Babesiosis and a dry cough

This 38-year-old female came to see me because an aunt that she is fond of told her she has Lyme disease. She has a variety of symptoms which have been progressively getting worse. She thinks symptoms for started about three years ago but her state of health has been declining precipitously over the last three months. Recent symptoms included migratory joint pain involving a wide range of joint: axial joins including neck and spine; large joints including shoulders hips and knees, medium sized joints including the elbows wrists and ankles and small joints including hands, feet and toes. Her hands become swollen and inflamed at times. Other symptoms include: profound fatigue, lack of endurance, progressive cognitive dysfunction, headache, numbness and tingling and a persistent cough. She has had an unusual persistent dry cough. She has experienced severely disrupted sleep inclusive of episodes of sleep paralysis which have been extraordinarily frightening. She has a history of spending a lot of time outdoors hiking but has no specific history of tick bite, rash or summer flu. 

Her workup showed Lyme seronegativity. From Labcorp not one band out of the 13 measured was present. The C6 peptide level was 0.35. Lyme Western Blots from so Stony Brook showed IgM bands 41, 20 and 93 and IgG bands 41 and 64. Antibody testsing for Babesia duncani was positive with the titer of 1:512. 

The dry cough.

When I saw the patient on the next visit to go over her labs, when pressed, she did admit to having classic air hunger.

I recall one patient who very clearly always knew when Babesia was becoming issue because of a recurring dry cough.

Okay, I think are test do show evidence of exposure to Lyme disease. I think I have come to understand why C6 peptide tests are not elevated more often than we see. The C6 peptide antibody tests is supposed to combine both IgM and IgG responses but primarily only represents IgG responses. I will reiterate here that Lyme disease in the vast majority of cases causes primarily IgM antibody responses irrespective of the stage of illness. The C6 antigen is so highly specific for Borrelia burgdorferi that cross-reactivity is really not an issue. There can be some mild nonspecific reactivity called background noise. Basically, any number greater than 0.1 is suspect for exposure. For example, I am currently seeing a patient whose C6 peptide went from undetectable to 0.15 after course of treatment and I think this could be a surrogate for seroconversion. Based on my research and experience I am pretty comfortable with the notion that C6 peptide levels of .3 or greater are evidence of prior exposure to Borrelia burgdorferi. These (Stony Brook) Western blots would have been graded positive if they had been obtained at IgeneX based on internal criteria. The 93 band is considered highly specific. Moreover, the 20 band and other markers in the low 20s probably represent Outer Surface Protein C variant reactions which are also highly specific. These reactions are not elicited with other Lyme Western blots available commercially.

But back to the cough.

Air hunger, a sensation of not being able to get in enough  oxygen when taking a breath seems to be a reliable indicator of babesiosis. I have never really understood why. I came across a paper published in the journal parasitology in 1999 which may offer an explanation. Hemmer et al reported “ Endothelial cell wall changes, pulmonary edema and respiratory distress in mice infected with the WA1 human Babesia parasite.” In mice experimentally infected with Babesia microti no pulmonary changes were detected. The B. duncani infected mice had severe pulmonary lesions. ( Most of us are not mice but these models may be usefull).

I think Babesia duncani is underappreciated. Please recall, a study in 2011 found nearly a third of patients tested for Lyme disease and co-infections at one laboratory were positive for Babesia duncani or WA1. 

Most of the positive reactions (I use Labcorp) report the lowest titer considered positive, 1:256. Some people have suggested that some of these are false positives or perhaps represents cross-reactivity with some other protozoan. I do not think so. You have to remember that a patient's serum has been diluted eight times to achieve a titer of 1:256. Perhaps unreported titers of 1:128 or even lower may also be evidence of infection. Certainly I have seen patients seroconvert. One patient with dramatic symptoms and a floridly positive blood smear went from a zero titer to a titer of 1024 after some treatment. 

I am now convinced that B. duncani is the predominant co-infection seen in patients with Lyme Borreliosis. I think this has not yet been widely reported because to date this organism has not been widely tested for.  Even now, many physicians habitually test only for B. microti.  It does appear that serological assays from Labcorp or Quest are reasonably accurate. For confirmation a blood smear or FISH test can be added.

I think this diagnosis can more frequently be supported by solid evidence than is widely acknowledged. Babesia microti is relatively rare in comparison to B duncani and other species of Babesia associated human disease such as MO1 and CA1 are probably uncommon.

Although is not the usual presenting symptom, a dry cough along with other pulmonary symptoms can be a marker for human babesiosis. It is worthwhile to note that seroconversion of babesiosis can occur just as it may with Lyme borreliosis.

Once again we must face the reality that serological testing for Lyme disease is abysmal. 

Back to the patient. My clinical diagnosis is supported by diagnostic testing and the patient and I have a clear understanding of where we need to go to make her better.