Pro-inflammatory immune responses are associated with clinical signs and symptoms of human anaplasmosis.

Human anaplasmosis (HA) is an emerging tick-borne disease that may present as a mild flu-like illness or a life threatening, sepsis-like condition. Although disease severity is hypothesized to relate to immunopathology and immune dysfunction in humans, studies to directly measure immune responses in infected humans have been very limited. We quantified cytokines in 80 confirmed HA patients using a multiplex chemiluminescence immunoassay system and compared similarly measured responses in 1000 control subjects. Pro-inflammatory cytokines were significantly elevated in HA patients (all seven p<0.0001). Interferon gamma (IFN-γ) concentrations were particularly high, with average concentrations 7.8 times higher in the HA patients than the controls. A subset of cytokines consisting of IL-1ß, IL-8, IL-6, TNF-α, and IL-10 was also coordinately high and significantly associated with severity of thrombocytopenia in HA patients. Patients with infections in the very acute stage (≤ 4 days ill) tended to have the highest IFN-γ, IL-12p70, and IL-2 levels. Higher concentrations of IL-13 and IL-5 were associated with diarrhea and vomiting. Our findings support a pathophysiological role for a pro-inflammatory response in HA, especially with regard to the modulation of hematopoiesis and subsequent hematopoietic complications.

Serologic screening of United States blood donors for Babesia microti using an investigational enzyme immunoassay.

BACKGROUND: The tick-borne pathogen Babesia microti has become recognized as the leading infectious risk associated with blood transfusion in the United States, yet no Food and Drug Administration-licensed screening tests are currently available to mitigate this risk. The aim of this study was to evaluate the performance of an investigational enzyme immunoassay (EIA) for B. microti as a screening test applied to endemic and nonendemic blood donor populations. STUDY DESIGN AND METHODS: The study aimed to test 20,000 blood donors from areas of the United States considered endemic for B. microti and 10,000 donors from a nonendemic area with the investigational B. microti EIA. Repeat-reactive samples were retested by polymerase chain reaction (PCR), blood smear, immunofluorescent assay (IFA), and immunoblot assay. In parallel, serum samples from symptomatic patients with confirmed babesiosis were tested by EIA, IFA, and immunoblot assays. RESULTS: A total of 38 of 13,757 (0.28%) of the donors from New York, 7 of 4583 (0.15%) from Minnesota, and 11 of 8363 (0.13%) from New Mexico were found repeat reactive by EIA. Nine of the 56 EIA repeat-reactive donors (eight from New York and one from Minnesota) were positive by PCR. The specificity of the assay in a nonendemic population was 99.93%. Among IFA-positive clinical babesiosis patients, the sensitivity of the assay was 91.1%. CONCLUSION: The B. microti EIA detected PCR-positive, potentially infectious blood donors in an endemic population and exhibited high specificity among uninfected and unexposed individuals. The EIA promises to provide an effective tool for blood donor screening for B. microti in a format amenable to high-throughput and cost-effective screening.