When Initial Testing Misses Lyme Disease

I will be discussing a 75-year-old Chinese man with a negative Lyme disease test. How often have doctors dismissed Lyme disease if the screening tests are negative?

Lamichhane and colleagues first discussed this case in the journal Case Reports in Infectious Diseases in 2018.

A 75-year-old Chinese man was evaluated in an emergency room for an unsteady gait. He had a history of hypertension, hyperlipidemia, coronary artery disease, diabetes mellitus, benign prostatic hyperplasia, and osteoarthritis.

His examination was normal. His blood tests showed mild anemia and a low platelet count. He was sent home.

Clinical Deterioration Despite Normal Examination

He was hospitalized four days later with a maximum fever of 105 degrees Fahrenheit and an unsteady gait. He found it difficult to maintain his balance. He suffered from rigors, chills, diaphoresis, diffuse myalgias, generalized weakness, malaise, confusion, and decreased appetite.

The most significant findings were continued mild anemia, a decrease in his white blood cells, and a marked reduction in his platelet count.

A Negative Lyme Disease Test

The doctors considered Lyme disease. He initially had a negative Lyme disease test. The doctors apparently did not request a Western blot test after the initial negative Lyme disease test.

The doctors suspected a bacterial infection. They prescribed ceftriaxone, ampicillin, and vancomycin.

By the next day, the man’s condition worsened. His heart rate climbed to over 200. His blood pressure dropped. He developed encephalopathy—brain disease, damage, or malfunction with symptoms ranging from memory loss or subtle personality changes to acute confusion and dementia.

This clinical deterioration prompted reconsideration of the diagnosis.

Expanded Testing Reveals the Diagnosis

His doctors then ordered more than the screening Lyme disease test. His blood tests were now positive for Lyme disease and Babesia. He was positive for Lyme disease by Lyme IgG and IgM ELISA test and Lyme IgM Western blot. He was also positive by Babesia microti IgG and IgM antibody tests.

The timing of these results raises important questions. Did the initial negative test reflect early seronegativity—testing before antibodies developed? Or did the initial test simply miss infection that was already present?

Either way, the patient’s deterioration while empirically treated with broad-spectrum antibiotics suggests that Lyme-specific therapy was needed.

Spinal Tap Confirms Neurologic Involvement

His doctors arranged for a spinal tap despite the absence of evidence of meningitis. His spinal tap was positive for Lyme disease by IgM and IgG Western blot bands. Three of 3 of his IgM Western blot bands were positive. Nine of 10 IgG Western blot bands were positive for Lyme disease. Doctors only need 2 of 3 IgM and 5 of 10 IgG Western blots to be positive according to CDC criteria.

Spinal taps have not been all that helpful in some studies. Less than one in ten patients with chronic neurologic Lyme disease had an abnormal spinal tap in a 1990 study by Logigian and colleagues.

The man was diagnosed with Lyme neuroborreliosis. He was prescribed doxycycline for 21 days.

He was not treated for Babesia. He would have benefited from treatment with medications like the combination of atovaquone and azithromycin.

Within 48 hours, his cognitive function and gait returned to normal, according to the authors.

Why This Case Was Challenging

The authors summarized the difficulties making a diagnosis of Lyme neuroborreliosis. The authors write, “Here we have presented a patient who had no characteristic clinical signs of LD, whose main symptoms were a high fever, encephalopathy, diffuse myalgia, and tachycardia.” A broad range of other tests were normal.

“The single diagnostic modality yielding concrete results was the patient’s CSF Lyme serology.”

This highlights a troubling reality: the diagnosis depended entirely on spinal tap serology—performed only after the patient deteriorated despite initial negative screening tests and empiric antibiotic therapy.

Had clinicians accepted the initial negative test as definitive, this diagnosis would never have been made.

Unanswered Questions About Babesia Co-infection

The patient tested positive for Babesia but received no treatment for this co-infection. This raises important clinical concerns.

He was over 50, placing him at higher risk of complications from Babesia. Untreated Babesia can cause persistent symptoms—fatigue, sweats, cognitive dysfunction—that significantly impair function.

It would have been helpful to have follow-up data assessing whether untreated Babesia contributed to ongoing symptoms after the acute illness resolved.

Frequently Asked Questions

Can Lyme disease cause encephalopathy?
Yes. Lyme neuroborreliosis can produce encephalopathy with confusion, memory impairment, and cognitive dysfunction. This case demonstrates severe encephalopathy requiring hospitalization.

Why was the initial Lyme test negative?
Early in infection, antibodies may not have developed yet. Alternatively, the screening test may have missed infection that was present. Follow-up testing confirmed both Lyme disease and Babesia co-infection.

Should doctors treat Lyme disease despite negative screening tests?
Yes, when clinical suspicion is high. This patient deteriorated until expanded testing was performed. Earlier empiric treatment might have prevented severe illness.

Was it appropriate to skip Babesia treatment?
No. The patient tested positive for Babesia and was over 50—a higher-risk group. Untreated Babesia can cause persistent symptoms and complications.

What is the long-term outcome for this patient?
Unknown. The case report documents rapid improvement with doxycycline but provides no long-term follow-up data. Untreated Babesia may have contributed to ongoing symptoms.

Clinical Takeaway

This case illustrates how initial negative Lyme disease tests can delay diagnosis and worsen outcomes. A 75-year-old man with fever, encephalopathy, and unsteady gait initially tested negative for Lyme disease. Clinicians did not pursue Western blot confirmation after the negative screening test. The patient deteriorated despite broad-spectrum antibiotics. Only when expanded testing was ordered—revealing both Lyme disease and Babesia co-infection—could appropriate treatment begin. Several critical lessons emerge. First, negative screening tests do not exclude Lyme disease, particularly in acutely ill patients. Second, clinical deterioration despite empiric antibiotic therapy should prompt reconsideration of tick-borne illness, not reassurance based on initial negative serology. Third, co-infections complicate both diagnosis and treatment—this patient’s positive Babesia serology went untreated despite his age placing him at higher risk for complications. How often have doctors dismissed Lyme disease when screening tests are negative? We don’t know the true number, but cases like this suggest the answer is: far too often. The patient’s rapid improvement with doxycycline confirms what clinical suspicion already suggested—tick-borne illness was present all along, despite initially negative testing.