Protection against pertussis in humans correlates to elevated serum antibodies and memory B cells

Pertussis is a respiratory infection caused by Bordetella pertussis that may be particularly severe and even lethal in the first months of life when infants are still too young to be vaccinated. Adults and adolescents experience mild symptoms and are the source of infection for neonates. Adoptive maternal immunity does not prevent pertussis in the neonate. We compared the specific immune response of mothers of neonates diagnosed with pertussis and mothers of control children. We show that women have pre-existing pertussis-specific antibodies and memory B cells and react against the infection with a recall response increasing the levels specific serum IgG, milk IgA, and the frequency of memory B cells of all isotypes. Thus, the maternal immune system is activated in response to pertussis and effectively prevents the disease indicating that the low levels of pre-formed serum antibodies are insufficient for protection. For this reason, memory B cells play a major role in the adult defense. The results of this study suggest that new strategies for vaccine design should aim at increasing long-lived plasma cells and their antibodies

Infants hospitalized for Bordetella pertussis infection commonly have respiratory viral coinfections

Background: Whether viral coinfections cause more severe disease than Bordetella pertussis (B. pertussis) alone remains unclear. We compared clinical disease severity and sought clinical and demographic differences between infants with B. pertussis infection alone and those with respiratory viral coinfections. We also analyzed how respiratory infections were distributed during the 2 years study. Methods: We enrolled 53 infants with pertussis younger than 180 days (median age 58 days, range 17–109 days, 64. 1% boys), hospitalized in the Pediatric Departments at “Sapienza” University Rome and Bambino Gesù Children’s Hospital from August 2012 to November 2014. We tested in naso-pharyngeal washings B. pertussis and 14 respiratory viruses with real-time reverse-transcriptase-polymerase chain reaction. Clinical data were obtained from hospital records and demographic characteristics collected using a structured questionnaire. Results: 28/53 infants had B. pertussis alone and 25 viral coinfection: 10 human rhinovirus (9 alone and 1 in coinfection with parainfluenza virus), 3 human coronavirus, 2 respiratory syncytial virus. No differences were observed in clinical disease severity between infants with B. pertussis infection alone and those with coinfections. Infants with B. pertussis alone were younger than infants with coinfections, and less often breastfeed at admission. Conclusions: In this descriptive study, no associations between clinical severity and pertussis with or without co-infections were found

Bulk and Surface-Mediated Polymorphs of Bio-Inspired Dyes Organic Semiconductors: The Role of Lattice Phonons in their Investigation

AbstractRaman spectroscopy of organic molecular materials in the low‐wavenumber region gives access to lattice vibrational modes and to the wealth of information on solid state properties that these can provide. In the field of organic electronics a useful application concerns the discrimination of the crystalline forms i. e. polymorphism of the semiconductor. The capability of characterizing and identifying the polymorphs of a compound is in fact the prerequisite for an exhaustive study of the charge transport characteristics which arise from the relationship between molecular, electronic, and crystal structures. Thus, the need is felt of a non‐invasive, non‐destructive tool such as Raman, which probes the crystal phase by detecting the lattice modes which are sensitive even to subtle variations of the packing. Here we review the contribution of the technique to the study of organic pigments displaying promising semiconducting properties and characterized by polymorphism both in their bulk and thin film phases

Attitude of Italian physicians toward pertussis diagnosis.

Resurgence of pertussis has been observed in several countries whereas Italy continues to be a low incidence country. We hypothesize that the low reported incidence of pertussis in Italy could be biased by the attitude of physicians to suspect and diagnose pertussis in different age groups. We investigated the attitude of Italian physicians toward pertussis diagnosis through clinical scenarios. A cross-sectional study was conducted in June 2012 sending online questionnaires to pediatricians and general practitioners (GPs) involved in ambulatory primary care. The questionnaire included five clinical scenarios of patients of different ages (45 d, 5 y, 11 y, 24 y, 58 y) with prolonged cough of at least 2 weeks. Respondents were asked to choose a diagnosis among a list of 14. We observed a decreasing trend of suspected pertussis diagnosis with increasing age of the patient (from 46% at 45 d to 0 at 58 y). In Italy pertussis is seldom suspected in the differential diagnosis of cough particularly in adults. This may cause a significant under-notification of pertussis, with a higher impact in older age groups. Educational programs should be reinforced to consider the differential diagnosis of pertussis in individuals with atypical presentation and in older age groups

The Hedgehog-GLI Pathway Regulates MEK5-ERK5 Expression and Activation in Melanoma Cells

Malignant melanoma is the deadliest skin cancer, with a poor prognosis in advanced stages. We recently showed that the extracellular signal-regulated kinase 5 (ERK5), encoded by the MAPK7 gene, plays a pivotal role in melanoma by regulating cell functions necessary for tumour development, such as proliferation. Hedgehog-GLI signalling is constitutively active in melanoma and is required for proliferation. However, no data are available in literature about a possible interplay between Hedgehog-GLI and ERK5 pathways. Here, we show that hyperactivation of the Hedgehog-GLI pathway by genetic inhibition of the negative regulator Patched 1 increases the amount of ERK5 mRNA and protein. Chromatin immunoprecipitation showed that GLI1, the major downstream effector of Hedgehog-GLI signalling, binds to a functional non-canonical GLI consensus sequence at the MAPK7 promoter. Furthermore, we found that ERK5 is required for Hedgehog-GLI-dependent melanoma cell proliferation, and that the combination of GLI and ERK5 inhibitors is more effective than single treatments in reducing cell viability and colony formation ability in melanoma cells. Together, these findings led to the identification of a novel Hedgehog-GLI-ERK5 axis that regulates melanoma cell growth, and shed light on new functions of ERK5, paving the way for new therapeutic options in melanoma and other neoplasms with active Hedgehog-GLI and ERK5 pathways

Effectiveness of one and two doses of acellular pertussis vaccines against laboratory-confirmed pertussis requiring hospitalisation in infants: results of the PERTINENT sentinel surveillance system in six EU/EEA countries, December 2015 – December 2019

Background Monitoring effectiveness of pertussis vaccines is necessary to adapt vaccination strategies. PERTINENT, Pertussis in Infants European Network, is an active sentinel surveillance system implemented in 35 hospitals across six EU/EEA countries. We aim to measure pertussis vaccines effectiveness (VE) by dose against hospitalisation in infants aged 14 days before symptoms. Unvaccinated were those who did not receive any dose. We calculated (one-stage model) pooled VE as 100*(1-odds ratio of vaccination) adjusted for country, onset date (in 3-month categories) and age-group (when sample allowed it). Results Of 1,393 infants eligible for vaccination, we included 259 cases and 746 controls. Median age was 16 weeks for cases and 19 weeks for controls (p < 0.001). Median birth weight and gestational age were 3,235 g and week 39 for cases, 3,113 g and week 39 for controls. Among cases, 119 (46 %) were vaccinated: 74 with one dose, 37 two doses, 8 three doses. Among controls, 469 (63 %) were vaccinated: 233 with one dose, 206 two doses, 30 three doses. Adjusted VE after at least one dose was 59 % (95 %CI: 36–73). Adjusted VE was 48 % (95 %CI: 5–71) for dose one (416 eligible infants) and 76 % (95 %CI: 43–90) for dose two (258 eligible infants). Only 42 infants were eligible for the third dose. Conclusions Our results suggest moderate one-dose and two-dose VE in infants. Larger sample size would allow more precise estimates for dose one, two and three.Peer ReviewedPostprint (published version

Effect of Early Administration of Clarithromycin or Azithromycin on Symptoms of Pertussis in Infants

Background: A resurgence of pertussis has been observed in several geographic areas in the post-COVID-19 era. Macrolides are the first-choice antibiotics for the treatment of pertussis. Limited data exist on the impact of the early administration of clarithromycin or azithromycin on infants' pertussis symptoms. Methods: This retrospective cohort study analyzed infants enrolled in an enhanced surveillance program for pertussis at a single Italian clinical reference center between 2015 and 2020. All cases were laboratory-confirmed. This study compared outcomes based on the timing of macrolide antibiotic treatment: early administration (within 7 days of cough onset) versus lateadministration (8 days or later). Key outcomes included cough duration, symptom frequency, and complication rates. Results: We studied 148 infants with confirmed pertussis. The median duration of coughing was 14 days in infants with early administration and 24 days in those with late administration. The occurrence of symptoms differed for apnea (62.6\% for early administration; 84.6\% for late administration). In a multivariable Cox model, the duration of the cough was lower in infants receiving antibiotics within 7 days from the beginning of the cough compared with those starting later (HR = 0.36, 95\% CI: 0.25-0.53, p &lt; 0.001). Clarithromycin was associated with a shorter duration of coughing (HR = 0.42, 95\% CI: 0.19-0.92, p = 0.030) independently from other factors. Regarding the occurrence of symptoms, children receiving antibiotics later were three times more likely to experience apnea compared to those treated early (p = 0.008). Conclusions: Early treatment with clarithromycin or azithromycin for infants with pertussis improves clinical symptoms. Clarithromycin may be more effective than azithromycin in shortening coughing. The early administration of antibiotics may also help prevent the spread of disease during the resurgence of pertussis and should be considered regardless of the laboratory confirmation, while taking into account the potential side effects of an unnecessary therapy