Can sexually transmitted infections (STIs) cause flu-like symptoms?

Can STIs Cause Flu-Like Symptoms?

Yes, several sexually transmitted infections can present with flu-like symptoms, most notably acute HIV infection (acute retroviral syndrome), secondary syphilis, and certain enteric STIs, making it essential to consider STI testing in patients with unexplained fever, malaise, and lymphadenopathy who have sexual exposure risk factors.

Primary STIs That Cause Flu-Like Symptoms

Acute HIV Infection (Acute Retroviral Syndrome)

• Fever, malaise, lymphadenopathy, and skin rash occur in the first few weeks after HIV infection, before antibody test results become positive 1
• These symptoms appear during the window period (typically 1-4 weeks post-exposure) when standard antibody tests may still be negative 1
• The CDC recommends that patients presenting with mononucleosis-like syndrome, unexplained lymphadenopathy, pyrexia of unknown origin, or aseptic meningitis/encephalitis should be routinely offered HIV testing 1
• Nucleic acid testing (HIV RNA or DNA PCR) must be performed immediately when acute retroviral syndrome is suspected, rather than waiting for antibody seroconversion, as standard antibody tests will be negative during this acute phase 1
• At least 95% of patients will have detectable HIV antibody within 6 months of infection 2

Secondary Syphilis

• Secondary syphilis can present as a febrile illness with rash and constitutional symptoms, similar to acute retroviral syndrome 1
• Patients should be evaluated for T. pallidum infection when presenting with systemic symptoms and sexual exposure history 2

Lymphogranuloma Venereum (LGV)

• LGV (caused by specific C. trachomatis serovars) can cause systemic symptoms including fever and malaise in addition to proctitis 1
• This is particularly relevant in men who have sex with men (MSM) who practice receptive anal intercourse 2

Enteric STIs with Systemic Manifestations

Proctocolitis and Enteritis

• Acute proctitis among persons who have recently practiced receptive anal intercourse can be caused by HSV, N. gonorrhoeae, C. trachomatis, and T. pallidum 2
• Enteritis usually results in diarrhea and abdominal cramping, with Giardia lamblia most commonly implicated in otherwise healthy patients 2
• Multiple stool examinations (typically three samples) may be necessary to detect Giardia, and symptoms can include fever, malaise, and constitutional symptoms lasting 2-6 weeks or becoming chronic 3

Clinical Approach and Diagnostic Algorithm

When to Suspect STI-Related Flu-Like Illness

Consider STI testing in patients with flu-like symptoms who have:

• Recent unprotected sexual contact (within 2-6 weeks) 1
• Mononucleosis-like syndrome with negative heterophile antibody test 1
• Unexplained fever with lymphadenopathy 1
• Rash accompanying systemic symptoms 1
• History of receptive anal intercourse with gastrointestinal symptoms 2
• MSM status, particularly with multiple partners 2

Essential Diagnostic Testing

For suspected acute HIV infection:

• Order HIV RNA or DNA PCR immediately—do not wait for antibody testing 1
• Standard HIV antibody tests will be negative during the acute phase 1

For comprehensive STI evaluation:

• Test simultaneously for Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas (optimal for detecting most common treatable STIs) 2
• Obtain syphilis serology using reverse algorithm (treponemal-specific test first, followed by RPR confirmation) 2
• For MSM and those practicing receptive anal intercourse, evaluate extragenital sites (rectal, oropharyngeal) for gonorrhea and chlamydia 2
• Consider stool examination for enteric pathogens if gastrointestinal symptoms present 2, 3

Critical Pitfalls to Avoid

Testing Errors

• Never rely solely on standard HIV antibody tests when acute retroviral syndrome is suspected—they will be negative during the window period 1
• Do not dismiss STI possibility based on symptom similarity to influenza—clinical definitions for influenza-like illness have limited specificity (55%-71%) 2
• Recognize that symptoms alone cannot reliably distinguish between different causes of systemic illness 3

Treatment Considerations

• Initiation of antiretroviral therapy during primary HIV infection can delay onset of HIV-related complications and may influence long-term prognosis 1
• HIV infection may alter the natural histories of many STDs and affect antimicrobial therapy efficacy, requiring close clinical follow-up 2
• Partner notification and treatment is essential to prevent reinfection, as 25%-40% of treatment "failures" are actually reinfections from untreated partners 2

Special Populations

• Immunocompromised patients (including those with undiagnosed HIV) may experience more severe and prolonged symptoms from enteric STIs 3
• Pregnant women with suspected STI-related systemic illness require urgent evaluation due to risks of maternal morbidity, fetal complications, and vertical transmission 2