Typhoid vaccines. Historical aspects of typhoid vaccine development, and currently available products

Typhoid fever is an acute infectious disease caused by Salmonella enterica subsp. enterica serovar Typhi (S. Typhi), which is still extremely common in endemic low- and middle-income countries of Asia and Africa. Industrialised countries may also be affected by typhoid fever outbreaks due to booming international tourism, and natural disasters. Given S. Typhi progressive resistance to antibiotics, high epidemiological burden, and lack of adequate sanitation and hygiene in a number of regions, the introduction of new treatment protocols and the improvement of preventive vaccination are critical tasks in global healthcare. The aim of the study was to highlight the main historical aspects of the typhoid vaccine development, to summarise data on the licensed vaccines and promising approaches to the development of new typhoid vaccines. The paper describes the current epidemiological situation of typhoid fever globally and in the Russian Federation. It dwells upon the global experience in typhoid vaccine development from the production of an inactivated vaccine to the development of conjugated vaccines. The paper summarises data on Russian and foreign-made typhoid fever vaccines currently available in the global pharmaceutical market. It outlines the main trends in the development of vaccines against the disease caused by S. Typhi. The paper demonstrates the need for improving the efficacy of existing vaccines and development of new typhoid combination vaccines.

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Review on the Recent Advances on Typhoid Vaccine Development and Challenges Ahead

Clinical Infectious Diseases ◽

10.1093/cid/ciaa504 ◽

2020 ◽

Vol 71 (Supplement_2) ◽

pp. S141-S150

Author(s):

Khalid Ali Syed ◽

Tarun Saluja ◽

Heeyoun Cho ◽

Amber Hsiao ◽

Hanif Shaikh ◽

...

Keyword(s):

Typhoid Fever ◽

Low Income ◽

Vaccine Development ◽

Middle Income ◽

Middle Income Countries ◽

Sanitation And Hygiene ◽

Contaminated Food ◽

Improved Sanitation ◽

Typhoid Vaccines ◽

And Control

Abstract Control of Salmonella enterica serovar typhi (S. typhi), the agent of typhoid fever, continues to be a challenge in many low- and middle-income countries. The major transmission route of S. typhi is fecal-oral, through contaminated food and water; thus, the ultimate measures for typhoid fever prevention and control include the provision of safe water, improved sanitation, and hygiene. Considering the increasing evidence of the global burden of typhoid, particularly among young children, and the long-term horizon for sustained, effective water and sanitation improvements in low-income settings, a growing consensus is to emphasize preventive vaccination. This review provides an overview of the licensed typhoid vaccines and vaccine candidates under development, and the challenges ahead for introduction.

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Why Is Eradicating Typhoid Fever So Challenging: Implications for Vaccine and Therapeutic Design

Vaccines ◽

10.3390/vaccines6030045 ◽

2018 ◽

Vol 6 (3) ◽

pp. 45 ◽

Cited By ~ 6

Author(s):

Yi-An Yang ◽

Alexander Chong ◽

Jeongmin Song

Keyword(s):

Typhoid Fever ◽

Treatment Strategies ◽

Significant Risk ◽

Multidrug Resistant ◽

Middle Income ◽

Salmonella Enterica Serovar Typhi ◽

Middle Income Countries ◽

Extensively Drug Resistant ◽

Typhoid Vaccines ◽

Do So

Salmonella enterica serovar Typhi (S. Typhi) and S. Paratyphi, namely typhoidal Salmonellae, are the cause of (para) typhoid fever, which is a devastating systemic infectious disease in humans. In addition, the spread of multidrug-resistant (MDR) and extensively drug-resistant (XDR) S. Typhi in many low and middle-income countries poses a significant risk to human health. While currently available typhoid vaccines and therapeutics are efficacious, they have some limitations. One important limitation is the lack of controlling individuals who chronically carry S. Typhi. However, due to the strict host specificity of S. Typhi to humans, S. Typhi research is hampered. As a result, our understanding of S. Typhi pathogenesis is incomplete, thereby delaying the development and improvement of prevention and treatment strategies. Nonetheless, to better combat and contain S. Typhi, it is vital to develop a vaccine and therapy for controlling both acutely and chronically infected individuals. This review discusses how scientists are trying to combat typhoid fever, why it is so challenging to do so, which approaches show promise, and what we know about the pathogenesis of S. Typhi chronic infection.

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Toxicity evaluation of recombinant Fim-C Salmonella typhi Protein on ddY Mice for Typhoid Vaccine Development

10.21203/rs.2.24308/v1 ◽

2020 ◽

Author(s):

Muktiningsih Nurjayadi ◽

Wibowo - Mangunwardoyo ◽

Kurnia - Agustini ◽

Gina Riesky Wulandari ◽

Gina - Astuti ◽

...

Keyword(s):

Typhoid Fever ◽

Vaccine Development ◽

Vaccine Candidate ◽

Lethal Dose ◽

Salmonella Typhi ◽

Acute Toxicity Test ◽

Typhoid Vaccine ◽

Toxicity Evaluation ◽

C Protein ◽

Male And Female

Abstract Background: Typhoid fever is caused by Salmonella typhi infection, commonly occurs in developing countries from bad sanitation and living conditions. Vaccination against the fever has been developed by means of induction of antibody through introduction of Fim-C, one of the virulence factor proteins on the cell surface of the bacterium. Recently, we have cloned and overexpressed the protein in Escherichia coli . The 31 kDa recombinant Fim-C induced immune response upon introduction to ddY mice at a concentration of 40-60 µg/mL, indicating its potency as an anti-typhoid fever vaccine candidate. Objective: In this study, the safety of the protein was evaluated through abnormal and acute toxicity test in ddY mice, as well as determine its lethal dose (LD50). Methods: Forty of equal number male and female mice were recruited and observed according to the physiology, body weight and temperature, and mortality rate was performed on fourteenth days after immunization. Results: No abnormalities were observed at 25 µg/mL while 60% mortality occurred at 125 µg/mL. The latter observation correlates with our finding that the LD50 of the recombinant Fim-C was 123.5 µg/mL. Conclusion: Our results suggest that the recombinant Fim-C protein is safe for use as anti typhoid fever vaccine.

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A Review of the Community Health Club Literature Describing Water, Sanitation, and Hygiene Outcomes

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18041880 ◽

2021 ◽

Vol 18 (4) ◽

pp. 1880

Author(s):

Jason Rosenfeld ◽

Ruth Berggren ◽

Leah Frerichs

Keyword(s):

Social Capital ◽

Collective Action ◽

Community Health ◽

Theory Of Change ◽

Health Promotion Program ◽

Review Of The Literature ◽

Middle Income ◽

Health Club ◽

Qualitative Evidence ◽

Sanitation And Hygiene

The Community Health Club (CHC) model is a community-based health promotion program that utilizes water, sanitation, and hygiene (WASH) education as the first stage of a longitudinal development process. Although the CHC model has been implemented in fourteen countries over 20 years, this is the first review of the literature describing the model’s outcomes and impact. We conducted a review of the literature that provided quantitative or qualitative evidence of CHC interventions focused on WASH in low- and middle-income countries. We identified 25 articles that met our inclusion criteria. We found six major outcomes: WASH behaviors and knowledge, social capital, collective action, health, and cost or cost-effectiveness. The most consistent evidence was associated with WASH behaviors and knowledge, with significant effects on defecation practices, hand washing behaviors, and WASH knowledge. We also found qualitative evidence of impact on social capital and collective action. CHCs catalyze favorable changes in WASH behaviors and knowledge, yielding outcomes commensurate with other WASH promotion strategies. This review provides insights into the model’s theory of change, helping identify areas for further investigation. The CHC model’s holistic focus and emphasis on individual and collective change offer promising potential to address multiple health and development determinants.

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Massachusetts’ Findings from Statewide Newborn Screening for Spinal Muscular Atrophy

International Journal of Neonatal Screening ◽

10.3390/ijns7020026 ◽

2021 ◽

Vol 7 (2) ◽

pp. 26

Author(s):

Jaime E. Hale ◽

Basil T. Darras ◽

Kathryn J. Swoboda ◽

Elicia Estrella ◽

Jin Yun Helen Chen ◽

...

Keyword(s):

Spinal Muscular Atrophy ◽

Newborn Screening ◽

New England ◽

Screening Program ◽

Muscular Atrophy ◽

Treatment Options ◽

Newborn Screening Program ◽

Treatment Protocols ◽

Screening Algorithm ◽

New Treatment

Massachusetts began newborn screening (NBS) for Spinal Muscular Atrophy (SMA) following the availability of new treatment options. The New England Newborn Screening Program developed, validated, and implemented a screening algorithm for the detection of SMA-affected infants who show absent SMN1 Exon 7 by Real-Time™ quantitative PCR (qPCR). We screened 179,467 neonates and identified 9 SMA-affected infants, all of whom were referred to a specialist by day of life 6 (average and median 4 days of life). Another ten SMN1 hybrids were observed but never referred. The nine referred infants who were confirmed to have SMA were entered into treatment protocols. Early data show that some SMA-affected children have remained asymptomatic and are meeting developmental milestones and some have mild to moderate delays. The Massachusetts experience demonstrates that SMA NBS is feasible, can be implemented on a population basis, and helps engage infants for early treatment to maximize benefit.

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The Inclusion of Rights of People with Disabilities and Women and Girls in Water, Sanitation, and Hygiene Policy Documents and Programs of Bangladesh and Cambodia: Content Analysis Using EquiFrame

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18105087 ◽

2021 ◽

Vol 18 (10) ◽

pp. 5087

Author(s):

Nathaniel Scherer ◽

Islay Mactaggart ◽

Chelsea Huggett ◽

Pharozin Pheng ◽

Mahfuj-ur Rahman ◽

...

Keyword(s):

Content Analysis ◽

People With Disabilities ◽

Analysis Tool ◽

Middle Income ◽

Policy Documents ◽

Sanitation And Hygiene ◽

Gender Inclusion ◽

Core Concepts ◽

Women And Girls ◽

And Gender

People with disabilities and as women and girls face barriers to accessing water, sanitation, and hygiene (WASH) services and facilities that fully meet their needs, especially in low- and middle-income countries. Women and girls with disabilities experience double discrimination. WASH policies should support and uphold the concepts of disability and gender inclusion, and they should also act as a guide to inform WASH programs and service delivery. Using a modified version of the EquiFrame content analysis tool, this study investigated the inclusion of 21 core concepts of human rights of people with disabilities and women and girls in 16 WASH policy documents and seven end-line program reports from Bangladesh and Cambodia. Included documents typically focused on issues of accessibility and neglected wider issues, including empowerment and support for caregivers. The rights of children and women with disabilities were scarcely focused on specifically, despite their individual needs, and there was a disconnect in the translation of certain rights from policy to practice. Qualitative research is needed with stakeholders in Bangladesh and Cambodia to investigate the inclusion and omission of core rights of people with disabilities, and women and girls, as well as the factors contributing to the translation of rights from policy to practice.

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Effects of Non-thermal Ultrasound on a Fibroblast Monolayer Culture: Influence of Pulse Number and Pulse Repetition Frequency

Sensors ◽

10.3390/s21155040 ◽

2021 ◽

Vol 21 (15) ◽

pp. 5040

Author(s):

Silvia Ronda Peñacoba ◽

Mar Fernández Gutiérrez ◽

Julio San Román del Barrio ◽

Francisco Montero de Espinosa

Keyword(s):

Short Pulse ◽

Pulse Repetition Frequency ◽

Pulse Number ◽

Repetition Frequency ◽

Pulse Repetition ◽

Treatment Protocols ◽

Culture Plate ◽

New Treatment ◽

Long Pulse

Despite the use of therapeutic ultrasound in the treatment of soft tissue pathologies, there remains some controversy regarding its efficacy. In order to develop new treatment protocols, it is a common practice to carry out in vitro studies in cell cultures before conducting animal tests. The lack of reproducibility of the experimental results observed in the literature concerning in vitro experiments motivated us to establish a methodology for characterizing the acoustic field in culture plate wells. In this work, such acoustic fields are fully characterized in a real experimental configuration, with the transducer being placed in contact with the surface of a standard 12-well culture plate. To study the non-thermal effects of ultrasound on fibroblasts, two different treatment protocols are proposed: long pulse (200 cycles) signals, which give rise to a standing wave in the well with the presence of cavitation (ISPTP max = 19.25 W/cm2), and a short pulse (five cycles) of high acoustic pressure, which produces a number of echoes in the cavity (ISPTP = 33.1 W/cm2, with Pmax = 1.01 MPa). The influence of the acoustic intensity, the number of pulses, and the pulse repetition frequency was studied. We further analyzed the correlation of these acoustic parameters with cell viability, population, occupied surface, and cell morphology. Lytic effects when cavitation was present, as well as mechanotransduction reactions, were observed.

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Stakeholder views on the acceptability of Human Infection Studies in Malawi

10.21203/rs.2.11346/v3 ◽

2019 ◽

Author(s):

Blessings M. Kapumba ◽

Kondwani Jambo ◽

Jamie Rylance ◽

Markus Gmeiner ◽

Rodrick Sambakunsi ◽

...

Keyword(s):

Vaccine Development ◽

Human Infection ◽

Stakeholder Perceptions ◽

Ethical Challenges ◽

Inclusion Criteria ◽

Government Officials ◽

District Health ◽

Middle Income ◽

Rural And Urban ◽

Ongoing Assessment

Abstract Background: Human infection studies (HIS) are valuable in vaccine development. Deliberate infection, however, creates challenging questions, particularly in low and middle-income countries (LMIC) where HIS are new and ethical challenges may be heightened. Consultation with stakeholders is needed to support contextually appropriate and acceptable study design. We examined stakeholder perceptions about the acceptability and ethics of HIS in Malawi, to inform decisions about planned pneumococcal challenge research and wider understanding of HIS ethics in LMIC. Methods: We conducted 6 deliberative focus groups and 15 follow-up interviews with research staff, medical students, and community representatives from rural and urban Blantyre. We also conducted 5 key informant interviews with clinicians, ethics committee members and district health government officials. Findings: Stakeholders perceived HIS research to have potential population health benefits, but they also had concerns, particularly related to safety of volunteers and negative community reactions. Acceptability depended on a range of conditions related to procedures for voluntary and informed consent, inclusion criteria, medical care or support, compensation, regulation, and robust community engagement. These conditions largely mirror those in existing guidelines for HIS and biomedical research in LMICs. Stakeholder perceptions pointed to potential tensions, for example balancing equity, safety and relevance in inclusion criteria. Conclusions: Our findings suggest HIS research could be acceptable in Malawi, provided certain conditions are in place. Ongoing assessment of participant experiences and stakeholder perceptions will be required to strengthen HIS research during development and roll-out. Key words: Human Infection Studies, pneumococcal, Malawi, acceptability, ethics

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Cytomegalovirus and Epstein–Barr Virus Associations with Neurological Diseases and the Need for Vaccine Development

Vaccines ◽

10.3390/vaccines8010035 ◽

2020 ◽

Vol 8 (1) ◽

pp. 35 ◽

Cited By ~ 2

Author(s):

Peter A. C. Maple

Keyword(s):

Infectious Mononucleosis ◽

Epstein Barr Virus ◽

Vaccine Development ◽

Neurological Diseases ◽

Human Herpesvirus ◽

Middle Income ◽

Barr Virus ◽

Wide Range ◽

Epstein Barr ◽

Human Herpesviruses

Herpesviruses have been isolated from a wide range of hosts including humans—for which, nine species have been designated. The human herpesviruses are highly host adapted and possess the capacity for latency, allowing them to survive in the host for life, effectively hidden from the immune system. This ability of human herpesviruses to modulate the host immune response poses particular challenges for vaccine development but at the same time proves attractive for the application of human herpesvirus vaccines to certain spheres of medicine. In this review, congenital cytomegalovirus (CMV) infection and hearing loss will be described followed by a comment on the status of current vaccine development. Secondly, the association of Epstein–Barr virus (EBV) infection with multiple sclerosis (MS) and how EBV vaccination may be of benefit will then be discussed. Prevention of congenital CMV by vaccination is an attractive proposition and several vaccines have been evaluated for potential use. Particularly challenging for the development of CMV vaccines are the needs to prevent primary infection, reinfection, and reactivation at the same time as overcoming the capacity of the virus to generate highly sophisticated immunomodulatory mechanisms. Cost and the practicalities of administering potential vaccines are also significant issues, particularly for low- and middle-income countries, where the burden of disease is greatest. An effective EBV vaccine that could prevent the 200,000 new EBV-associated malignancies which occur globally each year is not currently available. There is increasing interest in developing EBV vaccines to prevent MS and, in view of the association of infectious mononucleosis with MS, reducing childhood infectious mononucleosis is a potential intervention. Currently, there is no licensed EBV vaccine and, in order to progress the development of EBV vaccines for preventing MS, a greater understanding of the association of EBV with MS is required.

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Investigation of the Relation between Follicular Atresia and Granulosa Cells in Terms of Cell Death Mechanisms in Premature Ovarian Failure Model

Proceedings ◽

10.3390/proceedings2251529 ◽

2018 ◽

Vol 2 (25) ◽

pp. 1529 ◽

Cited By ~ 2

Author(s):

Damla Akogullari ◽

Elgin Turkoz Uluer ◽

H. Seda Vatansever

Keyword(s):

Cell Death ◽

Granulosa Cells ◽

Premature Ovarian Failure ◽

Ovarian Failure ◽

Blood Levels ◽

Failure Model ◽

Follicular Atresia ◽

Treatment Protocols ◽

New Treatment ◽

Cell Death Mechanisms

Premature Ovarian Failure; is characterized by the dysfunction or early depletion of ovarian reserves due to follicular loss in the ovary in women under age of 40. POF is the important cause of infertility and its etiology is still not clearly understood. Investigation of cell death mechanisms (CDM) that play a role in the follicular atresia (FA) triggered by excessive loss of granulosa cells (GCs) that provide metabolic support for oocyte and follicle development in the ovary will help to understand POF etiology. It was known that apoptosis and autophagy play a role in FA. Recent studies have shown that paraptosis, associated with endoplasmic reticulum stress (ERS), also exist in FA. POF model was established in C57BL/6 female mice by CTX and it was confirmed by increased follicle stimulating hormone (FSH), luteal hormone (LH) and decreased estradiol (E2) blood levels and follicle count. According to the results of the immunohistochemistry (IHC) cell death markers were significantly more expressed than control (C) and sham (S) groups in the POF model. In addition, more apoptotic cells were observed in the POF group compared to C and S in the TUNEL analysis. In consequence of this study apoptosis and autophagy as well as paraptosis play a role in the FA leading to POF, will help to develop new treatment protocols.

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