explain clinical differences – for instance, studies of
immune cell profiles in pediatric vs. adult EBV infection were reviewed to provide mechanistic
insight [12].
Throughout the process, we adhered to academic standards for evidence-based synthesis. This
article is written following a scientific format, including proper citation of sources [13].
References are listed in APA style at the end, and numeric citations [in square brackets] are used
in text to correspond with the reference list. No patient identifiers or sensitive data are present, as
this is a literature-based study.
Analysis and Results
Epidemiology and Global Patterns by Age - Global incidence and timing of EBV infection: The
timing of primary EBV infection – and thus the age at which infectious mononucleosis may
occur – varies widely around the world. In general, developing countries experience EBV
infection early in life, while developed countries see a later age of primary infection. For
example, a seroprevalence study in China found that over 50% of children were EBV-
seropositive by age 3, and over 90% by age 8 [16]. In contrast, studies in the United States and
Europe show a lower childhood seroprevalence; in the U.S., only around half of children 6–8
years old have evidence of EBV infection, with seroprevalence rising to ~85% by late
adolescence [14]. As a result of these patterns, the incidence of IM (symptomatic EBV infection)
is much higher in adolescents in North America and Europe, whereas many children in Africa,
Asia, and Latin America quietly acquire EBV in toddlerhood and are immune by their teen years.
Socioeconomic and environmental factors such as household crowding, sanitation, and family
size are known to influence this: lower socioeconomic status and larger household sizes facilitate
earlier EBV spread in childhood [15]. Conversely, higher socioeconomic status communities
tend to delay EBV exposure until interpersonal contact in adolescence (e.g. through kissing or
close contact in schools/universities), leading to the classic IM cases in high school or college-
aged youth.
Age-specific incidence: Infectious mononucleosis is relatively uncommon in children under 10
years in populations where EBV infection is often delayed. In those settings, the annual
incidence of IM in young children is very low (well below 1 case per 1,000 persons) [17]. The
incidence rises sharply in the 15–24 year age range – this is the peak period when primary EBV
infection results in IM. Reported incidence rates in adolescents/young adults range around 0.5%
per year in the general population, and can be higher in settings like colleges. For instance,
studies of university students have documented annual IM incidence from 9 up to 48 cases per
1,000 persons in that high-risk age group [18]. In contrast, adults over 30 are much less likely to
contract EBV for the first time (most are already seropositive) and even if they do, they may not
develop the full IM syndrome as frequently. In fact, primary EBV infection in older adulthood is
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relatively rare, and some evidence suggests that adults over 40–50 years old who are EBV-naïve
may experience more atypical or subdued presentations (or sometimes a “mono-like” illness
attributed to other viruses). Globally, the burden of IM as an illness falls mostly on adolescents
and young adults, given these epidemiologic trends.
Clinical Presentation in Children vs. Adults
Despite being caused by the same virus, EBV infection can look very different in a young child
compared to a teenager or adult. Below we compare the typical symptoms and signs of acute
infectious mononucleosis across age groups:
Young Children: Primary EBV infection in infants and young children is often mild or
asymptomatic. If symptoms occur, they are usually nonspecific – such as a low-grade fever,
irritability, poor feeding, or an upper respiratory tract infection picture. It is uncommon for
young children to exhibit the full triad of fever, sore throat, and lymphadenopathy that is
characteristic in adolescents [1][2]. Pharyngitis, if present, tends to be mild, and significant
tonsillar enlargement or exudates are not as common as in teenagers. Lymph node enlargement
might be minimal or attributed to other common childhood infections. Because of this, EBV
infections in children under ~5 years often go unrecognized; many such cases are presumed to be
just “viral colds.” One feature that can sometimes be noted in children is a moderate
hepatosplenomegaly (enlarged liver and spleen) and a high lymphocyte count on labs, but
without the child appearing very ill. In summary, the clinical course in young children is usually
benign and self-limited, resembling a minor illness.
Adolescents and Young Adults: This age group classically displays infectious mononucleosis in
its full form. Patients typically present with high fever, pronounced sore throat, and swollen
glands in the neck. Marked tonsillitis with white exudative patches on the tonsils and pharyngeal
inflammation are common, often causing severe throat pain and odynophagia (painful
swallowing). Fatigue is a prominent complaint and can be profound, sometimes lasting weeks
beyond the acute phase. Lymphadenopathy in IM often involves the posterior cervical lymph
nodes (along the back of the neck), and can also include generalized lymph node swelling
(axillary, inguinal nodes). About 50% of adolescents have palatal petechiae (tiny red spots on the
palate) on oral exam, which is a subtle but specific finding for IM [2]. Nearly all young adult
patients will have some combination of fever, pharyngitis, lymphadenopathy, and atypical
lymphocytosis in blood tests. Splenomegaly (enlarged spleen) is common by exam or ultrasound
(in over half of cases, especially after the first week of illness). Many adolescents also have some
liver inflammation – mild hepatitis with elevated liver enzymes occurs in the majority of cases,
although overt jaundice is uncommon in this age group (seen in <10% of young adults). Overall,
the illness in adolescents/young adults tends to be more severe and symptomatic than in children,
often causing the patient to be bedridden for a time. The duration of acute symptoms (fever, sore
throat) is usually 1–3 weeks, with gradual recovery, but lingering fatigue can persist for several
more weeks.
Older Adults: Primary EBV infection is rare beyond the middle ages, but when it does occur,
studies have noted a somewhat atypical clinical picture. Older adults are less likely to have the
triad of sore throat, lymph node swelling, and huge tonsils that we see in college-age patients
[20]. They may have little to no pharyngitis or lymphadenopathy, making the diagnosis of IM
less obvious. Instead, older adult patients with acute EBV may present with prolonged fever of
unknown origin, and they are more prone to develop jaundice from hepatitis [21]. One series
found that adults over 60 with primary EBV infection had jaundice in about 25% of cases,
compared to under 10% in younger patients [12]. They also had a lower frequency of lymph
node enlargement and splenomegaly. The illness in older adults might be mistaken for other
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causes of hepatitis or fever. Because almost all older adults have been infected earlier in life,
such presentations are infrequent, but they highlight that the classic IM symptoms are most
reliably seen in the adolescent and young adult population.
Immunological Response Differences
The differences in clinical severity between children and adults with EBV infection can be partly
explained by the distinct immunological responses. Young children’s immune systems respond
differently to EBV, often containing the virus before it triggers the intense T-cell reaction that
causes IM symptoms. Research indicates that innate immune cells, particularly Natural Killer
(NK) cells, play a crucial protective role in early life EBV infections. Children have higher
baseline levels of certain NK cell subsets that can rapidly target EBV-infected B cells. These NK
cells in young hosts may limit the initial proliferation of the virus [5][6]. In one study,
investigators found that a specific subset of NK cells (characterized as CD56^dim NKG2A^+
cells) is present at significantly higher frequency in children than in adolescents; this correlated
with better early control of EBV and fewer symptoms in the younger patients [5]. In practical
terms, this means the child’s innate immune response often curtails the infection before it
becomes clinically apparent as mononucleosis. By contrast, adolescents and adults rely more on
adaptive immunity (T lymphocytes) to fight EBV. When an EBV-naïve teenager gets infected,
the virus replicates in B cells and epithelial cells, and the immune system mounts a vigorous
cytotoxic T-cell response to clear these infected cells. It is this very robust T-cell response
(largely CD8^+ T cells attacking EBV-infected B cells) that causes the systemic symptoms of
IM: the release of inflammatory cytokines leads to fever and malaise, while lymphocyte
proliferation results in lymphadenopathy and splenomegaly. The large population of “atypical”
lymphocytes seen on blood smears during IM are activated T cells responding to EBV. In
children, because the virus may be held at lower levels by NK cells early on, the subsequent T-
cell response is blunted, resulting in milder or no symptoms [6].
Another immunological factor is the presence (or absence) of pre-existing memory lymphocytes.
There have been hypotheses that adolescents might have cross-reactive memory T cells (perhaps
from other viral infections like influenza) that amplify the response to EBV, although evidence is
mixed [15]. What is clear is that age at infection is a key determinant of the host-virus interaction
outcome: if EBV is contracted when the immune system is immature (infancy/early childhood),
the host tends to tolerate the infection with minimal illness. If contracted when the immune
system is mature and can mount a full attack, the result is the IM illness. This concept is
supported by animal model research as well. Experimental studies (in humanized mouse models)
have shown that depleting NK cells leads to more severe mononucleosis, whereas having robust
innate responses can prevent the emergence of IM even if infection occurs [16]. These findings
suggest that therapeutic strategies boosting early immune responses might mitigate disease
severity. They also provide a rationale for why vaccinating EBV-naïve individuals before
adolescence could prevent infectious mononucleosis – by priming the immune system to handle
the virus more like a primary childhood infection than a late encounter.
Laboratory Findings and Diagnosis
The classic laboratory hallmarks of infectious mononucleosis include an elevated white blood
cell count with lymphocytosis, often >50% lymphocytes, and at least 10% atypical lymphocytes
on a peripheral smear. Liver enzymes (ALT, AST) are mildly elevated in many cases (more so in
adults) and there can be mild elevations in bilirubin (especially in older patients as noted).
Heterophile antidiv tests (Monospot) are positive in the majority of adolescent and adult IM
cases, but they are notably less reliable in young children. Children under ~4 years old frequently
test negative on the Monospot despite having EBV infection, because the heterophile antidiv
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response may not develop robustly at that age [19]. In one analysis, the heterophile test was
positive in only around 50-75% of children under 12 with confirmed EBV, versus over 90% in
teens and young adults with IM. Therefore, diagnostic approach differs by age: for a teenager
with classic symptoms, a Monospot test is a quick and useful diagnostic (with specificity around
90-95% when positive). For a young child with suspected EBV (perhaps a prolonged
unexplained fever or liver enzyme elevation with lymphocytosis), clinicians often proceed to
EBV-specific serologies. A typical pattern confirming acute EBV is positive IgM to viral capsid
antigen (VCA) and absence of antibodies to EBV nuclear antigen (EBNA), which indicates a
new infection. These tests are more expensive and slower, so they are not done for every case,
but they are invaluable in pediatric cases or atypical presentations where the Monospot is
negative. PCR testing for EBV DNA can also confirm acute infection, though it’s used mostly in
complex cases or immunocompromised patients.
In terms of laboratory differences: children with IM tend to have higher lymphocyte counts
(sometimes extreme lymphocytosis) but lower titers of heterophile antibodies. Adults may show
more evidence of liver involvement (higher aminotransferases, occasionally a cholestatic
hepatitis picture in older adults). Both children and adults can develop autoantibodies during IM;
for instance, transient positive rheumatoid factor or antinuclear antibodies are reported, as well
as a mild autoimmune hemolytic anemia in up to 2-3% of cases (caused by anti-i antibodies).
There is no strong age predilection for these rare immuno-hematologic complications, though
some case series suggest they might occur more in adults.
In summary, diagnosing IM in an adolescent/adult is often straightforward with a Monospot test
in the right clinical context. Diagnosing IM in a young child might require a high index of
suspicion and use of specific EBV IgM serology, since the presentation is subtle and the
common screening test can be falsely negative.
Complications and Outcome
Most cases of infectious mononucleosis, whether in children or adults, are self-limiting and end
in full recovery. However, the risk and type of complications can differ by age:
Airway obstruction: One acute complication is upper airway obstruction due to grossly enlarged
tonsils and lymphoid tissue in the throat. This complication is more common in children,
especially those under adolescence [20]. Young children have smaller airways, and if EBV
causes massive tonsillar hypertrophy, they may develop difficulty breathing or swallowing. It is
documented that children with IM are at highest risk for airway compromise, and this is in fact a
leading reason for hospitalization in pediatric IM cases [21]. Adolescents can also get very
enlarged tonsils (kissing tonsils that nearly touch midline), but their larger airway diameter
means complete obstruction is less frequent. When threatened, the standard management is high-
dose corticosteroids to reduce inflammation, and in severe cases, airway monitoring or
intervention. Thus, while uncommon overall, significant airway obstruction due to IM is a
pediatric-focused concern.
Splenic rupture: The spleen typically enlarges during acute EBV IM due to lymphoid
proliferation and infiltration. Splenic rupture is a rare but serious complication, usually occurring
in the second or third week of illness when the spleen is fragile. This complication is actually
reported more often in adolescent and young adult patients, likely because they are more
physically active and have larger spleens due to the robust immune response. Traumatic rupture
can occur if a patient resumes sports or heavy lifting too soon. It has been noted in some case
series that males in their teens and twenties are the most common demographic for IM-related
splenic rupture. Children, who often have milder disease, are less frequently reported to have this
complication (and are also less likely to engage in activities that risk abdominal trauma during
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illness). To prevent this, all age groups are advised to avoid contact sports or vigorous activities
for at least 3-4 weeks of illness. The outcome of splenic rupture can be life-threatening internal
bleeding, requiring emergency surgery, so prevention is crucial. Fortunately, it is quite rare
(estimated in <0.5% of IM cases overall).
Neurologic complications: EBV IM can occasionally affect the nervous system. Examples
include meningoencephalitis, Guillain-Barré syndrome, Bell’s palsy, transverse myelitis, and
others. These complications are uncommon (<<5%) but can occur at any age. Some reports
suggest encephalitis might be seen more in younger patients, whereas peripheral neuropathies
(like Guillain-Barré) might appear in adolescents/adults, but the data are limited. Overall, no
strong age predisposition is confirmed for neurologic sequelae; both pediatric and adult cases are
described. Importantly, most neurologic complications, if they occur, tend to resolve over time
(for instance, IM-associated Guillain-Barré is usually treatable and patients often recover).
Hematologic complications: As noted, a small fraction of IM patients develop autoimmune
hemolytic anemia or thrombocytopenia. These tend to arise in the acute phase and usually
resolve spontaneously within weeks. If severe (e.g., anemia with hemoglobin drop or platelet
count <50k), short-term steroid therapy is often effective. There isn’t a clear age predilection,
although some older literature suggests adults were more often noted to have hemolytic anemia
than children in IM. This might be because adults were more thoroughly tested for it; in any case,
both can be affected.
Hepatic involvement: Nearly all patients have some liver involvement (elevated enzymes), but
clinical hepatitis with jaundice is more often observed in older adults, as mentioned. This usually
resolves without specific treatment, but in an older patient, it may prompt a workup for hepatitis
until EBV is recognized. Children and adolescents rarely become visibly jaundiced from EBV;
their liver enzyme elevations are usually transient and not associated with liver failure.
Fulminant hepatic failure from EBV is extremely rare, and when it occurs it’s often in the
context of immune deficiencies.
Chronic active EBV and other late complications: In normal hosts, EBV goes latent after the
acute phase. A very small subset of patients (more often in East Asia) can develop Chronic
Active EBV infection, a severe progressive illness with ongoing inflammation – this typically
occurs in children or young adults with certain immunological susceptibilities and is not the
common outcome of typical IM. We mention it for completeness: it is more of a pathological
rarity and not an expected outcome of standard IM in healthy individuals. Another context is X-
linked lymphoproliferative syndrome (Duncan disease), a rare hereditary disorder in boys that
leads to an inability to control EBV – these children develop fulminant, often fatal IM. That
again is a special case, outside the scope of routine IM outcomes.
Recovery and long-term outcomes: The recovery period from acute IM can differ in length by
age. Children, when they do have symptomatic EBV, tend to bounce back quicker. Within a
couple of weeks, most children are back to normal activity since their illness was mild to begin
with. Adolescents and young adults often report lingering fatigue for several weeks; about 10%
or more have fatigue that lasts 2–3 months, and a very small minority can have a post-viral
fatigue syndrome that stretches longer. This post-mononucleosis fatigue has been of interest in
adults as a possible trigger for chronic fatigue syndrome, though most people gradually improve.
Proper rest and graded return to activity are usually recommended. The overall prognosis for
typical infectious mononucleosis is excellent in both children and adults – it is usually self-
resolving. Death from acute IM is exceedingly rare in healthy individuals (estimated mortality
<0.1%) and would usually be due to complications like splenic rupture or encephalitis if it occurs.
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In summary, children with IM generally experience a shorter, milder course with rare
complications, whereas adolescents have a more intense illness that, while still usually benign in
outcome, carries a slightly higher risk of complications (airway issues, splenic injury, etc.). Older
adults, if affected, may show atypical features but still typically recover. Awareness of these
differences is important for clinicians. For example, a physician might not suspect IM in a
toddler with a mild fever, but knowing family history or community EBV prevalence could
prompt testing if atypical lymphocytes are found. Conversely, in a 20-year-old with classic
symptoms, the diagnosis is straightforward, but one must counsel about rest and monitor for
complications due to the higher symptomatic load.
Conclusion and Recommendations
Key Findings: Infectious mononucleosis due to EBV exhibits distinct patterns in children versus
adults. Children often have an asymptomatic or mild primary EBV infection, owing in part to a
strong innate immune response (especially NK cells) that contains the virus before it causes
widespread illness. In contrast, adolescents and young adults mount a vigorous adaptive immune
reaction that leads to the classic IM syndrome with significant throat infection, fever, lymph
node swelling, and fatigue. These differences mean that many pediatric EBV infections go
undiagnosed, while IM is a well-recognized clinical entity in teens. Adults beyond young
adulthood rarely encounter EBV for the first time, but if they do, their presentations can be
atypical (less throat-centric and more hepatic). Despite these variations, the management of EBV
infectious mononucleosis is largely supportive in all age groups, and most patients recover fully
with rest and symptomatic care. Children generally recover quickly, whereas adolescents might
need a longer convalescence due to more pronounced fatigue.
Clinical Practice Recommendations: Based on our review, we propose the following approaches
for clinicians managing suspected IM in different age groups:
Maintain an age-tailored suspicion: In young children, consider EBV infection in the differential
diagnosis of prolonged unexplained fever, significant lymphocytosis, or hepatosplenomegaly,
even if classic IM signs are absent. Don’t rely on heterophile test alone in this group; use EBV-
specific antidiv testing when diagnosis is important (e.g. to distinguish from other illnesses). In
adolescents and young adults, IM should be suspected in those with the triad of sore throat, fever,
and lymphadenopathy (especially posterior cervical) or when symptoms persist beyond a typical
viral pharyngitis [22]. A rapid heterophile test can confirm many cases, but if negative (and
illness is early or highly suggestive), follow up with EBV serologies rather than assuming it’s not
EBV. Recognize that older adults with fever and liver dysfunction could have primary EBV –
testing for EBV may be warranted in mononucleosis-like syndromes even if the patient is outside
the usual age range.
Patient counseling and supportive care: Once IM is diagnosed, education and supportive
management are the mainstays. Advise all patients (or parents) that plenty of rest, hydration, and
fever control (acetaminophen or NSAIDs) are important. Throat pain can be managed with
analgesics and saline gargles. Antibiotics are not indicated for uncomplicated IM (it is viral);
moreover, certain antibiotics like amoxicillin/ampicillin can trigger a well-known generalized
rash in the setting of EBV – a benign but alarming rash that should be avoided. This rash occurs
in the majority of IM patients given amoxicillin, so avoiding unnecessary antibiotics is crucial.
Activity restrictions: Because of the risk of splenic rupture, advise avoiding contact sports,
vigorous exercise, or heavy lifting for at least 3-4 weeks from symptom onset for adolescents and
adults. Younger children are usually not involved in high-impact sports, but they should still
avoid rough play. The exact duration of restriction can be tailored; some clinicians obtain an
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104
ultrasound to confirm spleen size has normalized before clearing athletes, especially if they are
high-level athletes. Generally, the rule of thumb is to err on the side of caution for at least one
month or until the patient is fully recovered and any splenomegaly has resolved.
Monitoring and interventions for complications: In children, monitor for any signs of airway
difficulty (stridor, inability to handle secretions). Early use of corticosteroids (e.g.
dexamethasone) is indicated if there is significant tonsillar hypertrophy threatening airway or if
there is severe swallowing impairment. In both children and adults, if there is abdominal pain or
left upper quadrant pain, evaluate promptly (as it could signal spleen issues). Hospitalize and
stabilize any suspected spleen rupture – although rare, this is a medical emergency. Check blood
counts in patients with particularly severe illness to catch hematologic complications; if platelet
counts or hemoglobin drop significantly, specialist consultation may be needed. For neurologic
symptoms, do appropriate investigations (lumbar puncture, etc.) to differentiate EBV-related
neurological complication from other causes, and manage supportively (e.g. IV immunoglobulin
for Guillain-Barré).
Follow-up: Arrange follow-up especially for adolescents to monitor recovery. Some may
experience prolonged fatigue – reassure them that this can be part of the normal recovery, but
also ensure other causes of fatigue are not overlooked. Advise a gradual return to full activities (a
step-wise increase in exercise tolerance once past the acute phase).
Public Health and Future Directions: From a public health standpoint, the differences in EBV
infection timing suggest that development of an EBV vaccine could markedly reduce cases of IM
by immunizing adolescents before they naturally contract the virus. Several research groups are
indeed working on EBV vaccine candidates
[6]
, with the goal of preventing primary EBV
infection or at least modulating it so that symptomatic IM does not occur. If successful, this
could also have downstream benefits of reducing EBV-associated cancers. More research is
needed in understanding the immune mechanisms that allow some people (especially children) to
control EBV without illness – this might unlock therapies that can help older patients. For
instance, enhancing NK cell responses or other innate immunity could be a therapeutic strategy
to explore for acute IM or for preventing severe cases. Additionally, while antiviral drugs (like
acyclovir) have not shown significant clinical benefit in routine IM, novel antivirals or immune-
modulating drugs might in the future shorten the disease course. Clinical trials could evaluate
whether any interventions during acute EBV infection (for example, immunotherapy or targeted
antivirals) can reduce symptom severity or long-term consequences.
Finally, long-term longitudinal studies are recommended to further clarify the connections
between symptomatic primary EBV (IM) and subsequent conditions like Hodgkin lymphoma or
multiple sclerosis. A better understanding of these links could inform screening or preventive
strategies in individuals who suffered a severe IM episode. In summary, infectious
mononucleosis remains an illness of considerable importance globally, and appreciating the
contrasts between its manifestation in children and adults can guide effective clinical
management and inspire targeted research to improve outcomes for all age groups.
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