Acute Infections

Christopher A. McGrew

Acute infections are a common source of morbidity and time loss from sports-related activity for all types of athletes. Within college and professional athletic training rooms, acute infections can be the cause of up to 50% of the visits to the trainer or physician (1). Most of these infections will be evaluated and treated in athletes in a similar way to those patients not involved in sports and athletic activity, but there are a variety of special circumstances that the health care provider who works with these populations should be aware of. Additionally, health care providers involved in the care of athletes need to be cognizant of the effects of acute infection on exercise as well as special considerations for treatment of specific illnesses and return-to-play decisions. (Skin infections such as tinea, herpes gladiatorum and methicillin-resistant Staphylococcus aureus (MRSA) are covered in Chapter 17 on Dermatology)

General Effects of Exercise on the Immune System

The innate immune system includes anatomic and physiologic barriers (e.g., skin, mucous membranes, temperature, pH), specialized cells (natural killer (NK) cells and phagocytes including neutrophils, monocytes, and macrophages) and inflammatory barriers. When the innate immune system fails to effectively combat an invading pathogen, the body mounts an acquired immune response. The acquired immune system includes special cells called B and T lymphocytes that are capable of secreting specialized chemicals such as antibodies and cytokines to regulate the immune response. T lymphocytes can also engage in direct cell-on-cell warfare. Acute episodes of vigorous activity have the following effects on the immune system (lasting 3 to 72 hours): stress hormone induced neutrophilia and lymphopenia, decrease in NK cell cytotoxic activity, decrease in the delayed type hypersensitivity response, increase in plasma cytokines, decrease in nasal and salivary Immunoglobulin A (IgA) concentrations and nasal neutrophil function and blunted major histocompatibility complex (MHC) II expression and antigen presentation in macrophages. Chronic exercise effects have been more difficult to document. Attempts thus far to compare resting immune function in athletes and nonathletes have failed to provide evidence that athletic endeavor is linked to many specific changes in the immune system, although epidemiologic studies have shown decreased upper respiratory infections in some groups of regular exercisers when compared to nonexercisers (“the J-curve theory”). Of all immune measures only NK cell activity has emerged as a somewhat consistent indicator differentiating the immune systems of athletes and nonathletes. NK cell activity has been reported to be higher in athletes when compared to nonathletes in several studies (2,3).

Effects of Acute Infections on Exercise Capacity—General Considerations

Acute infectious disease is often associated with a fever and it is difficult to differentiate some of the effects of fever on exercise from the effects of the acute illness. In general it is recognized that fever impairs muscle strength, aerobic power, endurance, coordination, fluid/temperature regulation and concentration (4,5,6). All of these effects are obviously detrimental to optimal performance. Additionally, acute infections are associated with a variety of immune system responses that are triggered by cytokines and are correlated to fever, malaise and anorexia along with other signs and symptoms (7). Acute viral illnesses can potentially hinder exercise capacity not only by the direct fever effects noted earlier, but also with such influences as muscle protein catabolism, tissue wasting and negative nitrogen balance. These effects result in decreased muscle performance, the full recovery of which may require weeks
to months after a week long febrile illness (8). Although the relation is not completely understood, exercise during or just after an acute viral illness may be a risk factor for rhabdomyolysis (9). Respiratory infections, probably the leading cause of acute illness in athletes, have been shown to have negative effects on respiratory function (10).

Pharmacotherapy Considerations

Most of the acute infections in athletes are viral in nature such as upper respiratory tract infections and gastroenteritis. Athletes often present requesting that everything possible be done to ensure that they train and compete. The temptation to presumptively treat these infections with antibiotics is great but should be resisted. Antibiotic treatment side effects such as diarrhea, rashes, nausea, yeast infection, and allergic reactions can negatively influence training and competition and are hard to justify when the antibiotics are not really treating a viral illness. (On the other hand, there does not appear to be a direct ergolytic effect on either muscle strength or endurance from the use of antibiotics.) The increasing problems of resistant strains of bacteria along with unnecessary costs of treatment are other issues to be considered as well. Photosensitivity is a potential problem with some antibiotics such as doxycycline. Quinolones are contraindicated in young athletes with open growth plates and there are case reports about fluoroquinolones and Achilles tendon problems (11). Additionally, potential performance decreasing effects need to be considered when prescribing to the athlete (e.g., sedating antihistamines would not be a good choice for many athletes). Even some antibiotics have been linked to decreased performances.

The use of agents to treat the symptoms of these acute infections must also be evaluated in the context of drug testing that athletes might be subjected to in various sports. Decongestants, antihistamines, cough suppressants, antidiarrheals, and bronchodilators are all commonly used. The health care professional treating athletes must be aware of various banned drug lists for the different sports and organizations that oversee these sports. Toll free telephone hot lines and internet websites are available for most of these groups such as the United States Olympic Committee and the National Collegiate Athletic Association (NCAA), which give details of the medications that are prohibited (http://www.usantidoping.org/).

Respiratory Tract Illnesses

Colds and Upper Respiratory Tract Infections

The upper respiratory tract is the most common site of infection in humans accounting for more than half of all acute illnesses. Upper respiratory tract infections (URTIs) involved affect the respiratory mucosa from the nose to the lower respiratory tree, not including the alveoli. Over 200 viruses are implicated as the cause of common colds/URTIs of which rhinoviruses, coronaviruses, respiratory syncytial virus, influenza virus and adenoviruses are the leading agents of infection. (Several bacteria are responsible for a small percentage of URTIs.) Viral URTIs occur throughout the year although there are seasonal peaks in the autumn and spring. Transmission occurs by aerosol and droplet spread, direct saliva contact and indirect saliva contact. These modes of transmission raise the obvious need for good hygiene in order to limit outbreaks among athletic teams. Frequent washing of hands by athletes and their coaches and attendants is the most vital step. Other important measures include avoidance of sharing of implements such as water bottles and towels, along with proper hydration and carbohydrate replacement before, during, and after exercise (12).

Symptoms and signs of URTIs are manifold and can include both local and systemic findings. The latter suggest a more serious infection and a greater need for restriction of activities (see “neck check” described later).

Some of the specific concerns for athletes include the following:

Intense exercise during the incubation phase of an infection may result in a more severe illness (13).
Intense exercise while infected with enteroviruses (such a coxsackievirus) may increase the risk for contracting myocarditis that has been reported as a cause of sudden death during exercise (8).
The aforementioned risk of rhabdomyolysis (9) has been reported in athletes performing intense exercise during, or just after the acute phase of a viral illness.

Unfortunately, there are no clinically proven methods of determining in advance which athletes are likely to be susceptible. Fortunately, myocarditis and rhabdomyolysis are rare sequelae.

In general the treatment of URTIs is aimed at symptom relief and support of the athlete’s fluid and energy needs. There are thousands of brand names and generic cold remedies on the market and most them include mixtures of antihistamines and decongestants. Oral and topical decongestants may help relieve upper respiratory symptoms. Topical nasal decongestants work better and faster than oral agents, but, because of rebound congestion or tolerance, the topical products can be used for only 3 to 5 days. If they are used continuously for 1 to 2 weeks or more, rhinitis medicamentosus—chronic nasal stuffiness—can occur as a result of drug dependency. First-generation antihistamines appear to reduce sneezing and nasal discharge but have no effect on nasal stuffiness. Though their benefits are thought to be due to anticholinergic effects rather than to their effect on histamine, anticholinergic side effects such as orthostasis and disruption of thermoregulation can impair athletic performance. There is no evidence that decongestants or antihistamines change the natural history of the illness.

Herbal and “natural” remedies have become increasingly popular but support for them is sparse. Fluids and easily digestible carbohydrate sources should be made readily available to the athlete and saltwater gargles and saline nasal irrigation are useful adjuncts to symptom relief without unwanted side effects. Warm fluids such as soups and teas may have temporary effects on relieving congestion symptoms along with cultural psychological benefits. Aspirin should not be used in athletes under the age of 21 for fever and myalgia relief because of the association with Reye’s Syndrome (13); instead acetaminophen and ibuprofen should be utilized. A few studies have supported the use of zinc gluconate lozenges in the first 24 to 48 hours of the onset of URTI for reduction of the duration and intensity of symptoms (13).

Athletes are responsible for everything that goes into their bodies. Some over the counter (OTC) preps contain banned substances. Athletes also need to be reminded that supplements are not Food and drug Administration (FDA) regulated and may also contain banned substances.

It is unlikely that heavy training during acute febrile illness would be very beneficial. When advising an athlete with acute illness on when to exercise, an intuitive “neck check” approach (14) has been suggested:

If the athlete only has symptoms “above the neck” such as sore throat, nasal congestion, and rhinorhea, then he/she can probably continue to exercise to the level of tolerance if symptoms improve during the first few minutes of the exercise session.

If the athlete has symptoms below the neck, such as chest congestion that causes respiratory compromise, fever (temperature greater than 38°C), chills, or mylagias, then abstinence from all but the mildest exercise is recommended.

It is useful to evaluate the type of activity that is planned when advising the athlete who is acutely ill. Distinctions can be made between sports as well as between training versus competition within a single sport. For example golf and diving obviously have different demands than soccer and basketball and the effects of an acute infection might be better tolerated in the former two examples as opposed to the latter. Training for football (e.g., a 2 to 3-hour continuous practice) is much more demanding metabolically than the 10 to 15 minutes of actual playing time for a given player with all of the “down time” that is involved in the football contest. In contrast, soccer with its continuous activity would present a much more continuous demand on the athlete that is similar to his/her practice. Another issue to consider is that an athlete may tolerate skills training in a particular area of their sport (e.g., batting practice or free throw shooting), but wouldn’t be able to tolerate intense conditioning drills for their sport. These are just a few examples of the variability for each athlete that should be considered when evaluating what activities are appropriate to partake in when an acute infection is present.

Influenza A and B deserve special consideration, due to their potential severity and potential for specific prevention. Pulmonary function is frequently abnormal for weeks and constitutional symptoms can be quite severe. This may have a tremendous impact on athletes and an outbreak in a team can be devastating. It seems to be of pragmatic value to recommend vaccination of athletes, especially those whose seasons are primarily during the winter months.

(Classic Influenza Vaccination Recommendations for inactivated influenza vaccination have targeted specific groups for annual immunization, including persons older than 6 months who are at high risk for complications from influenza because of age or presence of certain medical conditions, persons who are in close contact with those at high risk, persons aged 50 to 64 years, and close contacts of infants aged 0 to 6 months (1). Vaccination is also encouraged, when feasible, for children aged 6 to 23 months and their close contacts and caregivers. In addition, physicians should administer the flu vaccine to any person who wishes to reduce the likelihood of becoming ill with influenza. http://www.cdc.gov/mmwr.)

Influenza A and B have been shown to respond to oseltamivir orally and zanmivir by inhalation. These therapies are only effective if started within 24 to 36 hours of the onset of symptoms. Outbreaks in nonvaccinated teams may be curtailed with daily prophylaxis with one of these agents for 2 weeks after administration of vaccine (14).

The diagnosis of a URTI is usually straightforward; however, in some cases there may be some confusing issues. Chronic, recurrent and seasonal occurrence may indicate the possible contribution of allergic and/or vasomotor rhinitis that can mimic a URTI, especially if there is a strong cough component. These entities can often be very effectively treated with a well-planned treatment of nasal saline irrigation, oral antihistamines and/or nasally applied corticosteroids or cromolyn sodium. URTIs are often associated with concurrent wheezing and subclinical bronchospasm during the time of acute illness and frequently there are postinfection problems with training such as unaccustomed dyspnea and/or exercise related coughing. The measurement of expiratory peak flow rates may be helpful in evaluation of such patients and a trial of albuterol for pre-exercise inhalation may be useful in alleviating symptoms. Another problem is the overuse of antibiotics for URTIs that are overwhelmingly caused by viral agents. Antibiotics should be reserved for use in the very small percentage of patients with a URTI who develop purulent sinusitis, or whose URTI symptoms are due to Group A beta-hemolytic streptococcal pharyngitis, or whose severe, prolonged (>10 days) course might indicate infection with an antibiotic susceptible entity such as Mycoplasma pneumoniae, Chlamydia pneumoniae or Bordetella pertussis (14).

Pharyngitis

Most cases of pharyngitis are viral in nature, and require only symptomatic treatment such as warm saline gargles, antipyretics, analgesics, fluids, and appropriate rest. In athletes with large hydration and caloric demands, aggressive treatment of pain of the sore throat is very important so that
the athlete will not forego appropriate intake of food and liquids. As mentioned previously, the use of zinc gluconate lozenges may be useful for reducing the duration and severity of symptoms if started early after their onset (13). Sore throat associated with fever, swollen tonsils, exudates and tender anterior cervical adenopathy with the absence of coryza, cough, sinus congestion and other peripheral symptoms is suggestive of Group A beta-hemolytic streptococcus (GABHS) and/or infectious mononucleosis (IM); these entities call for more specific attention in diagnosis and treatment.

Group A Beta-hemolytic Streptococcus

Rapid strep tests are available for the diagnosis of GABHS, but throat culture is still the gold standard for diagnosis. Treatment for GABHS is primarily for prevention of rheumatic heart disease and can be started up to 10 days after the onset of illness. There is limited evidence that early treatment within 24 hours of onset of symptoms is effective in reducing the duration and severity of symptoms of streptococcal pharyngitis by a short period (less than a day) (15). Some athletes who have experienced GABHS previously may express a sentiment that they “get better quicker” with treatment and this will often prompt them to request antibiotic treatment at the first sign of any sore throat, so careful evaluation and education of these patients is necessary to avoid overtreatment. Penicillin is the first choice for treatment, but many options are available for the penicillin allergic such as erythromycin, clarithromycin, azithromycin and clindamycin. Return-to-activity criteria are the same as for any acute febrile illness.

Infectious Mononucleosis

IM is an acute, generally self-limiting, viral lymphoproliferative disease caused by the Epstein-Barr Virus (EBV). EBV is secreted in saliva and has an incubation period of 30 to 50 days so there is ample opportunity for the disease to be spread unknowingly. The attack rate is highest from ages 15 to 25 with 25% to 50% of those infected developing the classic syndrome which includes a 3 to 5 day prodrome with headache, fatigue, loss of appetite, malaise and myalgias, followed by the classic signs and symptoms over days 5 to 15 of sore throat with tonsillar enlargement, moderate fever, tender anterior and posterior cervical lymph nodes, petechiae of the palate, and swollen eyelids. A palpable enlarged spleen is present in 50% to 75% of cases; jaundice can occur in 10% to 15%. Serologic diagnosis (IgM) can be made with a rapid slide test based on heterophil antibody absorption (Monospot), but it may be negative in the first week to 10 days after onset of symptoms, so it should be repeated weekly if initially negative. Up to 10% to 15% of patients with clinical IM will repeatedly test negative for heterophil antibody (16). Other techniques such as immunoflourescence or enzyme linked immunosorbent assay may be necessary to make the diagnosis. Aggressiveness in “nailing down” the diagnosis is justified in some cases because of the return-to-play implications for the athlete (17).

Other laboratory tests are useful in IM. A complete blood count (CBC) may show moderately elevated concentration of WBCs with a marked lymphocytosis (>50%) and atypical lymphocytes (10% to 20% of white blood corpuscles (WBCs)). Liver function tests will show increased results in most cases reflecting mild hepatitis. GABHS is concurrent in 5% to 30% of cases and appropriate testing should be done. (Although the GABHS may not always be pathogenic, it seems prudent to treat with appropriate antibiotics—not ampicillin—when GABHS is cultured.)

Although IM affects most organ systems, complications occur in less than 5% of cases (17). Complications associated with IM can include splenic rupture, airway obstruction, peritonsillar abscess, autoimmune hemolytic anemia, thrombocytopenia, aplastic anemia, Guillan-Barre syndrome, encephalitis, aseptic meningitis, transverse myelitis, optic neuritis, severe hepatitis, hepatic necrosis, myocarditis, pericarditis, pneumonia, orchitis, and glomerulonephritis. There is no evidence to suggest that, with the possible exception of splenic rupture, significant complications are either triggered by exercise or more common in those who exercise as tolerated during and after the acute phase of the disease (18).

The spectrum of patient responses to IM ranges widely: many patients have significant acute symptoms along with significant weakness and extreme fatigue; on the other hand, some patients will only have mild symptoms that do not prompt a visit to a health care provider. After resolution of the acute clinical symptoms, fatigue and malaise may persist for longer periods—usually not longer than 6 weeks. Up to 10% of patients experience the fatigue and malaise for much longer. Some elite athletes may take up to 3 to 6 months to regain full performance capacity (18).

The treatment for IM is primarily symptomatic and supportive. This will include relative rest, acetaminophen or non-aspirin nonsteroid anti-inflammatory drugs (NSAIDs) for fever, aches, and throat pain. (NSAIDs should be avoided when there is thrombocytopenia or hemolysis.) Sore throat may also be aided by lozenges, salt water gargles, and in some cases viscous lidocaine. Codeine may be useful in those with refractory pain, but may cause constipation. Stool softeners can be used to avoid straining during bowel movements. Fluids and adequate nutrition that is palatable is important for minimizing weight loss and/or muscle wasting. Corticosteroids are only indicated for complications such as impending upper-airway obstruction (19,20).

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