Comparison of the Babesia duncani (WA1) IgG Detection Rates among Clinical Sera Submitted to a Reference Laboratory for WA1 IgG Testing and Blood Donor Specimens from Diverse Geographic Areas of the United States
Harry E. Prince,* Mary Lapé-Nixon, Hemlata Patel, and Cindy Yeh
Focus Diagnostics, Inc., Cypress, California 90630 *Corresponding author. Mailing address: Focus Diagnostics, 5785 Corporate Avenue, Cypress, CA 90630. Phone: (714) 822-2457. Fax: (714) 822-3839. E-mail: [email protected] Received June 24, 2010; Revised August 4, 2010; Accepted September 13, 2010.
ABSTRACT All reported cases of WA1 babesiosis have occurred in the Pacific coast region of the United States, suggesting that WA1 is limited to this geographic area.
However, we detected WA1 IgG in 27% of clinical sera sent to our laboratory for WA1 IgG testing from across the United States over a 2-year period, suggesting that exposure to WA1 or a closely related organism occurs outside Pacific coast states.
We sought to determine if this high WA1 IgG detection rate among clinical specimens merely reflects WA1 seroprevalence outside the Pacific region. WA1 IgG, as well as Babesia microti IgG, was measured in 900 blood donor specimens from 9 states.
Overall seroprevalence was 2.0% for WA1 and 0.4% for B. microti; regional seroprevalences ranged from 0 to 4% and 0 to 2%, respectively. Additional studies were performed to determine if WA1 IgG reactivity was attributable to polyclonal B-cell activation associated with acute Epstein-Barr virus (EBV) infection; 40 WA1 IgG-positive clinical sera and the 18 WA1 IgG-positive blood donor specimens were all negative for EBV capsid antigen (EBVCA) IgM (a marker of acute EBV infection), and 40 EBVCA IgM-positive sera were all negative for WA1 IgG.
These findings indicate that the high WA1 IgG detection rate among clinical specimens does not simply reflect the national WA1 seroprevalence among blood donors or nonspecific reactivity due to acute EBV infection. Rather, the findings suggest that infection with WA1 or a related organism is more common than indicated by the literature and is not limited to Pacific coast states.
DISCUSSION Our finding of increased WA1 IgG titers in 27% of clinical specimens submitted from diverse geographic areas suggests that infection with WA1, or a closely related organism, occurs throughout the United States.
It is possible that this high rate of WA1 IgG detection among clinical specimens merely reflects the prevalence of WA1 IgG in the general U.S. population; although small studies have assessed WA1 seroprevalence in Pacific coast states (3, 10, 12), similar studies have not been performed in other geographic areas. As a first step in testing this hypothesis, we measured WA1 IgG in serum or plasma specimens from blood donors residing in 9 states located in different geographic areas of the United States.
The results provide no support for the stated hypothesis; WA1 IgG was detected in only 2% of blood donor specimens, with similar detection rates (0 to 4%) in all geographic regions.
The WA1 seroprevalence rates we found among blood donors are consistent with the rates of 1 to 5% reported for Washington and northern California residents by 3 different groups of investigators (4, 13, 15).
In contrast, a fourth group (2) reported much higher WA1 IgG detection rates of 18% and 20% in two different donor groups. Similar to our approach, all investigators defined WA1 IgG detection as a serum titer of either ≥1:256 or ≥1:320.
It remains unclear what factors contributed to the higher seroprevalence values in one of the four published studies.
As a point of comparison, we evaluated the monthly B. microti IgG detection rate among patient sera submitted for this test and also measured B. microti IgG in the panel of 900 blood donor specimens. As expected, B. microti IgG detection among patient specimens showed a seasonal peak during the Northern Hemisphere summer months (14) in both years covered by the evaluation.
Among the 900-member blood donor panel, only 0.4% of specimens were positive for B. microti IgG, consistent with published reports of B. microti seroprevalence rates of ≤1% (5, 6, 10, 11). There are a number of limitations to our study. First, we cannot assume that the geographic location of the laboratory submitting a given WA1 IgG-positive clinical specimen is the same geographic region where the patient resides.
At least 2 laboratories in the Western region, 2 laboratories in the South, and one laboratory in the Northeast are large reference laboratories with a national client base. However, the possibility that all the WA1 IgG-positive clinical specimens we identified reflect tick exposure or transfusion in Pacific coast states appears highly unlikely.
A second limitation is that the very small number of WA1 IgG-positive sera obtained from documented cases of WA1 infection precludes the accurate determination of sensitivity, specificity, positive predictive value, and negative predictive value for the WA1 IgG IFA. The low WA1 IgG detection rate we observed among blood donor specimens suggests good assay specificity; however, blood donors are presumed to be afebrile, whereas patients whose sera are submitted for WA1 IgG testing are presumed to be febrile following tick exposure.
A thorough assessment of WA1 IgG reactivity in sera from patients with fever caused by other infections is thus required to define the specificity of the WA1 IgG assay.
As a first step in the process, we measured WA1 IgG in sera positive for EBVCA IgM and found that all were negative for WA1 IgG. We also measured EBVCA IgM in WA1 IgG-positive specimens from patients and blood donors and similarly found that all were negative for EBVCA IgM.
In addition to supporting the hypothesis that the WA1 IgG IFA exhibits good specificity, these data indicate that the previously documented (7) nonspecific reactivity in parasitic antibody IFAs linked to EBV-induced polyclonal B-cell activation does not characterize the WA1 IgG IFA.
Additional studies utilizing sera from patients with other febrile illnesses are needed for a complete assessment of the specificity of the WA1 IgG IFA.
A third limitation is the lack of clinical information for patients whose clinical specimens were positive for WA1 IgG; no information was available regarding travel history, transfusion history, symptoms, or tick exposure status. Without such data, it is difficult to interpret some of our findings.
For example, the female predominance among WA1 IgG-positive patients stands in stark contrast to the observation that all 9 documented WA1 cases occurred in males (4, 9, 13, 15) and to the male predominance observed for tick-borne infections in general (3, 16, 17, 18).
Similarly, the lack of a seasonal increase in WA1 IgG detection during North American summer months is atypical for a tick-borne infection (14). Finally, the lack of clinical data precludes establishment of a link between our evidence of exposure to WA1 or a related organism and clinical disease.
A thorough clinical study is thus needed to determine the organism triggering the production of WA1-reactive IgG, where and how the exposure occurred, and possible links between WA1 IgG detection and the symptoms prompting these patients to seek medical attention.
-------------------- (The ole disclaimer: I'm not a doctor.) Posts: 1349 | From VA | Registered: Jul 2006
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Bea posted this ages ago. Interesting article nonetheless.
Posts: 7545 | From The 5th Dimension - The Twilight Zone | Registered: Mar 2008
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