Inger Julander

Risk Assessment of Tuberculosis in Immunocompromised Patients. A TBNET Study

RATIONALEnIn the absence of active tuberculosis, a positive tuberculin skin test (TST) or interferon-γ release assay (IGRA) result defines latent infection with Mycobacterium tuberculosis, although test results may vary depending on immunodeficiency.nnnOBJECTIVESnThis study compared the performance of TST and IGRAs in five different groups of immunocompromised patients, and evaluated their ability to identify those at risk for development of tuberculosis.nnnMETHODSnImmunocompromised patients with HIV infection, chronic renal failure, rheumatoid arthritis, solid-organ or stem-cell transplantation, and healthy control subjects were evaluated head-to-head by the TST, QuantiFERON-TB-Gold in-tube test (ELISA), and T-SPOT.TB test (enzyme-linked immunospot) at 17 centers in 11 European countries. Development of tuberculosis was assessed during follow-up.nnnMEASUREMENTS AND MAIN RESULTSnFrequencies of positive test results varied from 8.7 to 15.9% in HIV infection (nu2009=u2009768), 25.3 to 30.6% in chronic renal failure (nu2009=u2009270), 25.0% to 37.2% in rheumatoid arthritis (nu2009=u2009199), 9.0 to 20.0% in solid-organ transplant recipients (nu2009=u2009197), 0% to 5.8% in stem-cell transplant recipients (nu2009=u2009103), and 11.2 to 15.2% in immunocompetent control subjects (nu2009=u2009211). Eleven patients (10 with HIV infection and one solid-organ transplant recipient) developed tuberculosis during a median follow-up of 1.8 (interquartile range, 0.2-3.0) years. Six of the 11 patients had a negative or indeterminate test result in all three tests at the time of screening. Tuberculosis incidence was generally low, but higher in HIV-infected individuals with a positive TST (3.25 cases per 100 person-years) than with a positive ELISA (1.31 cases per 100 person-years) or enzyme-linked immunospot result (1.78 cases per 100 person-years). No cases of tuberculosis occurred in patients who received preventive chemotherapy.nnnCONCLUSIONSnAmong immunocompromised patients evaluated in this study, progression toward tuberculosis was highest in HIV-infected individuals and was poorly predicted by TST or IGRAs. Clinical trial registered with www.clinicaltrials.gov (NCT 00707317).

The role of antibodies against alpha-toxin and teichoic acid in the diagnosis of staphylococcal infections.

SummaryAn enzyme-linked immunosorbent assay (ELISA) was used with purified α-toxin and teichoic acid preparations to measure the IgG and IgM response inStaphylococcus aureus infections. After determining antibodies in a normal population, cut-off levels were set for all age groups. ELISA with α-toxin was more sensitive than the antistaphylolysin neutralization test (ASTA). Determining IgM antibodies with the two antigens was found to be of limited diagnostic value. Positive IgG titers against α-toxin were found in 21 of 27 patients (78%) with endocarditis, 11 of 14 (79%) with complicated septicemia, eight of 20 (40%) with uncomplicated septicemia and in 12 of 22 (54%) with chronic osteomyelitis. The IgG responses to teichoic acid and α-toxin were somewhat different when measured by ELISA, and the parallel performance of the two assays resulted in improved serological diagnostics. The number of positive patients increased to 89%, 86%, 65% and 64%, respectively, in the four groups with a diagnostic specificity of 93%. In septicemic staphylococcal infections, the diagnosis could be established in all patients (28 of 28) with adequately spaced paired samples.ZusammenfassungZur Bestimmung der IgG-und IgM-Antwort bei Infektionen durchStaphylococcus aureus wurde ein Enzym-gebundener Immunsorbent-Test (ELISA) mit gereinigtem α-Toxin und Teichonsäure eingesetzt. Nach Bestimmung der Antikörper bei Normalpersonen wurden für alle Altersgruppen Grenzwerte festgelegt. ELISA mit α-Toxin war empfindlicher als der Antistaphylolysin-Neutralisationstest (ASTA). Die Bestimmung der IgM-Antikörper mit den beiden Antigenen war nur von beschränktem diagnostischen Wert. Die Titerbestimmung von IgG gegen α-Toxin war bei 21 von 27 Patienten mit Endokarditis (78%). 11 von 14 Patienten mit komplizierter Septikämie (79%), acht von 20 Patienten mit unkomplizierter Septikämie (40%) und bei 12 von 22 Patienten mit chronischer Osteomyelitis (54%) positiv. Die mit ELISA bestimmte IgG-Antwort auf Teichonsäure und α-Toxin wich von diesen Werten etwas ab; bei parallelem Einsatz beider Assays ließ sich die serologische Diagnostik verbessern. Der Prozentsatz positiver Fälle erhöhte sich in den vier Gruppen auf 89%, 86%, 65% und 64% bei einer diagnostischen Spezifität von 93%. Staphylokokkeninfektionen mit septischem Verlauf konnten bei Abnahme gepaarter Proben in angemessenem Abstand bei allen Patienten (28 von 28) diagnostiziert werden.An enzyme-linked immunosorbent assay (ELISA) was used with purified α-toxin and teichoic acid preparations to measure the IgG and IgM response inStaphylococcus aureus infections. After determining antibodies in a normal population, cut-off levels were set for all age groups. ELISA with α-toxin was more sensitive than the antistaphylolysin neutralization test (ASTA). Determining IgM antibodies with the two antigens was found to be of limited diagnostic value. Positive IgG titers against α-toxin were found in 21 of 27 patients (78%) with endocarditis, 11 of 14 (79%) with complicated septicemia, eight of 20 (40%) with uncomplicated septicemia and in 12 of 22 (54%) with chronic osteomyelitis. The IgG responses to teichoic acid and α-toxin were somewhat different when measured by ELISA, and the parallel performance of the two assays resulted in improved serological diagnostics. The number of positive patients increased to 89%, 86%, 65% and 64%, respectively, in the four groups with a diagnostic specificity of 93%. In septicemic staphylococcal infections, the diagnosis could be established in all patients (28 of 28) with adequately spaced paired samples. Zur Bestimmung der IgG-und IgM-Antwort bei Infektionen durchStaphylococcus aureus wurde ein Enzym-gebundener Immunsorbent-Test (ELISA) mit gereinigtem α-Toxin und Teichonsäure eingesetzt. Nach Bestimmung der Antikörper bei Normalpersonen wurden für alle Altersgruppen Grenzwerte festgelegt. ELISA mit α-Toxin war empfindlicher als der Antistaphylolysin-Neutralisationstest (ASTA). Die Bestimmung der IgM-Antikörper mit den beiden Antigenen war nur von beschränktem diagnostischen Wert. Die Titerbestimmung von IgG gegen α-Toxin war bei 21 von 27 Patienten mit Endokarditis (78%). 11 von 14 Patienten mit komplizierter Septikämie (79%), acht von 20 Patienten mit unkomplizierter Septikämie (40%) und bei 12 von 22 Patienten mit chronischer Osteomyelitis (54%) positiv. Die mit ELISA bestimmte IgG-Antwort auf Teichonsäure und α-Toxin wich von diesen Werten etwas ab; bei parallelem Einsatz beider Assays ließ sich die serologische Diagnostik verbessern. Der Prozentsatz positiver Fälle erhöhte sich in den vier Gruppen auf 89%, 86%, 65% und 64% bei einer diagnostischen Spezifität von 93%. Staphylokokkeninfektionen mit septischem Verlauf konnten bei Abnahme gepaarter Proben in angemessenem Abstand bei allen Patienten (28 von 28) diagnostiziert werden.

Elevated serum beta-2-microglobulin--a prognostic marker for development of AIDS among patients with persistent generalized lymphadenopathy.

SummaryFor evaluation of its prognostic value, the level of serum β-2-microglobulin was determined in early serum samples from 88 patients with persistent generalized lymphadenopathy in a prospective longitudinal study. Patients with serum β-2-microglobulin >2.6 mg/l were found to have a significantly higher risk of developing AIDS earlier when compared to patients with a lower level (p<0.001).ZusammenfassungIn einer prospektiven longitudinalen Studie wurden in frühen Serumproben von 88 Patienten mit persistierender generalisierter Lymphadenopathie Messungen des β-2-Mikroglobulin-Spiegels vorgenommen, um dessen Wert als prognostischer Faktor zu bestimmen. Das Risiko für den Übergang in AIDS erwies sich bei Patienten mit β-2-Mikroglobulin-Spiegeln von >2,6 mg/l als signifikant höher als bei Patienten mit niedrigeren Spiegeln (p<0,001).

Are white blood cell count, platelet count, erythrocyte sedimentation rate and C-reactive protein useful in the diagnosis of septicaemia and endocarditis?

In 851 predominantly adult patients with septicaemia or endocarditis data regarding white blood cell (WBC) count, platelet count, ESR and C-reactive protein (CRP) obtained within 3 days of admission were analyzed retrospectively. Among 232 patients with complete laboratory data none had the combination of normal ESR, negative CRP and lack of both leukocytosis and thrombocytopenia. CRP was positive (greater than 10 mg/l) in 93%, ESR was elevated (greater than 20 mm/h) in 90%, leukocytosis (WBC greater than 9 X 10(9)/l) was present in 60% and thrombocytopenia (platelets less than 150 X 10(9)/l) in 35% of the patients. Patients with pneumococcal infection had generally higher ESR and CRP values and WBC counts than patients with other infections.

Erythromycin for treatment of ornithosis

Patients with pneumonia not responding to treatment with betalactam drugs and patients where an atypical etiology is suspected from the beginning, are often given erythromycin to cover mycoplasma and legionella. Erythromycin has also been effective for Chlamydia pneumoniae. If, however, ornithosis is suspected the recommended drug has been tetracycline. Since we noted that several patients had a favourable course on erythromycin despite a final serological diagnosis of ornithosis, we retrospectively studied patients admitted with acute lower respiratory tract infection and a 4-fold titer rise to C. psittaci. We found 35 patients treated with a betalactam drug (n = 12), tetracycline (n = 2), or erythromycin (n = 5) alone, or with a betalactam, which because of non-responsiveness was followed by either tetracycline (n = 4) or erythromycin (n = 12). The data were analysed with survival analysis by a Cox regression model. There was a significant (p less than 0.001) effect of treatment on the time to defervescence, mainly due to a difference between the erythromycin treated group and the betalactam treated group. We found erythromycin to be at least as effective as tetracycline for treating C. psittaci pneumonia. Since erythromycin has to be used to cover legionella in patients with severe pneumonia when an atypical etiology cannot be excluded, it is an important conclusion that this drug seems to cover C. psittaci as well.

Serum triglyceride elevations in patients with septicemia.

Among 239 patients with septicemia or endocarditis 41 (17%) had serum triglyceride levels in excess of 2.2 mmol/l (mean 3.1 mmol/l). This was more common in infectious with gram-negative rods than gram-positive cocci (p less than 0.001). A return to normal levels occurred in 22/37 patients during the course of the infection.

Serum Triglyceride Elevations in Patients with Septicemia

AbstractAmong 239 patients with septicemia or endocarditis 41 (17%) had serum triglyceride levels in excess of 2.2 mmol/l (mean 3.1 mmol/l). This was more common in infections with gramnegative rods than gram-positive cocci (p < 0.001). A return to normal levels occurred in 22/37 patients during the course of the infection.