📄 Sciences Methods and Technologies
International Journal (SciMeTech)

Volume 1 · Issue 2 · 2025
ISSN: 3085-5284
Diarrheal Diseases: Investigating Mechanisms, Causative Factors, and Innovations in Treatment Approaches
Zuhair Dardona, Lina El-Khairy, Mounia Amane, Samia Boussaa
Pages 1–27 · 1. PhD Parasitology-Epidemiology, Governmental Medical Services, Gaza, Palestine · 2. Nutrition and Dietetics Department, Faculty of Pharmacy, Birzeit University, Birzeit, Palestine · 3. ISPTIS-Higher Institute of Nursing and Health Techniques, Ministry of Health and Social Protection, Marrakech, Morocco · 4. ISPTIS-Higher Institute of Nursing and Health Techniques, Ministry of Health and Social Protection, Rabat, Morocco
⬇ PDF
Abstract
Diarrheal diseases remain a critical global health concern, particularly affecting young children and under-resourced communities. This paper investigates the fundamental mechanisms and clinical impacts of diarrheal diseases, while also showcasing the latest advancements in their treatment. Focusing on the root causes, it offers an in-depth look at the innovative strategies developed to tackle these diseases. Diarrhea can arise from a range of factors, including viral, bacterial, and parasitic infections, as well as food allergies, intolerances, digestive tract disorders, and medication side effects. The main mechanisms underlying diarrhea include elevated osmotic load, increased secretions, and reduced absorption. These processes are frequently triggered by enteric infections from pathogens such as norovirus, rotavirus, Campylobacter, Escherichia coli, Giardia lamblia, Entamoeba histolytica, among others. Additionally, diarrheal diseases can cause severe dehydration, electrolyte imbalances, and malnutrition, particularly in at-risk populations. Persistent diarrhea, lasting beyond four weeks, may stem from ongoing infections, inflammatory bowel diseases, or other gastrointestinal disorders. These chronic conditions can profoundly affect quality of life, hinder cognitive development, and negatively impact overall health outcomes. On the other hand, recent advancements in treatment have introduced several promising approaches. Oral rehydration therapy has proven effective in reducing both the severity and recurrence of acute diarrhea. Moreover, improvements in molecular diagnostics have enhanced the detection of enteropathogens, allowing for more precise and targeted treatments. The use of probiotics and antimicrobial therapies is also being investigated to restore healthy gut flora and address infectious diarrhea more effectively.
Keywords: Diarrhea, Diseases, Pathogenesis, Treatment, Implication, Risk factors, Infections, Enteropathogens

References

  1. Woods TA. Diarrhea. In: Walker HK, Hall WD, Hurst JW, editors. Clinical methods: The history, physical, and laboratory examinations. 3rd ed. Chapter 88. Butterworths; 1990. Available from: https://www.ncbi.nlm.nih.gov/books/NBK414/
  2. Levy J, Teach SJ, Duryea TK, Wiley JF II. Diagnostic approach to diarrhea in children in resource-abundant settings. 2024. Available from: https://www.uptodate.com/contents/diagnostic-approach-to-diarrhea-in-children-in-resource-abundant-settin
  3. Soki-Milutinovic A, Pavlovic-Markovic A, Tomasevic RS, Lukic S. Diarrhea as a clinical challenge: general practitioner approach. Dig Dis. 2022;40(3):282-9.
  4. Schiller LR. Diarrhea. Med Clin North Am. 2000;84(5):1259-74.
  5. Nemeth V, Pfleghaar N. Diarrhea. In: StatPearls [Internet]. StatPearls Publishing; 2022 Nov 21. Available from: https://www.ncbi.nlm.nih.gov/books/NBK448082/
  6. Schiller LR, Pardi DS, Sellin JH. Chronic diarrhea: diagnosis and management. Clin Gastroenterol Hepatol. 2017;15(2):182-93.
  7. Burgers K, Lindberg B, Bevis ZJ. Chronic diarrhea in adults: evaluation and differential diagnosis. Am Fam Physician. 2020;101(8):472-80.
  8. Kang G. Viral diarrhea. In: International Encyclopedia of Public Health. 2017;360.
  9. Magdesian KG, Dwyer RM, Arguedas MG. Viral diarrhea. In: Equine Infectious Diseases. 2014;198.
  10. World Health Organization. Diarrhoeal disease. [Internet]. Available from: https://www.who.int/news-room/fact-sheets/detail/diarrhoeal-disease. Accessed September 7, 2024.
  11. Mahmood RMU, Alfatlawi IO, Jawd SM. Review on causes of diarrhea (bacterial, parasitic, viral) in children. J Clin Trials Regul. 2021;3(1):2582-4422.
  12. Dehydration and diarrhea. Dehydration and diarrhea. Paediatr Child Health. 2003;8(7):459-68. Available from: https://doi.org/10.1093/pch/8.7.459
  13. Koletzko S, Osterrieder S. Acute infectious diarrhea in children. Dtsch Arztebl Int. 2009;106(33):539-48. Available from: https://doi.org/10.3238/arztebl.2009.0539.
  14. Abadin MZU, Iftikar M, Arshad N, Mahmood Z, Tahira B, Shafiq M, Butt TK. Frequency of electrolyte imbalance in children with pediatric acute diarrhea. 2023.
  15. Salehi M, Nourbakhsh SMK, Ardakani MV, Abdollahi A, Khaki PA, Aliramezani A. Bilateral hip septic arthritis caused by nontyphoidal Salmonella group D in a 16-year-old girl with COVID-19: A case report. Int J Surg Case Rep. 2022;95:107202. Available from: https://doi.org/10.1016/j.ijscr.2022.107202
  16. Centers for Disease Control and Prevention (CDC). Salmonella technical information. [Internet]. 2023 Mar 8. Available from: https://www.cdc.gov/salmonella/general/technical.html
  17. Troeger C, Blacker BF, Khalil IA, Rao PC, Cao S, Zimsen SR, et al. Estimates of the global, regional, and national morbidity, mortality, and aetiologies of diarrhoea in 195 countries: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Infect Dis. 2018;18(11):1211-28.
  18. Hodges K, Gill R. Infectious diarrhea: cellular and molecular mechanisms. Gut Microbes. 2010;1(1):4-21. Available from: https://doi.org/10.4161/gmic.1.1.11036.
  19. LeClair CE, McConnell KA. Rotavirus. In: StatPearls. StatPearls Publishing; 2023. Available from: https://www.ncbi.nlm.nih.gov/books/NBK558951/.
  20. Crawford S, Ramani S, Tate J, et al. Rotavirus infection. Nat Rev Dis Primers. 2017;3:17083. Available from: https://doi.org/10.1038/nrdp.2017.83.
  21. Dennehy PH. Transmission of rotavirus and other enteric pathogens in the home. Pediatr Infect Dis J. 2000;19(10).
  22. Centers for Disease Control and Prevention. Rotavirus: clinical overview. [Internet]. Available from: https://www.cdc.gov/rotavirus/hcp/clinical-overview/index.html. Accessed September 8, 2024.
  23. Alkali BR, Daneji AI, Magaji AA, Bilbis LS. Clinical symptoms of human rotavirus infection observed in children in Sokoto, Nigeria. Adv Virol. 2015;2015(1):890957.
  24. Burnett E, Parashar UD, Tate JE. Real-world effectiveness of rotavirus vaccines, 2006–19: a literature review and meta-analysis. Lancet Glob Health. 2020;8(9).
  25. Varghese T, Kang G, Steele AD. Understanding rotavirus vaccine efficacy and effectiveness in countries with high child mortality. Vaccines. 2022;10(3):346. Available from: https://doi.org/10.3390/vaccines1003046.
  26. Robilotti E, Deresinski S, Pinsky BA. Norovirus. Clin Microbiol Rev. 2015;28(1):134-64.
  27. Capece G, Gignac E. Norovirus. In: StatPearls. StatPearls Publishing; 2023. Available from: https://www.ncbi.nlm.nih.gov/books/NBK513265/.
  28. Carlson KB, Dilley A, O'Grady T, et al. A narrative review of norovirus epidemiology, biology, and challenges to vaccine development. npj Vaccines. 2024;9:94. Available from: https://doi.org/10.1038/s41541-024-00884-2
  29. Xiao S, Tang JW, Li Y. Airborne or fomite transmission for norovirus? A case study revisited. Int J Environ Res Public Health. 2017;14(12):1571. Available from: https://doi.org/10.3390/ijerph14121571.
  30. Mattison CP, Cardemil CV, Hall AJ. Progress on norovirus vaccine research: public health considerations and future directions. Expert Rev Vaccines. 2018;17(9):773-84.
  31. Ahmed SM, Hall AJ, Robinson AE, Verhoef L, Premkumar P, Parashar UD, Koopmans M, Lopman BA. Global prevalence of norovirus in cases of gastroenteritis: a systematic review and meta-analysis. Lancet Infect Dis. 2014;14(8):725-30. Available from: https://doi.org/10.1016/S1473-3099(14)70767-4.
  32. Zhang P, Hao C, Di X, Chuzihao X, Jinsong L, Guisen Z, et al. Global prevalence of norovirus gastroenteritis after emergence of the GII.4 Sydney 2012 variant: a systematic review and meta-analysis. Front Public Health. 2024;12:1373322.
  33. do Nascimento LG, Fialho AM, de Andrade JDS R, et al. Human enteric adenovirus F40/41 as a major cause of acute gastroenteritis in children in Brazil, 2018 to 2020. Sci Rep. 2022;12:11220. Available from: https://doi.org/10.1038/s41598-022-15413-1.
  34. Kumthip K, Khamrin P, Ushijima H, Maneekarn N. Enteric and non-enteric adenoviruses associated with acute gastroenteritis in pediatric patients in Thailand, 2011 to 2017. PLoS One. 2019;14(8). Available from: https://doi.org/10.1371/journal.pone.0220263.
  35. Qiu FZ, Shen XX, Li GX, Zhao L, Chen C, Duan SX, Guo JY, Zhao MC, Yan TF, Qi JJ, Wang L, Feng ZS, Ma XJ. Adenovirus associated with acute diarrhea: a case-control study. BMC Infect Dis. 2018;18(1):450. Available from: https://doi.org/10.1186/s12879-018-3340-1.
  36. Daham SN, Altaie AA, ALdeen NWK. Human astrovirus and associated with gastroenteritis and encephalitis. Rafadian J Sci. 2024;33(2 E).
  37. Yeh PJ, Wu RC, Chen CL, Chiu CT, Lai MW, Chen CC, et al. Cytomegalovirus diseases of the gastrointestinal tract in immunocompetent patients: a narrative review. Viruses. 2024;16(3):346.
  38. Levine MM. Escherichia coli that causes diarrhea: enterotoxigenic, enteropathogenic, enteroinvasive, enterohemorrhagic, and enteroadherent. J Infect Dis. 1987;155(3):377-89.
  39. Li, Y., Xia, S., Jiang, X., Feng, C., Gong, S., Ma, J., ... & Yin, Y. (2021). Gut microbiota and diarrhea: an updated review. Frontiers in cellular and infection microbiology, 11, 625210.
  40. Hodges K, Gill R. Infectious diarrhea: cellular and molecular mechanisms. Gut Microbes. 2010;1(1):4-21. Available from: https://doi.org/10.4161/gmic.1.1.11036. Accessed September 8, 2024.
  41. Kaper J, Nataro J, Mobley H. Pathogenic Escherichia coli. Nat Rev Microbiol. 2004;2:123-40. Available from: https://doi.org/10.1038/nrmicro818.
  42. Lim JY, Yoon J, Hovde CJ. A brief overview of Escherichia coli O157 and its plasmid O157. J Microbiol Biotechnol. 2010;20(1):5-14.
  43. Evans DJ Jr, Evans DG. Escherichia coli in diarrheal disease. In: Baron S, editor. Medical microbiology. 4th ed. Galveston: University of Texas Medical Branch; 1996. Chapter 25. Available from: https://www.ncbi.nlm.nih.gov/books/NBK7710/.
  44. Nataro JP, Bopp CA, Fields PI, Kaper JB, Strockbine NA. Escherichia, Shigella, and Salmonella. In: Manual of Clinical Microbiology. 11th ed. Washington, DC: ASM Press; 2011. p. 603-26.
  45. Ohl ME, Miller SI. Salmonella: a model for bacterial pathogenesis. Annu Rev Med. 2001;52(1):259-74.
  46. Strockbine NA, Bopp CA, Fields PI, Kaper JB, Nataro JP. Escherichia, Shigella, and Salmonella. In: Manual of Clinical Microbiology. 11th ed. Washington, DC: ASM Press; 2015. p. 685-713.
  47. Dekker JP, Frank KM. Salmonella, Shigella, and Yersinia. Clin Lab Med. 2015;35(2):225-46.
  48. Pokharel P, Dhakal S, Dozois CM. The diversity of Escherichia coli pathotypes and vaccination strategies against this versatile bacterial pathogen. Microorganisms. 2023;11(2):344.
  49. World Health Organization. Campylobacter. [Internet]. Available from: https://www.who.int/news-room/fact-sheets/detail/campylobacter. Accessed September 8, 2024.
  50. Liu F, Lee SA, Xue J, Riordan SM, Zhang L. Global epidemiology of campylobacteriosis and the impact of COVID-19. Front Cell Infect Microbiol. 2022;12:979055. doi: 10.3389/fcimb.2022.979055.
  51. Kaakoush NO, Castano-Rodriguez N, Mitchell HM, Man SM. Global epidemiology of Campylobacter infection. Front Microbiol. [Internet]. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4472117/. Accessed September 8, 2024.
  52. Sandhu BK, McBride SM. Clostridioides difficile. Trends Microbiol. 2018;26(12):1049-50.
  53. Negrut N, Bungau S, Behl T, Khan SA, Vesa CM, Bustea C, et al. Risk factors associated with recurrent Clostridioides difficile infection. Healthcare. 2020 Sep;8(3):352.
  54. Mada PK, Alam MU. Clostridioides difficile infection. In: StatPearls [Internet]. StatPearls Publishing; 2024. Available from: https://www.ncbi.nlm.nih.gov/books/NBK431054/. Accessed September 9, 2024.
  55. Centers for Disease Control and Prevention. Emerging Infections Program, Healthcare-Associated Infections - Community Interface Surveillance Report, Clostridioides difficile infection (CDI), 2022. [Internet]. Available from: https://www.cdc.gov/healthcare-associated-infections/media/pdfs/2022-CDI-Report-508.pdf. Accessed September 9, 2024.
  56. Adelman MW, Goodenough D, Sefton S, Mackey C, Thomas S, Fridkin SK, et al. Changes in treatment of community-onset Clostridioides difficile infection after release of updated guidelines, Atlanta, Georgia, 2018. Anaerobe. 2021;70:102364. doi:10.1016/j.anaerobe.2021.102364.
  57. Czepiel J, Drozdz M, Pituch H, Kuijper EJ, Perucki W, Mielimonka A, et al. Clostridium difficile infection: review. Eur J Clin Microbiol Infect Dis. 2019;38(7):1211-21. doi:10.1007/s10096-019-03539-6.
  58. World Health Organization. Cholera. [Internet]. Available from: https://www.who.int/news-room/fact-sheets/detail/cholera. Accessed September 9, 2024.
  59. Finkelstein RA. Cholera, Vibrio cholerae O1 and O139, and other pathogenic vibrios. In: Baron S, editor. Medical Microbiology. 4th ed. Chapter 24. Galveston: University of Texas Medical Branch; 1996. Available from: https://www.ncbi.nlm.nih.gov/books/NBK8407/.
  60. Ojeda Rodriguez JA, Hashmi MF, Kahwaji CI. Vibrio cholerae infection. In: StatPearls [Internet]. StatPearls Publishing; 2024. Available from: https://www.ncbi.nlm.nih.gov/books/NBK526099/.
  61. Shaikh H, Lynch J, Kim J, Exclet JL. Current and future cholera vaccines. Vaccine. 2020;38
  62. Worku T, Haile T, Sahile S, Duguma T. Parasitic etiology of diarrhea and associated factors among under-five-year children attending Mizan-Tepi University Teaching Hospital, Southwest Ethiopia. Pan Afr Med J. 2023;45:187. doi:10.11604/pamj.2023.45.187.38263.
  63. Bouree P, Bisaro F. Diarrhees parasitaires [Parasitic diarrhea]. Presse Med. 2007 Apr;36(4 Pt 2):706-16. French. doi:10.1016/j.lpm.2006.12.028.
  64. Khurana S, Gur R, Gupta N. Chronic diarrhea and parasitic infections: Diagnostic challenges. Indian J Med Microbiol. 2021;39(4):413-6.
  65. Stauffer W, Ravdin JI. Entamoeba histolytica: an update. Curr Opin Infect Dis. 2003;16(5):479-85.
  66. Lin FH, Chen BC, Chou YC, Chien WC, Chung CH, Hsieh CJ, et al. The epidemiology of Entamoeba histolytica infection and its associated risk factors among domestic and imported patients in Taiwan during the 2011-2020 period. Medicina (Kaunas). 2022;58(6):820. doi:10.3390/medicina58060820.
  67. El-Dib NA. Entamoeba histolytica: an overview. Curr Trop Med Rep. 2017;4:11-20.
  68. Leung AKC, Leung AAM, Wong AHC, Sergi CM, Kam JKM. Giardiasis: an overview. Recent Pat Inflamm Allergy Drug Discov. 2019;13(2):134-43. doi:10.2174/1872213X13666190618124901.
  69. Maruf MM, Banerjee A, Banerjee D, Bhattacharya SK. An overview on human enteric parasites. IJCMCR. 2024;43(4):5.
  70. Dixon BR. Giardia duodenalis in humans and animals—transmission and disease. Res Vet Sci. 2021;135:283-9.
  71. Gerace E, Lo Presti VDM, Biondo C. Cryptosporidium infection: epidemiology, pathogenesis, and differential diagnosis. Eur J Microbiol Immunol. 2019;9(4):119-23. doi:10.1556/1886.2019.00019.
  72. Dumaine JE, Tandel J, Striepen B. Cryptosporidium parvum. Trends Parasitol. 2020;36(5):485-6.
  73. Korich DG, Mead JR, Madore MS, Sinclair NA, Sterling C. Effects of ozone, chlorine dioxide, chlorine, and monochloramine on Cryptosporidium parvum oocyst viability. Appl Environ Microbiol. 1990;56(5):1423-8.
  74. Ortolani C, Pastorello EA. Food allergies and food intolerances. Best Pract Res Clin Gastroenterol. 2006;20(3):467-83.
  75. Tuck CJ, Biesiekierski JR, Schmid-Grendelmeier P, Pohl D. Food intolerances. Nutrients. 2019;11(7):1684. https://doi.org/10.3390/nu11071684
  76. Gargano D, Appanna R, Santonicola A, De Bartolomeis F, Stellato C, Cianferoni A, et al. Food allergy and intolerance: a narrative review on nutritional concerns. Nutrients. 2021;13(5):1638. https://doi.org/10.3390/nu13051638.
  77. Murray PR, Rosenthal KS, Pfaller MA. Medical microbiology. Elsevier Health Sciences; 2015.
  78. Toney RC, Wallace D, Sekhon S, Agrawal RM. Medication induced constipation and diarrhea. Pract Gastroenterol. 2008;32(5):12.
  79. Wienbeck M, Erckenbrecht J, Strohmeyer G. Wirkung von Antazida auf die Darmmotilität [Effect of antacids on intestinal motility]. Z Gastroenterol. 1983;21 Suppl:111-6.
  80. Akbarali HI, Muchhala KH, Jessup DK, Cheatham S. Chemotherapy induced gastrointestinal toxicities. Adv Cancer Res. 2022;155:131-66.
  81. Chassany O, Michaux A, Bergmann JF. Drug-induced diarrhoea. Drug Saf. 2000;22(1):53-72. https://doi.org/10.2165/00002018-200022010-00005.
  82. Ensari A. The malabsorption syndrome and its causes and consequences. Pathobiol Hum Dis. 2014;1266-87. https://doi.org/10.1016/B978-0-12-386456-7.03804-1.
  83. Wehkamp J, Götz M, Herrlinger K, Steurer W, Stange EF. Inflammatory bowel disease: Crohn's disease and ulcerative colitis. Dtsch Arztebl Int. 2016;113(5):72.
  84. Schiller LR. Diarrhea and malabsorption in the elderly. Gastroenterol Clin North Am. 2009;38(3):481-502.
  85. Riddle MS, Connor BA, Beeching NJ, DuPont HL, Hamer DH, Kozarsky P, et al. Guidelines for the prevention and treatment of travelers' diarrhea: a graded expert panel report. J Travel Med. 2017;24(Suppl 1)
  86. Leung AK, Leung AA, Wong AH, Hon KL. Travelers' diarrhea: a clinical review. Recent Pat Inflamm Allergy Drug Discov. 2019;13(1):38-48.
  87. Robinson H. Risk factors, prevention, and treatment options for travelers' diarrhea. Int J Adv Eng Technol Innov. 2024;10(2):215-36.
  88. Thiagarajah JR, Donowitz M, Verkman AS. Secretory diarrhoea: mechanisms and emerging therapies. Nat Rev Gastroenterol Hepatol. 2015;12(8):446-57. https://doi.org/10.1038/nrgastro.2015.111.
  89. Pray C, Alfawaz M, Daniel P, Malecka-Wojciesko E, Szczepanek M. Diarrhea. In: McMaster Textbook of Internal Medicine. Medycyna Praktyczna; 2024. Available from: https://empendium.com/mcmtextbook/chapter/B31.1.1.2. Accessed September 9, 2024.
  90. Hodges K, Gill R. Infectious diarrhea: cellular and molecular mechanisms. Gut Microbes. 2010;1(1):4-21. https://doi.org/10.4161/gmic.1.1.11036.
  91. Keely SJ, Barrett KE. Intestinal secretory mechanisms and diarrhea. Am J Physiol Gastrointest Liver Physiol. 2022;322(4)
  92. Camilleri M, Sellin JH, Barrett KE. Pathophysiology, evaluation, and management of chronic watery diarrhea. Gastroenterology. 2017;152(3):515-32. e2. https://doi.org/10.1053/j.gastro.2016.10.014.
  93. World Health Organization. Unit 2 - Pathophysiology of watery diarrhoea: dehydration and rehydration. In: Medical Education: Teaching Medical Students about Diarrhoeal Diseases. World Health Organization; 1992. http://apps.who.int/iris/handle/10665/40343.
  94. Protic M, Jojic N, Bojic D, Milutinovic S, Necic D, Bojic B, et al. Mechanism of diarrhea in microscopic colitis. World J Gastroenterol. 2005;11(35):5535.
  95. Nemeth V, Pfleghaar N. Diarrhea. In: StatPearls [Internet]. StatPearls Publishing; 2022 Nov 21. Available from: https://www.ncbi.nlm.nih.gov/books/NBK448082/.
  96. Sokic-Milutinovic A, Pavlovic-Markovic A, Tomasevic RS, Lukic S. Diarrhea as a clinical challenge: general practitioner approach. Dig Dis. 2022;40(3):282-9.
  97. Sandle GI. Infective and inflammatory diarrhoea: mechanisms and opportunities for novel therapies. Curr Opin Pharmacol. 2011;11(6):634-9.
  98. Babb C, Badji H, Bhuiyan MTR, Cornick J, Qureshi S, Sonye C, et al. Evaluation of fecal inflammatory biomarkers to identify bacterial diarrhea episodes: systematic review and protocol for the Enteries for Global Health Shigella surveillance study. Open Forum Infect Dis. 2024 Mar;11(Suppl 1)
  99. Spiller R. Role of motility in chronic diarrhoea. Neurogastroenterol Motil. 2006;18(12):1045-55. https://doi.org/10.1111/j.1365-2982.2006.00836.x.
  100. Sarna SK. Colonic motility: From bench side to bedside. Morgan & Claypool Life Sciences; 2010. Available from: https://www.ncbi.nlm.nih.gov/books/NBK53474/.
  101. Read NW, Cann P, Rao S, Edwards CA. Motility-related disorders: irritable bowel syndrome, pseudo-obstruction, other conditions. Curr Opin Gastroenterol. 1985;1(1):85-8.
  102. Spiller R. Role of motility in chronic diarrhoea. Neurogastroenterol Motil. 2006;18(12):1045-55. https://doi.org/10.1111/j.1365-2982.2006.00836.x.
  103. Camilleri M, Sellin JH, Barrett KE. Pathophysiology, evaluation, and management of chronic watery diarrhea. Gastroenterology. 2017;152(3):515-32.
  104. Schulzke JD, Ploeger S, Amasheh M, Fromm A, Zeissig S, Troeger H, et al. Epithelial tight junctions in intestinal inflammation. Ann NY Acad Sci. 2009;1165(1):294-300.
  105. Camilleri M, Sellin JH, Barrett KE. Pathophysiology, evaluation, and management of chronic watery diarrhea. Gastroenterology. 2017;152(3):515-32. e2. https://doi.org/10.1053/j.gastro.2016.10.014.
  106. Keely SJ, Barrett KE. Intestinal secretory mechanisms and diarrhea. Am J Physiol Gastrointest Liver Physiol. 2022;322(4)
  107. Guerrant RL, Van Gilder T, Steiner TS, Thielman NM, Slutsker L, Tauxe RV, et al. Practice guidelines for the management of infectious diarrhea. Clin Infect Dis. 2001;32(3):331-51.
  108. Nemeth V, Pfleghaar N. Diarrhea. [Updated 2022 Nov 21]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan- Available from: https://www.ncbi.nlm.nih.gov/books/NBK448082/.
  109. Soleimani A, Foroozanfard F, Tamadon MR. Evaluation of water and electrolytes disorders in severe acute diarrhea patients treated by WHO protocol in eight large hospitals in Tehran: a nephrology viewpoint. J Ren Inj Prev. 2016;6(2):109-12. https://doi.org/10.15171/jrip.2017.21.
  110. Shah GS, Das BK, Kumar S, Singh MK, Bhandari GP. Acid base and electrolyte disturbance in diarrhoea. Kathmandu Univ Med J (KUMJ). 2007;5(1):60-2.
  111. World Health Organization. Readings on diarrhea: student manual. Geneva: World Health Organization; 1992. Available from: https://iris.who.int/handle/10665/40343.
  112. Daley SF, Avva U. Pediatric dehydration. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024. Available from: https://www.ncbi.nlm.nih.gov/books/NBK436022/.
  113. Lamberti LM, Fischer Walker CL, Black RE. Systematic review of diarrhea duration and severity in children and adults in low- and middle-income countries. BMC Public Health. 2012;12:276. https://doi.org/10.1186/1471-2458-12-276.
  114. Richard SA, Black RE, Gilman RH, Guerrant RL, Kang G, Lanata CF, et al. Diarrhea in early childhood: short-term association with weight and long-term association with length. Am J Epidemiol. 2013;178(7):1129-38.
  115. Wierzba TF, Muhib F. Exploring the broader consequences of diarrhoeal diseases on child health. Lancet Glob Health. 2018;6(3)
  116. Assis AMO, Barreto ML, Santos LMP, Fiaccone R, da Silva Gomes GS. Growth faltering in childhood related to diarrhea: a longitudinal community based study. Eur J Clin Nutr. 2005;59(11):1317-23.
  117. Guerrant RL, DeBoer MD, Moore SR, Scharf RJ, Lima AA. The impoverished gut—a triple burden of diarrhoea, stunting and chronic disease. Nat Rev Gastroenterol Hepatol. 2013;10(4):220-9.
  118. Chang SM, Walker SP, Grantham-McGregor S, Powell CA. Early childhood stunting and later behaviour and school achievement. J Child Psychol Psychiatry. 2002;43(6):775-83.
  119. Weiner M, Epstein FH. Signs and symptoms of electrolyte disorders. Yale J Biol Med. 1970;43(2):76-109.
  120. Abuzerr S, Nasseri S, Yunesian M, Hadi M, Mahvi AH, Nabizadeh R, et al. Prevalence of diarrheal illness and healthcare-seeking behavior by age-group and sex among the population of Gaza Strip: a community-based cross-sectional study. BMC Public Health. 2019;19:1-10.
  121. Lamberti LM, Fischer Walker CL, Black RE. Systematic review of diarrhea duration and severity in children and adults in low- and middle-income countries. BMC Public Health. 2012;12(1):276. https://doi.org/10.1186/1471-2458-12-276.
  122. Ismail MA, Abdilahi MM, Abdeeq BA, Jama M. Prevalence and associated factors of acute diarrhea among under-five children living in Hargeisa Internally Displaced Persons, Somaliland: a community-based cross-sectional study. Pan Afr Med J. 2024;47.
  123. Binder HJ, Brown I, Ramakrishna BS, Young GP. Oral rehydration therapy in the second decade of the twenty-first century. Curr Gastroenterol Rep. 2014;16:1-8.
  124. Chavda VP, Vuppu S, Mishra T, Kamaraj S, Sharma N, Punetha S, et al. Combatting infectious diarrhea: innovations in treatment and vaccination strategies. Expert Rev Vaccines. 2024;23(1):246-65. https://doi.org/10.1080/14760584.2023.2295015.
  125. Dupont HL, Sanchez JF, Ericsson CD, Gomez JM, Dupont MW, Luna AC, et al. Comparative efficacy of loperamide hydrochloride and bismuth subsalicylate in the management of acute diarrhea. Am J Med. 1990;88(6)
  126. Mayer EA, Bradesi S. Alosetron and irritable bowel syndrome. Expert Opin Pharmacother. 2003;4(11):2089-98.
  127. Keenum AJ, Stockton MD. Rifaximin (Xifaxan) for traveler's diarrhea. Am Fam Physician. 2005;72(12):2525.
  128. Jumani RS, Spector JM, Izadneghadar R, Kelly P, Diagana TT, Manjunatha UH. Innovations in addressing pediatric diarrhea in low resource settings. ACS Infect Dis. 2019;6(1):14-24.
  129. Ceruelos AH, Romero-Quezada LC, Ledezma JR, Contreras LL. Therapeutic uses of metronidazole and its side effects: an update. Eur Rev Med Sci. 2019;23(1):397-401.
  130. Shreiner AB, Kao JY, Young VB. The gut microbiome in health and in disease. Curr Opin Gastroenterol. 2015;31(1):69-75.
  131. Szajewska H, Ruszczyński M, Radzikowski A. Probiotics in the prevention of antibiotic-associated diarrhea in children: a meta-analysis of randomized controlled trials. J Pediatr Gastroenterol Nutr. 2006;42(5)
  132. Gao J, Li X, Zhang G, Sadiq FA, Simal-Gandara J, Xiao J, et al. Probiotics in the dairy industry—advances and opportunities. Compr Rev Food Sci Food Saf. 2021;20(4):3937-82.
  133. Hempel S, Newberry SJ, Maher AR, Wang Z, Miles JN, Shanman R, et al. Probiotics for the prevention and treatment of antibiotic-associated diarrhea: a systematic review and meta-analysis. JAMA. 2012;307(18):1959-69.
  134. Antimotility and antisecretory drugs. In: Anesthetic pharmacology. Cambridge University Press; 2011. Chapter 53. Available from: https://www.cambridge.org/core/books/abs/anesthetic-pharmacology/antimotility-and-antisecretory-drugs/403C61818ED7FDB848418A9ACEEF19E4
  135. Sayed RM, El-Masry HM, Kasem IAE. Role of antisecretory drug in treatment of children with acute watery diarrhea: A randomized controlled trial. Al-Azhar Assiut Med J. 2022;20(4):345-9.
  136. Bhan MK, Bhatnagar S. Racecadotril: is there enough evidence to recommend it for treatment of acute diarrhea? Indian Pediatr. 2004;41(12):1203-4.
  137. Thiagarajah JR, Ko EA, Tradtranitp L, Donowitz M, Verkman AS. Discovery and development of antisecretory drugs for treating diarrheal diseases. Clin Gastroenterol Hepatol. 2014;12(2):204-9.
  138. Barr W, Smith A. Acute diarrhea in adults. Am Fam Physician. 2014;89(3):180-9.
  139. Liu J, Platts-Mills JA, Juma J, Kabir F, Nkeze J, Okoi C, Operario DJ, Uddin J, Ahmed S, Alonso PL, Antonio M, Becker SM, Blackwelder WC, Breiman RF, Faruque AS, Fields B, Gratz J, Haque R, Hossain A, Hossain MJ, ... Houpf ER. Use of quantitative molecular diagnostic methods to identify causes of diarrhoea in children: a reanalysis of the GEMS case-control study. Lancet. 2016;388(10051):1291-301. doi:10.1016/S0140-6736(16)31529-X.
  140. Sokic-Milutinovic A, Pavlovic-Markovic A, Tomasevic RS, Lukic S. Diarrhea as a clinical challenge: general practitioner approach. Dig Dis. 2022;40(3):282-9.
  141. Shen N, Tao Y, Du BL, Cao Q. Molecular diagnostic practices for infectious gastroenteritis. Chin Med J. 2020;133(12):1485-6.
SciMeTech · Volume 1, Issue 2 · 2025 · ISSN 3085-5284