Can a Blood Smear Diagnose Lyme Disease?
Can a blood smear detect Lyme disease?
Why microscopy may find some tick-borne infections but miss others
The limitations of testing for Borrelia miyamotoi
Can a blood smear diagnose Lyme disease? Although spirochetes may occasionally be observed under specialized circumstances, a routine peripheral blood smear is not considered a reliable method for diagnosing Lyme disease caused by Borrelia burgdorferi.
Blood smears can be useful for detecting certain other tick-borne infections, including babesiosis and, less consistently, anaplasmosis and ehrlichiosis. However, the ability to see an organism under a microscope depends on when the blood is collected, how many organisms are circulating, the preparation used, and the experience of the person examining the smear.
The limitations of blood-smear testing are particularly important in Borrelia miyamotoi disease, or BMD. As Telford and colleagues demonstrated, a blood smear may fail to detect B. miyamotoi even in patients with PCR-confirmed infection.1
What is a peripheral blood smear?
A peripheral blood smear is prepared by placing a small amount of blood on a glass slide, staining it, and examining it under a microscope. Thin smears allow clinicians to evaluate the appearance of individual blood cells, while thick smears concentrate a larger volume of blood and may make certain organisms easier to detect.
The usefulness of a blood smear varies considerably among tick-borne diseases. Some organisms infect red or white blood cells and may therefore be visible during the acute phase. Other organisms circulate at concentrations that are too low or too transient to be reliably detected by routine microscopy.
Can Lyme disease be seen on a blood smear?
Routine blood smears are not considered a dependable diagnostic test for Lyme disease. The Lyme disease spirochete, Borrelia burgdorferi, is generally not present in peripheral blood in sufficient numbers for reliable identification by standard microscopy.
This differs from tests that look for the immune response to infection or use molecular methods to look for microbial DNA. However, every testing method has limitations, and laboratory results must be interpreted in the context of the patient’s history, symptoms, physical findings, and timing of testing. These broader limitations are discussed in Lyme disease test accuracy.
A reported spirochete-like structure on a blood smear does not, by itself, establish that the organism is Borrelia burgdorferi. Cellular debris, fibrin strands, other microorganisms, and imaging artifacts may resemble spirochetes and contribute to false-positive interpretations.
Dark-field microscopy is also not recommended as a routine diagnostic test for Lyme disease because of poor sensitivity and the potential for false-positive findings.2
What did the Borrelia miyamotoi blood-smear study find?
Telford and colleagues investigated whether standard blood smears could detect Borrelia miyamotoi in patients with acute BMD.1
The researchers examined blood samples from 20 patients who had tested positive for B. miyamotoi by polymerase chain reaction, or PCR. They looked for evidence of infection using standard malariological thick smears prepared from anticoagulated blood samples.
After examining 100 thick-smear fields from each of the 20 patient samples, the investigators did not find evidence of B. miyamotoi in any of the patients.
Evidence of BMD was found in only 2 of the 20 patient samples after the examination was expanded to 300 thick-smear fields.
[bctt tweet=”Blood smears have poor sensitivity for confirming Borrelia miyamotoi disease.” username=”DrDanielCameron”]
The authors concluded that microscopy of blood smears was not sensitive enough to confirm a diagnosis of BMD.1
Why can a blood smear miss Borrelia miyamotoi?
Borrelia miyamotoi is a relapsing-fever spirochete that may circulate in the bloodstream during an acute febrile episode. This might suggest that the organism would be easy to identify microscopically. However, the number of circulating organisms can vary substantially during the illness.
Detection may depend on whether the sample was collected during a period of spirochetemia, how much blood was examined, the type of smear used, and the microscopist’s experience. Even when organisms are circulating, they may not be present in enough of the examined fields to be found during a routine review.
Testing performed outside the optimal diagnostic window may therefore be negative even when the patient has been infected.
Why blood smears work better for some tick-borne infections
Blood smears can play an important role in diagnosing some tick-borne coinfections, but a negative smear does not reliably exclude them.
Babesiosis
Babesia parasites infect red blood cells and may be visible on thin or thick peripheral blood smears. Microscopy can provide important evidence of active babesiosis and can also be used to estimate the percentage of infected red blood cells in patients with significant parasitemia.6
However, Babesia parasitemia can fluctuate or fall below the detection limit of routine microscopy. Microscopic findings may sometimes become difficult to find within a relatively brief period, including in patients who have not yet received treatment.
In my clinical experience, Babesia organisms that were initially visible may no longer be found on a smear a week or two later, even though the patient remains ill. This observation should not be interpreted as a fixed timeline for every patient, but it illustrates why a later negative smear does not exclude an earlier infection or necessarily explain the patient’s continuing symptoms.
When clinical suspicion remains high despite a negative smear, examination of additional manually reviewed smears or molecular testing may be appropriate, depending on the timing and severity of illness. Antibody testing may document exposure but does not necessarily establish whether parasites are currently circulating. Additional information is available in the Babesia and Lyme disease guide.
Anaplasmosis
During acute anaplasmosis, clusters of organisms called morulae may occasionally be seen within granulocytes, particularly neutrophils. These findings are most likely to be found during the first week of illness.4
However, blood-smear examination is not sufficiently sensitive to rule out anaplasmosis. Microscopic findings may disappear as the acute phase evolves, after antibiotic exposure, or as the number of infected cells declines.
The absence of visible morulae does not determine whether the patient has recovered clinically. Symptoms or laboratory abnormalities may continue even when morulae are no longer seen, so the smear must be interpreted with the timing of illness, treatment history, PCR findings, and overall clinical presentation.
PCR performed on whole blood is generally more useful during the early phase of illness, although no diagnostic test is perfect.4
Ehrlichiosis
In ehrlichiosis, morulae may occasionally be seen within white blood cells. With Ehrlichia chaffeensis, they are most often described in monocytes.5
As with anaplasmosis, blood-smear microscopy has limited sensitivity. The absence of visible morulae does not exclude ehrlichiosis.
Symptoms or laboratory abnormalities may continue even when morulae are no longer visible. The smear should therefore be interpreted alongside the timing of illness, treatment history, PCR results, serologic findings, and the overall clinical presentation.
PCR is generally most useful early in the illness. Serologic testing may initially be negative and may require comparison of acute and convalescent samples.5
Why a negative blood smear does not rule out infection
The finding of an organism on a blood smear can provide valuable diagnostic evidence. The reverse, however, is not necessarily true: failure to find an organism does not prove that the patient was not infected.
A blood smear examines only a small portion of the patient’s circulating blood. Detection depends on the density and distribution of organisms at the time the sample is collected. Organisms may circulate intermittently or decline below the detection threshold even while symptoms or laboratory abnormalities continue.
This distinction is important in babesiosis, anaplasmosis, and ehrlichiosis. Microscopic findings may no longer be detectable even though patients remain ill. A negative smear should therefore be interpreted alongside the timing of illness, prior treatment, symptoms, routine laboratory abnormalities, PCR results, antibody testing, and the overall clinical presentation.
The disappearance of organisms or morulae from a smear should not automatically be equated with clinical recovery.
How is Borrelia miyamotoi disease diagnosed?
Current diagnostic approaches for Borrelia miyamotoi disease include PCR and antibody-based testing.3 PCR is most likely to detect the organism when spirochetes are circulating in the blood, particularly during an acute febrile episode and before antibiotic treatment.
Serologic testing may be more useful later in the illness, after the immune system has had time to produce detectable antibodies. Early antibody tests may be negative, and some available assays may react with other relapsing-fever Borrelia species.
A positive Lyme disease antibody test does not necessarily confirm Borrelia miyamotoi disease. B. miyamotoi is a relapsing-fever Borrelia rather than a member of the B. burgdorferi group responsible for Lyme disease, although cross-reactive results can occur.
Editor’s note: The clinical sensitivity of available PCR and antibody tests for BMD remains an important limitation. A negative result may not exclude infection, particularly when testing is performed outside the optimal diagnostic window.
Frequently Asked Questions
Can Lyme disease be diagnosed with a blood smear?
No. A routine peripheral blood smear is not considered a reliable method for diagnosing Lyme disease caused by Borrelia burgdorferi. The organisms are generally not present in peripheral blood in sufficient numbers for dependable detection.
Can Borrelia spirochetes be seen in peripheral blood?
Relapsing-fever Borrelia may sometimes be visible when large numbers of spirochetes are circulating. However, routine microscopy has poor sensitivity for Borrelia miyamotoi, and a spirochete-like structure cannot be assumed to be Borrelia burgdorferi without confirmatory testing.
Can a blood smear detect Borrelia miyamotoi disease?
A blood smear may occasionally detect Borrelia miyamotoi, but sensitivity is poor. In the Telford study, the organism was found in only 2 of 20 PCR-positive patients after 300 thick-smear fields were examined.
Can babesiosis be diagnosed with a blood smear?
Yes. Babesia parasites infect red blood cells and may be identified on thin or thick blood smears. However, parasitemia can be low or fluctuate, so a negative smear does not exclude babesiosis.
Can anaplasmosis or ehrlichiosis be seen on a blood smear?
Sometimes. Morulae may be seen in white blood cells during the early phase of anaplasmosis or ehrlichiosis. Because sensitivity is limited and the findings may disappear quickly, blood smears should not be used alone to exclude either infection.
Does a negative blood smear mean the infection has cleared?
No. Organisms may fall below the detection limit while the patient remains symptomatic. A negative smear should not automatically be interpreted as microbiologic eradication or clinical recovery.
Clinical Takeaway
Blood-smear findings must be interpreted differently for each tick-borne infection. Routine peripheral blood smears are not reliable for diagnosing Lyme disease and have poor sensitivity for confirming Borrelia miyamotoi disease.
Smears can provide important diagnostic evidence in babesiosis and may occasionally reveal morulae in anaplasmosis or ehrlichiosis. However, the period during which these organisms are microscopically visible may be brief, and findings may no longer be detectable even though a patient remains ill.
A positive smear can be meaningful, but a negative smear should not be used by itself to exclude a tick-borne infection, establish microbiologic eradication, or determine why symptoms continue.
Related Articles
Learn more about Borrelia miyamotoi disease and the diagnostic challenges surrounding tick-borne infections:
Borrelia miyamotoi detected in Canada
Doctors face challenges in diagnosing Borrelia miyamotoi
Persistent Lyme disease overview
References
- Telford SR III, Goethert HK, Molloy PJ, Berardi V. Blood smears have poor sensitivity for confirming Borrelia miyamotoi disease. J Clin Microbiol. 2019;57(3):e01468-18.
- Önal U, Saraç-Pektaş F, Sağlık İ. Is there a role for dark field microscopy in the diagnosis of Lyme disease? A narrative review. Infect Dis Clin Microbiol. 2023;5(4):281–286.
- Centers for Disease Control and Prevention. Clinical guidance for hard tick relapsing fever. Centers for Disease Control and Prevention. 2024.
- Centers for Disease Control and Prevention. Clinical testing and diagnosis for anaplasmosis. Centers for Disease Control and Prevention. 2024.
- Centers for Disease Control and Prevention. Clinical testing and diagnosis for ehrlichiosis. Centers for Disease Control and Prevention. 2024.
- Centers for Disease Control and Prevention. Babesiosis: laboratory diagnosis. DPDx. Centers for Disease Control and Prevention.
Dr. Daniel Cameron, MD, MPH
Lyme disease clinician with over 30 years of experience and past president of ILADS.
Symptoms • Testing • Coinfections • Recovery • Pediatric • Prevention
Did they wait for how many hours, rechecking the findings hourly?
Those kind of spirochaetes bore themselves easily into the red blood cells as well as white blood cells. They dive to other tissues as well, particularly to bloodless ones. Like intervertebral discs, other joints, ligaments and tendons. It may take anything from 2-12 hours to see these bacteria coming out of those cells. That is when they can be seen moving in the plasma.
I summarized the frustration by the authors when testing for Borrelia miyamotoi. Hopefully your suggestion or others will lead to better tests.
Has anyone had testing for Lyme disease through urine . Ceres Urine Antigen?
My husband has been blood tested for Lyme, nope doesn’t have it. What he does have is severe abdominal pain that radiates and spends his life with the need to have a bowel movement. He is now on 2 Morphine’s , that do nothing really for the intense undiagnosed pain! He had to retire 3 years ago because he’s so ill. My son found this blog and the urine testing.
After spending all day in ER and once again checking with CT scans and bloodwork, pancreas, liver, gallbladder etc , all perfect, we need to find his problem. I think it’s Lyme disease. He’s was an avid bow hunter, always in the woods or outdoors, a tick magnet too. Walk out the door and BAM! He didn’t have to be in the woods or grass , just outside. Had the series of 3 vaccines to prevent Lyme disease when it came out in the 90’s. We live in VA, now deemed high in tick and Lyme’s.
Any help as to where to start?
I have not used the urine tests. I can not evaluate their reliability.
To Joyce Mahon – Both my husband and myself became ill with what was first diagnosed as Lymes disease. However my husband deteriorated rapidly until he put in the hospital with “diagnosis unknown”. He also most died before an excellent Infectious disease MD did blood slides and other test and discovered he had both Babesiosis & Ehrlichiosis and he was finally treated effectively, literally saving his life. Several years later I became very sick with high fevers and joint pain all over my body. I was taken to the hospital and admitted as a “toxic” patient as they could not diagnosis what I had. It was definitely not Lymes disease. Again it was finally diagnosed by an infectious disease MD as Borrelia Miyamotoi and treated appropriately and recovered. Again I am sick and the ER only checks for Lymes and tells me there is nothing wrong. So I now have an appointment with a top infectious disease specialist this week hoping it will be diagnosed properly. Please know that most ERs and physicians do not not test for these diseases and you must find a specialist who will. I urge you to do so as these diseases can leave lasting damage and potentially can be fatal.
I live on a dirt road surrounded by woods in NJ with lots of deer and other wildlife and there is little I can do about the ticks even though I use tick spray on myself and have my property sprayed several times each year. Good luck and best wishes. .
Where were you able to get blood slides. I am sure I have tick borne disease and I am near death.