literature review on total quality management pdf

• DOI: 10.1108/tqm-04-2021-0113
• Corpus ID: 239676399

A literature review on total quality management (models, frameworks, and tools and techniques) in higher education

• N. Jasti , V. Venkateswaran , +1 author K. S. Sangwan
• Published in The TQM Journal 7 September 2021
• Education, Business

20 Citations

Quality management research in arab countries: current status and future directions, an empirical study into the use of 7 quality control tools in higher education institutions (heis), unveiling the status of tqm-performance link in the private, public, and third sectors: a systematic review, the culture of excellence and its dimensions in higher education, does internal control contribute to quality management in higher education institutions indonesia's adoption experience of the coso integrated framework, adopting a digital transformation in moroccan research structure using a knowledge management system: case of a research laboratory, the challenges and obstacles of implementing quality and development programs at jordanian business companies (field study), the interdependence of total quality management and organisational learning to managerial innovation, blending “hard” and “soft” tqm for academic excellence: the university of siena experience in the field of life sciences, lean management practices perception and their influence on organizational performance in a public higher education institution, 62 references, lean six sigma and quality frameworks in higher education – a review of literature, twenty years of research on total quality management in higher education: a systematic literature review, constructs of quality in higher education services, findings of quality management studies in primary and secondary education: a systematic literature review, total quality management elements and results in higher education institutions: the greek case, total quality management in uk higher education institutions, developing a performance management model for the implementation of tqm practices in public education centres, an empirical study of total quality management in engineering educational institutions of india, lean production: literature review and trends, use of multiple methodologies for developing a customer-oriented model of total quality management in higher education, related papers.

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From total quality management to Quality 4.0: A systematic literature review and future research agenda

• Review Article
• Open access
• Published: 13 March 2023
• Volume 10 , pages 191–205, ( 2023 )

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• Hu-Chen Liu 1 ,
• Ran Liu 1 ,
• Xiuzhu Gu 2 &
• Miying Yang 3  

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Quality 4.0 is an emerging concept that has been increasingly appreciated because of the intensification of competition, continually changing customer requirements and technological evolution. It deals with aligning quality management practices with the emergent capabilities of Industry 4.0 to improve cost, time, and efficiency and increase product quality. This article aims to comprehensively review extant studies related to Quality 4.0 to uncover current research trends, distil key research topics, and identify areas for future research. Thus, 46 journal articles extracted from the Scopus database from 2017 to 2022 were collected and reviewed. A descriptive analysis was first performed according to the year-wise publication, sources of publication, and research methods. Then, the selected articles were analyzed and classified according to four research themes: Quality 4.0 concept, Quality 4.0 implementation, quality management in Quality 4.0, and Quality 4.0 model and application. By extracting the literature review findings, we identify the Quality 4.0 definitions and features, develop the quality curve theory, and highlight future research opportunities. This study supports practitioners, managers, and academicians in effectively recognizing and applying Quality 4.0 to enhance customer satisfaction, achieve innovation enterprise efficiency, and increase organizational competitiveness in the era of Industry 4.0.

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Liu, HC., Liu, R., Gu, X. et al. From total quality management to Quality 4.0: A systematic literature review and future research agenda. Front. Eng. Manag. 10 , 191–205 (2023). https://doi.org/10.1007/s42524-022-0243-z

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Received : 31 July 2022

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Please note you do not have access to teaching notes, a systematic literature review on total quality management critical success factors and the identification of new avenues of research.

The TQM Journal

ISSN : 1754-2731

Article publication date: 9 January 2017

The purpose of this paper is to present a systematic literature review to identify new avenues of research in line with the ongoing changes in quality and management required to firms, especially regarding customers.

Design/methodology/approach

This study uses a systematic review of the literature contained in the three databases Ebsco, JSTOR, and Springerlink and on the search engine Google Scholar.

An analysis of the literature identifies three different clusters of papers: “identification” papers, which show that customer focus has gained importance in recent times; “implementation” papers, which highlight that a general or shared model or scale to successfully implement total quality management (TQM) does not yet exist; and “impact-on-performance” papers, which show that few studies have considered the relationship between TQM and the issues of both marketing and performance, underlining the most significant gap in the TQM literature.

Research limitations/implications

This study is limited by the small number of databases and search engines used and by the restricted number of keywords used in searching these sources.

Practical implications

This work highlights a gap in the existing research and thus an incomplete consideration of the interplay between management, marketing, and quality issues, all centered on customers and other stakeholders. Researchers and firms are thus advised to adopt a wider view that considers the role of the quality process to support the firm’s engagement of customers in activities that enhance both the customer role and customer satisfaction.

Originality/value

This study uses a systematic literature review to review all critical factors of TQM and identifies new research avenues and different approaches to implementing TQM, focusing on the central role that customers play in achieving firm success.

• Total quality management
• Systematic literature review
• Firm performance
• Critical success factors (CSFs)
• Stakeholder involvement
• Customer centrality and involvement

Aquilani, B. , Silvestri, C. , Ruggieri, A. and Gatti, C. (2017), "A systematic literature review on total quality management critical success factors and the identification of new avenues of research", The TQM Journal , Vol. 29 No. 1, pp. 184-213. https://doi.org/10.1108/TQM-01-2016-0003

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Total Quality Management and Organizational Performance: A Literature Review

15 Pages Posted: 19 Oct 2022 Last revised: 24 Oct 2022

Samuel Antwi

Zhejiang Gongshang University

Bernard Darkwa

University of cape coast.

Date Written: February 1, 2021

The purpose of this study was to review past literatures on Total Quality Management (TQM) and organizational performance. Experts in the field keeps on modifying what total quality management should be with the sole purpose of improving on the existing or previous practices. This topic has generated much attention in recent times because consumers demand value for money whilst organization has the responsibility to maintain their reputation by offering quality products and/services to their customers. On top of this, every organization seeks to improve and they can do so by implementing some quality management practices. In this study, the researcher reviewed history and evolution of total quality management, concept of total quality management, concept of performance, quality management practices and the others.

Keywords: Total Quality Management; Organizational Performance

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• Volume 73, Issue 10
• The road to a world-unified approach to the management of patients with gastric intestinal metaplasia: a review of current guidelines
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• http://orcid.org/0000-0003-0121-6850 Mario Dinis-Ribeiro 1 , 2 ,
• http://orcid.org/0000-0002-2049-9959 Shailja Shah 3 ,
• http://orcid.org/0000-0001-5964-7579 Hashem El-Serag 4 ,
• http://orcid.org/0000-0002-9137-2779 Matthew Banks 5 ,
• http://orcid.org/0000-0002-3029-9272 Noriya Uedo 6 ,
• Hisao Tajiri 7 ,
• http://orcid.org/0000-0002-8721-7696 Luiz Gonzaga Coelho 8 ,
• http://orcid.org/0000-0003-2691-7522 Diogo Libanio 1 , 2 ,
• http://orcid.org/0000-0002-9503-8639 Edith Lahner 9 ,
• http://orcid.org/0000-0002-4997-4098 Antonio Rollan 10 ,
• http://orcid.org/0000-0003-2282-0248 Jing-Yuan Fang 11 ,
• http://orcid.org/0000-0002-4518-8591 Leticia Moreira 12 , 13 ,
• Jan Bornschein 14 ,
• http://orcid.org/0000-0001-8439-9036 Peter Malfertheiner 15 ,
• Ernst J Kuipers 15 ,
• http://orcid.org/0000-0002-0011-3924 Emad M El-Omar 16
• 1 Department of Gastroenterology , Porto Comprehensive Cancer Center & RISE@CI-IPO, University of Porto , Porto , Portugal
• 2 MEDCIDS (Department of Community Medicine, Health Information, and Decision) , University of Porto , Porto , Portugal
• 3 Division of Gastroenterology , University of California and Jennifer Moreno Veterans Affairs San Diego Healthcare System , San Diego , California , USA
• 4 Gastroenterology and Hepatology , Baylor College of Medicine , Houston , Texas , USA
• 5 University College London Hospital , University College London Hospitals NHS Foundation Trust , London , UK
• 6 Gastrointestinal Oncology , Osaka International Cancer Institute , Osaka , Japan
• 7 Endoscopy , The Jikei University School of Medicine , Tokyo , Japan
• 8 Instituto Alfa de Gastrenterologia , Hospital das Clínicas, Universidade Federal de Minas Gerais , Belo Horizonte , Brazil
• 9 Department of Medical-Surgical Sciences and Translational Medicine , Sant'Andrea Hospital , Rome , Italy
• 10 Facultad de Medicina Clinica Alemana-Universidad del Desarrollo , Santiago , Chile
• 11 Division of Gastroenterology and Hepatology , Shanghai Institute of Digestive Disease , Shanghai , China
• 12 Gastroenterology , Hospital Clinic de Barcelona , Barcelona , Spain
• 13 Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD) , Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) , Barcelona , Spain
• 14 MRC Translational Immune Discovery Unit , MRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford , Oxford , UK
• 15 Medical Department II , LMU University Clinic , München , Germany
• 16 UNSW Microbiome Research Centre , University of New South Wales , Sydney , New South Wales , Australia
• Correspondence to Professor Mario Dinis-Ribeiro, Department of Gastroenterology, RISE—Health Research Network, Porto, 4200-072, Portugal; mario.ribeiro{at}ipoporto.min-saude.pt

Objective During the last decade, the management of gastric intestinal metaplasia (GIM) has been addressed by several distinct international evidence-based guidelines. In this review, we aimed to synthesise these guidelines and provide clinicians with a global perspective of the current recommendations for managing patients with GIM, as well as highlight evidence gaps that need to be addressed with future research.

Design We conducted a systematic review of the literature for guidelines and consensus statements published between January 2010 and February 2023 that address the diagnosis and management of GIM.

Results From 426 manuscripts identified, 16 guidelines were assessed. There was consistency across guidelines regarding the purpose of endoscopic surveillance of GIM, which is to identify prevalent neoplastic lesions and stage gastric preneoplastic conditions. The guidelines also agreed that only patients with high-risk GIM phenotypes (eg, corpus-extended GIM, OLGIM stages III/IV, incomplete GIM subtype), persistent refractory Helicobacter pylori infection or first-degree family history of gastric cancer should undergo regular-interval endoscopic surveillance. In contrast, low-risk phenotypes, which comprise most patients with GIM, do not require surveillance. Not all guidelines are aligned on histological staging systems. If surveillance is indicated, most guidelines recommend a 3-year interval, but there is some variability. All guidelines recommend H. pylori eradication as the only non-endoscopic intervention for gastric cancer prevention, while some offer additional recommendations regarding lifestyle modifications. While most guidelines allude to the importance of high-quality endoscopy for endoscopic surveillance, few detail important metrics apart from stating that a systematic gastric biopsy protocol should be followed. Notably, most guidelines comment on the role of endoscopy for gastric cancer screening and detection of gastric precancerous conditions, but with high heterogeneity, limited guidance regarding implementation, and lack of robust evidence.

Conclusion Despite heterogeneous populations and practices, international guidelines are generally aligned on the importance of GIM as a precancerous condition and the need for a risk-stratified approach to endoscopic surveillance, as well as H. pylori eradication when present. There is room for harmonisation of guidelines regarding (1) which populations merit index endoscopic screening for gastric cancer and GIM detection/staging; (2) objective metrics for high-quality endoscopy; (3) consensus on the need for histological staging and (4) non-endoscopic interventions for gastric cancer prevention apart from H. pylori eradication alone. Robust studies, ideally in the form of randomised trials, are needed to bridge the ample evidence gaps that exist.

• surveillance
• gastric carcinoma

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Data are available on reasonable request. All data analysed are available in proper databases depending on publisher.

https://doi.org/10.1136/gutjnl-2024-333029

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WHAT IS ALREADY KNOWN ON THIS TOPIC

Since 2010, several guidelines and expert consensus statements have been published worldwide providing evidence-based recommendations for the management of patients with gastric intestinal metaplasia (GIM), a precancerous condition associated with increased risk of gastric cancer.

Likely due to heterogeneous populations, methods and wording across different guidelines, controversy, confusion and misperceptions remain in the management of patients with GIM, which might compromise the optimal care of these potentially high-risk patients.

WHAT THIS STUDY ADDS

We conducted a systematic review and synthesised all available, published international guidelines describing the management of patients with GIM and, here, provide the first unified, global perspective for clinicians.

Irrespective of the patient’s country of origin or ethnicity, the index or surveillance endoscopy must include staging of GIM by performing endoscopic and histopathological mapping (risk stratification).

Only individuals with a high-risk GIM phenotype (ie, corpus-extended GIM, OLGIM stages III/IV, moderate-to-severe GIM, incomplete GIM subtype, persistent refractory Helicobacter pylori infection or first-degree family history of gastric cancer) merit regular surveillance, with a 3-year interval unless multiple risk factors are present.

Individuals with focal GIM changes limited to the antrum and no other risk factors for gastric cancer do not require ongoing endoscopic surveillance follow-up.

H. pylori testing (and its eradication if present) is unanimously recommended.

HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

Clinical recommendations and policies must include risk stratification of gastric cancer among individuals with GIM.

There is an opportunity to enhance the research agenda in this field to better define: populations who warrant screening; the optimal method for endoscopic surveillance (eg, endoscopic staging, use of image enhancement, etc) and the optimal interval for surveillance; development of non-invasive diagnostic and prognostic biomarkers for GIM; assessment of interventions beyond H. pylori eradication to prevent gastric cancer and management of GIM in specific situations (eg, autoimmune gastritis without H. pylori , hereditary syndromes), among others.

Introduction

Gastric adenocarcinoma (GC) is a preventable cancer. In 2022, there were approximately 970 000 new GC cases and nearly 760 000 related fatalities. The International Agency for Research on Cancer projects that the number of new GC cases will increase to 1.8 million by 2040, with an associated 1.3 million deaths if current trends continue. This projection underscores the critical importance of both primary and secondary prevention efforts. 1 2

Helicobacter pylori eradication, healthy dietary habits and smoking cessation are mainstays for primary GC prevention. However, primary prevention alone is insufficient for successfully decreasing GC burden and mortality, and effective secondary and tertiary prevention through strategies for early diagnosis is imperative. 3 4 In the majority of cases, intestinal-type GC develops through a cascade of gastric preneoplastic mucosal changes before neoplastic progression occurs. Furthermore, early gastric cancer (ie, prior to submucosal invasion) can be cured through endoscopic or surgical resection, whereas there are no curative options for advanced-stage diagnoses. The slow stepwise progression and the opportunity for curative resection of early lesions underlie the rationale and effectiveness of secondary and tertiary prevention for combatting GC burden and mortality. These key concepts can be extrapolated, in theory, to all countries that have the appropriate infrastructure, and this is reflected in international guidelines for gastric intestinal metaplasia (GIM) diagnosis and management.

The ‘Correa cascade’ considers the occurrence of GC in a chronic state of mucosal inflammation, including the presence of atrophic changes and GIM. GIM in most cases occurs on a background of atrophy, although atrophic changes may not be clinically apparent in the setting of diffuse GIM. 5 Conversely, atrophy may occur in the absence of GIM. Although moderate-to-severe gastric atrophy is associated with an increased risk of GC, the endoscopic and histopathological staging and risk stratification for gastric atrophy as compared with GIM are subject to more inter-observer, and even intra-observer, variability. Therefore, we have focused on guidance for GIM management as opposed to atrophy in the absence of confirmed GIM.

The prevalence of GIM when broadly considering all adults undergoing endoscopy with biopsies ranges from 5% to 30%, and is potentially even higher among individuals with additional risk factors. 6 7 Despite this high prevalence and known association with GC, no specific guidelines existed for the management of GIM until 2012 and this was reflected by significant heterogeneity in clinical practice for GIM and low adherence to endoscopic surveillance and appropriate staging protocols. 8 9 To address this, scientific societies internationally independently evaluated the published literature according to predefined methodology (eg, Grading of Recommendations, Assessment, Development and Evaluations (GRADE)) to develop evidence-based guidance on the management of precancerous conditions, specifically GIM.

Currently, non-invasive biomarkers have not demonstrated sufficient, reproducible accuracy for GIM diagnosis. Endoscopy and histology thus remain the mainstay for diagnosis, surveillance and staging of GIM. We hypothesise that the availability of multiple international guidelines with varying methodologies and presentation may confuse clinicians regarding GIM management, especially endoscopic surveillance, which invariably would impact clinical care.

We therefore conducted a systematic review and qualitative synthesis of all published and indexed evidence-based guidelines or expert consensus statements on GIM management, including which individuals should receive screening for staging of the gastric mucosa for future risk determination; and which individuals should undergo GIM surveillance. This work primarily aims to provide clinicians worldwide with a comprehensive perspective, and secondarily to inform future guideline processes as well as the research agenda.

We performed a systematic review in PubMed on 20 February 2024, with the following query: (guidelines OR statements OR consensus) AND (atrophy OR atrophic gastritis OR intestinal metaplasia OR precancerous OR premalignant OR preneoplasia OR dysplasia) AND (gastric OR stomach).

We limited the search to include publications between 1 January 2010 and the search date. We also searched the complete list of references of the included articles and used experts’ (authors’) knowledge of other references to determine other guidelines that might have been missed during the electronic search. We included all guidelines and consensus statements that evaluated and discussed the diagnosis and management of GIM. Documents were considered ‘guidelines’ or ‘consensus statements’ as long as they were commissioned by an accredited international or national GI society (eg, European Society for Gastrointestinal Endoscopy, American Gastroenterological Association) and described the methodological approach for delivering clinical recommendations or suggestions. We excluded documents that did not include GIM management. Hereafter, we use the term ‘guideline’ to also encompass consensus statements and clinical practice updates, with differences in methodology acknowledged where appropriate.

From each guideline, the following information was abstracted and summarised:

Scientific society(ies) supporting the guideline.

Year of publication and literature search dates.

Scope of the guideline (eg, management of GIM only vs other, eg, H. pylori eradication).

Geographic region and population to which the guideline refers.

Methodology (GRADE vs other).

Recommendations or discussions regarding upper gastrointestinal endoscopy (UGIE) screening for eligible populations to allow for the opportunistic identification of GC and/or gastric precancerous conditions (GIM).

Recommendations or suggestions regarding surveillance once GIM is diagnosed.

Recommended/Suggested endoscopic surveillance intervals in those considered eligible for surveillance.

The recommended/suggested endoscopic approach (quality parameters) to optimise the detection of gastric precancer/cancer, and staging.

The stated risk stratification parameters in patients with GIM, including histological staging systems, and respective definitions.

Recommendations/Suggestions regarding potential therapeutic interventions for GC prevention once GIM is diagnosed (eg, H. pylori testing/eradication; lifestyle modifications).

Intentionally, at least one author from each of the geographic regions encompassed was asked to co-author this manuscript. Each author was asked to critically review the summary for inconsistencies concerning their region’s published guidelines. The topics of endoscopic and histological diagnosis and staging of GIM are extensively described in prior literature and are not the focus of the article. An in-depth discussion of quality metrics in UGIE and population-based screening of GC and precancerous conditions is outside the scope of this article, apart from identifying whether these aspects are included in international guidelines and summarising the respective recommendations and guidance.

Literature search

The systematic literature search yielded 426 manuscripts, of which 411 were excluded based on title and abstract screening. No additional articles were identified through manual review of the references, and one was identified through co-authors’ expert knowledge. 10 A total of 16 articles met eligibility criteria and were included in this qualitative review. 10–25

Seven of these 16 articles were from Europe, 5 were from the Americas (3 from the USA, 2 from Latin America) and 4 were from the Asia-Pacific region (111 from China, 2 from Japan, 1 from Taiwan). The 2012 and 2019 updates of the European Society of Gastrointestinal Endoscopy (ESGE)/European Helicobacter and Microbiota Study Group/European Society of Pathology (ESP) guidelines (MAPS I and MAPS II, respectively), the British Society of Gastroenterology (BSG) guidelines (2019), Italian (2019), Asociación Española de Gastroenterología/Sociedad Española de Endoscopia Digestiva and Sociedad Española de Anatomía Patológica (2021), Asociacion Chilena de Endoscopia Digestiva/Sociedad Chilena de Gastroenterolgía (2014), American Gastroenterology Association (AGA) guidelines (2019), American Society of Gastrointestinal Endoscopy (ASGE, 2015) and Chinese guidelines (2023) were specifically dedicated to the management of precancerous conditions, including GIM. In contrast, the Maastricht, Taipei, Kyoto, Brazilian and Japan Gastroenterological Endoscopy Society guidelines primarily focused on H. pylori management and included statements or recommendations regarding the management of GIM. The Italian and Spanish guidelines are not adaptations of MAPS I and/or II, which is why they are considered separately in this review. The AGA Clinical Practice Update published in 2021 focuses on atrophic gastritis as a precancerous condition but provides guidance on GIM management including surveillance and is therefore included. All included guidelines used either GRADE methodology or a consensus approach. Nearly all the guidelines primarily addressing the management of precancerous conditions used GRADE methodology, with the exception of the Chinese Society of Gastroenterology, Cancer Collaboration Group of Chinese Society of Gastroenterology/Chinese Medical Association guidelines, which used a consensus approach. In contrast, guidelines that included GIM management as a secondary focus more often used a consensus approach ( table 1 ). Nevertheless, the overall clinical guidance regarding GIM management did not differ substantially based on the robustness of the methodology (ie, GRADE vs consensus).

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Description of included guidelines and consensus documents according to their main purpose/scope and geographic region

Opportunistic detection of GIM during screening or diagnostic endoscopy

GIM is typically asymptomatic and can only be detected endoscopically as currently available non-invasive biomarkers have not demonstrated reliable accuracy for the diagnosis. Thus, opportunities to diagnose GIM are either via screening UGIE in asymptomatic individuals (ie, opportunistic detection) or via diagnostic UGIE in individuals with a clinical indication for endoscopy. None of the international guidelines recommend screening for GIM per se; instead, screening is for early detection of GC. Some guidelines do, though, make clear statements that all endoscopies must include an assessment for the presence of precancerous changes, namely GIM. Many guidelines align in recommending that a high-quality endoscopic examination using virtual technologies (eg, narrow band imaging (NBI), linked colour imaging (LCI), blue light imaging (BLI)) or conventional chromoendoscopy, along with endoscopic biopsies, should be performed to enhance the endoscopic detection of GIM. One exception is the Japanese guideline, which does not recommend gastric biopsies. Instead, it relies solely on endoscopic detection and staging ( table 2 ). For those individuals diagnosed with GIM, many but not all guidelines also recommend the use of histological staging systems, primarily OLGIM, and histological subtyping of GIM given the implications for risk stratification ( table 2 ).

Recommendations for opportunistic diagnosis, surveillance and therapeutic interventions in individuals with GIM according to the diverse guidelines/consensus and their scope and region

Guidelines that include opportunistic detection through endoscopic screening . As of this writing, the Japanese guideline, the Spanish guideline, the British guideline and the Maastricht guideline offer recommendations regarding true population-based screening for GC. In Japan, references to GC risk stratification and potential non-invasive approaches are named. The Spanish guidelines recommend against the routine use of UGIE for GC screening in the general Spanish population given the low GC incidence overall, and suggest screening only for those with a family history of GC. This is similar to the recommendations of the German guideline and the Maastricht guideline. The Maastricht guideline, which is focused on H. pylori diagnosis and management, recommends that endoscopy with gastric biopsies be performed in asymptomatic individuals with a family history of GC starting at age 45 years and older. Neither the Spanish nor Maastricht guidelines call out other high-risk groups (eg, early generation immigrants from countries where GC is endemic). The 2019 British guidelines state there is insufficient evidence to support endoscopic screening in the overall low-risk UK population, but do provide a weak recommendation that UGIE screening with biopsies should be considered for individuals aged ≥50 years with multiple risk factors for GC, notably rating the quality of evidence as low but achieving 100% consensus agreement. The Chilean guidelines stipulate that age >40 years is sufficient for endoscopic screening for GC and its precancerous conditions considering that Chile is a high GC incidence country; however, the Chilean guidelines list an additional criterion that patients have at least one other clinical indication for endoscopy (eg, abdominal pain) and thus, this cannot be considered true population-based screening. The Italian guideline recommends that a family history of GC and long-term PPI use warrants offering UGIE screening for precancerous conditions; clearly, though, many individuals warranting long-term PPI use may qualify for a diagnostic as opposed to a screening endoscopy. The ASGE guidelines on GIM management do not include recommendations on GC screening, but a separate document on race and ethnic considerations in UGIE more broadly mentions that endoscopic GC screening may be considered in certain high-risk populations in the USA (eg, immigrants from high-risk regions, first-degree family history) starting at age 40 years; no other guidance, such as mucosal staging protocol or recommendations for subsequent surveillance intervals, is provided. 26

Guidelines that include opportunistic GIM detection through diagnostic endoscopy . The 2012 MAPS I guideline states that for H. pylori diagnosis and gastric mucosal staging, gastric samples from the antrum and corpus should be obtained during a diagnostic upper endoscopy. This recommendation was reiterated and refined in the updated 2019 MAPS II guideline. It mandated that all first-time diagnostic endoscopies include gastric antrum and corpus biopsies, without mention of whether this is necessary for patients who have been non-invasively tested for H. pylori already or who are otherwise considered low risk for GC. Similar to MAPS I/II, the Chinese guidelines recommend biopsies from the antrum and corpus to diagnose H. pylori and stage the gastric mucosa to determine the need for ongoing surveillance. The 2020 Japanese guidelines recommend endoscopic risk stratification using Kimura-Takemoto classification or virtual chromoendoscopy of GIM since advanced precancerous changes including GIM can be reliably detected endoscopically. 27

Guidelines that do not address opportunistic detection of GIM . The AGA guidelines do not address endoscopic screening or opportunistic detection during a diagnostic endoscopy for a non-screening indication. Instead, the document provides recommendations for the management of patients with already confirmed GIM, which is most often identified incidentally in the USA. The AGA guidelines acknowledge risk factors for GC, such as specific races and ethnicities, early generation immigrant groups and family history of GC, where an individualised approach may be considered.

In summary, there is high heterogeneity among guidelines regarding recommendations on the use of endoscopy for GC screening or opportunistic detection of GIM. It seems reasonable to consider that the index or surveillance endoscopy must include staging of GIM, if present. Revised or updated guidelines may consider clarifying these recommendations .

Individuals with established GIM diagnosis: surveillance versus no surveillance

All guidelines are aligned regarding the need to risk stratify patients with GIM to determine their need for ongoing surveillance, as well as in mandating H. pylori eradication if present.

All guidelines agree that patients with GIM are considered to have a high-risk phenotype if GIM affects both the gastric antrum (±incisura) and corpus (corpus-extended GIM), if there is moderate-to-severe GIM staged using OLGIM (ie, OLGIM III/IV), if GIM is of the incomplete subtype (vs complete subtype), and if there is a family history of GC in a first-degree relative. These are all factors consistently highlighted in the literature as the most important predictors of progression and may be used to identify individuals at the highest risk of GC, with most guidelines distinctly prioritising histological staging.

According to most guidelines, the presence of any high-risk phenotype is sufficient to identify those patients with GIM who merit surveillance. In contrast, the Spanish guidelines recommend surveillance for extensive GIM if at least one other risk factor, for example, incomplete type or family history of GC, is present.

All guidelines are also aligned in their recommendations that patients with a low-risk GIM phenotype, which is substantially more common than the high-risk phenotype, do not require ongoing endoscopic surveillance. Most guidelines agree that the presence of antrum-limited GIM that is non-severe (OLGIM I-II) may not warrant surveillance, assuming adequate staging metrics during the index gastroscopy and the absence of high-risk qualifiers, including persistent H. pylori infection, incomplete GIM subtype and family history of GC in a first-degree relative. However, factors such as tobacco smoking and dietary factors, which are associated with GC, are not fully accounted for as risk stratification metrics. In patients with limited, mild GIM but with additional risk factors for gastric cancer (eg, family history or high-risk race/ethnicity), MAPS II, BSG, China, Chilean and the AGA guidelines recommend endoscopic surveillance, whereas this is not mentioned in the Japanese, Taipei and Brazilian guidelines. However, the Japanese guideline recommends surveillance regardless of the extent of GIM because of the high GC incidence in the population and the relative availability of endoscopy.

Most guidelines do not provide guidance on how to properly risk stratify patients when information is missing. For example, if patients have insufficient biopsies (eg, only antrum), complete histological staging may not be possible. However, the AGA guidelines, MAPS I/II and the Spanish guidelines do provide guidance on short-interval endoscopy (<12 months) for risk stratification purposes if the quality of the initial examination is questionable.

In summary, advanced stages of GIM—such as GIM affecting both the gastric antrum (± incisura ) and corpus (corpus-extended GIM), moderate-to-severe GIM staged using OLGIM (ie, OLGIM III/IV ) or GIM of the incomplete subtype—are considered the phenotypes of interest for endoscopic surveillance to detect early neoplasia. In contrast, low-risk GIM phenotypes generally do not warrant surveillance in the absence of additional risk factors for advanced gastric neoplasia .

Approach to endoscopic surveillance

When surveillance is recommended, all guidelines recommend endoscopy as the only acceptable modality given the insufficient performance of currently available non-invasive biomarkers and biomarker panels. Few guidelines detail upper endoscopy quality metrics—for example, mucosal cleansing protocol, visualisation technique (high-definition white light±virtual or conventional chromoendoscopy), photodocumentation, or withdrawal time—within the guideline document, except for the BSG guidelines. Most guidelines do provide suggestions for the biopsy protocol, although with heterogeneity. Most guidelines suggest that biopsies from the antrum/incisura and corpus be obtained separately following a systematic protocol 5 to allow for histological staging, while targeted biopsies should also be obtained separately for lesions suspicious for advanced pathology. However, MAPS II states that the benefit of performing biopsies in patients under surveillance is not established, and biopsies should only be performed if any irregular area/suspicious lesion is identified. Figure 1 summarises these approaches. Some guidelines have accompanying articles (eg, AGA, Spanish society) that detail quality metrics in upper endoscopy with specific sections on best practices for the detection and surveillance of preneoplastic conditions. 28 29

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Synthesis of most commonly accepted biopsies protocols according to endoscopic findings. In the presence of gastric intestinal metaplasia (GIM), targeted biopsies should be performed. In the absence of GIM, random biopsies from the antrum and corpus are acceptable, with a biopsy from the incisura angularis being optimal but optional. 5 HD-WLE, high-definiton wight light endoscopy; IEE, image- enhanced endoscopy; NBI, narrow band imaging.

In summary, practice guidelines vary with respect to details and approach to the endoscopic surveillance exam .

Surveillance intervals

While there is generally agreement regarding who warrants surveillance, there is notable heterogeneity regarding recommended surveillance intervals. Surveillance every 3 years for patients with any high-risk GIM phenotype is the most commonly recommended (7 out of 16 guidelines) ( figure 2 ). If there is a family history of GC in a first-degree relative, MAPS II, the BSG and the Chinese guidelines suggest considering a shorter surveillance interval. In contrast, the Chilean, Brazilian, Japanese and Taiwanese guidelines also recommend considering an interval shorter than 3 years, but they do not provide additional criteria for determining who qualifies for the shortened interval.

Algorithm synthesising the major recommendations for managing individuals with gastric intestinal metaplasia (GIM) according to country of origin when applicable. Both the European Society of Gastrointestinal Endoscopy (ESGE) guidelines and three US guidance documents (two American Gastroenterology Association, one American Society of Gastrointestinal Endoscopy) are included. *Patients with gastric cancer (GC) should still undergo endoscopic and histological staging of the surrounding mucosa to facilitate additional risk stratification. EGD, esophagogastroduodenoscopy; Hp, Helicobacter pylori ; y, years; IEE, image-enhanced endoscopy.

The AGA, on the other hand, recommends that a surveillance interval of up to 5 years may also be acceptable, but does not provide additional information on who might qualify for this extended interval. Notably, the AGA Clinical Practice Update advocates for a 3-year interval in individuals with advanced atrophic gastritis with or without GIM.

In summary, international guidelines vary with respect to evidence-based guidance regarding appropriate endoscopic surveillance intervals among individuals with GIM enrolled in surveillance. Surveillance is generally suggested every 3 years, but the South American and Asian guidelines favour a lower threshold for more intensive surveillance in patients with additional risk factors, while the US guidelines allow for potentially longer intervals .

Non-endoscopic therapeutic interventions

Other than surveillance, there is no definitive endoscopic management for GIM in the absence of visible neoplastic lesions. The mainstay non-endoscopic intervention for patients with GIM is testing for H. pylori infection, either through histology or other non-invasive non-serological methods. Confirming eradication after treatment in those who test positive is a strong recommendation in all guidelines. GIM can progress even once H. pylori is successfully eradicated, and this fact is acknowledged in most guidelines.

There is more heterogeneity regarding non-endoscopic non- H. pylori interventions in patients with GIM for GC risk/mortality reduction. MAPS II and the Chinese guidelines suggest offering low-dose aspirin to patients at higher risk of GC who also have a cardiovascular indication. In contrast, the German guidelines advise against the use of aspirin if the sole indication is GC prevention. The Chinese recommendations also refer to the supplementation of certain vitamins/minerals, including selenium and folate, and garlic. The Maastricht guidelines state that medical and special dietary chemoprevention cannot be recommended in patients with severe GIM (or severe atrophy) post- H. pylori eradication in the absence of sufficient evidence for benefit. None of the other guidelines offered guidance for any other non-invasive interventions for individuals with GIM.

Specific situations

Management of individuals with GIM in special situations, for example, postpartial gastrectomy and hereditary syndromes (eg, Lynch syndrome, familial adenomatous polyposis) is not addressed in general. Many guidelines offer limited guidance for patients with autoimmune gastritis diagnosed with GIM and for those diagnosed with gastric neoplasia (dysplasia/GC). A comprehensive discussion of these topics is beyond the scope of this document.

Reducing the global burden of GC is a shared goal worldwide. Most GCs have precursor conditions and lesions that can be detected endoscopically and histologically, which facilitates opportunities for prevention and curative resection of early GC. Population-based screening for GC is not recommended outside of a few East Asian countries. 30 That said, several international societies including from Europe and the Americas acknowledge the potential impact of targeted screening for high-risk groups, although with varying definitions of what qualifies as ‘high-risk’, which most certainly reflects the limited literature. Current studies are conducted to determine the role of endoscopy and other measures for screening in Europe (eg, Towards Gastric Cancer Screening Implementation in the European Union (TOGAS EU4H–2022–PJ–01)). Endoscopic screening for early GC detection and prevention (eg, resection of dysplasia) must be balanced with the fact that endoscopy in most countries is a limited resource, is costly, invasive, inconvenient for patients and poses small but measurable risk.

GIM is a defined precancerous condition that is amenable to surveillance for early GC detection. However, most patients with GIM are at low risk of progression and the risk/burden of endoscopy likely outweighs the theoretical benefit of detecting early neoplasia in these patients. Accordingly, clinicians must be equipped with clear evidence-based guidance to ensure that resources are appropriately allocated to high-risk patients with GIM while minimising the burden and potentially unnecessary anxiety among low-risk patients with GIM. Furthermore, there is a push to maximise the sustainability of endoscopy for cancer prevention by optimising the populations for which it is recommended, and ensuring each exam generates the highest-quality information to minimise unnecessary repeat procedures. 31 32 The presence of GIM, along with the determination of a high-risk versus low-risk phenotype, is the most consistent marker for GC risk, and thus appropriate endoscopic surveillance and adjunct therapeutic interventions (eg, H. pylori eradication, smoking cessation) allow an invaluable opportunity for efficient secondary prevention of GC. For these reasons, we aimed to generate a document that summarises and compares the currently published guidelines and consensus documents on GIM management.

We conclude that international guidelines are aligned in two main recommendations regarding (1) the need for risk-stratified surveillance (as opposed to universal surveillance) and (2) mandatory H. pylori eradication in patients with GIM. Otherwise, there was heterogeneity regarding recommendations for opportunistic detection of GIM during UGIE, the execution of risk stratification (ie, use of histological staging systems such as OLGIM), the approach to the endoscopic examination with respect to defined quality metrics and gastric sampling protocols, surveillance intervals and adjunctive modalities for non-invasive interventions for GC risk reduction in patients with GIM (eg, chemoprevention agents apart from H. pylori eradication; diet modifications and supplementation). This heterogeneity reflects the current gaps in evidence and lack of robust, high-quality data, as well as the heterogeneity of the populations served by each of the guidelines. Indeed, it is expected that guidelines serving high-GC incidence populations (eg, Latin America, Asia-Pacific) may favour a stricter approach, for example, shorter endoscopic intervals, while those serving low-GC incidence populations may favour a less aggressive approach. However, this may not be appropriate, particularly since there are no compelling data to support changing surveillance practices based solely on the country of practice or patient ethnicity, independent of other risk parameters. 33

Certainly, the prevalence of gastric precancerous conditions and GC is higher in certain populations based on country of origin and ethnicity. Additionally, the risk of developing GC overall (and mortality) is higher in early generation immigrants from high-GC regions who have moved to low-GC regions. 34 35 However, among individuals already diagnosed with precancerous conditions, the risk of progression to GC is independent of the country of origin and ethnicity, 33 meaning that other factors (eg, GIM subtype, persistent H. pylori , family history) should be used to determine the need and intervals for surveillance. Thus, the variations in recommendations, especially regarding the surveillance interval, across international guidelines may relate to perceived risk of progression but lacks strong evidence. For example, the Chilean guidelines recommend a 1-year surveillance interval in patients with OLGIM III/IV, whereas the Spanish guidelines recommend surveillance only if there is at least one additional risk factor for progression (eg, family history of GC), and the AGA suggests that up to a 5-year interval may be appropriate.

Other nuances when considering recommendations for GIM management in the context of each guideline and the population served relate to the respective healthcare infrastructure and resource availability, age of the population as well as cultural, lifestyle and dietary practices. The training of the clinical providers including the endoscopists and pathologists and their familiarity with GIM detection and staging is also of relevance. For example, broadly speaking, endoscopists in the USA have lower familiarity with GIM detection and endoscopic staging versus endoscopists from high-GC incidence countries, particularly Japan and South Korea where routine population-based screening occurs. In the USA, histological staging with OLGIM and GIM subtyping are not routine practice, particularly compared with many European and Latin American countries. The primary benefit of endoscopic surveillance is the opportunity for early detection of neoplasia and curative resection, which has substantial implications for GC mortality reduction. However, the success of endoscopic surveillance hinges on the accurate detection of precancerous and cancerous lesions. Considering that the endoscopic miss rate for early GC is approximately 10% based on a meta-analysis, and may be higher in less experienced hands, interventions are needed to improve and standardise the endoscopic surveillance exam. To this end, few guidelines specify the quality metrics that must be achieved to qualify as a high-quality upper endoscopic exam. However, the importance of such metrics is becoming increasingly recognised. In 2024, the AGA published its first consensus report providing ‘best practice advice’ statements for how to perform a high-quality upper GI endoscopy and included metrics specific for the GIM surveillance exam, which complements the AGA guideline on GIM management published in 2020. 28 Similarly, the Spanish GI society also published a supplemental document on quality metrics in upper endoscopy to accompany the guideline, which lacked such metrics. The ESGE addresses appropriate biopsy sampling according to MAPS guidelines as a quality criterion together with others to define the quality of an upper endoscopy. 29 32

Accurate endoscopic and histological staging of GIM is critical, as this is a primary determinant for the branchpoint of whether or not to recommend endoscopic surveillance. While there was consistency regarding which factors (eg, OLGIM III/IV, incomplete GIM subtype, anatomic extension) constitute a high-risk phenotype, there was heterogeneity regarding which metrics are routinely recommended. For example, in the USA, there is no guideline recommendation for pathologists to perform OLGIM staging or to report the histological subtype when GIM is present, and therefore this information is rarely available for clinical decision-making. In addition, there was heterogeneity regarding the ‘weight’ of each risk stratification parameter. Family history and OLGIM III/IV generally hold the most weight and in some guidelines warrant a shorter than 3-year surveillance interval; however, other guidelines, such as the Spanish guidelines, recommended surveillance in patients with extensive GIM only if additional risk factors are present (eg, incomplete GIM, family history of GIM), or if there is a prior or current history of gastric neoplasia. This heterogeneity stems both from the lack of robust evidence, as no randomised clinical trials exist, and from the diverse classifications that determine the presence of this phenotype. 36–38 More robust and precise risk stratification markers (eg, tissue-based markers) could improve risk stratification and, ideally, consistency across guidelines.

Fortunately, most people with GIM who originate from low GC-risk countries fall into an overall low-risk phenotype and may not warrant or benefit from endoscopic surveillance. Accordingly, most guidelines are aligned in recommending against surveillance in patients with low-risk GIM phenotype. The two exceptions are the Chilean and Japanese guidelines, which recommend that all individuals with GIM should be surveilled once diagnosed. This universal recommendation reflects the high GC incidence and mortality in these countries and acknowledges that mild antrum-limited GIM carries some, although very low, level of elevated GC risk. However, the sustainability of such an approach has been questioned, given that endoscopy is a limited and costly resource. Among patients with GIM, the condition is extensive in 7%–25% based on studies from low GC incidence countries and in 16%–26% based on studies from high-incidence areas. 5 39 40 The true prevalence of incomplete GIM versus complete GIM (vs mixed) is not well established, and studies reporting these figures vary significantly. However, incomplete GIM is more commonly observed in patients with extensive GIM and those with prior or current H. pylori infection. Notably, all of the guidelines that mention histological subtyping of GIM consider the presence of incomplete GIM as sufficient for categorising someone as high-risk and warranting endoscopic surveillance. However, the merits of this classification are based solely on observational studies (and meta-analyses of these studies), which are subject to bias. Despite this, studies consistently demonstrate that incomplete GIM is associated with several-fold higher risk of GC compared with patients with only complete-type GIM.

Unmet needs

Randomised trials on GC screening, gastric precancer surveillance and intervention strategies are lacking, and this stands in stark contrast to colorectal cancer screening and postpolypectomy colonoscopy surveillance, as well as oesophageal adenocarcinoma screening and Barrett’s oesophagus surveillance. Generating robust evidence is a critical unmet need, particularly as it relates to endoscopic surveillance intervals and developing, validating and positioning risk stratification metrics with high discrimination values. Specific research priority areas include non-invasive and tissue-based biomarkers for diagnosis, staging and prognosis of GIM; improved uptake and consistency of adherence to guidelines, the development of quality metrics linked to patient-specific outcomes (eg, gastric neoplasia detection rate), leveraging non-invasive therapeutic interventions for halting or reversing GIM progression (eg, diet modifications; chemoprevention) apart from H. pylori eradication, leveraging newer technologies such as artificial intelligence and image-enhanced endoscopy to improve the detection of gastric preneoplasia/neoplasia and specific guidance regarding GIM management in special situations such as hereditary syndromes, postsurgical stomach, after endoscopic resection of neoplasia, and in autoimmune gastritis.

This is the first systematic review of all position statements regarding GIM. At the time of this writing, new guidelines are being updated or developed in the USA, Germany and by ESGE (MAPS III), but are not yet publicly available. Reassuringly, GIM guidelines have demonstrated increased uptake in clinical practice during the last decade. For example, retrospective studies from the USA, 41 reported that H. pylori diagnosis, multiple biopsies and the recommendation for surveillance significantly increased among US doctors following the 2019 AGA guideline. Also, in Europe, the ESGE considered biopsy sampling according to the so-called MAPS protocol as a minor but relevant quality parameter. 32

In conclusion, irrespective of the country of origin when performing an UGIE, the best care must include staging of GIM by performing histopathological mapping. In most guidelines, only individuals at a higher risk (corpus extended GIM, OLGIM stages III/IV, incomplete GIM subtype, persistent H. pylori infection or first-degree family history of gastric cancer) merit regular surveillance at a 3-year interval if no concurrent risk factors are present. Importantly, the most common group, those individuals with focal GIM changes limited to the antrum and no other risk factors for GC, do not require follow-up in most cases, but there are exceptions. H. pylori testing (and its eradication if present) is unanimously recommended and should be synergistically suggested for primary prevention of GC.

Supplemental material

Ethics statements, patient consent for publication.

Not applicable.

Ethics approval

This manuscript did not involve animal experiences or patients' data or interventions.

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Supplementary materials

Supplementary data.

This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

• Data supplement 1

X @mdinisribeiro, @ShailjaShahMD, @diogolibanio, @MoreiraR_Leti, @emadelomar

MD-R and SS contributed equally.

Correction notice This article has been corrected since it publishes Online First. The first sentence of the results section in the abstract has been corrected.

Contributors MD-R, SS and EME-O developed the protocol, conducted the review and revised the final draft of the manuscript. All the authors collected data, provided input for the protocol and revised the draft of the manuscript, approving the final version. MD-R, SS and EME-O are the guarantors.

Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors. JB is supported by the UK Medical Research Council in the context of the Clinical Academic Research Partnership (MRC CARP) scheme (Grant ref.: MR/W029960/1).

Competing interests No conflicts of interest are declared by MD-R, SS, HE-S, MB, NU, HT, LGC, DL, EL, AR, J-YF, LM, JB, EJK, EME-O. PM is a member of advisory board/lecturer of Aboca, Alfasigma, Allergosan, Bayer, Biocodex, Menarini advisory boards/lectures.

Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

Provenance and peer review Not commissioned; externally peer reviewed.

Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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• Commentary Commentary on: the management of patients with gastric intestinal metaplasia David Y Graham Yi-Chia Lee Gut 2024; - Published Online First: 18 Sep 2024. doi: 10.1136/gutjnl-2024-333684

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A systematic literature review of Total Quality Management (TQM) implementation in the organization

2021, International Journal of Production Management and Engineering

In today’s market situation and complex business environment, organization must be able to deliver the customer’s requirement and the expectations which are critical to the satisfaction such as high product quality, faster delivery and competitive cost. Organization need to apply a comprehensive concept and method on managing those requirements. The concept of Total Quality Management (TQM) is considered as one of a popular concept used to manage the quality of product and services comprehensively. This research is to observe is this concept and method still relevant to be use and effectively improved the business performance as well as customer satisfaction. It is a systematic literature review to the literatures from many industry sectors that were collected and reviewed in detail. The result show that this concept is still being used by many organizations around the world and its successfully help the organization to improve their competitiveness, business growth and the sustaina...

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• Published: 17 September 2024

Multi-organ clinical manifestations of Mpox: an umbrella review of systematic reviews

• Prakasini Satapathy 1 , 2   na1 ,
• Mahalaqua Nazli Khatib 3   na1 ,
• Shilpa Gaidhane 4 ,
• Quazi Syed Zahiruddin 5 ,
• Hayam A Alrasheed   ORCID: orcid.org/0009-0002-6186-848X 6 ,
• Maha F. Al-Subaie   ORCID: orcid.org/0009-0001-6558-7143 7 , 8 ,
• Nawal A. Al Kaabi   ORCID: orcid.org/0000-0002-7680-1141 9 , 10 ,
• Mohammed Garout   ORCID: orcid.org/0000-0003-1317-1186 11 ,
• Mubarak Alfaresi   ORCID: orcid.org/0000-0003-2523-835X 12 , 13 ,
• Tarek Sulaiman   ORCID: orcid.org/0000-0003-1590-6203 14 ,
• Ali A. Rabaan   ORCID: orcid.org/0000-0002-6774-9847 8 , 15 , 16 ,
• Martin Krsak 17 ,
• Andrés F. Henao-Martinez 17 ,
• Carlos Franco-Paredes 18 , 22 ,
• Hashem Abu Serhan 19 &
• Ranjit Sah 20 , 21 , 23  

BMC Infectious Diseases volume  24 , Article number:  992 ( 2024 ) Cite this article

Metrics details

Mpox is a severe viral zoonosis that has emerged as a public health concern due to its potential for human-to-human transmission and severe illness. Understanding its clinical manifestations is crucial for effective management and control. Several systematic reviews have assessed various manifestations of Mpox. This umbrella review synthesizes evidence on Mpox’s manifestations across different organ systems.

We conducted an umbrella review, adhering to Joanna Briggs Institute (JBI) methodology and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, focusing on systematic reviews of Mpox manifestations. We performed a literature search up to 25th September 2023, in databases like PubMed, Embase, and Web of Science. We included systematic reviews of observational studies, case reports, case series, or RCTs reporting any manifestations of Mpox in humans, focusing on a global scope. AMSTAR 2 was used to evaluate the quality of systematic reviews, and data has been synthesized in narrative and tabular manners.

A total of 25 systematic reviews were included, uncovering diverse manifestations of Mpox, such as cutaneous, cardiovascular, oral, ophthalmic, gastrointestinal, respiratory, and pregnancy-related. Cutaneous manifestations (up to 100%) were the most prevalent, featuring lesions and rashes. Constitutional symptoms of viral illness were reported in ~ 60% to > 85% of the cases. Significant respiratory symptoms were present in ~ 50% of cases overall. Headaches were the leading neurological symptom present in > 30%. Symptoms of gastrointestinal involvement ranged from 39% (oral lesions) with decreasing frequency to low diarrhea at ~ 5%, with proctitis percentages ranging from high teens to mid-twenties. Ophthalmic manifestations (6% but with wide variations among studies). Many primary studies included in the systematic reviews consisted of case reports and case series. A wide range of manifestations across different organ systems was observed. Negative outcomes for pregnancies were reported, but evidence is limited. Adverse cardiovascular and neurological outcomes were identified, though only a few studies provided insights into these findings.

Mpox exhibits diverse manifestations, impacting multiple organ systems, with substantial variations. The findings highlight the importance of ongoing, nuanced, and region-specific research and management strategies for Mpox. The reliance on case reports and series underscores the need for more high-quality, long-term studies to deepen our understanding and management of this significant public health concern.

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Introduction

Mpox is a rare but potentially severe viral zoonosis, likened to human smallpox due to similarities in clinical presentation and pustular rash manifestation [ 1 ]. It was first discovered in 1958 when outbreaks of a pox-like disease occurred in monkeys kept for research, lending the disease its name. It is caused by the Mpox virus, a member of the Orthopoxvirus genus, which includes variola virus, the cause of smallpox. The virus predominantly circulates in remote parts of Central and West Africa, near tropical rainforests. Human monkeypox (HMPX) was first discovered in 1970 in the Democratic Republic of the Congo (DRC) [ 2 ].

The prevalence of Mpox has been relatively low; however, it has substantial public health significance due to its potential for human-to-human transmission and its capacity to cause severe illness, including fatalities [ 3 , 4 ]. The disease typically presents with fever, headache, muscle aches, and a characteristic progressive pox-like rash. The manifestations of Mpox vary widely, affecting different organ systems and causing a broad spectrum of clinical signs and symptoms, which are often correlated with the extent and severity of the disease [ 3 ]. Given the significance of Mpox as a public health concern, especially in a world that has eradicated its relative, smallpox, it is essential to have a robust understanding of its clinical manifestations. Understanding the myriad of clinical presentations is crucial to identify, diagnose, and manage cases effectively and to implement appropriate control measures to prevent further spread.

Several systematic reviews have been published on various manifestations of Mpox. These cover epidemiology, symptoms, clinical presentations, mortality, and effects on different organ systems [ 5 , 6 , 7 , 8 ]. The current understanding of Mpox is predominantly centered around its cutaneous manifestations, but there are significant gaps in knowledge regarding its effects on other organ systems. For instance, the extent and nature of Mpox’s involvement in the respiratory, gastrointestinal, and neurological systems remain largely elusive. Moreover, there’s a limited understanding of the factors contributing to the variability in the disease’s severity and progression. The reasons why some individuals experience only mild symptoms while others suffer from severe, life-threatening complications are not yet fully understood, necessitating further research in this area. Another area that requires more attention is the long-term effects of Mpox. The potential chronic conditions or sequelae that may follow recovery from Mpox are not well-documented, which is a crucial gap, especially for guiding long-term patient care and rehabilitation strategies. Additionally, the impact of Mpox on special populations, such as immunocompromised individuals, children, pregnant women, and the elderly, is not adequately understood. These groups may have different disease experiences and outcomes, highlighting the need for more detailed investigation. These gaps in knowledge underscore the need for comprehensive research to fully understand the multifaceted nature of Mpox and its impact on diverse patient populations.

Umbrella reviews are an innovative methodological approach to synthesize evidence from multiple systematic reviews into one overarching review, providing high-level, comprehensive insights [ 9 ]. The primary objective of this umbrella review is to synthesize evidence from multiple systematic reviews on Mpox, focusing on its various clinical manifestations across different organ systems. By consolidating data from diverse studies, this review aims to provide a holistic view of Mpox’s clinical characteristics and the variability in its presentations. This comprehensive synthesis will help in enhancing our understanding of the disease, guiding healthcare professionals in its management, and informing public health strategies to curb its spread.

This umbrella review has been conducted, adhering to the established standards and protocols outlined in the Joanna Briggs Institute (JBI) methodology and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (Table S1 ) [ 10 , 11 , 12 ]. An umbrella review, also known as a review of reviews, is a distinct form of evidence synthesis that compiles data from multiple systematic reviews related to a specific topic or question, in this case, the clinical manifestations of Mpox. This methodology is especially valuable when addressing complex, multifaceted health issues that have been the subject of numerous reviews, allowing for a broader and more comprehensive understanding of the available evidence. We employed rigorous criteria for the selection of systematic reviews to ensure relevance and quality. Each selected review was required to meet specific standards regarding methodology, scope, and the robustness of findings. Our synthesis process involved extracting key data points from each review, analyzing patterns and discrepancies, and summarizing the evidence to provide an overarching insight into the clinical spectrum of Mpox. This structured approach enables us to present a consolidated view of the disease’s impact on different organ systems, capturing variability in clinical presentations and outcomes across different populations and study settings. The review has been registered in PROSPERO: CRD42023468364.

Inclusion criteria

We included studies involving the general population, without restricting to specific subgroups, to provide a comprehensive overview of Mpox’s impact across diverse demographics. The exposure of interest was clearly defined as cases of Mpox, excluding other infections to eliminate confounding influences. The outcomes of our review were categorized into three main groups: Major Health Outcomes and Associated Risk Factors (such as atherosclerosis and high blood pressure); Specific Organ System Effects (including respiratory diseases and neurological effects); and Broader Health Implications (like effects on pregnancy and developmental outcomes). These outcomes were chosen to explore both the direct effects of the virus and its broader health implications. Regarding study designs, our review included systematic reviews of randomized controlled trials (RCTs), observational studies, longitudinal studies, and other empirical study types up to case reports, providing a rich variety of data sources. We excluded policy discussions, opinion pieces, reviews that do not include original data, and animal studies to maintain a focus on empirical human data. Only articles available in English are included. The geographic scope of our review was global, considering studies from any region to ensure a wide epidemiological perspective. The detailed criteria for inclusion in our review can be found in Table S2 .

Literature search

We performed comprehensive literature search in databases such as PubMed, Embase, Web of Science, and the Cochrane Database of Systematic Reviews from inception upto 25th September 2023. We employed search terms including “mpox,” “monkeypox,” and “mpxv,” coupled with “meta-analysis” or “systematic review” to curate relevant systematic reviews. To refine the search results, an English language filter was applied. Detailed search strategy is furnished in Table S3 .

The process of screening and selecting systematic reviews was undertaken by two independent reviewers (SG and PS). They utilized the Nested Knowledge software for the removal of duplicates and screening purposes [ 13 , 14 ]. The preliminary screening involved reviewing the titles and abstracts of each article, followed by a thorough reading of the full texts. In instances where discrepancies between the reviewers arose, a third, senior reviewer was consulted to reconcile differences and reach a resolution.

Data extraction

Data extraction was conducted by two reviewers, utilizing a pre-tested data extraction form. The data collated from the included systematic reviews comprised the name of the authors, year of publication, databases searched and date, the number and nature of the included studies, the tools used for assessing risk of bias, geographical location/region of the studies, the range of years of the studies, the results of the quality assessment, and the pertinent outcomes.

Quality assessment

To assess the methodological quality of included systematic reviews in our study on Mpox, we employed the AMSTAR 2 tool, recognized for its comprehensive and rigorous approach tailored specifically to systematic reviews [ 15 , 16 ]. This tool is adept at evaluating critical domains crucial for the validity of a review’s conclusions, such as literature search adequacy, risk of bias, and handling of study heterogeneity. This approach aligns with our objective to ensure the reliability and accuracy of our synthesis, given the diverse clinical presentations of Mpox. The quality assessment was collaboratively performed by two reviewers, with studies graded as high, moderate, low, or critically low based on AMSTAR 2 criteria. Reviews were categorized as high quality if they addressed all critical domains with no more than one non-critical weakness, including a comprehensive literature search, explicit statement of research questions, thorough risk of bias assessment, and robust discussion on study heterogeneity and publication bias. Moderate quality reviews met most critical criteria but had several minor methodological weaknesses in non-critical areas, such as less detailed search strategies or incomplete bias discussions. Low quality reviews had multiple flaws across both critical and non-critical domains, including incomplete literature searches and insufficient bias consideration, affecting the reliability of their conclusions. Finally, reviews were deemed critically low quality if they failed to meet multiple critical domains, displaying major methodological shortcomings that likely significantly impaired the validity of their findings, such as lacking transparent reporting and inadequate risk of bias assessments. Any discrepancies in the quality assessment were resolved by a third reviewer, ensuring a thorough and unbiased evaluation.

Data synthesis

Data synthesis and summarising is performed through a coherent narrative synthesis and are also structured in tabular form to facilitate comprehension and interpretation. We have categorized the manifestations of Mpox by the affected organ systems: Oral, Ophthalmic, Cardiovascular, Neurological, cutaneous, gastrointestinal, respiratory, and general manifestations. Each of these categories is appended with a succinct summary to offer clear insights into the varied manifestations within each organ system. A detailed table outlines the specifics of each systematic review involved in our analysis, presenting various pertinent aspects and main information of each review. Different manifestations are comprehensively summarized, and tables are integrated to heighten clarity and alignment with the available systematic reviews. Priority is assigned to the findings of the highest-rated systematic reviews by AMSTAR-2.

Literature search outcome

A total of 207 records were identified from various databases, of which 114 were duplicates. Consequently, 93 records underwent primary screening, with 35 of these progressing to full-text screening. Ten records were subsequently excluded for various reasons. Ultimately, 25 systematic reviews were deemed eligible and included in the synthesis. The screening process and selection of articles are depicted in Fig.  1 .

PRISMA flow chart depicting screening and study selection process

Characteristics of included systematic reviews

The important characteristics of the included systematic reviews are given in Table  1 . The range of included studies by reviews is diverse, encompassing cross-sectional studies, case reports, case controls, case series, and cohorts. Most of the systematic reviews were published in recent years; however, they include primary studies dating from previous decades up to the present. These reviews incorporate studies from various regions, providing a comprehensive overview of global-level data. The Newcastle–Ottawa Scale (NOS), the Joanna Briggs Institute (JBI) checklist, the National Heart, Lung, and Blood Institute (NHLBI) quality assessment tools, and the National Institutes of Health (NIH) quality assessment tools are the predominant methodologies employed for quality assessment in these reviews. The clinical manifestations discussed within the systematic reviews are varied, including cutaneous, cardiovascular, neurological, respiratory, gastrointestinal, oral, and ophthalmic manifestations, among others. The overall quality of the primary studies varied, ranging from very poor to high quality. Out of the 25 systematic reviews, 16 performed meta-analysis. Most of the reviews were categorized as critically low quality according to AMSTAR 2 criteria. Many of them did not register the protocol, and some reviews did not perform or consider accounting for the risk of bias in primary studies Table S4 .

Manifestation of Mpox in humans

These findings categorized based on different organ systems, are summarized in Table  2 .

Cutaneous manifestations

Skin lesions and rashes are a universal manifestation in Mpox, with a rash being observed in 100% of patients in one study [ 17 ], and skin lesions having a prevalence of 95.2% (CI: 93.3 to 96.9%) [ 18 ]. Another study revealed a notable prevalence of 85.7% (95% CI : 68.3 to 94.30) for rashes [ 19 ]. The disease is marked by a diversity in lesion types. Pustular lesions were observed in 46% of cases, papular and ulcerating lesions in 33%, vesicular lesions in 27%, and macular lesions in 13% [ 8 ]. The lesions have a typical progression, starting as vesicular eruptions, evolving into pustules, with some ulcerating, forming scabs, and subsequently resolving. Exanthem and maculopapular pinkish exanthem were also identified as types of lesions present in Mpox [ 6 ]. The majority of patients before 2022 experienced moderate skin rash severity (53.6%, 95% CI: 46.6 to 60.5), whereas, post-2022, most patients predominantly experienced mild skin rash severity (84.9%, 95% CI: 71.9 to 92.5) [ 20 ]. Complications such as ocular lesions, secondary bacterial skin infections, hemorrhagic pustules, and ulcerated or necrotic lesions were also reported [ 21 ].

The anatomical distribution of lesions before 2022 was extensive. Facial lesions were exceedingly prevalent, found in 98.0% (95% CI: 97.1 to 98.6) of patients [ 20 ]. Trunk lesions were reported in 93.8-95.2% of patients, and limb lesions were observed in 91.0-94.9% of cases [ 20 ]. Genital lesions and oral lesions were also significant, observed in 53.5%(95% CI: 36.8 to 69.5) to 53.58% and 37.47% of cases, respectively [ 20 ]. In the 2022 outbreak and subsequent ones, there was a shift in the prevalence of lesion locations. The genital area emerged as a common site with a prevalence of 50.83% (95% CI: 40.12 to 61.50) [ 22 ]. Perianal lesions were noted in 35.44% (95% CI: 28.04 to 43.19), limb lesions in 30.82% (95% CI: 14.24–50.37%); facial lesions in 27.67% (95% CI: 22.78 to 32.82), trunk lesions in 26.74% (95% CI: 18.16 to 36.24), and oral lesions in 9.86% (95% CI: 2.13 to 21.59) of the patients [ 22 ]. The prevalence of lesions in the anal/perianal area, a previously unreported location, was marked at 39.8% (95% CI: 30.4 to 49.9) [ 20 ]. Lesions on the limbs were most common on arms, forearms, and legs [ 8 ]. Anogenital lesions, including vesicular, macular, pustular, or ulcerated lesions on the penile shaft, were often accompanied by painful inguinal lymphadenopathies or pubic erythema and pruritus [ 8 ]. Numerous rectal lesions with few perianal and cutaneous lesions were also reported [ 8 ]. The location of the rash was notably related to the site of sexual contact, including the genital, anal, or oral regions [ 23 ]. A significant variance in rash distribution was noted between African and European studies. Rash frequency was significantly higher in African studies (100%) compared to European studies (22%, 95% CI: 14 to 32). Additionally, the distribution of the rash in the pelvic area and groins was significantly higher in European studies (75%, 95% CI: 65 to 84) compared to African studies (30%, 95% CI: 28 to 33%) [ 21 ].

Cardiovascular manifestations

Cardiovascular complications in Mpox virus cases are notable for a variety of symptoms and diagnostic findings, primarily involving myocarditis. The complications are often associated with distinctive symptoms like chest pain sometimes radiating to the left arm and dyspnea, were identified in examined cases [ 23 , 24 ]. Electrocardiographic evaluations across studies have disclosed various abnormalities, including sinus tachycardia and widespread ST-segment elevation, reflecting the diversified cardiac involvements in Mpox [ 23 , 24 ]. Specifically, ST-Elevation was identified in 44% of patients, with sinus tachycardia and normal sinus rhythm recorded in 22% and 33% of patients, respectively [ 24 ]. This finding was based on the findings of 6 studies which include only total of 9 patients. CMR imaging elucidated areas of increased signal intensity and findings consistent with necrosis and myocardial edema [ 23 ]. Late gadolinium enhancement and edema were prevalent in 40% of the patients analyzed through CMR [ 24 ]. Echocardiographic assessments depicted normal wall motion in 67% and reduced ejection fraction in 43% of the patients [ 24 ]. The elevated levels of high-sensitivity troponins, ranging from 0.165 to 21.20 ng/ml, were a consistent finding [ 23 ]. Other cardiac biomarkers like Creatine Kinase (291–740 U/L) and N-terminal prohormone B-type natriuretic peptide (155–1258 pg/ml) were also found to be elevated, indicating extensive cardiac implications [ 23 ].

Neurological manifestations

The neurological manifestations of Mpox are extensive, with headache being the leading symptom, reported in 18 out of 22 studies, affecting 47.84% of participants [ 25 ]. The pooled prevalence of headaches was reported at 31% [ 26 ], and varied findings have been reported regarding its prevalence in different outbreaks, with 48% in previous outbreaks compared to 36% in 2022 outbreaks [ 27 ]. Myalgia and fatigue are also prevalent, reported in 27.5% and 17.73% of participants, respectively [ 25 ]. Myalgia was reported with a prevalence of 36.0% and 30.8% [ 18 , 19 ]. Fatigue, asthenia, or malaise were particularly prevalent, affecting 38.7% of patients [ 18 ]. There is variation in the prevalence of neurological symptoms between different studies and outbreaks. Headache was more prevalent in non-endemic regions (36%, 95% CI: 24 to 47) compared to endemic regions (24%, 95% CI: 1 to 57)) [ 28 ]. It was also more prevalent in prior outbreaks (37%, 95% CI: 11 to 66) compared to the 2022 outbreak (23%, 95% CI: 14 to 34) [ 28 ].

Seizure, confusion, and encephalitis were reported with prevalences of 2.7% (95% CI: 0.7 to 10.2%), 2.4% (95% CI: 1.1 to 5.2), and 2.0% (95% CI: 0.5 to 8.2) respectively [ 29 ]. Seizures were particularly noted in three patients, with one case involving a 43-year-old man with HIV-1 infection who died following repeated seizures [ 25 ]. Encephalitis details include cases involving a female neonate and a 6-year-old girl [ 25 ]. Photophobia was reported in 39 patients (4.43%), and visual deficits were reported in five patients (0.57%) [ 25 ]. Other reported manifestations included dizziness, coma, encephalomyelitis, and transverse myelitis [ 25 ].

Several pediatric cases have been reported, with symptoms like headache and malaise being common. A 2-year-old female developed headache and malaise [ 26 ]. Another 6-year-old female presented with malaise, anorexia, and headache, and a provisional diagnosis of encephalitis was made [ 26 ]. Brain MRI in this case showed diffuse cortical, thalamic, and brainstem edema, meningeal enhancement, and signal abnormalities [ 26 ].

Oral manifestations

The prevalence of oropharyngeal rash was 52.4% pre-2022 outbreak, reducing to 18.3% (95% CI: 13.2 to 24.9) in post-2022 outbreaks [ 20 ]. Variations in prevalence are also seen based on geographic locations, with a higher prevalence of 62.67% (95% CI: 52.75 to 72.12) in endemic countries compared to 15.62% (95% CI: 10.24 to 21.69) in non-endemic ones [ 30 ]. A meta-analysis investigated the prevalence of oral manifestations of human Mpox infection in 4042 individuals, out of which 1433 exhibited oral manifestations [ 30 ]. The overall pooled prevalence of oral manifestations was 36.75% (95% CI: 23.77 to 50.65), with sore throat being the predominant oral manifestation at 39.96% (95% CI: 21.42 to 59.91), followed by mouth sore at 24.80% (95% CI: 8.14 to 46.32), tonsillitis at 18.24% (95% CI: 0.34 to 52.54), and mouth rash at 17.99% (95% CI: 15.66 to 20.43) [ 30 ].

Oral ulcers are a common manifestation, recorded in 96% of the patients in one study [ 17 ], and another study observed a pooled prevalence of 7% (95% CI: 1 to 19), with a higher occurrence in prior outbreaks (13%, 95% CI: 2.0 to 30) compared to the 2022 outbreak (2%, 95% CI: 0.0 to 5.0) [ 28 ]. Tonsillar signs and oral exanthem are reported with a pooled prevalence of 3% (95% CI: 0.00 to 9.0), with variations in prevalence between prior outbreaks and the 2022 outbreak [ 28 ]. The prevalence of oral ulcers has been reported to be 33% (95% CI: 31 to 35), while dysphagia has been observed in 57% (95% CI: 54 to 59) of cases, and odynophagia in 31% (95% CI: 27 to 35) of cases [ 31 ]. There have been highlighted instances showcasing significant oral, perioral, enoral, and tonsillar lesions. These instances include cases of isolated enoral peritonsillar abscesses with unilateral cervical lymphadenopathy (LAP) without the presence of cutaneous lesions, and cases displaying oropharyngeal erythema, tonsillar enlargement, and associated bilateral cervical LAP [ 8 ]. The prevalence of oral lesions was reported to be 37.47% for outbreaks occurring prior to 2022 and 9.86% for outbreaks post-2022 for Mpox [ 22 ].

Specific studies have reported a prevalence of 62.67% (95% CI: 52.75 to 72.12) in Africa, 27.48% (95% CI: 7.19 to 52.99) in North America, and 15.07% (95% CI: 7.02 to 24.95) in Europe [ 30 ]. A prospective observational study from the DRC reported a 77.78% prevalence of sore throat, while another study observed a 70% prevalence of oral lesions in patients with Mpox from the DRC [ 30 ].

Ophthalmic manifestations

The prevalence of conjunctivitis is notably high, recorded at 96% in one study [ 17 ], and 12% in another, with a remarkable difference in prevalence noted between outbreaks before 2022 (17%) and the current multicountry outbreak (1%). Another study reported the prevalence of conjunctivitis at 7.1% [ 19 ], and the weighted prevalence is reported as 6%, with reports of up to 60% prevalence in certain latitudes [ 32 ]. Geographic variations are also observed, with no patients from non-African countries reporting vision loss [ 5 ]. There are notable differences in the rate of ophthalmic manifestations between previous MPX outbreaks and the current outbreak, with a higher prevalence of conjunctivitis, eye lesions involving the cornea and/or conjunctiva, and involvement of the eyelids reported in previous outbreaks [ 7 ]. Various studies have documented a range of ophthalmic manifestations such as photophobia, eye pain, eye lesions involving the cornea and conjunctiva, and lesions involving the eyelids, including vesicles, pustules, or pseudo-pustules [ 5 , 7 ]. Specific complications associated with these manifestations include keratitis, corneal ulceration, unilateral blindness, and impaired vision [ 7 ]. The involvement of the eyelids can present single or multiple umbilicated papules in 3% of patients and can lead to eyelid deformation, with severe cases of skin necrosis reported [ 32 ]. A pooled prevalence of 13.89% (95% CI: 6.92 to 22.67) for conjunctival lesions and a prevalence of 14.37% (95% CI: 6.91 to 23.71) for eye rash is reported [ 5 ]. Redness, pain, and discharge in the eye are observed in 9.26% of the cases, with vision loss reported in 7.69% and vision changes in 2.31%. Cases of severe conjunctivitis with erythematous sclera, corneal edema, opacity, and keratitis with confluent corneal lesions spreading into the sclera have been reported [ 32 ]. Additionally, uveitis, described in four case reports, had mild inflammation accompanied by corneal compromise, with keratic precipitates and superior limbitis observed [ 32 ].

Respiratory manifestations of Mpox

Respiratory manifestations are a significant aspect of Mpox, with cough being a common symptom, reported with an overall prevalence of 48.55% (95% CI: 34.67% to 62.54) [ 22 ]. Another study indicated a similar prevalence for cough, noting it in 53% of cases in previous outbreaks compared to 17% in 2022 outbreaks [ 19 ]. In contrast, the prevalence of cough in nonendemic countries during the 2022 outbreak was significantly lower, recorded at 10.17% (95% CI: 1.68 to 23.50) [ 22 ]. Upper respiratory symptoms are also predominant, with an overall prevalence of 97% [ 17 ]. One review also categorized respiratory symptoms as rare clinical features, with a prevalence of 19.5% [ 19 ]. The significant variations in the prevalence of different respiratory symptoms, especially between different outbreaks, highlight the dynamic nature of Mpox and its respiratory manifestations. Beyond cough, other respiratory symptoms like nasal congestion and shortness of breath have a pooled prevalence of 1%, with similar prevalence in both prior and the 2022 outbreaks and in both endemic and non-endemic regions [ 28 ]. A remarkable difference in the prevalence of sore throat is also noted, being 71% in previous outbreaks versus 28% in 2022 outbreaks [ 19 ]. A rare case of nasal necrosis has been reported in a 40-year-old HIV-positive man [ 19 ].

Gastrointestinal manifestations

Abdominal pain is a recognized gastrointestinal symptom of Mpox, noted to have an overall prevalence of 9% (95%: 8 to 10) [ 31 ]. There is documented variance in the prevalence of abdominal pain, with African studies reporting higher incidences compared to non-African studies [ 31 ]. Anorexia, characterized by a decreased appetite, has also been reported, with a prevalence of 47% (95% CI: 41 to 53), underscoring the substantial impact of Mpox on the gastrointestinal system and dietary patterns [ 31 ]. Nausea and vomiting are common, with prevalences of 10% and 12% respectively [ 22 , 31 ]. Diarrhea, on the other hand, is less common, with a 5% (95% CI: 4 to 6) prevalence [ 31 ].

The prevalence of proctitis is documented at 11% (95% CI: 12 to 13), and issues related to rectal/anal pain and rectal bleeding are also notable, with prevalences of 25% (95% CI: 24 to 27) and 12% (95% CI: 11 to 13) respectively [ 31 ]. In the 2022 outbreak in nonendemic countries, a significant prevalence of 16.82% for rectal pain was reported [ 22 ]. Dysphagia has a varied prevalence, with reports as high as 70.08% (95% CI: 19.55 to 100) [ 22 ] and as low as 2% [ 8 ]. There is also a reported general prevalence of 23% for either pharyngitis or dysphagia.

Pregnancy related manifestations

Only two systematic reviews reported details on pregnancy related manifestations mainly conducted in DRC [ 33 , 34 ]. Mpox infection during pregnancy has been associated with a high incidence of spontaneous early miscarriages and second-trimester losses [ 34 ]. Another review revealed that 39% of the cases experienced miscarriages and a substantial 77% (95% CI: 26.0 to 100) incidence of overall fetal and perinatal loss [ 33 ]. Furthermore, the incidence of fetal loss was found to be 67% following first-trimester infection and increased to 82% with second-trimester infection. Vertical transmission of Mpox is a significant concern, with an estimated incidence of 62% (95 CI: 9 to 99) [ 33 ]. It is further reported that only 23% (95% CI: 0 to 74) of fetuses surviving to birth [ 33 ]. Although no Neonatal Death (NND) was reported within 30 days from birth, there has been a reported case of NND at 6.5 weeks of age due to malnutrition and a neonatal rash. The occurrence of preterm births before 37 weeks of gestation has been seen as another complication with an incidence of 8.0% (95% CI: 0 to 92) [ 33 ].

Other general and constitutional symptoms

Fever is widely identified as a prominent manifestation of Mpox, with studies documenting its prevalence at 81.34% (95% CI: 60.36 to 96.21) and 58.4% (95% CI: 54.9 to 61.8) [ 18 , 22 ]. Lymphadenopathy, notably impacting the cervical and inguinal regions, is a recurring feature, observed in 53.0% (95% CI: 48.7 to 57.3) to 85% of cases [ 17 , 18 ]. The reports significantly contribute to the understanding of its prevalence in Mpox. Fatigue is another common symptom, with its prevalence ranging from 46.18% in nonendemic regions during the 2022 outbreak to 75% [ 21 ]. The incidence of chills is reported at 23.8% and 67.91% (95% CI: 47.05% to 85.77) [ 18 , 22 ], and other systemic manifestations like myalgia and sweating are reported in approximately 43% (17.47 to 70.58) of cases [ 22 ]. A specific emphasis is placed on the occurrence of scrotal or penile edema, with a reported prevalence of 10.7% (95% CI: 6.3 to 17.7) [ 19 ]. Instances of axillary, cervical, and inguinal lymphadenopathy have been recorded in various outbreaks [ 27 ].

This study constitutes the inaugural umbrella review conducted on Mpox, aiming to aggregate and comprehensively summarize its various manifestations to date. Our objective was to provide a bird’s eye view of the extensive range of MPox’s effects on human organ systems, offering a broader understanding of its diverse manifestations. It became evident that Mpox impacts the human body as a whole, with its manifestations prevailing across different organ systems, the most common of which was cutaneous. We were able to identify a sufficient number of systematic reviews evaluating the clinical manifestations of Mpox, allowing for a more inclusive analysis of its effects. However, concerns arose regarding the types of primary studies included. Many consisted of case series and case reports, contributing to a substantial portion of the systematic reviews. The prevalence of such studies highlights a significant gap in the availability of long-term studies for numerous outcomes. For instance, there is a pronounced need for more expansive research into the cardiovascular manifestations of Mpox. Similarly, the complications of Mpox infection during pregnancy are another area where information is notably limited.

Mpox exhibits a multifaceted and evolving nature, characterized by varied manifestations impacting multiple organ systems. The prevalence and types of manifestations, particularly cutaneous ones, indicate significant variability and evolution, hinting at possible mutations or adaptations of the virus over time, as evidenced by changes observed in post-2022 outbreaks. The near-universal presence of diverse skin lesions is pivotal for diagnosis, reflecting the virus’s primary interaction with the host [ 35 ]. The geographical variations observed in the prevalence of symptoms between African and non-African regions suggest the influence of environmental and genetic factors on disease presentation, necessitating region-specific approaches to management and treatment, though the portal of entry and the mode of exposure likely also play a role in diverse manifestations. Moreover, the systemic impact of Mpox is evident through the prevalence of severe cardiovascular and neurological complications, emphasizing the need for comprehensive multisystem monitoring and holistic management to detect and address potential long-term health implications. Particularly vulnerable populations, such as pediatric patients and pregnant women, experience heightened risks and severe consequences, underscoring the importance of specialized care and stringent prenatal monitoring to mitigate adverse outcomes related to vertical transmission, like spontaneous miscarriages and neonatal complications. The variability in respiratory and gastrointestinal symptoms between different outbreaks highlights the dynamic nature of the disease and the necessity for ongoing research and surveillance to develop targeted interventions and treatments. In essence, the complex interplay of manifestations in Mpox requires a nuanced, multidisciplinary approach, informed by continuous research and a deep understanding of the disease’s evolving nature and geographical variations, to effectively manage and mitigate its impacts.

While our umbrella review has provided valuable insights into the diverse clinical manifestations of Mpox, it is important to note the inclusion of studies categorized as low or critically low quality, according to AMSTAR 2 criteria, presents certain challenges. The presence of these studies inherently affects the reliability and generalizability of our findings. Low-quality studies often suffer from methodological flaws such as inadequate control for confounding factors, poor handling of data, and insufficient reporting of outcomes, which can introduce bias into the synthesis process. These methodological shortcomings might lead to overstated or inaccurate representations of Mpox’s clinical manifestations, impacting our ability to draw definitive conclusions. Moreover, the generalizability of the results is compromised as studies with such deficiencies do not adequately represent the broader patient population or the full spectrum of clinical presentations.

The clinical manifestations of Mpox can vary based on gender and different transmission pathways. In terms of gender, the recent outbreak of Mpox has shown unique clinical signs, especially among men who have sex with men (MSM) [ 36 ]. In this group, rashes have been observed primarily around the genital or anal area, with subsequent spread throughout the body. Severe cases in this population can lead to complications such as hemorrhagic disease, necrotic disease, and inflammation of vital organs. Additionally, the majority of reported cases among homosexual or bisexual males have shown a high co-infection rate with human immunodeficiency virus (HIV), with a significant percentage of lesions occurring in the anal and genital regions. Regarding transmission pathways, Mpox can be transmitted through various routes, including animal-to-human, person-to-person, and fomites [ 37 , 38 , 39 ]. Human-to-human transmission is believed to occur through direct contact with respiratory droplets from infected individuals, and vertical transmission can occur from infected mothers to their newborns [ 40 ]. The recent outbreak of Mpox has seen a shift in transmission patterns, with most cases not associated with contact with infected animals or travel but linked to sexual contact between individuals. This outbreak has highlighted the importance of understanding the diverse transmission pathways of Mpox, especially in the context of the 2022 epidemic that mainly affected MSM. Clade I and Clade II of the Mpox virus exhibit distinct characteristics that significantly impact their transmission pathways and the severity of the disease [ 41 ]. Clade I is primarily associated with transmission through direct contact with infected wild animals, close contact with infected individuals, and contact with contaminated materials. Clade II shares similar transmission routes, including direct contact with infected animals and individuals, as well as through contaminated materials. These differing pathways are crucial for understanding the spread of Mpox and have implications for the severity of outbreaks, necessitating targeted public health interventions and control measures to manage transmission effectively. Additionally, the Mpox virus shows specific tropism for tissues such as the skin, mucous membranes, and lymph nodes, yet the precise virus ligands responsible for this tissue specificity remain unidentified [ 42 ]. This lack of identification shows the complexity of the interactions between the Mpox virus and host cells, influencing the virus’s ability to infect particular tissues and propagate within the host. Understanding these mechanisms is vital for elucidating the pathogenesis of Mpox and developing targeted therapeutic and preventive strategies, enhancing our ability to effectively combat this virus and minimize its public health impact.

The findings from this study on Mpox have significant public health and clinical implications, underscoring the need for an adaptable, informed response to this evolving disease. Several viral infectious diseases are emerging [ 43 , 44 , 45 ]. The wide range of manifestations across multiple organ systems, particularly the variability in cutaneous symptoms and the emergence of severe cardiovascular and neurological complications, call for heightened surveillance and a multidisciplinary approach to patient care. Public health strategies must consider the geographical and temporal variations in symptom prevalence, tailoring interventions to specific regional needs and potential virus adaptations [ 46 ]. Clinically, this necessitates vigilance in diagnosis and treatment, especially for vulnerable groups like pregnant women and pediatric patients, to mitigate the risks of severe outcomes and vertical transmission. The diverse presentations highlight the importance of ongoing research and capacity building in healthcare systems, ensuring they are equipped to handle the multifaceted challenges posed by this virus. The effectiveness of vaccines in preventing Mpox infection underscores the necessity for strategic vaccination programs, particularly targeting high-risk groups to prevent outbreaks and control the disease’s spread [ 47 ]. Alongside vaccination, the importance of contact tracing and monitoring, including healthcare personnel, is crucial in preventing further transmission and containing outbreaks. To effectively manage Mpox, healthcare systems must be prepared with robust surveillance and detection mechanisms that promptly identify cases and track outbreaks. Infection control measures in healthcare facilities, including the use of personal protective equipment (PPE), are vital to prevent transmission to healthcare workers and other patients [ 48 ]. Additionally, the global nature of Mpox outbreaks demands international collaboration and coordination to share data, best practices, and resources, ensuring a unified response. Public education and awareness campaigns play a critical role in promoting prevention measures, reducing stigma, and encouraging individuals to seek medical attention if symptoms arise, further bolstering the public health response to Mpox [ 49 ]. In essence, these findings call for a concerted effort in public health planning, clinical management, and research to effectively address the complexities of Mpox and safeguard community health.

Our study has several limitations. We restricted our inclusion to articles published solely in English, potentially overlooking relevant studies in other languages. There is also a high possibility of overlap in primary studies included in multiple systematic reviews within our umbrella review, which could potentially skew the findings. We could not perform a meta-analysis due to the high variability of study designs and variations in PICO (Population, Intervention, Comparison, Outcome). Moreover, many of our findings predominantly rely on case reports and case series, which could introduce a degree of bias into these results. More high-quality observational studies are required to comprehensively understand the impact of Mpox in humans.

This umbrella review provides an extensive synthesis of the clinical manifestations of Mpox, underscoring the disease’s complex and dynamic nature. Our findings reveal the prevalence of severe complications across various organ systems, including cutaneous, cardiovascular, neurological, and respiratory systems, highlighting the urgent need for detailed and region-specific management strategies. The study significantly contributes to the existing knowledge by delineating the broad spectrum of Mpox effects, which is critical for developing targeted interventions and enhancing diagnostic accuracy. However, our conclusions are tempered by the predominance of case reports and series in the included systematic reviews, which limits the robustness and generalizability of our results. This limitation underlines an urgent need for more comprehensive, high-quality observational studies that can provide deeper insights into the long-term effects of Mpox and its varying clinical presentations across different populations. Future research should focus on longitudinal studies to better understand the disease’s progression, treatment outcomes, and potential chronic conditions following recovery. By addressing these gaps, we can better tailor our clinical and public health strategies to effectively combat the evolving threat of Mpox and safeguard vulnerable communities.

Data availability

Availability of data and materials: Data pertaining to this study are available with the authors. and can be obtained by contacting the corresponding author.

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Acknowledgements

The authors acknowledge Nested-Knowledge, MN, USA for providing access for the software.

This study received no funding.

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Prakasini Satapathy and Mahalaqua Nazli Khatib contributed equally to this work.

Authors and Affiliations

Center for Global Health Research, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences, Saveetha Medical College and Hospital, Saveetha University, Chennai, India

Prakasini Satapathy

Medical Laboratories Techniques Department, AL-Mustaqbal University, Hillah, Babil, 51001, Iraq

Division of Evidence Synthesis, Global Consortium of Public Health and Research, Datta Meghe Institute of Higher Education, Wardha, India

Mahalaqua Nazli Khatib

One Health Centre (COHERD), Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education, Wardha, India

Shilpa Gaidhane

South Asia Infant Feeding Research Network (SAIFRN), Division of Evidence Synthesis, Global Consortium of Public Health and Research, Datta Meghe Institute of Higher Education, Wardha, India

Quazi Syed Zahiruddin

Department of Pharmacy Practice, College of Pharmacy, Princess Nourah Bint Abdulrahman University, Riyadh, 11671, Saudi Arabia

Hayam A Alrasheed

Research Center, Dr. Sulaiman Alhabib Medical Group, Riyadh, 13328, Saudi Arabia

Maha F. Al-Subaie

College of Medicine, Alfaisal University, Riyadh, 11533, Saudi Arabia

Maha F. Al-Subaie & Ali A. Rabaan

College of Medicine and Health Science, Khalifa University, Abu Dhabi, 127788, United Arab Emirates

Nawal A. Al Kaabi

Sheikh Khalifa Medical City, Abu Dhabi Health Services Company (SEHA), Abu Dhabi, 51900, United Arab Emirates

Department of Community Medicine and Health Care for Pilgrims, Faculty of Medicine, Umm Al-Qura University, Makkah, 21955, Saudi Arabia

Mohammed Garout

Department of Microbiology, National Reference laboratory, Cleveland clinic Abu Dhabi, Abu Dhabi, 92323, United Arab Emirates

Mubarak Alfaresi

Department of Pathology, College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, 505055, United Arab Emirates

Infectious Diseases Section, Medical Specialties Department, King Fahad Medical City, Riyadh, 12231, Saudi Arabia

Tarek Sulaiman

Molecular Diagnostic Laboratory, Johns Hopkins Aramco Healthcare, Dhahran, 31311, Saudi Arabia

Ali A. Rabaan

Department of Public Health and Nutrition, The University of Haripur, Haripur, 22610, Pakistan

Division of Infectious Diseases, Department of Medicine, University of Colorado Anschutz Medical Center, Aurora, CO, USA

Martin Krsak & Andrés F. Henao-Martinez

Hospital Infantil de México, Federico Gómez, Ciudad de, Federico Gómez, México, USA

Carlos Franco-Paredes

Department of Ophthalmology, Hamad Medical Corporation, Doha, Qatar

Hashem Abu Serhan

Department of Clinical Microbiology, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth , Pune, Maharashtra, 411000, India

Tribhuvan University Teaching Hospital, Kathmandu, 46000, Nepal

Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, 46000, USA

Department of Public Health Dentistry, Dr. D.Y. Patil Dental College and Hospital, Dr. D.Y. Patil Vidyapeeth, Pune 411018, Maharashtra, India

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Author contributions: - Author Contributions: Conceptualization and Methodology - PS, MNK, AFH-M, MFA-S, NAAK; Data Curation - SG, QSZ, MG, MA, TS; Formal Analysis - PS, MNK, MK, AAR, CFP; Writing - Original Draft Preparation - HAR, HAS, RS, NAAK, MFA-S; Writing - Review & Editing - MG, MA, TS, AAR, MK; Final Approval of the Version to be Published - All authors.

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Satapathy, P., Khatib, M.N., Gaidhane, S. et al. Multi-organ clinical manifestations of Mpox: an umbrella review of systematic reviews. BMC Infect Dis 24 , 992 (2024). https://doi.org/10.1186/s12879-024-09884-y

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DOI : https://doi.org/10.1186/s12879-024-09884-y

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