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      Comparative immunogenicity and efficacy of equivalent outer membrane vesicle and glycoconjugate vaccines against nontyphoidal Salmonella

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          Abstract

          Significance Bacteria, such as nontyphoidal Salmonella, are responsible for a large global burden of disease. Due to limited need in developed countries and consequent lack of commercial incentive, vaccines are unavailable against many bacteria. Glycoconjugates constitute the standard bacterial vaccine approach, but can be costly, particularly where multivalent preparations are required. This report compares a low-cost vesicle-based technology, known as Generalized Modules for Membrane Antigens (GMMA), with glycoconjugate in bivalent vaccines against nontyphoidal Salmonella. In head-to-head immunogenicity and infection studies in mice, GMMA performed at least as well as equivalent glycoconjugate vaccine, indicating good potential of this approach. Given that many bacteria are amenable to genetic engineering for GMMA production, the GMMA strategy could provide a breakthrough for a range of needed bacterial vaccines.

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          Most cited references32

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          Maintaining protection against invasive bacteria with protein-polysaccharide conjugate vaccines.

          Polysaccharide-encapsulated organisms are the leading cause of bacterial meningitis and pneumonia in children. The use of protein-polysaccharide conjugate vaccines in developed countries over the past two decades has markedly decreased the burden of disease and mortality from these organisms through direct protection of the immunized and through herd immunity. In the next decade, the widespread use of conjugate vaccines in the developing world should prevent millions of deaths. In this Science and Society article, we describe how vaccine-induced immunity wanes rapidly after vaccination in early childhood and argue that strategies that sustain protection in the population must be considered.
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            Salmonella infections in immunocompromised adults.

            Clinical syndromes caused by Salmonella infection in humans are divided into typhoid fever, caused by Salmonella typhi and Salmonella paratyphi, and a range of clinical syndromes, including diarrhoeal disease, caused by a large number of non-typhoidal salmonella serovars (NTS). Typhoid is a human-restricted and highly adapted invasive disease, but shows little association with immunocompromise. In contrast, NTS have a broad vertebrate host range, epidemiology that often involves food animals, and have a dramatically more severe and invasive presentation in immunocompromised adults, in particular in the context of HIV. Immunocompromise among adults, including underlying severe or progressive disease, chronic granulomatous disease, defects or blockade of specific cytokines (particularly IL-12/IL-23/IL-17 and TNF), and HIV, is associated with suppurative foci and with primary bacteraemic disease, which may be recurrent. These patients have markedly increased mortality. Worldwide, invasive recurrent NTS bacteraemia associated with advanced HIV disease is a huge problem, and the epidemiology in this context may be more human-restricted than in other settings. This review will describe the presentation and pathogenesis of NTS in different categories of immunocompromised adults, contrasted to typhoid fever.
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              • Article: not found

              Antimicrobial resistance and management of invasive Salmonella disease.

              Invasive Salmonella infections (typhoidal and non-typhoidal) cause a huge burden of illness estimated at nearly 3.4 million cases and over 600,000 deaths annually especially in resource-limited settings. Invasive non-typhoidal Salmonella (iNTS) infections are particularly important in immunosuppressed populations especially in sub-Saharan Africa, causing a mortality of 20-30% in vulnerable children below 5 years of age. In these settings, where routine surveillance for antimicrobial resistance is rare or non-existent, reports of 50-75% multidrug resistance (MDR) in NTS are common, including strains of NTS also resistant to flouroquinolones and 3rd generation cephalosporins. Typhoid (enteric) fever caused by Salmonella Typhi and Salmonella Paratyphi A remains a major public health problem in many parts of Asia and Africa. Currently over a third of isolates in many endemic areas are MDR, and diminished susceptibility or resistance to fluoroquinolones, the drugs of choice for MDR cases over the last decade is an increasing problem. The situation is particularly worrying in resource-limited settings where the few remaining effective antimicrobials are either unavailable or altogether too expensive to be afforded by either the general public or by public health services. Although the prudent use of effective antimicrobials, improved hygiene and sanitation and the discovery of new antimicrobial agents may offer hope for the management of invasive salmonella infections, it is essential to consider other interventions including the wider use of WHO recommended typhoid vaccines and the acceleration of trials for novel iNTS vaccines. The main objective of this review is to describe existing data on the prevalence and epidemiology of antimicrobial resistant invasive Salmonella infections and how this affects the management of these infections, especially in endemic developing countries.
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                Author and article information

                Journal
                Proceedings of the National Academy of Sciences
                Proc Natl Acad Sci USA
                Proceedings of the National Academy of Sciences
                0027-8424
                1091-6490
                October 09 2018
                October 09 2018
                October 09 2018
                September 27 2018
                : 115
                : 41
                : 10428-10433
                Article
                10.1073/pnas.1807655115
                3e1a48c9-d3ec-45d7-a70d-9923b91806b3
                © 2018
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