ObjectivesPrompt antibiotic treatment of early stage Lyme borreliosis (LB) prevents progression to severe multisystem disease. There is a clinical need to improve the diagnostic specificity of early stage Lyme assays in the period prior to the mounting of a robust serology response. Using a novel analyte harvesting nanotechnology, Nanotrap particles, we evaluated urinary Borrelia Outer surface protein A (OspA) C-terminus peptide in early stage LB before and after treatment, and in patients suspected of late stage disseminated LB.MethodWe employed Nanotrap particles to concentrate urinary OspA and used a highly specific anti-OspA monoclonal antibody (mAb) as a detector of the C-terminus peptides. We mapped the mAb epitope to a narrow specific OspA C-terminal domain OspA236-239 conserved across infectious Borrelia species but with no homology to human proteins and no cross-reactivity with relevant viral and non-Borrelia bacterial proteins. 268 urine samples from patients being evaluated for all categories of LB were collected in a LB endemic area. The urinary OspA assay, blinded to outcome, utilized Nanotrap particle pre-processing, western blotting to evaluate the OspA molecular size, and OspA peptide competition for confirmation.ResultsOspA test characteristics: sensitivity 1.7 pg/mL (lowest limit of detection), % coefficient of variation (CV) = 8 %, dynamic range 1.7–30 pg/mL. Pre-treatment, 24/24 newly diagnosed patients with an erythema migrans (EM) rash were positive for urinary OspA while false positives for asymptomatic patients were 0/117 (Chi squared p < 10−6). For 10 patients who exhibited persistence of the EM rash during the course of antibiotic therapy, 10/10 were positive for urinary OspA. Urinary OspA of 8/8 patients switched from detectable to undetectable following symptom resolution post-treatment. Specificity of the urinary OspA test for the clinical symptoms was 40/40. Specificity of the urinary OspA antigen test for later serology outcome was 87.5 % (21 urinary OspA positive/24 serology positive, Chi squared p = 4.072e−15). 41 of 100 patients under surveillance for persistent LB in an endemic area were positive for urinary OspA protein.ConclusionsOspA urinary shedding was strongly linked to concurrent active symptoms (e.g. EM rash and arthritis), while resolution of these symptoms after therapy correlated with urinary conversion to OspA negative.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0701-z) contains supplementary material, which is available to authorized users.

A survey of hepatitis B patients, asymptomatic hepatitis B antigen (HB8Ag) carriers, and control subjects was conducted to determine the relationship between antigenemia and antigen excretion in saliva, urine, and stool. Radioimmunoassay was used to detect HB8Ag. Specificity-confirmed HBeAg was detected in the saliva of 6 (30%) of 20 antigenemic patients, 1 (5%) of 20

Delayed hypersensitivity to hepatitis B surface antigen (HBsAg) in patients with disease from the clinical spectrum of hepatitis and in controls was examined by an indirect assay of macrophage migration inhibitory factor. Activity was demonstrated in cases of acute or persistently active hepatitis. Steroids and pregnancy had a suppressive effect. Samples from a patient with transfusion-related HBsAg hepatitis were also assayed. A broad clinical spectrum of disease is associated with the presence of hepatitis B surface antigen (HBsAg) in the blood. It has been suggested that the host's immune response is related to the clinical type of disease [1-4]. Delayed hypersensitivity, a cellular immune response to antigenic stimulation, is recognized as an important immunological phenomenon in the pathogenesis and/or prevention of many diseases. Skin testing has been the classical method of studying delayed hypersensitivity to many antigens in animals and humans. In 1951 Henle et al. [5] reported skin reactions in humans to am

In a military population antibody to hepatitis B core antigen (anti-HBc) was found in 39% of acute hepatitis cases negative for hepatitis B surface antigen (HBS Ag) and in 96% of HBs Ag-positive cases. Persistence of antibody to HBs Ag (anti-HBs) in convalescent-phase sera was significantly greater (P less than 0.001) in individuals with acute HBs Ag-positive hepatitis B than in patients with clinical HBs Ag-negative hepatitis B. The prevalence of anti-HBc in the absence of HBs Ag, anti-HBs, and clinical disease was 3.2% in this military population. In longitudinal studies of hepatitis B infection, the presence of anti-HBc preceded anti-HBs and improved the ability to determine the onset of sublicnical infection. Anti-HBc is a useful serologic marker for the study of the epidemiology of hepatitis B and improves the efficiency of detection of hepatitis B virus infection.

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A sustained outbreak of viral hepatitis occurred at an Army base in Texas between January 1971 and June 1973. Seven hundred ninety-two admissions but no deaths were recorded in a military population of 35,000. Cases were sporadic, with highest attack rates in low-ranking soldiers with disciplinary problems. Twenty-nine per cent of patients had histories of intravenous drug use within six months prior to hospitalization; most of the rest had close personal contact with jaundiced persons. Of 505 patients tested, 31% were seropositive for hepatitis B antigen (HBSAg) by counterelectrophoresis. Comparison of 38 hepatitis patients (cases) to 34 orthopedic patients (controls) revealed marked differences in rates of exposure to jaundiced persons are shared needles. Sixteen (94%) of 17 antigenemic cases tested were of subtype ayw. Seven (78%) of nine NBSAg-negative cases tested were antibody (anti-HBS) positive three months later.

The prevalence of Hepatitis B surface antigen (HB8Ag) and antibody (anti-HBs) seropositivity and the association of seropositivity with demographic, personal health, and professional experiences were studied in a cohort of Army Medical Department officer personnel. Serologic evidence of Hepatitis B infection was found in 5.0 per cent of personnel and was associated with age, sex, place of birth, history of hepatitis, history of blood transfusion, and previousThe risk of Hepatitis B virus infection in health care personnel has been evaluated through longitudinal studies of hospital associated outbreaks' as well as through cross-sectional studies of hospital workers2' 3 and specialty groups.4Reports have defined high risk settings such as dialysis units,5 6 oncology units,7 operating theaters,8 and laboratories,9 as well as high risk practitioners such as anesthesiologists.' 0 Cross sectional studies of the staff of any single health care facility may not be broadly representative or contain enough individuals in any one specialty to assess risk. We identified a cohort of health care personnel representing a diversity of personal and professional experiences and report here the results of questionnaire and serologic studies. Subjects and Methods

Sera from a survey of 6,026 people were tested for hepatitis B surface antigen by using radioimmunoassay and counterelectrophoresis. Forty-eight sera (0.79%) were positive by counterelectrophoresis and 152 sera (2.52%) were positive by radioimmunoassay, using the most liberal of the recommended criteria for positivity (i.e., counts 3 standard deviations above the mean). Absorption tests performed on the 152 radioimmunoassay-positive sera showed that 10 (6.6%) were false-positive reactions to guinea pig protein, 74 (48.6%) were due to false-positive reaction(s) with other protein(s) in the test system, and 68 (44.8%) were true positives. There was a strong correlation between the degree of elevation of radioactive counts and the proportions of sera that were true positives; all 49 sera with counts >50 standard deviation units above the mean were true positives, but only 19 (18.4%) of the 103 sera with counts <50 standard deviation units were true positives. A few sera with high counts required absorption with type-specific (type D) antisera. The following conclusions were reached from this study: (i) absorption tests should be run on all radioimmunoassay-positive, counterelectrophoresis-negative sera; (ii) most (about 90%) false positives are not due to anti-guinea-pig protein reactions; and (iii) radioimmunoassay, in combination with absorption tests, yields a modest increase (about 35%) in detection of true positives over use of counterelectrophoresis alone.