Thank you all for the comments! Most of you realized that there was something special about this case given the classic morphologic features of babesiosis (with many tetrads/maltese cross forms), supportive clinical history, and yet repeatedly negative PCR tests for B. microti. (The fact that I chose this as the 250th case probably also let you know that there was something unusual about it!)
As some of you mentioned, the blood film results are diagnostic for babesiosis, regardless of the PCR results, and therefore further work-up is not necessarily required for patient care.
However, we were very curious to know what the causative species of his infection was and felt that the negative PCR had important epidemiologic considerations. Therefore, we sequenced the amplified DNA and also sent the specimen to the CDC for further testing. Results from all studies showed that this patient was infected with the newly described MO-1 strain, reported to date only from Missouri. Unfortunately, this patient died despite initiation of treatment, thus showing that the MO-1 strain is a potentially serious infection in certain hosts.
If the patient had been from the west coast of the U.S., you could also consider B. duncani as a potential causative agent, while travel to Europe could have placed him at risk for B. divergens. Serologic testing shows some cross-reactivity between the different Babesia species so it might have been helpful in confirming that the patient had babesiosis. However, it's important to remember that it takes several weeks to generate a detectable immune response and he might have been seronegative at the time of presentation.
Thank you all for your continued support and feedback for my milestone case.
And now, our poem from Blaine Mathison:
To separate Babesia from malaria
Might send one into a bout of hysteria.
But the cytoplasm's vacuolated.
And no pigment has been generated.
With no travel to a malaria endemic area.