Infectious Disease in Sports

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Infectious Disease in Sports

• Britt Marcussen, MD
• Department of Family Medicine
• University of Iowa

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UI Sports Medicine 6-0
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Seeking Sponsorship ?
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Influenza

• Definition Influenza or flu is an infection
  caused by the influenza viruses. Influenza
  spreads around the world in seasonal epidemics
  that result in 250,000 to 500,000 deaths each
  year (41,000 on average in the US). Occasional
  pandemics occur when a particularly virulent and
  contagious strain of flu have been know to cause
  50 million deaths.

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Classification

• There are three viral types A/B/C
• A The most virulent and responsible for all
  pandemics thus far. Mutates rapidly
• B Not as virulent. Mutates slower. Humans
  have some baseline immunity.
• C Much less common and usually only produces
  mild symptoms.

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Influenza Viral Structure

• Envelope Contains the glycoprotein's
  Hemaggutinin (binding) and Neuraminidase
  (release) and thus the H N classification.
• Core contains the RNA that contains the genes
  for protein coding
• During viral replication because there are no RNA
  proofreading enzymes errors in transcription
  occur, thus altering the surface proteins. These
  mutations are what is responsible for antigenic
  drift.

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Signs and Symptoms

• The typical presentation is fairly rapid onset of
  fever, chills and body aches. Other symptoms can
  include HA, cough, nasal congestion and sore
  throat. You can also get GI symptoms of nausea,
  vomiting and diarrhea especially in children.
  None of these clinical symptoms or signs are
  particularly specific and are common to most of
  the hundreds of known respiratory viruses

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Morbidity/Mortality

• Increased in the young (lt5), old (gt65) and those
  with other co morbid conditions.
• Death is usually the result of a secondary
  infection, usually pneumonia.
• During pandemics the excess mortality is in
  younger patient population and is a result of the
  cytokine storm induced by the virus which leads
  to pulmonary edema and hemorrhage.

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Transmission

• Possible mechanism of spread
• Direct transmission from hard surfaces
• Direct transmission for large particle contact
  (up to 1 meter away)
• Inhalation of suspended particle (5micrometer)?.
• The virus can live on hard surfaces up three days
  and in mucus for up to two weeks!

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Testing

• Rapid test for A/B are available and are
  reasonably accurate (sensitivity 50-70 and
  specificity of 90-95).
• They are most accurate during the first 4-5 days.
• Test only when results will influence decision
  making( i.e., hospitalized patients, considering
  treatment of the individual or contacts/infection
  control). During outbreaks in patient with
  typical symptoms no testing is necessary.

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Treatment

• Must start within 48 hours!
• At best decreases the duration of illness by 1-2
  days.
• It is unclear whether treatment decreases the
  severity of symptoms, complications or mortality.

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Treatment

• Agents Amantidine, rimantidine, oseltamivir
  (Tamiflu), zanamivir (Relenza).
• The adamantanes are not currently recommended due
  to high resistance rates, but this may change!
• Most healthy adults with no risk factors for
  complications require no treatment.

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Treatment

• High risk groups
• Pregnancy up to two weeks postpartum
• The young and old (lt5 and gt65)
• Chronic medical conditions (CV/pulmonary disease,
  renal/hepatic disease, diabetes,
  immunosuppressed, 19 yos or younger on aspirin,
  obesity/BMI over 30
• Severe disease/pronounce lower respiratory tact
  symptoms.
• Prophylaxis of close contacts is not generally
  recommended, especially if 48 hours has passed
  since the time of exposure.

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Prevention

• The infectious period starts 24 hour prior to the
  onset of symptoms and at least for 24 hour after
  fever abates.
• Stay home until fever free for 24 hours. For
  health care workers its or 7 days which ever is
  longer!
• Patients on antiviral are considered infectious
  until they have completed at least 4 days of
  therapy.
• Surgical masks are recommended for health care
  workers caring for suspected cases.
• General Advise Wash your hands, dont pick your
  nose, avoid sick people, eat well, sleep well and
  avoid stress.
• Medical offices Triage/vaccination of
  staff/masking/designated waiting areas.

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Vaccination

• Advised for everyone over 6 months of age.
• This years vaccine will include H1N1, a seasonal
  H3N2 and a B component.
• There are two vaccines available an inactivated
  injectable form and a live attenuated intranasal
  form
• Why everyone
• An estimated 85 of the population has and
  indication for vaccination.
• People under 50 do get ill and spread infection.
• We are now able to supply the vaccine.

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Vaccination

• Special populations and considerations
• One dose if 8 and older, 2 dose 4 weeks apart if
  8 and under and did not receive at least one dose
  of the 2009 H2N1 vaccine plus at least one dose
  of seasonal flu vaccine previousely.
• No nasal vaccine for those under 2 or over 50.
  Pregnancy, age lt19 and on aspirin, lung disease,
  diabetes, weakend immune system, kidney failure.
• No vaccine at all if you have a severe egg
  allergy, history of Gillain-Barre within 6 weeks
  of previous vaccination.
• Multidose vial contains Mercury.
• 6-35 months get ½ dose.
• Avoid Fluviron in those 8 and under due to fever
  and febrile seizure risk.
• If 65 and older consider high dose Fluzone (4x
  the antigen).
• Better immune response but ? better protection.

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Vaccination

• NNT in Health Adults (Cochrane review)
• Under ideal conditions (vaccine match) 33
• Under usual conditions 100
• One case of vaccine related Gillian
  Barre/million vaccinated.
• 15/36 studies were industry sponsored.
• Vaccine effectiveness under the age of two is not
  yet established despite the guild lines.
• may not need to change from year to year.
• New DNA vaccine to the inner less variable part
  of the HA protein shows some promise and -The
  are over 200 viruses that cause influenza like
  illness which represent about 90 of the
  circulating virus each year.

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Summary of Last Years Flu Season

• Overall vaccination coverage was 41, 27 for
  H1N1.
• H1N1 was very wide spread peaking in June/July
  and again in October.
• Deaths from April 09 to April 10 were
  approximately 12,470. 9,570 were in the 18-64
  year age group! In an average year up to 40,000
  deaths will be attributed to flu.
• Hospitalizations were approximately 274,000 with
  160,000 from the 18-64 age group.

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Summary of Last Years Flu

• 2009 NEJM 3691935-1944
• Looked at 272 hospitalized patients
• 45 were lt18 50 were 18-65
• In a usual year 60 of the hospitalized
  patients will be gt65.
• New obesity link?
• 45 of hospitalized patients were obese

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1918 Pandemic Prospective

• Mortality was 10-20 primarily young adults
  (cytokine storm-massive hemorrhage)
• WW1 troop movement and close quarters help
  facilitate the spread
• 3-6 of the global population died (50-100
  million)
• 500,000 to 700,000 died in the US (more than in
  the war).
• In Samoa 90 of the population died.
• The virus has been identified as an Avian H1N1
  virus and sequenced from frozen remains in Alaska
  and preserved soldiers.
• Will modern medicine help when this type of stain
  emerges again? Vaccination/antibiotics/better
  equipped hospitals.

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Influenza and Sports

• Asian Youth Games 2009 (BJSM 2010 44528-532).
• 1210 athletes, 810 staff from 43 countries one
  week after WHO declared H1N1 a pandemic.
• All athletes had twice daily temp. recorded
• Any athlete with flu like symptoms was tested and
  if positive placed on medication put in
  isolation. Close contacts were placed on
  medication and quarantined.
• Masks and thermometers were provided to all
  athletes and officials.
• All confirmed cases of H1N1 were admitted to the
  Hospital for isolation after special transport
  was arranged. Close contacts were placed on
  medication and isolated at government quarantine
  facilities for 7 days. Close contact was defined
  as 2m for more than one hour.
• Temperature scanners were place at strategic
  locations in the games village.
• Medical care was made available 24/7 to all
  participants family and staff. With hot zone and
  cold zone triage. All medical staff in the hot
  zone were required to wear gloves/gowns/N95
  masks. Mobile high efficiency air filter systems
  were installed in the hot zone.
• 6 cases, 42 quarantined, no event outbreaks were
  identified.

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• Case Football team arrives and passes through
  thermal scans. After arrival 2 team members who
  did not make the trip due to illness are found to
  have H1N1. First match is the next day. What do
  you do?

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• Emergency panel assembles and determines that all
  are close contacts.
• All 21 team/team personal are screened. 4 are
  positive, the rest are quarantined.

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The Athlete and Influenza

• Athletes may be at higher risk during times of
  high training load and stress.
• Athletes may be at higher risk due to close
  contact with other athletes during training and
  competition.
• Athletes may be at higher risk due to there
  living/travel circumstances
• Athletes may be at higher risk due to sharing of
  water bottles towel and other personal items.
• Good hygiene and infectious control measure
  should be stressed.

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The Athlete and Influenza

• We should do are best to recognizes the typical
  symptoms of flu in our athletes and staff (i.e.,
  abrupt onset of f/c/HA/cough/ST/rhinnorhea) and
  treat if appropriate and minimize exposing
  others. PPV 79-88
• Not all need to be seen in the clinic as
  uncomplicated cases resolve in 3-7 days.
• Cough and malaise can last several weeks so
  training loads may need adjusting.
• We need to be aware of the incubation periods are
  1-4 days. Viral shedding occurs for 24 hour
  prior to symptoms and lasts 5-10 days.

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Return to Play

• Must be individualized based on
• Symptom severity
• Fever/myalgia/severe cough warrant activity
  limitation (neck check)
• Symptom duration/infectious period.
• Sport and current demand
• Must include monitoring for secondary
  infection/pneumonia.

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Influenza Update

• Flu is sporadic in Iowa at the moment but
  increasing.
• Both influenza A and B have been identified.
• All strains so far (including H1N1) are covered
  by the vaccine.

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Mononucleosis in Athletes

• Infectious Mononucleosis (IM) is a common medical
  condition effecting thousands of young athletes
  each year.
• It an important clinical entity for the sports
  medicine team for several reasons
• It can have a profound and somewhat lasting
  effect on athletic performance.
• There are a number of potentially serious
  complications including splenic rupture.
• Therefore, there are often complex and difficult
  decisions for the medical team regarding return
  to play.

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Goals

• Describe the etiology and pathophysiology of IM.
• Describe the clinical presentation of IM.
• Provide guidelines for making the diagnosis of
  IM.
• Discuss the potential complications IM focusing
  on splenic rupture.
• Discuss treatment and RTP.

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Epidemiology

• IM is cause by Epstein Barr Virus (EBV) a herpes
  virus.
• The peak incidence of clinical IM is in
  adolescents and young adults.
• Between 30-70 of freshman remain vulnerable.
• The risk of developing IM is between 1-3 per
  year.
• In childhood it is often subclinical or difficult
  to distinguish from other respiratory illness.
• It is more likely to be symptomatic and severe
  the older you are when you acquire the infection.
• Eventually 90-95 of the adult population will
  show serologic evidence of infection.
• The incidence clinical infection in the US is 30
  times higher in whites compared to blacks.

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Transmission and Pathogenesis

• EBV is transmitted primarily through saliva thus
  its popular description as the kissing disease
• Other possible modes of spread include sexual
  contact, sneezing and the sharing cups and food.
• Host cells include epithelial cells/monocytes/B
  lymphocytes and T lymphocytes.
• The incubation is as long as 30-50 days.
• The virus is shed for weeks to months.
• There is evidence of intermittent shedding in
  oral secretions for decades.
• Despite the bodies immune response to the virus
  it enters a dormant phase.

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Clinical Features

• Sore throat (82), fever (76) and fatigue (76)
  are the most common clinical symptoms
• Clinical Findings/Signs
• Lymphadenopathy Posterior cervical
  chaingtanterior. Auxiliary and inguinal nodes can
  be involved. Node are often large and tender.
• Pharyngitis Exudates are seen in 30-50 or more
  and can be white to gray. Hypertrophy may be
  impressive. Palatal petechiae can be present.
  Group A Strep can be present in up to
  30...colonization?

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Clinical Features

• Fatigue
• May be persistent and severe.
• May have a fair amount of daily variability
• Women seem to have more severe and more prolonged
  fatigue.
• Usually resolves in one month but may last up to
  six.
• Performance may lag for 3 months.
• A small subset of patients will have persistent
  fatigue. The reasons for this are unclear.

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Clinical Features

• Skin
• a rash can be present and can be maculopapular to
  urticarial to petechial.
• Rash development after administration of
  Amoxicillin (up to 95 of the time) is common but
  can occur with other antibiotics (40-60 with
  other beta lactams).
• Petecial rash should alert you to check for
  hematologic complications (aplastic anemia,
  thrombocytopenia, hemolytic anemia, HUS, DIC)
• Petechiae and any GI symptoms seems to predict a
  longer and more severe course.
• Periorbital edema

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Clinical Features

• Abdominal
• Splenomegaly
• Probably occurs in most cases but clinically
  detectable in 15-65 as the sensitivity and
  specificity of the clinical exam is 20-70 and
  69-100 respectively. This may be even worse in
  our athletes many of whom have well developed
  musculature making it even more difficult to
  detect. Be aware there are reported cases of
  rupture from too vigorous an examination! More
  to come.
• Hepatomegaly
• Can occur but is much less common.
  Transaminases can be elevated but are not
  clinically important to follow.
• Neurologic These are rare occurring in only 1-5
  of cases
• Guillain-Barre, Facial Nerve Palsy, encephalitis,
  meningitis, transverse myelitis and other
  neuritis.

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Differential Diagnosis

• HIV-rash, GI symptoms, cough, weight loss etc
• Group A Strep-Seasonal, no posterior chain nodes,
  no splenomegaly, less tonsillar hypertrophy, less
  fatigue more fever.
• Cytomegalovirus-Usually minimal to no sore
  throat, otherwise can look very similar.
• Toxoplasma Gondii-small anterior tender
  andenopathy.
• Human Herpes Simplex 6/7

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Laboratory Testing

• The most common lab finding with IM is
  lymphocytosis defined as gt4500/mcl or gt50.
  Atypical Lymphocyte count of gt10 on a peripheral
  smear.
• The monospot test or the heterophile antibody
  test is a group of IgM antibodies that cross
  react with antigens found on sheep and horse
  blood cells.
• Sensitivity increase through the first few weeks
  of illness with false negatives of 25 in the 1st
  week falling to 5 by week 3.
• Once present the test can stay positive for up to
  1 year.
• In the presents of typical symptoms the test has
  a sensitivity of around 85 and a specificity of
  approximately 94
• Patients with HIV type 1/cancer/lupis can
  generate false positive results.

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Laboratory Continued

• Specific IgM and IgG to viral capsid antigens
  (VCA) can be measure when the diagnosis is in
  doubt. Sensitivity and specificity for IM is 97
  and 94 respectively.
• IgG takes weeks to appear and indicates in most
  cases old infection.
• IgM appears early in the disease usually
  disappears by 3-6 months but can persist in up to
  20.
• IgG to the nuclear antigen (EBNA) can also be
  measured. This can be detected starting around
  6-12 weeks and indicates that the virus is
  entering the latent phase. Therefore, it can be
  used to help exclude an acute infection.
• All of these tests are useful primarily in cases
  when the diagnosis is in question or you suspect
  a false negative monospot.

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Immune Response
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Laboratory

• Many patients with IM will have a mild hepatitis.
  Liver Function tests can be mildly elevated.
• There is no correlation of LFT elevation and
  spleen size.
• There is no evidence to support the use of
  serially monitoring as a guild to clinical
  improvement or return to play.

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Laboratory Summary

• Patients with a clinical picture consistent with
  IM should have a CBC and a herterophile test
• If the heterophile test is positive then no more
  testing is needed.
• If the heterophile test is negative and the
  clinical suspicion is high then a repeat test can
  be performed in a week.
• If the clinical syndrome is prolonged or symptoms
  are atypical then VCA IgM and IgG and EBNA IgG
  can be measured.

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Complications

• Most patients who contract IM have an
  uncomplicated and often subclinical course thus
  require only supportive care.
• Severe complications occur in less than 5 and
  include
• Airway obstruction
• Dehydration
• Splenic rupture
• Aplastic anemia/thrombocytopenia
• Neurologic-GB/Meningitis, encephalitis
• Myocarditis
• Lymphoma
• HUS
• DIC
• Chronic Fatigue Syndrome?

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Treatment

• Antiviral medication
• 5 randomized trials of acyclovir have show
  decrease viral shedding during treatment only.
  No significant effect on clinical symptoms or
  duration of illness has been demonstrated
• One small trial (20 patients) with valacyclovir
  did show a reduction in the number and severity
  of symptoms scores.

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Treatment

• Corticosteroids (Cochrane review 2010)
• 17 studies most with low patient numbers and
  widely varying methodology.
• Return to work/school-2 studies no change
• There may be an early effect of reduced severity
  of ST at 12-24 hours, but this effect is lost 36
  hours.
• In one study using both steroid and acyclovir
  showed diminished symptoms at 2 and 4 days.
  Furthermore, the ST was gone at 7 days in the
  treatment group and 9 days in the placebo group
  but no statistic significance was reported.

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Treatment

• Fatigue-2 studies and no change with steroid use
  was noted.
• Steroid plus valacyclovir showed slight
  improvement but the study was underpowered.
• Fever
• Steroids in three trials found modest reduction
  in the number of days of fever.
• One trial of steroids and acyclovir showed no
  difference.

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Treatment

• None of the studies systematically tracked
  complications that may have resulted from
  corticosteroid treatment
• Corticosteroid use suppresses the hosts immune
  response and predisposes to secondary infections.
• In these studies there was one reported case of
  acute diabetes, one peri-tonsillar cellulites and
  one empyema.
• It is unknown what effect using an
  immunomodulator will have on the risk of EBV
  associated malignancies.

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Treatment

• The conclusion is that there is not enough data
  to recommend corticosteroids or antivirals for
  the treatment of uncomplicated IM.
• It is probably reasonable to use corticosteroids
  in cases in which significant respiratory,
  neurologic or hematologic complications arise.

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Treatment

• Vaccines
• Trails using vaccine developed against the
  glycoprotein subunit of the virus did not appear
  to protect against acquiring infection but were
  less likely to have symptoms.

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EBV Autoimmune Disorders and Cancer

• Association of symptomatic EBV infections and
  various autoimmune processes and cancers have
  been identified including
• Burkitts Lymphoma-virtually all African patients
  with BL have high titers of EBV
• Hodgkins Lymphoma-EBV nucleic acids in 20-40.
• Nasopharyngeal carcinoma
• Multiple Sclerosis

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Airway Obstruction/Complicated Cases

• This is a result of marked tonsillar enlargement,
  autoimmune processes and lymphoid infiltration.
• Can be treated with corticosteroids (i.e.,
  prednisone at 40-80 mg/day) /- antivirals.
• Clinical expert opinion still favors their use of
  corticosteroids in cases of severe tonsillar
  hypertrophy with upper airway obstruction and in
  cases involving hemolytic anemia,
  thrombocytopenia or myocarditis.

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Splenic Rupture

• Splenomegaly is nearly always present with IM,
  but rupture is rare (0.1-0.2).
• It tends to occur in the first three weeks of
  illness and can be traumatic or spontaneous.
  Cases of splenic rupture have been reported out
  to 7 weeks.
• Even in the case of rupture fatalities are rare.

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Splenic Rupture

• The nature of athletics puts this population at
  particularly high risk for this complication.
• Many have advocated that the spleen be normal
  prior to return to contact sports.
• The problem is that radiologic assessment of the
  spleen is difficult due to individual variability
  and lack of normative data for the athletic
  population.

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Splenic Imaging

• The spleen can be imaged with CT or ultrasound.
  CT offers superior detailed imaging but
  significant radiation exposure therefore
  ultrasound has become the image modality of
  choice in determining spleen size.
• In cases of suspected rupture CT would be the
  image modality of choice.

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The Problem with Athletes

• Normative data for spleen size in adults shows
  that the upper limits of normal are 12-14 cm in
  length (linear length correlates highly with CT
  volume).
• Spleen size correlates with height and in tall
  athletes. In one study of tall athletes 30 of
  the men and 13 of the women were shown to have
  lengths greater than 12.
• There is a lot of variability in spleen size.
  Hosey et al. showed spleen size correlated
  reasonable well with body size. The average
  spleen was 10.65 with a range of 5.59-17.06 cm.
  Males and females differed significantly even
  when height and weight were controlled for.
• In a recent study done by Cockle et al. showed a
  mean length of 12.19 in 66 tall athletes.

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What to do with the Spleen?

• The data suggest that due to the variable nature
  of normal spleen size in the athlete population
  using population based normative data to
  determine spenomegaly is suspect at best.
• Therefore, a single measurement of spleen size in
  an athlete with IM is of limited utility.

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Return to Play

• The timing of RTP is complicated by the following
  factors
• The incubation period for IM is 4-7 weeks and the
  symptom onset can be insidious thus making
  pinpointing the onset of illness difficult and
  calling into question the studies looking at the
  timing of splenic rupture relative to symptom
  onset.
• Currently there is not a reliable means
  determining if the spleen is back to its normal
  size in the athletic population in particular.

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Return to Play

• Current best advice
• Prior to RTP all athletes should be afebrile,
  well hydrated, asymptomatic (good energy level)
  and have no palpable spleen.
• A minimum of 3 weeks should have elapsed since
  symptom onset prior to returning to any
  non-contact activities.
• The timing of return to strenuous activity and
  contact is controversial. This would include
  such activities as weight lifting/rowing or any
  activity requiring valsalva. Returning athletes
  to these activities should be handled more
  conservatively.
• The risk of transmission from athlete to athlete
  is low except in close contact sports such as
  wrestling and therefore is not an issue in RTP in
  most situations.
• Little is know regarding whether early return to
  activity impacts the nature time course of the
  illness.
• Imaging of the spleen is of limited utility due
  to lack or normative data and the high degree of
  individual variability in splenic size.

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