Etiology and Epidemiology of Diarrhea

Celia C. Carlos, M.D.* and Mediadora C. Saniel, M.D.*

(*Research Institute for Tropical Medicine, Alabang, Muntinlupa, Metro Manila; Please address correspondence to: Dr. Celia Carlos, Clinical Department, Research Institute for Tropical Medicine, Department of Health Compound, Alabang, Muntinlupa, Metro Manila)

ABSTRACT
Infection causes (bacterial, viral, and parasitic) account for most cases of diarrhea. A potential pathogen can be identified in up to 70% of acute diarrheas presenting at treatment facilities and in about 50% of cases from the community. In general, the same pathogens are responsible for diarrhea worldwide, with only variations in the frequency of occurrence of each pathogen in different localities. The following are the commonest etiologic agents of diarrhea for all ages in decreasing order of prevalence obtained from pooled data worldwide: rotavirus, ETEC, shigella, campylobacter, Vibrio cholerae, and non-typhoidal salmonella. Similar organisms have been isolated from epidemiologic studies done in the Philippines. Other important viral agents of diarrhea are Norwalk and adenovirus; among parasites, cryptosporidium, Entamoeba histolytica, and Giardia intestinalis. A number of pathogens have also been associated with the presence of bloody stools and cases of persistent diarrhea. The usual pathogenic mechanisms for infectious diarrhea are toxin production and tissue invasion. Noninfectious causes of diarrhea include drugs, surgical conditions, systemic infections and food intolerance. [Phil J Microbiol Infect Dis 1990; 19(2):51-53] Key words: Diarrhea; etiology; epidemiology; enteropathogens.

Diarrheal diseases are one of the leading causes of childhood morbidity and mortality in developing countrie s. An estimated 1,000 million episodes occur each year in children under 5 years of age. Diarrhea causes an estimated 5 million deaths in children under 5 years of age per year. About 80% of these deaths occur in children in the first 2 years of life. Approximately one third of deaths among children under five are caused by diarrhea.1 In the Philippines, diarrheal disease is the second leading cause of morbidity and 6th leading cause of mortality for all ages. It is the third leading cause of infant deaths.2 Surveys done in La Union, Bohol, and Bukidnon in 1985 showed that every Filipino child suffered an average of 2.8 episodes annually. 3 Most diarrheal illnesses are acute, usually lasting no more than 3 days and are secondary to -5 infectious causes (bacterial, viral, and parasitic). Infectious agents that cause diarrheal disease are usually spread by the fecal-oral route, specifically by a) ingestion of contaminated food or water and b) contact with contaminated hands. The usual pathogenic mechanisms for infectious diarrhea include toxin production, tissue invasion, or invasion of intestinal cells with consequent alteration of their function and reproduction. Today, with newer techniques available, laboratories capable of comprehensive laboratory studies can identify potential pathogens in up to 70% of acute diarrheas presenting to hospital or treatment facilities and in about half of cases occuring in the community. Mixed infections with two or more enteropathogens occur in 15% to 20% of cases, but their clinical significance is difficult to interpret; one or more of the organisms recovered may be responsible for the diarrhea. In general, the same pathogens are responsible for diarrhea in infants and young children worldwide; however, the frequency and proportion of the specific diarrheal pathogens identified may be different in different places and laboratories. The most common organisms responsible for most cases of diarrhea obtained from pooled data worldwide include rotavirus, ETEC, shigella, campylobacter, Vibrio cholerae, and non-typhoidal salmonella, Table 1. 4 Hospital- and community-based etiology studies done in the Philippines showed the predominance of rotavirus and enterotoxigenic E. coli as causes of diarrhea,5,6 Table 2. Serologic surveys conducted in

Metro Manila showed early acquisition of antibodies to rotavirus. Whereas rotavirus accounted for only 7% of sporadic diarrhea in the community, it was detected in 35% of hospitalized cases suggesting that rotavirus causes a more severe and dehydrating diarrhea. In addition to rotavirus, it appears that infection due to Norwalk virus is also not uncommon.
Table 1. Etiologic agents causing most cases or diarrhea Organism Rotavirus Enterotoxigenic Escherichia coli (ETEC) No agent found Shigella Campylobacter Vibrio cholerae Non-typhoidal Salmonella Type Virus Bacteria --Bacteria Bacteria Bacteria Bacteria Proportion of cases Up to 50% or cases coming to health facilities, 5% to 10% of cases in the community Up to 25% of diarrhea in all ages 25% or more 5% to 10% 5% to 15% In endemic areas may cause 5% to 10% of cases seen in health facilities Up to 10% of cases

Table 2. Frequency of isolation or etiologic agents or acute diarrhea in children less than 5 years or age Hospital Study RITM Pathogen 1985-1986; 1985-1987 Rotavirus 35 (3)* ETEC 18 (11) V. cholerae 01 11 (4) Salmonella 10 (7) Aeromonas 7 (16) EPEC 6 (8) Shigella 4 (0) C. jejuni 3 (1) Cryptosporidium 4 (0) E. histolytica 3 (1) TOTAL % Positive for any pathogen 76 (43) * expressed as percent positive in cases (controls) ** not done Community Study Alabang, Muntinlupa 1982-1984 7 (1) 9(8) 1 (0) 10 (9) nd** 6 (3) 4 (2) 2 (2) nd nd 35 (23)

Studies on the prevalence of antibodies to Norwalk virus in Manila showed that 43% of individuals would have detectable levels by age 12 years.7 Isolation rates for salmonella, shigella, EPEC, V. cholerae 01 and other vibrios, Campylobacter jejuni, and Aeromonas sp. differed from study to study. No local studies have been done to determine the prevalence of the newer bacterial agents, namely, enterohemorrhagic and enteroadherent E. coli, and Clostridium difficile. Contrary to popular belief, Entamoeba histolytica was detected in less than 5% of cases.6,8 This data proves the relatively low prevalence of E. histolytica cysts and trophozoites in the general population. The most extensive prevalence survey done in the Philippines showed that only 5% of 14,205 stool specimens were positive for the parasite and 6% of 19,771 sera had antibody titers ~ 1:128 by indirect hemagglutination. 9 The percentage isolation of Giardia intestinalis was likewise low. In addition to the etiologic agents mentioned above, other conditions causing or are associated with diarrhea include drugs, surgical conditions, other diseases (e.g. malaria, schistosomiasis, measles), systemic infections, and food intolerance (e.g. lactase deficiency). A number of pathogens have also been associated with persistent diarrhea (diarrhea episode lasting for at least 14 days) and dysentery {diarrhea associated with blood and pus cells in the stools). These "types" of diarrhea are important in that they are more likely to have severe consequences. Studies have shown that one-third to one half of all diarrhea-associated deaths among children occurred following episodes of persistent diarrhea10 where dysentery accounts for

10% to 15% of diarrheal episodes in children under the age of 5, but up to 25% of diarrheal deaths.4 Less than half of all children with persistent diarrhea have a recognized enteric pathogen in their feces. Enteropathogens that are isolated with greater frequency from episodes of persistent diarrhea include enteroadherent E. coli {EAEC), enteropathogenic E. coli {EPEC) and cryptosporidium. 10 The mechanisms by which these agents cause persistent diarrhea is probably related to their capacity to adhere to or invade the bowel mucosa. Dysentery is caused primarily by bacteria, which invade the epithelial cells of the small intestine and colon, produce, a variety of toxins, disrupt the cell and cause an inflammatory response. A number of organisms have been found in dysentery cases, and more than one pathogenic organism is found in many cases. However, shigella is the most common (from 33% to 62% of cases in 3 studies).4 The second most common cause of dysentery, particularly in children younger than 1 year, is campylobacter. Other organisms which may cause dysentery include: 1) Invasive E. coli, 2) P. shigelloides, 3) salmonella, and Aeromonas spp. REFERENCES
1. Snyder JD, Merson MH. The magnitude of the global problem of acute diarrheal disease: a review of active surveillance data. Bull WHO 1982; 60:605-613. 2. 1986 Philippine Health Statistics, National Census and Statistics Office. 3. National Program on the Control of Diarrheal Diseases. Report of the Joint MOH-WHO-Unicef-USAID Comprehensive Program Review, January-February, 1985. Ministry of Health, Manila, 1985. 4. Readings on Diarrhoea. Manila, Association of Philippine Medical Colleges Foundation Inc. and USAID, June, 1990. 5. Saniel MC, Sta. Maria A, Sanvictores E, et al. Prospective study of diarrhea in infants and young children in a peri-urban community; morbidity pattern and etiologies. In: Tzipori S, ed. Infectious Diarrhea in the Young: Strategies for Control in Humans and Animals. The Netherlands; Elsevier,1985. pp. 113-116. 6. Saniel MC, MoriIes RR, Monzon OT, et al. The relative importance of various enteropathogens in the etiology of acute diarrhea: a hospital-based study in urban Philippines. In: SEAMIC Proceedings of the 14th SEAMIC workshop: Gastrointestinal infections in Southeast Asia (V). SEAMIC. Southeast Asian Medical Information Center/International Medical Foundation of Japan, 1988. pp. 91-96. 7. Cukor IG, Blacklow NR, Echevarria P, et al. Comparative study of the acquisition of antibody to Norwalk virus in pediatric populations. Infect Immunol 1980; 29:822-823. 8. Adkins HJ, Escamilla J, Santiago LT, et al. Two-year survey of etiologic agents of diarrheal disease at San Lazaro Hospital, Manila Republic of the Philippines. J Clin Microbiol 1987; 25: 1143-1147. 9. Cross JH, Basaca-Sevilla V. Biomedical surveys in the Philippines. A special publication of the US Naval Medical Research Unit No.2, Manila, Philippines. 10. WHO Program for the Control of Diarrhoeal Diseases. CD update on persistent diarrhea. No.4, March 1989.