[Interdisciplinary AWMF guideline for the treatment of primary antibody deficiencies]. / Interdisziplinäre AWMF-Leitlinie zur Therapie primärer Antikörpermangelerkrankungen.

BACKGROUND: Currently, management of antibody deficient patients differs significantly among caregivers. Evidence and consensus based (S3) guidelines for the treatment of primary antibody deficiencies were developed to improve the management of these patients. METHODS: Based on a thorough analysis of current evidence (systematic literature search in PubMed; deadline November 2011) 14 recommendations were finalized during a consensus meeting in Frankfurt in November 2011 using structured consensus methods (nominal group technique). Experts were nominated by their scientific societies/patient initiatives (Tab. 1). RESULTS: The guidelines focus on indication, practical issues and monitoring of immunoglobulin replacement therapy as well as on different routes of administration. Furthermore recommendations regarding supportive measures such as antiinfective therapy, vaccinations and physiotherapy are given. Combining literature evidence and experience of caregivers within this evidence and consensus based guidelines offers the chance to improve the quality of care for anti-body deficient patients.

Virulence factors and genotypes of Staphylococcus aureus from infection and carriage in Gabon.

Staphylococcus aureus isolates from developed countries have been extensively analyzed with respect to their virulence patterns and clonal relatedness but there is only sparse information on the molecular diversity of S. aureus isolates from Africa. In particular, little is known about S. aureus isolates from asymptomatic carriers compared with isolates causing infections. From 2008 to 2010, we prospectively collected S. aureus isolates from asymptomatic carriers and infections in Lambaréné, Gabon, Central Africa. For these isolates, we determined major virulence factors, and performed multilocus sequence typing (MLST) and spa typing. Among 163 S. aureus isolates from asymptomatic carriers, we found the MLST clonal complexes (CCs) 5, 6, 7, 8, 9, 15, 25, 30, 45, 88, 101, 121 and 152; 3.7% were methicillin-resistant (MRSA). The clinical isolates were associated with CCs 5, 8, 9, 15, 88, 121 and 152; 11% were MRSA. Sequence types 1 and 88 were significantly associated with infection and sequence type 508 was associated with carriage. Remarkably, there was a high prevalence of Panton-Valentine leukocidin (PVL) -encoding genes both in disease-related isolates (57.4%) and in carrier isolates (40.5%). We found differences in the clonal structure and virulence pattern of Gabonese S. aureus isolates from asymptomatic carriers and infections. Of note, S. aureus isolates from Gabon show a very high prevalence of PVL-encoding genes, which exceeds the rates observed for developed countries.

Proposal to elevate Mycobacterium avium complex ITS sequevar MAC-Q to Mycobacterium vulneris sp. nov.

The Mycobacterium avium complex (MAC) consists of four recognized species, Mycobacterium avium, Mycobacterium colombiense, Mycobacterium intracellulare and Mycobacterium chimaera, and a variety of other strains that may be members of undescribed taxa. We report on two isolates of a scotochromogenic, slowly growing, non-tuberculous Mycobacterium species within the M. avium complex from a lymph node and an infected wound after a dogbite of separate patients in The Netherlands. The extrapulmonary infections in immunocompetent patients suggested a high level of virulence. These isolates were characterized by a unique nucleotide sequence in the 16S rRNA gene, 99% similar to Mycobacterium colombiense, and the MAC-Q 16S-23S internal transcribed spacer (ITS) sequence. Sequence analyses of the hsp65 gene revealed 97% similarity to M. avium. The rpoB gene sequence was 98% similar to M. colombiense. Phenotypically, the scotochromogenicity, positive semi-quantitative catalase and heat-stable catalase tests, negative tellurite reductase and urease tests and susceptibility to hydroxylamine and oleic acid set these isolates apart from related species. High-performance liquid chromatography analysis of cell-wall mycolic acid content revealed a unique pattern, related to that of M. avium and M. colombiense. Together, these findings supported a separate species status within the Mycobacterium avium complex. We propose elevation of scotochromogenic M. avium complex strains sharing this 16S gene and MAC-Q ITS sequence to separate species status, for which the name Mycobacterium vulneris sp. nov. is proposed. The type strain is NLA000700772T (=DSM 45247T=CIP 109859T).

Rapid diagnosis of Mycobacterium tuberculosis meningitis by enumeration of cerebrospinal fluid antigen-specific T-cells.

SETTING: Hospital in-patients with suspected tuberculous meningitis (TBM), predominantly in India. OBJECTIVE: To determine whether interferon-gamma (IFN-gamma) secreting Mycobacterium tuberculosis antigen-specific T-cells are present in the cerebrospinal fluid (CSF) of patients with TBM and to evaluate the feasibility of CSF enzyme-linked immunospot (ELISpot) for the diagnosis of active TBM. DESIGN: Prospective blinded hospital-based study. RESULTS: The overnight ELISpot assay detected M. tuberculosis antigen-specific IFN-gamma secreting T-cells in CSF from nine of 10 prospectively recruited patients with TBM, and zero of seven control patients with meningitis of other aetiology. This corresponds to a diagnostic sensitivity of 90% (95%CI 56-100) and specificity of 100% (95%CI 59-100). CONCLUSION: This pilot study demonstrates proof-of-principle for a new T-cell-based diagnostic test for TBM which is rapid, sensitive and specific.

Rapid diagnosis of CNS tuberculosis by a T-cell interferon-gamma release assay on cerebrospinal fluid mononuclear cells.

Central nervous system tuberculosis remains a clinical diagnostic challenge. The ex vivo Mycobacterium tuberculosis-specific enzyme-linked immunospot assay (ELISPOT) is a novel assay for the rapid detection of M. tuberculosis-specific T-lymphocytes in the peripheral blood. However, when performed on peripheral blood, this assay cannot distinguish between active tuberculosis or latent tuberculosis infection. On the assumption that M. tuberculosis-specific T-lymphocytes migrate to sites of infection, we were able to demonstrate high levels of M. tuberculosis-specific cells by ELISPOT in the cerebrospinal fluid of a patient with tuberculous meningitis and intracerebral tuberculoma four weeks before cerebrospinal fluid culture became positive for M. tuberculosis by culture.

Aortitis diagnosed by F-18-fluorodeoxyglucose positron emission tomography in a patient with syphilis and HIV coinfection.

The most common manifestation of cardiovascular syphilis, a rare diagnosis since the introduction of penicillin, is aortitis of the ascending aorta. Since the majority of patients with uncomplicated aortitis are asymptomatic, early diagnosis is difficult. We report the case of an HIV-positive patient with asymptomatic syphilitic aortitis that was incidentally diagnosed with F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET). We conclude that FDG-PET could become a promising new imaging technique for both diagnosis and follow-up of patients with syphilitic aortitis.

Stability of antibodies to Bordetella antigens in German adults.

To estimate the rate of asymptomatic exposure to Bordetella pertussis antigens in the German adult population and to evaluate the stability of antibodies to these antigens, antibody levels against Bordetella antigens and their variability over time were measured in German adult blood donors. One hundred forty-six regular blood donors (41 females, 105 males) were tested repeatedly for antibodies of isotypes IgG and IgA to pertussis toxin, filamentous hemagglutinin (FHA) and pertactin over a period of 2-5 years. Overall, 86% and 56% had IgG or IgA antibodies to pertussis toxin, respectively, 100% and 92% had IgG or IgA antibodies to FHA, respectively, and 83% and 93% had IgG or IgA antibodies to pertactin, respectively. One significant titer increase of both IgG anti-FHA and IgG anti-pertactin, one of IgG anti-FHA, and two of IgA anti-FHA as well as one significant decrease of IgG anti-pertussis toxin were observed during an observation period of 480.5 person-years. Antibody concentrations in men and women were not different. The data show that the level of antibodies to pertussis toxin, FHA, and pertactin remains stable over several years. Furthermore, depending on the definition of serological evidence, the rate of significant increases or decreases suggesting unrecognized exposure to Bordetella antigens was estimated to be between <0.2 and 1.0 per 100 person-years in the population studied.

Comparison of five commercial enzyme-linked immunosorbent assays for detection of antibodies to Bordetella pertussis.

Measuring antibodies to Bordetella pertussis antigens is mostly done by enzyme-linked immunosorbent assays (ELISAs). We compared the performance of five commercially available ELISA kits with the help of 65 serum specimens which were repetitively tested for evaluation of the kits. The specimens contained 20 paired serum samples from patients with clinical pertussis, 15 samples were from children vaccinated with a diphtheria-tetanus-acellular pertussis vaccine, seven specimens were taken from an interlaboratory comparison of ELISAs, and there were three reference preparations from the Food and Drug Administration's (FDA's) Laboratory of Pertussis and from our laboratory. Reference values were obtained from the FDA or from results obtained with an in-house ELISA. Commercial ELISAs were compared with respect to their reproducibility and variability, their ability to detect significant titer rises in paired serum samples, their ability to detect an immune response after vaccination, and the comparability of semiquantitative and quantitative results. Reproducibility was generally good (>89%), intra-assay variation ranged from 2.4 to 28.7%, and indeterminate results were recorded in up to 18.5% of all specimens. Most kits correctly identified the antibody response to an acellular pertussis vaccine. None of the commercial kits identified all cases of pertussis correctly, and the sensitivity ranged between 60 and 95%. All five commercial ELISAs showed great discrepancies when comparing semiquantitative results and contained obviously different antigen preparations. Our data suggest that the five commercial ELISAs tested here need further improvement and standardization.