Human Nasal Challenge with Streptococcus pneumoniae Is Immunising in the Absence of Carriage

Infectious challenge of the human nasal mucosa elicits immune responses that determine the fate of the host-bacterial interaction; leading either to clearance, colonisation and/or disease. Persistent antigenic exposure from pneumococcal colonisation can induce both humoral and cellular defences that are protective against carriage and disease. We challenged healthy adults intra-nasally with live 23F or 6B Streptococcus pneumoniae in two sequential cohorts and collected nasal wash, bronchoalveolar lavage (BAL) and blood before and 6 weeks after challenge. We hypothesised that both cohorts would successfully become colonised but this did not occur except for one volunteer. The effect of bacterial challenge without colonisation in healthy adults has not been previously assessed. We measured the antigen-specific humoral and cellular immune responses in challenged but not colonised volunteers by ELISA and Flow Cytometry. Antigen-specific responses were seen in each compartment both before and after bacterial challenge for both cohorts. Antigen-specific IgG and IgA levels were significantly elevated in nasal wash 6 weeks after challenge compared to baseline. Immunoglobulin responses to pneumococci were directed towards various protein targets but not capsular polysaccharide. 23F but not 6B challenge elevated IgG anti-PspA in BAL. Serum immunoglobulins did not increase in response to challenge. In neither challenge cohort was there any alteration in the frequencies of TNF, IL-17 or IFNγ producing CD4 T cells before or after challenge in BAL or blood. We show that simple, low dose mucosal exposure with pneumococci may immunise mucosal surfaces by augmenting anti-protein immunoglobulin responses; but not capsular or cellular responses. We hypothesise that mucosal exposure alone may not replicate the systemic immunising effect of experimental or natural carriage in humans

A Disease Without History? Evidence for the Antiquity of Head and Neck Cancers

There has been a long-running debate in anthropological, archaeological, and medical literature regarding the prevalence of cancer in various ancient human populations. At one extreme, some scholars have claimed that past human societies had rates of cancer roughly equivalent to those seen among modern peoples; at the other extreme, some researchers have effectively claimed that cancer is a disease of modernity. The present study aims to shed further light on this topic, at least insofar as cancers of the head and neck are concerned. A review of ancient art, medical texts, and paleopathological reports revealed somewhat discordant accounts of the age, geographical distribution, and prevalence of head and neck cancers. While representations of these neoplastic conditions in art are relatively rare and patchy in geographic distribution, descriptions of suspect lesions in ancient medical texts are rather more widespread, if unevenly distributed geographically, and the paleopathological record was found to contain surprisingly abundant evidence for cancers of the head and neck, especially as compared to what are, in modern societies, more ubiquitous cancers of the breast, lung, or prostate. While establishing the absolute prevalence of any of these conditions in antiquity is impossible, the present work establishes that cancers of the head and neck have long been present, and perhaps even prevalent, in human societies