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Current Opinion in Infectious Diseases Oct 2018Diarrhoea is a major global health problem, and recent studies have confirmed Shigella as a major contributor to this burden. Here, we review recent advances in Shigella... (Review)
Review
PURPOSE OF REVIEW
Diarrhoea is a major global health problem, and recent studies have confirmed Shigella as a major contributor to this burden. Here, we review recent advances in Shigella research; focusing on their epidemiology, pathogenesis, antimicrobial resistance, and the role of the gut microbiome during infection.
RECENT FINDINGS
Enhanced epidemiological data, combined with new generation diagnostics, has highlighted a greater burden of Shigella disease than was previously estimated, which is not restricted to vulnerable populations in low-middle income countries. As we gain an ever more detailed insight into the orchestrated mechanisms that Shigella exploit to trigger infection, we can also begin to appreciate the complex role of the gut microbiome in preventing and inducing such infections. The use of genomics, in combination with epidemiological data and laboratory investigations, has unravelled the evolution and spread of various species. Such measures have identified resistance to antimicrobials as a key contributor to the success of specific clones.
SUMMARY
We need to apply novel findings towards sustainable approaches for treating and preventing Shigella infections. Vaccines and alternative treatments are under development and may offer an opportunity to reduce the burden of Shigella disease and restrict the mobility of antimicrobial resistant clones.
Topics: Anti-Bacterial Agents; Antibiosis; Communicable Disease Control; Diarrhea; Dysentery, Bacillary; Gastrointestinal Microbiome; Global Health; Humans; Shigella; Shigella Vaccines
PubMed: 30048255
DOI: 10.1097/QCO.0000000000000475 -
Human Vaccines & Immunotherapeutics Dec 2023The ongoing COVID-19 pandemic highlights that complications and mortality associated with infectious diseases increase with age. Various vaccines are recommended for... (Review)
Review
The ongoing COVID-19 pandemic highlights that complications and mortality associated with infectious diseases increase with age. Various vaccines are recommended for adults, but coverage rates remain suboptimal. Although co-administration would improve vaccine uptake and timely immunization, this is not routine practice in adults. We review key data on co-administration of vaccines in children and adults to reassure healthcare providers about its safety and advantages. In European countries and the United States, combined tetanus, diphtheria, and acellular pertussis boosters as well as meningococcal and human papillomavirus vaccines are recommended for healthy adolescents and adults of certain ages. Vaccination against influenza (annually), pneumococcal disease, and herpes zoster is recommended for older adults and specific risk groups. While co-administration is well established in children, it is less common in adults. Travelers can also receive multiple co-administered vaccines. Pediatric and travel vaccine co-administration has a well-established positive benefit-risk profile and is an efficient and cost-saving strategy to improve coverage. Healthcare providers could more often recommend and practice vaccine co-administration; this would not risk patient safety and health, would improve protection against vaccine-preventable diseases, and would help comply with national vaccination calendars. Recommending bodies may consider revising vaccination schedules to reduce the number of visits.
Topics: Adolescent; Humans; Child; United States; Aged; Vaccination Coverage; Pandemics; COVID-19; Vaccination; Tetanus Toxoid; Diphtheria-Tetanus-acellular Pertussis Vaccines
PubMed: 37039318
DOI: 10.1080/21645515.2023.2195786 -
The Lancet. Microbe Feb 2023Vaccines can be highly effective tools in combating antimicrobial resistance as they reduce infections caused by antibiotic-resistant bacteria and antibiotic consumption... (Review)
Review
Vaccines can be highly effective tools in combating antimicrobial resistance as they reduce infections caused by antibiotic-resistant bacteria and antibiotic consumption associated with disease. This Review looks at vaccine candidates that are in development against pathogens on the 2017 WHO bacterial priority pathogen list, in addition to Clostridioides difficile and Mycobacterium tuberculosis. There were 94 active preclinical vaccine candidates and 61 active development vaccine candidates. We classified the included pathogens into the following four groups: Group A consists of pathogens for which vaccines already exist-ie, Salmonella enterica serotype Typhi, Streptococcus pneumoniae, Haemophilus influenzae type b, and M tuberculosis. Group B consists of pathogens with vaccines in advanced clinical development-ie, extra-intestinal pathogenic Escherichia coli, Salmonella enterica serotype Paratyphi A, Neisseria gonorrhoeae, and C difficile. Group C consists of pathogens with vaccines in early phases of clinical development-ie, enterotoxigenic E coli, Klebsiella pneumoniae, non-typhoidal Salmonella, Shigella spp, and Campylobacter spp. Finally, group D includes pathogens with either no candidates in clinical development or low development feasibility-ie, Pseudomonas aeruginosa, Acinetobacter baumannii, Staphylococcus aureus, Helicobacter pylori, Enterococcus faecium, and Enterobacter spp. Vaccines are already important tools in reducing antimicrobial resistance and future development will provide further opportunities to optimise the use of vaccines against resistance.
Topics: Anti-Bacterial Agents; Bacterial Vaccines; Escherichia coli; Drug Resistance, Bacterial; Enterococcus faecium
PubMed: 36528040
DOI: 10.1016/S2666-5247(22)00303-2 -
Jornal de Pediatria 2020To restate the epidemiological importance of Shigella in acute diarrhea with blood, providing an overview of the treatment and stressing the need for the correct... (Review)
Review
OBJECTIVE
To restate the epidemiological importance of Shigella in acute diarrhea with blood, providing an overview of the treatment and stressing the need for the correct indication of antibiotic therapy.
SOURCES OF DATA
A search was carried out in the Medline and Scopus databases, in addition to the World Health Organization scientific documents and guidelines, identifying review articles and original articles considered relevant to substantiate the narrative review.
SYNTHESIS OF DATA
Different pathogens have been associated with acute diarrhea with blood; Shigella was the most frequently identified. The manifestations of shigellosis in healthy individuals are usually of moderate intensity and disappear within a few days. There may be progression to overt dysentery with blood and mucus, lower abdominal pain, and tenesmus. Conventional bacterial stool culture is the gold standard for the etiological diagnosis; however, new molecular tests have been developed to allow the physician to initiate targeted antibacterial treatment, addressing a major current concern caused by the increasing resistance of Shigella. Prevention strategies include breastfeeding, hygiene measures, health education, water treatment, and the potential use of vaccines.
CONCLUSIONS
Acute diarrhea is an important cause of mortality in children under 5 years and shigellosis is the leading cause of acute diarrhea with blood worldwide. The current concern is the increase in microbial resistance to the recommended antibiotics, which brings an additional difficulty to therapeutic management. Although no vaccine is yet available against Shigella, several candidates are undergoing clinical trials, and this may be the most cost-effective preventative measure in future.
Topics: Diarrhea; Dysentery, Bacillary; Feces; Humans; Pharmaceutical Preparations; Shigella
PubMed: 31604059
DOI: 10.1016/j.jped.2019.08.006 -
Vaccine Aug 2019
Topics: Animals; Congresses as Topic; Dysentery, Bacillary; Enterotoxigenic Escherichia coli; Escherichia coli Infections; Escherichia coli Vaccines; Humans; Immunization; Mexico; Shigella; Shigella Vaccines
PubMed: 31300286
DOI: 10.1016/j.vaccine.2019.06.085 -
Vaccines Aug 2022is the leading cause of global diarrheal deaths that currently lacks a licensed vaccine. Shigellosis drives antimicrobial resistance and leads to economic impact... (Review)
Review
is the leading cause of global diarrheal deaths that currently lacks a licensed vaccine. Shigellosis drives antimicrobial resistance and leads to economic impact through linear growth faltering. Today, there is a robust pipeline of vaccines in clinical development which are broadly divided into parenteral glycoconjugate vaccines, consisting of O-antigen conjugated to carrier proteins, and oral live attenuated vaccines, which incorporate targeted genetic mutations seeking to optimize the balance between reactogenicity, immunogenicity and ultimately protection. Proof of efficacy has previously been shown with both approaches but for various reasons no vaccine has been licensed to date. In this report, we outline the requirements for a vaccine and describe the current pipeline in the context of the many candidates that have previously failed or been abandoned. The report refers to papers from individual vaccine developers in this special supplement of which is focused on vaccines. Once readouts of safety and immunogenicity from current trials of lead candidate vaccines among the target population of young children in low- and middle-income countries are available, the likely time to licensure of a first vaccine will become clearer.
PubMed: 36146457
DOI: 10.3390/vaccines10091376 -
Vaccines Sep 2022In recent years, there has been a resurgence of interest in the development of vaccines against driven by the growing awareness of the impact of this pathogen on global...
In recent years, there has been a resurgence of interest in the development of vaccines against driven by the growing awareness of the impact of this pathogen on global health [...].
PubMed: 36146614
DOI: 10.3390/vaccines10091536 -
Pathogens (Basel, Switzerland) Oct 2021Significant advancement has been made in the development of vaccines against bacterial pathogens. However, several roadblocks have been found during the evaluation of... (Review)
Review
Significant advancement has been made in the development of vaccines against bacterial pathogens. However, several roadblocks have been found during the evaluation of vaccines against intracellular bacterial pathogens. Therefore, new lessons could be learned from different vaccines developed against unrelated intracellular pathogens. Bacillary dysentery and melioidosis are important causes of morbidity and mortality in developing nations, which are caused by the intracellular bacteria and , respectively. Although the mechanisms of bacterial infection, dissemination, and route of infection do not provide clues about the commonalities of the pathogenic infectious processes of these bacteria, a wide variety of vaccine platforms recently evaluated suggest that in addition to the stimulation of antibodies, identifying protective antigens and inducing T cell responses are some additional required elements to induce effective protection. In this review, we perform a comparative evaluation of recent candidate vaccines used to combat these two infectious agents, emphasizing the common strategies that can help investigators advance effective and protective vaccines to clinical trials.
PubMed: 34832508
DOI: 10.3390/pathogens10111353 -
Vaccine Aug 2019PATH hosted the second Vaccines Against Shigella and Enterotoxigenic Escherichia coli (VASE) Conference in Mexico City in June 2018, again providing experts from around... (Review)
Review
PATH hosted the second Vaccines Against Shigella and Enterotoxigenic Escherichia coli (VASE) Conference in Mexico City in June 2018, again providing experts from around the world an opportunity to participate in a highly collaborative forum to discuss progress in the development of new enteric vaccines. Through a combination of plenary sessions and posters, keynote presentations, and workshops, the 2018 VASE Conference aimed to accelerate communication and progress among those working to achieve the goal of licensed vaccines against these two bacterial pathogens. Many presentations recognized the importance of diarrheal disease and long-term sequelae caused by infections with Shigella and enterotoxigenic E. coli (ETEC). Other presentations explored new strategies for vaccine development, including the search for novel, possibly conserved, antigens for more effective vaccines. Much progress is being made as some vaccine candidates are now moving through clinical trials. Research presented in oral and poster presentations at the VASE Conference covered a range of topics, including: the global burden of disease, epidemiology, and health economics; host parameters and genomics that predict responses to infection and disease; preclinical evaluations of vaccine antigens and models of enteric diseases; and vaccine candidates in clinical trials and human challenge studies. This article reviews key points and highlighted research presented in each of the plenary conference sessions and poster presentations at the 2018 VASE Conference.
Topics: Animals; Antigens, Bacterial; Clinical Trials as Topic; Congresses as Topic; Diarrhea; Disease Models, Animal; Dysentery, Bacillary; Enterotoxigenic Escherichia coli; Escherichia coli Infections; Escherichia coli Vaccines; Host-Pathogen Interactions; Humans; Immunization; Macaca mulatta; Mice; Shigella; Shigella Vaccines
PubMed: 31358236
DOI: 10.1016/j.vaccine.2019.02.070 -
Vaccine Jul 2023There is a need for vaccines effective against shigella infection in young children in resource-limited areas. Protective immunity against shigella infection targets the...
There is a need for vaccines effective against shigella infection in young children in resource-limited areas. Protective immunity against shigella infection targets the O-specific polysaccharide (OSP) component of lipopolysaccharide. Inducing immune responses to polysaccharides in young children can be problematic, but high level and durable responses can be induced by presenting polysaccharides conjugated to carrier proteins. An effective shigella vaccine will need to be multivalent, targeting the most common global species and serotypes such as Shigella flexneri 2a, S. flexneri 3a, S. flexneri 6, and S. sonnei. Here we report the development of shigella conjugate vaccines (SCV) targeting S. flexneri 2a (SCV-Sf2a) and 3a (SCV-Sf3a) using squaric acid chemistry to result in single point sun-burst type display of OSP from carrier protein rTTHc, a 52 kDa recombinant protein fragment of the heavy chain of tetanus toxoid. We confirmed structure and demonstrated that these conjugates were recognized by serotype-specific monoclonal antibodies and convalescent sera of humans recovering from shigellosis in Bangladesh, suggesting correct immunological display of OSP. We vaccinated mice and found induction of serotype-specific OSP and LPS IgG responses, as well as rTTHc-specific IgG responses. Vaccination induced serotype-specific bactericidal antibody responses against S. flexneri, and vaccinated animals were protected against keratoconjunctivitis (Sereny test) and intraperitoneal challenge with virulent S. flexneri 2a and 3a, respectively. Our results support further development of this platform conjugation technology in the development of shigella conjugate vaccines for use in resource-limited settings.
Topics: Humans; Child; Animals; Mice; Child, Preschool; Shigella Vaccines; Shigella flexneri; Vaccines, Conjugate; Dysentery, Bacillary; Shigella; Lipopolysaccharides; O Antigens; Antibodies, Bacterial; Immunoglobulin G
PubMed: 37400283
DOI: 10.1016/j.vaccine.2023.06.052