The antibody-secreting cell response to infection: kinetics and clinical applications

Despite the availability of advances in molecular diagnostic testing for infectious disease, there is still a need for tools that advance clinical care and public health. Current methods focus on pathogen detection with unprecedented precision, but often lack specificity. In contrast, the host immune response is highly specific for the infecting pathogen. Serological studies are rarely helpful in clinical settings, as they require acute and convalescent antibody testing. However, the B cell response is much more rapid and short-lived, making it an optimal target for determining disease aetiology in patients with infections. The performance of tests that aim to detect circulating antigen-specific antibody-secreting cells (ASCs) has previously been unclear. Test performance is reliant on detecting the presence of ASCs in the peripheral blood. As such, the kinetics of the ASC response to infection, the antigen specificity of the ASC response, and the methods of ASC detection are all critical. In this review, we summarize previous studies that have used techniques to enumerate ASCs during infection. We describe the emergence, peak, and waning of these cells in peripheral blood during infection with a number of bacterial and viral pathogens, as well as malaria infection. We find that the timing of antigen-specific ASC appearance and disappearance is highly conserved across pathogens, with a peak response between day 7 and day 8 of illness and largely absent following day 14 since onset of symptoms. Data show a sensitivity of ~90% and specificity >80% for pathogen detection using ASC-based methods. Overall, the summarised work indicates that ASC-based methods may be very sensitive and highly specific for determining the etiology of infection and have some advantages over current methods. Important areas of research remain, including more accurate definition of the timing of the ASC response to infection, the biological mechanisms underlying variability in its magnitude and the evolution and the B cell receptor in response to immune challenge. Nonetheless, there is potential of the ASC response to infection to be exploited as the basis for novel diagnostic tests to inform clinical care and public health priorities

Congenital syphilis in Switzerland: gone, forgotten, on the return.

INTRODUCTION: Acquired syphilis has re-emerged in many Western European countries. In contrast to international guidelines, screening for syphilis in pregnancy is not generally recommended in Switzerland. There has been an increase in the incidence of laboratory syphilis notifications in recent years, regardless of gender and age. METHODS: We conducted a retrospective study, evaluating the total numbers of pregnant women with positive syphilis serology (Treponema pallidum Particle Agglutination assay, TPPA) from 2000 to 2009, and evaluated the clinical management and outcome of their offspring. In addition, we sought to determine cases of infectious syphilis (primary, secondary, and early latent syphilis) reported to the Swiss Federal Office of Public Health in women of childbearing age, which has previously been shown to precede changes in the incidence of congenital syphilis within a population. RESULTS: Out of 13,833 women who gave birth at our institution, positive syphilis serology was found in 9 pregnant women during the 10 years studied. A total of 6 pregnant women were diagnosed having syphilis infection during pregnancy. Regarding their offspring, 8 of the 9 newborns were tested serologically. One neonate experienced congenital syphilis because the adequately treated mother developed re-infection after treatment. Within the Swiss population, infectious syphilis cases in women of childbearing age increased substantially from 2006 to 2009. CONCLUSIONS: The epidemiologic data suggest that congenital syphilis could become a medical problem in Switzerland due to the rise of infectious syphilis cases in women of childbearing age that have been shown to be followed by changes in the congenital syphilis incidence. The persistence of congenital syphilis in Switzerland along with this rise of infectious syphilis in women of childbearing age suggests a potential for improvement of prenatal care and syphilis control programmes

Detection of mostly viral pathogens and high proportion of antibiotic treatment initiation in hospitalised children with community-acquired pneumonia in Switzerland - baseline findings from the first two years of the KIDS-STEP trial.

AIMS OF THE STUDY: Globally, since the introduction of conjugate-vaccines against encapsulated bacteria, respiratory viruses have caused most hospitalisations for community-acquired pneumonia. The aim of this study was to describe pathogens detected and their association with clinical findings in Switzerland. METHODS: Baseline data were analysed for all trial participants enrolled between September 2018 and September 2020 into the KIDS-STEP Trial, a randomised controlled superiority trial on the effect of betamethasone on clinical stabilisation of children admitted with community-acquired pneumonia. Data included clinical presentation, antibiotic use and results of pathogen detection. In addition to routine sampling, nasopharyngeal specimens were analysed for respiratory pathogens using a panel polymerase chain reaction test covering 18 viral and 4 bacterial pathogens. RESULTS: 138 children with a median age of 3 years were enrolled at the eight trial sites. Fever (obligatory for enrolment) had been present for median 5 days before admission. Most common symptoms were reduced activity (129, 93.5%) and reduced oral intake (108, 78.3%). Oxygen saturation <92% was found in 43 (31.2%). Forty-three participants (29.0%) were already on antibiotic treatment prior to admission and 104 participants (75.4%) received antibiotic treatment on admission. Pathogen testing results were available from 132 children: 31 (23.5%) had respiratory syncytial virus detected, 21 (15.9%) human metapneumovirus. The pathogens detected showed expected seasonal and age preponderance and were not associated with chest X-ray findings. CONCLUSIONS: In the context of the predominantly viral pathogens detected, the majority of antibiotic treatment is probably unnecessary. The ongoing trial, as well as other studies, will be able to provide comparative pathogen detection data to compare pre- and post-COVID-19-pandemic settings