BackgroundDespite a worldwide decrease, sub-Saharan Africa (sSA) still has high incidence and the highest percentage of under 5 deaths (55%) in the world. This is due to several causes, including ...high incidence of infectious disease, often neglected or underreported, lacking effective treatments or vaccines. During our activities on Typhoid fever, Sclavo Vaccines Association (SVA) and Fondazione Achille Sclavo (FAS) came across increasing evidences in sSA of marked morbidity and mortality due to an unreported disease in children and HIV patients: invasive Non-Typhoidal Salmonellosis (iNTS)MethodsSVA and FAS, two nonprofit Italian institutions devoted to supporting development of vaccines for LICs, committed to catalyze funds and a group of institutions to fight this disease of the most vulnerable. The institutions applied for national and European funding, receiving first a validation at the local level, followed by funding from the EC and EDCTP. This stepwise approach created the necessary know-how to prepare solid projects, supporting a valid candidate vaccine fit for use in LICs. The projects synergistically address reasons why this disease is neglected: low epidemiology knowledge and disease awareness, lack of candidate vaccines and financial commitments.ResultsTwo projects were rejected at the national and EU level: finally a grant was obtained in Italy from the Tuscany Region (S-Afrivac) concentrating on epidemiology, disease modeling and vaccine and assay development. The successful conclusion of this project worked to open doors for two EU grants: the H2020 EC Vacc-iNTS and the EDCTP Pedvac-iNTS projects. Within 4 years, these projects multiplied tenfold the funds devoted in the EU to iNTS vaccine development.ConclusionThe validation of targeted projects against neglected diseases at the national level followed by synergistic submission to European Agencies in appropriate calls addressing all causes of neglection may significantly increase success in fighting these modern plagues of LMICs
IntroductionInvasive non-typhoidal Salmonellosis (iNTS) is mainly caused by Salmonella enterica serovars Typhimurium and Enteritidis and is estimated to result in 77 500 deaths per year, ...disproportionately affecting children under 5 years of age in sub-Saharan Africa. Invasive non-typhoidal Salmonellae serovars are increasingly acquiring resistance to first-line antibiotics, thus an effective vaccine would be a valuable tool in reducing morbidity and mortality from infection. While NTS livestock vaccines are in wide use, no licensed vaccines exist for use in humans. Here, a first-in-human study of a novel vaccine (iNTS-GMMA) containing S. Typhimurium and S. Enteritidis Generalised Modules for Membrane Antigens (GMMA) outer membrane vesicles is presented.Method and analysisThe Salmonella Vaccine Study in Oxford is a randomised placebo-controlled participant-observer blind phase I study of the iNTS-GMMA vaccine. Healthy adult volunteers will be randomised to receive three intramuscular injections of the iNTS-GMMA vaccine, containing equal quantities of S. Typhimurium and S. Enteritidis GMMA particles adsorbed on Alhydrogel, or an Alhydrogel placebo at 0, 2 and 6 months. Participants will be sequentially enrolled into three groups: group 1, 1:1 randomisation to low dose iNTS-GMMA vaccine or placebo; group 2, 1:1 randomisation to full dose iNTS-GMMA vaccine or placebo; group 3, 2:1 randomisation to full dose or lower dose (dependant on DSMC reviews of groups 1 and 2) iNTS-GMMA vaccine or placebo.The primary objective is safety and tolerability of the vaccine. The secondary objective is immunogenicity as measured by O-antigen based ELISA. Further exploratory objectives will characterise the expanded human immune profile.Ethics and disseminationEthical approval for this study has been obtained from the South Central—Oxford A Research Ethics Committee (Ethics REF:22/SC/0059). Appropriate documentation and regulatory approvals have been acquired. Results will be disseminated via peer-reviewed articles and conferences.Trial registration numberEudraCT Number: 2020-000510-14.
Non-typhoidal salmonella can cause serious, life-threatening invasive infections involving the bloodstream and other normally sterile sites. We aimed to systematically review the prevalence of ...complications and case-fatality ratio (CFR) of non-typhoidal salmonella invasive disease to provide contemporary global estimates and inform the development of vaccine and non-vaccine interventions.
We did a global systematic review and meta-analysis of studies investigating the complications and mortality associated with non-typhoidal salmonella invasive disease. We searched Embase, MEDLINE, Web of Science, and PubMed for peer-reviewed, primary research articles published from database inception up to June 4, 2021, with no restrictions on language, country, date, or participant demographics. Only studies reporting the proportion of complications or deaths associated with non-typhoidal salmonella invasive disease, confirmed by culture of samples taken from a normally sterile site (eg, blood or bone marrow) were included. We excluded case reports, case series, policy reports, commentaries, editorials, and conference abstracts. Data on the prevalence of complications and CFR were abstracted. The primary outcomes were to estimate the prevalence of complications and CFR of non-typhoidal salmonella invasive disease. We calculated an overall pooled CFR estimate and pooled CFR stratified by UN region, subregion, age group, and by serovar when available with a random-effects meta-analysis. A risk-of-bias assessment was done, and heterogeneity was assessed with Cochran's Q Test, I2, and τ2. This study was done in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, and is registered with PROSPERO, CRD42020202293.
The systematic review returned a total of 8770 records. After duplicates were removed, 5837 titles and abstracts were screened, yielding 84 studies from 35 countries after exclusions. Of these included studies, 77 (91·7%) were hospital-based and 66 (78·6%) were located in Africa or Asia. Among 55 studies reporting non-typhoidal salmonella disease-associated complications, a total of 45 different complications were reported and 1824 complication events were identified among 6974 study participants. The most prevalent complication was septicaemia, occurring in 171 (57·2%) of 299 participants, followed by anaemia in 580 (47·3%) of 1225 participants. From 81 studies reporting the CFR of non-typhoidal salmonella invasive disease, the overall pooled CFR estimate was 14·7% (95% CI 12·2–17·3). When stratified by UN region, the pooled CFR was 17·1% (13·6–21·0) in Africa, 14·0% (9·4–19·4) in Asia, 9·9% (6·4–14·0) in Europe, and 9·6% (0·0–25·1) in the Americas. Of all 84 studies, 66 (78·6%) had an overall high risk of bias, 18 (21·4%) had a moderate risk, and none had a low risk. Substantial heterogeneity (I2>80%) was observed in most (15 65·2% of 23) CFR estimates.
Complications were frequent among individuals with non-typhoidal salmonella invasive disease and approximately 15% of patients died. Clinicians, especially in African countries, should be aware of non-typhoidal salmonella invasive disease as a cause of severe febrile illness. Prompt diagnoses and management decisions, including empiric antimicrobial therapy, would improve patient outcomes. Additionally, investments in improving clinical microbiology facilities to identify non-typhoidal salmonella and research efforts towards vaccine development and non-vaccine prevention measures would prevent non-typhoidal salmonella invasive disease-associated illness and death.
EU Horizon 2020 research and innovation programme.
We sought to collate and summarize high-quality data on non-typhoidal Salmonella invasive disease (iNTS) incidence to provide contemporary incidence estimates by location and year.
We systematically ...searched the databases Embase + MEDLINE, Web of Science, and PubMed for articles published on the incidence of iNTS from inception of the database through 8 May 2020 with no language, country, date, or demographic restrictions applied. A meta-analysis was performed to report pooled iNTS incidence as a rate of cases per 100,000 per year.
Among 13 studies eligible for analysis, there were 68 estimates of incidence. Overall pooled incidence (95% CI) was 44.8 (31.5–60.5) per 100,000 persons per year. When stratified by region, pooled incidence was significantly higher in Africa than Asia, 51.0 (36.3–68.0) compared to 1.0 (0.2–2.5), respectively. Incidence was consistently higher in children aged <5 years compared with older age groups. Incidence displayed considerable heterogeneity in both place and time, varying substantially between locations and over consecutive years in the same location.
iNTS incidence varies by region, location, age group, and over time. Concerted efforts are needed to address the limited high-quality data available on iNTS disease incidence.
Abstract On 17 and 18 July 2015, a meeting in Siena jointly sponsored by ADITEC and GlaxoSmithKline (GSK) was held to review the goals of the Global Health 2035 Grand Convergence, to discuss current ...vaccine evaluation methods, and to determine the feasibility of reaching consensus on an assessment framework for comprehensively and accurately capturing the full benefits of vaccines. Through lectures and workshops, participants reached a consensus that Multi-Criteria-Decision-Analysis is a method suited to systematically account for the many variables needed to evaluate the broad benefits of vaccination, which include not only health system savings, but also societal benefits, including benefits to the family and increased productivity. Participants also agreed on a set of “core values” to be used in future assessments of vaccines for development and introduction. These values include measures of vaccine efficacy and safety, incident cases prevented per year, the results of cost-benefit analyses, preventable mortality, and the severity of the target disease. Agreement on this set of core assessment parameters has the potential to increase alignment between manufacturers, public health agencies, non-governmental organizations (NGOs), and policy makers (see Global Health 2035 Mission Grand Convergence 1 ). The following sections capture the deliberations of a workshop (Working Group 4) chartered to: (1) review the list of 24 parameters selected from SMART vaccines (see the companion papers by Timmis et al. and Madhavan et al., respectively) to determine which represent factors (see Table 1 ) that should be taken into account when evaluating the role of vaccines in maximizing the success of the Global Health 2035 Grand Convergence; (2) develop 3–5 “core values“ that should be taken into account when evaluating vaccines at various stages of development; and (3) determine how vaccines can best contribute to the Global Health 2035 Grand Convergence effort.
Invasive non-Typhoidal Salmonella (iNTS) is one of the leading causes of blood stream infections in Sub-Saharan Africa, especially among children. iNTS can be difficult to diagnose, particularly in ...areas where malaria is endemic and difficult to treat, partly because of the emergence of antibiotic resistance. We developed a mathematical model to evaluate the impact of a vaccine for iNTS in 49 countries of sub-Saharan Africa. Without vaccination we estimate 9.2 million new iNTS cases among children below 5 years old in these 49 countries from 2022 to 2038, 6.2 million of which between 2028 and 2038. The introduction of a 85% (95%) efficacy vaccine in 2028 would prevent 2.6 (2.9) million of these new infections. We provide the country-specific impact of a iNTS vaccine considering the different age structures and vaccine coverage levels.
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