Increased lytic efficiency of bovine macrophages trained with killed mycobacteria

Innate immunity is evolutionarily conserved in multicellular organisms and was considered to lack memory until very recently. One of its more characteristic mechanisms is phagocytosis, the ability of cells to engulf, process and eventually destroy any injuring agent. We report the results of an ex vivo experiment in bovine macrophages in which improved clearance of Mycobacterium bovis (M. bovis) was induced by pre-exposure to a heat killed M. bovis preparation. The effects were independent of humoral and cellular adaptive immune responses and lasted up to six months. Specifically, our results demonstrate the existence of a training effect in the lytic phase of phagocytosis that can be activated by killed mycobacteria, thus suggesting a new mechanism of vaccine protection. These findings are compatible with the recently proposed concept of trained immunity, which was developed to explain the observation that innate immune responses provide unspecific protection against pathogens including other than those that originally triggered the immune response.Funding for these studies was provided by the EU project WildTBVac (Contract #613799) and by grants from the Instituto Nacional de Investigación y Tecnología Agraria y alimentaria (INIA, RTA2011-00049) and the Ministry of Science (MINECO, AGL2014-56305) and European Funds Regional Development (FEDER).Peer Reviewe

Protection against Diarrhea Associated with Giardia intestinalis Is Lost with Multi-Nutrient Supplementation: A Study in Tanzanian Children

Giardia intestinalis is a well-known cause of diarrhea in industrialized countries. In children in developing countries, asymptomatic infections are common and their role as cause of diarrhea has been questioned. In a cohort of rural Tanzanian pre-school children, we assessed the association between the presence of Giardia at baseline and subsequent diarrhea risk. The study was conducted in the context of a randomised trial assessing the effect of supplementation with zinc and other micro-nutrients on malaria, and half of the children daily received a multi-nutrient supplement. Surprisingly, we found that the presence of Giardia at baseline was associated with a substantial reduction in diarrhea risk. Multivariate statistical analysis showed that this protection could not be explained by differences in age or walking distance to the dispensary between children with and without Giardia. Because we cannot exclude that children differed in other (unmeasured) characteristics, we cannot draw firm conclusions about the causality of the observed association, but our findings support the view that the parasite is not an important cause of diarrhea in highly endemic settings. Striking was that the Giardia-associated protection was lost when children received multi-nutrients. Our data do not provide information about the mechanisms involved, but suggest that multi-nutrients may influence the compositionor pathogenicity of intestinal biota

Immunogenicity and efficacy of oral vaccines in developing countries: lessons from a live cholera vaccine

Oral vaccines, whether living or non-living, viral or bacterial, elicit diminished immune responses or have lower efficacy in developing countries than in developed countries. Here I describe studies with a live oral cholera vaccine that include older children no longer deriving immune support from breast milk or maternal antibodies and that identify some of the factors accounting for the lower immunogenicity, as well as suggesting counter-measures that may enhance the effectiveness of oral immunization in developing countries. The fundamental breakthrough is likely to require reversing effects of the 'environmental enteropathy' that is often present in children living in fecally contaminated, impoverished environments

Drug resistance beyond XDR-TB: results from a large individual patient data meta-analysis.

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Drug resistance beyond extensively drug-resistant tuberculosis: individual patient data meta-analysis

The broadest pattern of tuberculosis drug resistance for which a consensus definition exists is extensively drug-resistant tuberculosis (XDR-TB). It is not known if additional drug resistance portends worsened patient outcomes. This study compares treatment outcomes of XDR-TB patients with and without additional resistance to explore the need for a new definition.Individual patient data on XDR-TB outcomes were included in a meta-analysis comparing outcomes between XDR-alone and three non-mutually exclusive XDR-TB patient groups: XDR plus resistance to all the second-line injectables (sli) capreomycin and kanamycin/amikacin (XDR+2sli); XDR plus resistance to second-line injectables and to 651 Group 4 drug, i.e.: ethionamide/prothionamide, cycloserine/terizidone or PAS (XDR+sliG4); and XDR+sliG4 plus resistance to ethambutol and/or pyrazinamide (XDR+sliG4EZ).Of 405 XDR-TB cases, 301 were XDR-alone; 68 XDR+2sli; 48 XDR+sliG4; and 42 XDR+sliG4EZ. In multivariate analysis, the odds of cure were significantly lower in XDR+2sli (adjusted Odds Ratio (aOR): 0.4; 95% Confidence Interval: 0.2-0.8) compared to XDR-alone, while odds of failure+death were higher in all XDR patients with additional resistance (aOR range: 2.6-2.8).Patients with additional resistance beyond XDR-TB showed poorer outcomes. Limitations in availability, accuracy and reproducibility of current DST methods preclude the adoption of a useful definition beyond the one currently used for XDR-TB