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Diarrhea is the third leading cause of childhood mortality in India, and is responsible for 13% of all deaths/year in children under 5 years of age. Information on diarrheal diseases, its determinants and preventive and control strategies need to be reviewed for better planning and organization of health services. This study reviewed literature on diarrheal disease control among under-five children in India from literature published in PubMed, Google search engine and other databases on the internet. Data were described in terms of disease burden in India, determinants, management and intervention strategies, preventive strategies, and role of public health and scope for future action. This review calls for a comprehensive diarrheal disease control strategy, through improved case management, addressing social determinants of health and research in the field of cost-effective interventions to reduce the burden of diarrhea among children in India. With < almost one year left to reach the 2015 Millennium Development Goal on reducing child mortality, progress on control of diarrheal diseases must be accelerated.

Current data and trends in morbidity and mortality for the sub-Saharan Region as presented in this new edition reflect the heavy toll that HIV/AIDS has had on health indicators, leading to either a stalling or reversal of the gains made, not just for communicable disorders, but for cancers, as well as mental and neurological disorders.

Diarrheal diseases continue to be a leading cause of mortality and morbidity across the globe. The use of next-generation sequencing data has provided major insights into understanding epidemiological spread, antimicrobial resistance, vaccine effects, and basic mechanisms of bacterial and viral evolution. Furthermore, we discuss how genomic data have informed investigations across enteric pathogens, such as Shigella, Vibrio cholerae, Salmonella Typhi, rotavirus, and norovirus.

BACKGROUND : Diarrheal diseases substantially affect public health impact in low- and middle-income countries (LMIC), particularly in Africa, where previous studies have indicated a lack of comprehensive data. With a growing number of primary studies on enteric infections in Africa, this study aimed to estimate the incidence and mortality of diarrheal pathogens across all ages in Africa in the year 2020. We also explored different methodological assumptions to allow comparison with other approaches. METHODS : Through a systematic review and meta-analysis of data from African LMICs, we estimated the etiology proportions for diarrheal diseases and deaths. We combined the etiology proportions with incidence data collected from a population survey in Africa from 2020 and mortality data from the Global Health Observatory of WHO. RESULTS : We estimated 1,008 billion diarrhea cases (95% UI 447 million-1,4 billion) and 515,031 diarrhea deaths (95% UI 248,983-1,007,641) in the African region in 2020. In children under five, enteroaggregative E. coli (EAEC) (44,073 cases per 100,000 people, 95% UI 18,818 − 60,922) and G. lamblia (36,116 cases per 100,000 people, 95% UI 15,245 − 49,961) were the leading causes of illness. Enteroinvasive E. coli (EIEC) (155 deaths per 100,000 people, 95% UI 106.5-252.9) and rotavirus (61.5 deaths per 100,000 people, 95% UI 42.3-100.3) were the primary causes of deaths. For children over five and adults, Salmonella spp. caused the largest number of diarrheal cases in the population of children ≥ 5 and adults (122,090 cases per 100,000 people, 95% UI 51,833 − 168,822), while rotavirus (16.4 deaths per 100,000 people, 95% UI 4.2–36.7) and enteroaggregative E. coli (EAEC) (14.6 deaths per 100,000 people, 95% UI 3.9–32.9) causing the most deaths. Geographically, the highest incidence of diarrhea was in Eastern Africa for children under five (114,389 cases per 100,000 people, 95% UI 34,771 − 172,884) and Central Africa for children over five and adults (117,820 cases per 100,000 people, 95% UI 75,111–157,584). Diarrheal mortality was highest in Western Africa for both children below five and above (children < 5: 194.5 deaths per 100,000 people, 95% UI 120-325.4; children ≥ 5 and above: 33.5 deaths per 100,000 people, 95% UI 12.9–75.1). CONCLUSION : These findings provide new information on the incidence and mortality of sixteen pathogens and highlight the need for surveillance and control of diarrheal infectious diseases in Africa. The cause-specific estimates are crucial for prioritizing diarrheal disease prevention in the region.

•Shigella infections cause substantial mortality and morbidity in children and adults.•Results from animal studies and challenge models spur Shigella vaccine development.•Various immune mechanisms show potential for durable and protective mucosal response.•Several vaccines are being evaluated either alone or in association with an adjuvant. Shigella are gram-negative bacteria that cause severe diarrhea and dysentery. In 2013, Shigella infections caused an estimated 34,400 deaths in children less than five years old and, in 2010, an estimated 40,000 deaths in persons older than five years globally. New disease burden estimates from newly deployed molecular diagnostic assays with increased sensitivity suggest that Shigella-associated morbidity may be much greater than previous disease estimates from culture-based methods. Primary prevention of this disease should be based on universal provision of potable water and sanitation methods and improved personal and food hygiene. However, an efficacious and low-cost vaccine would complement and accelerate disease reduction while waiting for universal access to water, sanitation, and hygiene improvements. This review article provides a landscape of Shigella vaccine development efforts. No vaccine is yet available, but human and animal challenge–rechallenge trials with virulent Shigella as well as observational studies in Shigella-endemic areas have shown that the incidence of disease decreases following Shigella infection, pointing to biological feasibility of a vaccine. Immunity to Shigella appears to be strain-specific, so a vaccine that covers the most commonly detected strains (i.e., S. flexneri 2a, 3a, 6, and S. sonnei) or a vaccine using cross-species conserved antigens would likely be most effective. Vaccine development and testing may be accelerated by use of animal models, such as the guinea pig keratoconjunctivitis or murine pneumonia models. Because there is no correlate of protection, however, human studies will be necessary to evaluate vaccine efficacy prior to deployment. A diversity of Shigella vaccine constructs are under development, including live attenuated, formalin-killed whole-cell, glycoconjugate, subunit, and novel antigen vaccines (e.g., Type III secretion system and outer membrane proteins).

Introduction Salmonella spp. are a major cause of foodborne diarrheal disease, particularly in low- and middle-income countries. Poor sanitation and unsafe food handling facilitate the transmission and persistence of Salmonella in human, animal, and environmental sources. This study focused on assessing the prevalence of Salmonella spp . obtained from stool, food, and environmental samples in Addis Ababa and its surrounding towns. Methods A total of 552 samples were collected, comprising 386 stool samples from diarrheic outpatients along with full demographic data and 166 food and environmental samples, including meat ( n  = 57) and sewage from slaughterhouses ( n  = 16), chicken intestines ( n  = 42), and chicken droppings ( n  = 51). Stool samples were transported in Cary-Blair transport media while food and environmental samples were collected in buffered peptone water. Samples were enriched in selenite broth and cultured on MacConkey and Xylose Lysine Deoxycholate (XLD) agar, and differentiated as lactose fermenting and non-lactose fermenting. Biochemical tests, including Triple Sugar Iron (TSI), Urea, Citrate, and Lysine Iron Agar (LIA), were performed for presumptive identification of the isolates, which were further confirmed using polyvalent Salmonella antisera. All biochemically identified isolates were further subjected to PCR test targeting inv A gene and serovar-specific markers. Results Behavioral analysis indicated that 26.8% of patients reported consumption of raw or undercooked food prior to illness, and a significant association was observed between Salmonella infection and raw food consumption ( p  < 0.001). Among the 386 stool samples analyzed, 8.56% (33/386) tested positive for Salmonella by PCR. Among food and environmental sources, the highest prevalence was observed in chicken intestinal samples (28.57%, 12/42), followed by meat samples, specifically cattle lymph nodes (21.88%, 7/31), chicken droppings (7.69%, 4/52), surface swabs (7.41%, 2/26), and wastewater samples (6.25%, 1/16). Generally, Salmonella was confirmed in 61 of 552 samples (11.05%) using PCR targeting the conserved inv A gene. Screening revealed source-specific detection patterns, with higher positivity in animal intestinal samples compared with environmental sources, highlighting potential reservoirs of Salmonella within a One Health framework. Conclusion Salmonella spp. pose a significant public health threat across interconnected human, animal, and environmental settings in Addis Ababa and surrounding areas. Strengthening sanitation, improving food safety practices along the animal-to-human food chain, and enhancing integrated surveillance are essential to reduce transmission and mitigate the burden of salmonellosis within a One Health framework.

Diverse extracellular and intracellular cues activate mammalian mitogen-activated protein kinases (MAPKs). Canonically, the activation starts at cell surface receptors and continues via intracellular MAPK components, acting in the host cell nucleus as activators of transcriptional programs to regulate various cellular activities, including proinflammatory responses against bacterial pathogens. For instance, binding host pattern recognition receptors (PRRs) on the surface of intestinal epithelial cells to bacterial pathogen external components trigger the MAPK/NF-κB signaling cascade, eliciting cytokine production. This results in an innate immune response that can eliminate the bacterial pathogen. However, enteric bacterial pathogens evolved sophisticated mechanisms that interfere with such a response by delivering virulent proteins, termed effectors, and toxins into the host cells. These proteins act in numerous ways to inactivate or activate critical components of the MAPK signaling cascades and innate immunity. The consequence of such activities could lead to successful bacterial colonization, dissemination, and pathogenicity. This article will review enteric bacterial pathogens’ strategies to modulate MAPKs and host responses. It will also discuss findings attempting to develop anti-microbial treatments by targeting MAPKs.

Background: Diarrheal disease remains a significant public health issue, particularly affecting young children and older adults. Despite efforts to control and prevent these diseases, their incidence continues to be a global concern. Understanding the trends in diarrhea incidence and the factors influencing these trends is crucial for developing effective public health strategies. Objective: This study aimed to explore the temporal trends in diarrhea incidence and associated factors from 1990 to 2019 and to project the incidence for the period 2020–2040 at global, regional, and national levels. We aimed to identify key factors influencing these trends to inform future prevention and control strategies. Methods: The eXtreme Gradient Boosting (XGBoost) model was used to predict the incidence from 2020 to 2040 based on demographic, meteorological, water sanitation, and sanitation and hygiene indicators. SHapley Additive exPlanations (SHAP) value was performed to explain the impact of variables in the model on the incidence. Estimated annual percentage change (EAPC) was calculated to assess the temporal trends of age-standardized incidence rates (ASIRs) from 1990 to 2019 and from 2020 to 2040. Results: Globally, both incident cases and ASIRs of diarrhea increased between 2010 and 2019. The incident cases are expected to rise from 2020 to 2040, while the ASIRs and incidence rates are predicted to slightly decrease. During the observed (1990–2019) and predicted (2020–2040) periods, adults aged 60 years and above exhibited an upward trend in incidence rate as age increased, while children aged < 5 years consistently had the highest incident cases. The SHAP framework was applied to explain the model predictions. We identified several risk factors associated with an increased incidence of diarrhea, including age over 60 years, yearly precipitation exceeding 3000 mm, temperature above 20 °C for both maximum and minimum values, and vapor pressure deficit over 1500 Pa. A decreased incidence rate was associated with relative humidity over 60%, wind speed over 4 m/s, and populations with above 80% using safely managed drinking water services and over 40% using safely managed sanitation services. Conclusions: Diarrheal diseases are still serious public health concerns, with predicted increases in the incident cases despite decreasing ASIRs globally. Children aged < 5 years remain highly susceptible to diarrheal diseases, yet the incidence rate in the older adults aged 60 plus years still warrants additional attention. Additionally, more targeted efforts to improve access to safe drinking water and sanitation services are crucial for reducing the incidence of diarrheal diseases globally.

Shigella is the leading bacterial cause of diarrhoea and the second leading cause of diarrhoeal mortality among all ages. It also exhibits increasing levels of antibiotic resistance. The greatest burden is among children under five in low- and middle-income countries (LMICs). As such, a priority strategic goal of the World Health Organization (WHO) is the development of a safe, effective and affordable vaccine to reduce morbidity and mortality from Shigella-attributable dysentery and diarrhea, including long term outcomes associated with chronic inflammation and growth faltering, in children under 5 years of age in LMICs. In addition, a safe and effective Shigella vaccine is of potential interest to travellers and military both to prevent acute disease and rarer, long-term sequelae. An effective Shigella vaccine is also anticipated to reduce antibiotic use and thereby help diminish further emergence of enteric pathogens resistant to antimicrobials. The most advanced vaccine candidates are multivalent, parenteral formulations in Phase 2 and Phase 3 clinical studies. They rely on O-antigen-polysaccharide protein conjugate technologies or, alternatively, outer membrane vesicles expressing penta-acylated lipopolysaccharide that has been detoxified. Other parenteral and oral formulations, many delivering a broader array of Shigella antigens, are at earlier stages of clinical development. These formulations are being assessed in alignment with the WHO Preferred Product Characteristics, which call for a 1 to 2 dose primary immunization series given during the first 12 months of life, ideally starting at 6 months of age. This ‘Vaccine Value Profile’ (VVP) for Shigella is intended to provide a high-level, holistic assessment of the information and data that are currently available to inform the potential public health, economic and societal value of pipeline vaccines and vaccine-like products. This VVP was developed by a working group of subject matter experts from academia, non-profit organizations, government agencies and multi-lateral organizations. All contributors have extensive expertise on various elements of the Shigella VVP and collectively aimed to identify current research and knowledge gaps. The VVP was developed using only existing and publicly available information.