What is the next step in management for a patient with post-infectious fatigue following infectious mononucleosis, treated chlamydial pharyngeal infection, and HSV-1 infection, who has completed appropriate treatment and has a positive HSV 2 IgG inhibition test, with ongoing symptoms of fatigue and residual throat discomfort?

Management of Post-Infectious Fatigue with Positive HSV-2 Serology

Immediate Action: Counsel on HSV-2 Diagnosis

The patient has newly diagnosed HSV-2 infection based on positive IgG inhibition testing, which requires counseling on transmission prevention, partner notification, and consideration of suppressive antiviral therapy—this takes priority over the post-infectious fatigue management. 1

The HSV-2 IgG inhibition test being positive confirms true HSV-2 infection (not a false positive from cross-reactivity with HSV-1), as the inhibition assay specifically differentiates between HSV-1 and HSV-2 antibodies. 1

HSV-2 Management Protocol

Counseling Requirements

• Inform the patient they have genital herpes (HSV-2) and can transmit the virus to sexual partners even without active lesions or symptoms. 1
• Discuss that most HSV-2 transmission occurs during asymptomatic viral shedding. 1
• Advise consistent condom use to reduce (but not eliminate) transmission risk. 1
• Recommend disclosure to current and future sexual partners. 1

Antiviral Therapy Decision

• Consider daily suppressive therapy with valacyclovir 500 mg once daily or 1000 mg once daily, which reduces viral shedding and decreases transmission risk to uninfected partners. 1
• Alternatively, offer episodic therapy (valacyclovir 500 mg twice daily for 3 days at first sign of outbreak) if the patient prefers treatment only during symptomatic episodes. 1
• The decision between suppressive versus episodic therapy depends on outbreak frequency, transmission concerns to partners, and patient preference. 1

Post-Infectious Fatigue Management

No Additional Antibiotics or Antivirals for Fatigue

Do not prescribe additional antibiotics or repeat the doxycycline course, as post-infectious fatigue following EBV is not caused by persistent bacterial or viral infection and does not respond to antimicrobial therapy. 2

The Infectious Diseases Society of America explicitly recommends against additional antibiotic therapy for patients with persistent nonspecific symptoms such as fatigue following recommended treatment for infectious diseases, when there is no objective evidence of reinfection or treatment failure. 2

Expected Timeline and Reassurance

• Inform the patient that post-infectious fatigue following infectious mononucleosis commonly persists for weeks to months (often 2-3 months, sometimes longer). 3, 4
• Explain that profound fatigue tends to resolve within three months in most patients with infectious mononucleosis. 4
• Clarify that EBV antibody titers remain positive long-term and do not correlate with symptom resolution, so repeat EBV testing is not indicated. 4

Evidence-Based Interventions for Post-Viral Fatigue

• Refer to physical therapy for a graded exercise program emphasizing strengthening (not endurance) to prevent deconditioning while avoiding post-exertional malaise. 5
• Consider referral for group-based cognitive behavioral therapy (CBT) focused on activity pacing, functional planning, and self-management strategies, which showed mean difference of -39.0 [95% CI -51.8 to -26.2] in fatigue severity in post-viral fatigue syndromes. 5
• Implement activity modification with gradual return to baseline function rather than complete rest or aggressive reconditioning. 5

Supportive Care Measures

• Continue vitamin D supplementation if deficient, as this supports immune function during recovery. 4
• Optimize sleep hygiene and consider melatonin if sleep disturbance is contributing to fatigue. 5
• Maintain adequate hydration and balanced nutrition. 4

Throat Discomfort Management

• Continue lidocaine mouthwash as needed for residual canker sores, which are self-limited. 6
• Avoid spicy, acidic, or irritating foods that may exacerbate oral mucosal irritation. 6
• No repeat pharyngeal chlamydia testing is needed now, as testing can remain positive up to 4 weeks post-treatment and the patient completed appropriate doxycycline therapy. 2

Critical Safety Precautions

Splenic Rupture Prevention

• Reinforce strict avoidance of contact sports, heavy lifting, and strenuous exercise for 8 weeks from initial infectious mononucleosis diagnosis or until splenomegaly resolves (whichever is longer). 4
• Provide explicit return precautions for left upper quadrant abdominal pain, nausea, vomiting, lightheadedness, or shoulder pain (referred pain from splenic capsule irritation), as spontaneous splenic rupture occurs in 0.1-0.5% of infectious mononucleosis cases and is potentially life-threatening. 4

Follow-Up Plan

• Schedule follow-up in 2-4 weeks to review HSV-2 counseling, assess antiviral therapy response if initiated, and monitor fatigue trajectory. 1
• Reassess at 3 months if fatigue persists to evaluate for chronic fatigue syndrome, which infectious mononucleosis is a recognized risk factor for developing. 4
• No repeat HSV serology is needed, as IgG antibodies remain positive lifelong. 1

Common Pitfalls to Avoid

• Do not attribute persistent fatigue to "chronic EBV infection" or prescribe prolonged antiviral therapy, as there is no convincing biological evidence for symptomatic chronic EBV infection causing post-infectious fatigue. 2, 7
• Do not repeat EBV serologies or order EBV PCR testing, as these do not guide management and positive results do not indicate active infection requiring treatment. 2
• Do not prescribe immunomodulatory therapy or prolonged antibiotic courses, as these lack evidence and carry risk of serious adverse events. 2
• Do not overlook the HSV-2 diagnosis—this requires specific counseling and management separate from the fatigue concerns. 1
• Do not recommend complete bed rest, as this promotes deconditioning; instead, encourage gradual activity modification. 5