scholarly journals Consensus Report on Shigella Controlled Human Infection Model: Conduct of Studies

2019 ◽  
Vol 69 (Supplement_8) ◽  
pp. S580-S590 ◽  
Author(s):  
Kawsar R Talaat ◽  
A Louis Bourgeois ◽  
Robert W Frenck ◽  
Wilbur H Chen ◽  
Calman A MacLennan ◽  
...  
Keyword(s):  
District Of Columbia ◽  
Human Infection ◽  
Morbidity And Mortality ◽  
World Health ◽  
Infection Model ◽  
Shared Experiences ◽  
Infection Models ◽  
Health Organization ◽  
Consensus Report ◽  
Selection Of

Abstract Shigella causes morbidity and mortality worldwide, primarily affecting young children living in low-resource settings. It is also of great concern due to increasing antibiotic resistance, and is a priority organism for the World Health Organization. A Shigella vaccine would decrease the morbidity and mortality associated with shigellosis, improve child health, and decrease the need for antibiotics. Controlled human infection models (CHIMs) are useful tools in vaccine evaluation for early up- or down-selection of vaccine candidates and potentially useful in support of licensure. Over time, the methods employed in these models have become more uniform across sites performing CHIM trials, although some differences in conduct persist. In November 2017, a Shigella CHIM workshop was convened in Washington, District of Columbia. Investigators met to discuss multiple aspects of these studies, including study procedures, clinical and immunological endpoints, and shared experiences. This article serves as a uniform procedure by which to conduct Shigella CHIM studies.

scholarly journals Consensus Report on Shigella Controlled Human Infection Model: Introduction and Overview

2019 ◽  
Vol 69 (Supplement_8) ◽  
pp. S577-S579 ◽  
Author(s):  
Calman A MacLennan ◽  
Anastazia Older Aguilar ◽  
A Duncan Steele
Keyword(s):  
Best Practices ◽  
Vaccine Development ◽  
Disease Process ◽  
The United States ◽  
Human Infection ◽  
Infection Model ◽  
Infectious Agents ◽  
Vaccine Candidates ◽  
Infection Models ◽  
Consensus Report

Abstract In recent years, controlled human infection models (CHIMs) have become available for a range of infectious agents and have proved invaluable for understanding the disease process, pathogenesis, and mechanisms of immunity. CHIM studies have also contributed significantly to advancing development of a number of vaccines by providing an indication of vaccine efficacy. The Shigella CHIM has been established in 3 sites in the United States, and it is likely that the CHIM will play an important regulatory role for advancing the range of Shigella vaccine candidates that are currently in development. This supplement describes the harmonization of best practices across sites, with a view to maximizing the contribution that CHIM studies can make to Shigella vaccine development.

scholarly journals Establishment of a Controlled Human Infection Model with a Lyophilized Strain of Shigella sonnei 53G

mSphere ◽  
2020 ◽  
Vol 5 (5) ◽  
Author(s):  
Robert W. Frenck ◽  
Michelle Dickey ◽  
Akamol E. Suvarnapunya ◽  
Lakshmi Chandrasekaran ◽  
Robert W. Kaminski ◽  
...  
Keyword(s):  
Vaccine Development ◽  
Human Infection ◽  
Shigella Sonnei ◽  
World Health ◽  
Infection Model ◽  
Sample Collection ◽  
Open Label ◽  
Content Type ◽  
Infection Models ◽  
Study Results

ABSTRACT Controlled human infection models (CHIMs) are useful for vaccine development. To improve on existing models, we developed a CHIM using a lyophilized preparation of Shigella sonnei strain 53G produced using current good manufacturing practice (cGMP). Healthy adults were enrolled in an open-label dose-ranging study. Following administration of a dose of rehydrated S. sonnei strain 53G, subjects were monitored for development of disease. The first cohort received 500 CFU of 53G, and dosing of subsequent cohorts was based on results from the previous cohort. Subjects were administered ciprofloxacin on day 5 and discharged home on day 8. Subjects returned as outpatients for clinical checks and sample collection. Attack rates increased as the dose of S. sonnei was increased. Among those receiving the highest dose (1,760 CFU), 70% developed moderate to severe diarrhea, 50% had dysentery, and 40% had fever. Antilipopolysaccharide responses were observed across all cohorts. An S. sonnei CHIM using a lyophilized lot of strain 53G was established. A dose in the range of 1,500 to 2,000 CFU of 53G was selected as the dose for future challenge studies using this product. This model will enable direct comparison of study results between institutions and ensure better consistency over time in the challenge inoculum. IMPORTANCE Controlled human infection models (CHIMs) are invaluable tools utilized to understand the human response to infection, potentially leading to protective immune mechanisms and allowing efficacy testing of enteric countermeasures, including vaccines, antibiotics, and other products. The development of an improved Shigella CHIM for both Shigella sonnei and Shigella flexneri is consistent with international efforts, supported by international donors and the World Health Organization, focused on standardizing Shigella CHIMs and using them to accelerate Shigella vaccine development. The use of lyophilized Shigella challenge strains rather than plate-grown inoculum preparations is considered an important step forward in the standardization process. Furthermore, the results of studies such as this justify the development of lyophilized preparations for additional epidemiologically important S. flexneri serotypes, including S. flexneri 3a and S. flexneri 6.

scholarly journals Generating the Evidence for Typhoid Vaccine Introduction: Considerations for Global Disease Burden Estimates and Vaccine Testing Through Human Challenge

2019 ◽  
Vol 69 (Supplement_5) ◽  
pp. S402-S407
Author(s):  
James E Meiring ◽  
Alberto Giubilini ◽  
Julian Savulescu ◽  
Virginia E Pitzer ◽  
Andrew J Pollard
Keyword(s):  
Burden Of Disease ◽  
Disease Burden ◽  
Field Trials ◽  
Human Infection ◽  
World Health ◽  
Infection Model ◽  
Human Populations ◽  
Urban Centers ◽  
Vaccine Introduction ◽  
Health Organization

Abstract Typhoid fever has had a major impact on human populations, with the causative pathogen Salmonella enterica serovar Typhi implicated in many outbreaks through history. The current burden of disease is estimated at 11–18 million infections annually, with the majority of infections located in Africa and South Asia. Data that have been used to estimate burden are limited to a small number of blood-culture surveillance studies, largely from densely populated urban centers. Extrapolating these data to estimate disease burden within and across countries highlights the lack of precision in global figures. A number of approaches have been developed, characterizing different geographical areas by water-based risk factors for typhoid infection or broader measures of health and development to more accurately extrapolate incidence. Recognition of the substantial disease burden is essential for policy-makers considering vaccine introduction. Typhoid vaccines have been in development for >100 years. The Vi polysaccharide (ViPS) and Ty21a vaccines have had a World Health Organization (WHO) recommendation for programmatic use in countries with high burden for 10 years, with 1 ViPS vaccine also having WHO prequalification. Despite this, uptake and introduction of these vaccines has been minimal. The development of a controlled human infection model (CHIM) enabled the accelerated testing of the newly WHO-prequalified ViPS–tetanus toxoid protein conjugate vaccine, providing efficacy estimates for the vaccine, prior to larger field trials. There is an urgency to the global control of enteric fever due to the escalating problem of antimicrobial resistance. With more accurate burden of disease estimates and a vaccine showing efficacy in CHIM, that control is now a possibility.

scholarly journals IMPORTANCE OF CLASSICAL MORPHOLOGY IN THE DIAGNOSIS OF MYELODYSPLASTIC SYNDROME

2015 ◽  
Vol 7 ◽  
pp. e2015035 ◽  
Author(s):  
Rosangela Invernizzi ◽  
Federica Quaglia ◽  
Matteo Giovanni Della Porta
Keyword(s):  
Molecular Techniques ◽  
Classification Systems ◽  
World Health ◽  
Hematopoietic Stem ◽  
Morphological Alterations ◽  
Diagnosis And Classification ◽  
The Moment ◽  
Health Organization ◽  
Selection Of

Myelodysplastic syndromes (MDS) are hematopoietic stem cell disorders characterized by dysplastic, ineffective, clonal and neoplastic hematopoiesis. MDS represent a complex hematological problem: differences in disease presentation, progression and outcome  have necessitated the use of classification systems to improve diagnosis, prognostication and treatment selection. However, since a single biological or genetic reliable diagnostic marker has not yet been discovered for MDS, quantitative and qualitative dysplastic morphological alterations of bone marrow precursors and of peripheral blood cells are still fundamental for diagnostic classification. In this paper World Health Organization (WHO) classification refinements and current minimal diagnostic criteria proposed by expert panels are highlighted and related problematic issues are discussed. The recommendations should facilitate diagnostic and prognostic evaluations in MDS and selection of patients for new effective targeted therapies. Although in the future morphology should be supplemented with new molecular techniques, the morphological approach, at least for the moment, is still the cornerstone for the diagnosis and classification of these disorders.

Construction of the World Health Organization child growth standards: selection of methods for attained growth curves

2005 ◽  
Vol 25 (2) ◽  
pp. 247-265 ◽  
Author(s):  
E. Borghi ◽  
M. de Onis ◽  
C. Garza ◽  
J. Van den Broeck ◽  
E. A. Frongillo ◽  
...  
Keyword(s):  
World Health Organization ◽  
Growth Curves ◽  
Child Growth ◽  
World Health ◽  
Growth Standards ◽  
The World ◽  
Health Organization ◽  
Selection Of

The Effect Of Fe Tablet Consumption On Hemoglobin (Hb) Increase In Pregnant Women: A Systematic Literature Review

2020 ◽  
Vol 6 (2) ◽  
pp. 8-13
Author(s):  
Admin midwiferia ◽  
Pratiwi Cahya Skania ◽  
Djaswadi Dasuki ◽  
Fitriana Siswi Utami
Keyword(s):  
Pregnant Women ◽  
Critical Appraisal ◽  
World Health ◽  
Exclusion Criteria ◽  
Iron Supplements ◽  
Level Increase ◽  
The World ◽  
Life Threatening ◽  
Health Organization ◽  
Selection Of

Anemia is still a problem in developing countries. The World Health Organization states that there are still more than 50 percent of women in the world suffering from anemia. anemia can cause life-threatening bleeding, miscarriage, low birth weight and premature birth. WHO defines anemia as a condition where the hemoglobin level is less than 11 mg / dL in the first and last trimester or 10.5 mg / dL in the second trimester or the hematocrit level is less than 37 percent. The study aim to determine the effect of Fe tablets consumption on hemoglobin (Hb) level increase in pregnant women and to find out the factors related to the compliance of pregnant women taking Fe tablets.  This Systematic Literature Publication and Science uses databases with the period 2008-2018. The selection of articles was based on the inclusion and exclusion criteria. The Appraisal study employed The Joanna Briggs Institute Critical Appraisal Tools. Taking Fe tablets is very influential in increasing levels of Hb in pregnant women who suffer from anemia. Effective iron supplements to reduce anemia in pregnancy. Support from family and closest people has an important role in increasing adherence to taking Fe tablets.

scholarly journals 2-Methyl-pentanoyl-carnitine (2-MPC): a urine biomarker for patent Ascaris lumbricoides infection

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ole Lagatie ◽  
Ann Verheyen ◽  
Stijn Van Asten ◽  
Maurice R. Odiere ◽  
Yenny Djuardi ◽  
...  
Keyword(s):  
Ascaris Lumbricoides ◽  
Large Scale ◽  
Infection Intensity ◽  
World Health ◽  
Infection Model ◽  
Metabolome Analysis ◽  
Control Programs ◽  
Urine Biomarker ◽  
Intestinal Worms ◽  
Health Organization

Abstract Infections with intestinal worms, such as Ascaris lumbricoides, affect hundreds of millions of people in all tropical and subtropical regions of the world. Through large-scale deworming programs, World Health Organization aims to reduce moderate-to-heavy intensity infections below 1%. Current diagnosis and monitoring of these control programs are solely based on the detection of worm eggs in stool. Here we describe how metabolome analysis was used to identify the A. lumbricoides-specific urine biomarker 2-methyl pentanoyl carnitine (2-MPC). This biomarker was found to be 85.7% accurate in determining infection and 90.5% accurate in determining a moderate-to-heavy infection. Our results also demonstrate that there is a correlation between 2-MPC levels in urine and A. lumbricoides DNA detected in stool. Furthermore, the levels of 2-MPC in urine were shown to rapidly and strongly decrease upon administration of a standard treatment (single oral dose of 400 mg albendazole). In an Ascaris suum infection model in pigs, it was found that, although 2-MPC levels were much lower compared to humans, there was a significant association between urinary 2-MPC levels and both worm counts (p = 0.023) and the number of eggs per gram (epg) counts (p < 0.001). This report demonstrates that urinary 2-MPC can be considered an A. lumbricoides-specific biomarker that can be used to monitor infection intensity.

scholarly journals Assessing viability and infectivity of foodborne and waterborne stages (cysts/oocysts) of Giardia duodenalis, Cryptosporidium spp., and Toxoplasma gondii: a review of methods

Parasite ◽  
2018 ◽  
Vol 25 ◽  
pp. 14 ◽  
Author(s):  
Angélique Rousseau ◽  
Stéphanie La Carbona ◽  
Aurélien Dumètre ◽  
Lucy J. Robertson ◽  
Gilles Gargala ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Exposure Assessment ◽  
Foodborne Pathogens ◽  
Giardia Duodenalis ◽  
Human Infection ◽  
Control Measures ◽  
World Health ◽  
Protozoan Parasites ◽  
Analytical Strategy ◽  
Health Organization

Giardia duodenalis, Cryptosporidium spp. and Toxoplasma gondii are protozoan parasites that have been highlighted as emerging foodborne pathogens by the Food and Agriculture Organization of the United Nations and the World Health Organization. According to the European Food Safety Authority, 4786 foodborne and waterborne outbreaks were reported in Europe in 2016, of which 0.4% were attributed to parasites including Cryptosporidium, Giardia and Trichinella. Until 2016, no standardized methods were available to detect Giardia, Cryptosporidium and Toxoplasma (oo)cysts in food. Therefore, no regulation exists regarding these biohazards. Nevertheless, considering their low infective dose, ingestion of foodstuffs contaminated by low quantities of these three parasites can lead to human infection. To evaluate the risk of protozoan parasites in food, efforts must be made towards exposure assessment to estimate the contamination along the food chain, from raw products to consumers. This requires determining: (i) the occurrence of infective protozoan (oo)cysts in foods, and (ii) the efficacy of control measures to eliminate this contamination. In order to conduct such assessments, methods for identification of viable (i.e. live) and infective parasites are required. This review describes the methods currently available to evaluate infectivity and viability of G. duodenalis cysts, Cryptosporidium spp. and T. gondii oocysts, and their potential for application in exposure assessment to determine the presence of the infective protozoa and/or to characterize the efficacy of control measures. Advantages and limits of each method are highlighted and an analytical strategy is proposed to assess exposure to these protozoa.

scholarly journals Epigenetic Mechanisms Underlying COVID-19 Pathogenesis

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1142
Author(s):  
Syuzo Kaneko ◽  
Ken Takasawa ◽  
Ken Asada ◽  
Norio Shinkai ◽  
Amina Bolatkan ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Methylation Status ◽  
Therapeutic Strategies ◽  
Human Infection ◽  
World Health ◽  
Epigenetic Mechanisms ◽  
Angiotensin I ◽  
Angiotensin I Converting Enzyme ◽  
Health Organization ◽  
Molecular Framework

In 2019, a novel severe acute respiratory syndrome called coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was reported and was declared a pandemic by the World Health Organization (WHO) in March 2020. With the advancing development of COVID-19 vaccines and their administration globally, it is expected that COVID-19 will converge in the future; however, the situation remains unpredictable because of a series of reports regarding SARS-CoV-2 variants. Currently, there are still few specific effective treatments for COVID-19, as many unanswered questions remain regarding the pathogenic mechanism of COVID-19. Continued elucidation of COVID-19 pathogenic mechanisms is a matter of global importance. In this regard, recent reports have suggested that epigenetics plays an important role; for instance, the expression of angiotensin I converting enzyme 2 (ACE2) receptor, an important factor in human infection with SARS-CoV-2, is epigenetically regulated; further, DNA methylation status is reported to be unique to patients with COVID-19. In this review, we focus on epigenetic mechanisms to provide a new molecular framework for elucidating the pathogenesis of SARS-CoV-2 infection in humans and of COVID-19, along with the possibility of new diagnostic and therapeutic strategies.

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