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Diarrheal disease in a developing nation
THE AMERICAN JOURNAL OF GASTROENTEROLOGY © 2000 by Am. Coll. of Gastroenterology Published by Elsevier Science Inc.
Vol. 95, No. 1, Suppl., 2000 ISSN 0002-9270/00/$20.00 PII S0002-9270(99)00810-2
Diarrheal Disease in a Developing Nation Hugo Ribeiro, Jr., M.D. Diarrheal Diseases Research Unit, Pediatric University Hospital of Bahia, Salvador, Bahia, Brazil
ABSTRACT Infants and young children from many developing nations face a serious public health threat from diarrhea. In the northeast region of Brazil, diarrheal disease causes significant morbidity and mortality. Although diarrheal deaths in this region have been declining since the early 1980s, the hospitalization rate remains high. Diarrhea may account for 25% of total healthcare costs in northeast Brazil. Many patients become ill because of poor environmental conditions and because their caregivers lack awareness of basic hygiene. Many also return to the hospital after initial treatment because health workers do not provide appropriate preventive and home care instruction to patients in 99% of cases. Antibiotics have no effect in 85–95% of pediatric diarrheal cases in the region. Improvement of preventive home care management in association with probiotic bacteria, which have been effective against several forms of diarrhea in developing nations, may be useful in managing diarrheal disease in infants. (Am J Gastroenterol 2000;95(Suppl.): S14 –S15. © 2000 by Am. Coll. of Gastroenterology)
INTRODUCTION Diarrheal diseases are a serious, worldwide health problem. A 1980 World Health Organization (WHO) report found that the number of deaths worldwide from diarrhea ranged from 5 to 10 million per year, with 0.7–1 billion acute episodes occurring annually in children younger than 5 yr of age (1). Recent global estimates suggest that diarrhea kills about 3.2 million young children every year (almost a third of all infant deaths in developing countries), with a per-child average of three to four acute episodes per year. Lifethreatening diarrhea is generally more common in developing nations, but it is not exclusive to them. Gastroenteritis with diarrhea has been cited as a major cause of hospitalization of children in the United States (2). In 1988, the Centers for Disease Control reported that “diarrheal deaths constitute an important and preventable fraction of postneonatal mortality in the United States.” (3) This report focuses on the current situation for pediatric diarrheal disease in Brazil, specifically in the northeastern state of Bahia. In recent years, education and the widespread use of oral rehydration therapy (ORT) have reduced the number of diarrheal deaths in northeastern Brazil. However, the rate of hospitalization for diarrhea remains high, placing an enormous burden on the healthcare system. Morbidity and hospitalization rates might be substantially reduced with improved case management and an increased emphasis on
patient education. New therapies would be welcome, as the vast majority of patients who require medical therapy do not respond to antibiotics. A probiotic strain, Lactobacillus GG (LGG), which has shown efficacy in preventing and treating various forms of diarrhea in developed nations, may provide benefits to many Brazilian children.
EPIDEMIOLOGY Most pediatric patients in Brazil experience frequent acute diarrheal episodes of short duration. In the northeast region, we average three to five cases of diarrhea per child per year. Although the duration of each episode is short, when one considers episode frequency over the course of a year, children in northeastern Brazil have diarrhea approximately 30% of the time. Diarrheal disease causes morbidity and mortality throughout Brazil, but the problem is most pronounced in the northeast (4). For example, more than half of all diarrheal deaths among Brazilian children younger than 5 yr occurred in the northeast region between 1980 and 1992 (5). Although the majority of deaths today occur in children younger than age 2 yr, diarrhea still kills more children from northeastern Brazil in their first year than any other illness (4). Diarrheal disease also contributes to high rates of malnutrition among those who survive (4). Despite the high concentration of disease, however, there were signs of improvement over the same period. Infant deaths attributed to diarrhea fell from 41% in 1980 to 25% in 1989; similar decreases were seen among children aged 1– 4 yr (6).
BURDEN OF ILLNESS The significant reduction in total diarrheal deaths has not been matched by a similar decline in the proportion of cases hospitalized, and healthcare costs associated with this failure strain limited public health resources. Work done in the Public Health Institute at the Federal University of Bahia showed that from 1992 to 1996, the duration of an average hospital stay for diarrheal disease remained at about 6 days. The per-case cost of hospitalization increased slightly, but most of this increase can be traced to price corrections and inflation, not to a more expensive case management approach. We estimate that diarrhea accounts for approximately 20 –25% of total hospitalization costs in Brazil, or about $19 million per year; with the present state of healthcare, avoiding one diarrheal death costs about $15,000.
AJG – January, Suppl., 2000
Many patients seeking emergency treatment for diarrhea are hospitalized, and many of them end up dying. An admission rate of about 5% of patients presenting with diarrhea might be expected, but ⬎43% of patients younger than age 4 yr who seek emergency treatment for diarrhea are admitted to our hospitals. The rate of death after hospitalization for diarrhea is about 80% among young children in the northeast region.
TREATMENT The high incidence of infectious diarrhea among children in northeast Brazil has led to a range of interventions. Perhaps the most important of these has been the introduction of ORT. ORT has become the global treatment of choice for acute childhood diarrhea, regardless of etiology, and its use has resulted in a dramatic decrease in diarrhea-related morbidity and mortality in developing countries (7). In northeastern Brazil, Victora and coworkers concluded that ORT has a significant impact after finding an inverse relationship between ORT use and infant diarrhea mortality (8). However, ORT can neither prevent diarrheal episodes nor reduce their duration. In addition, many patients require immediate treatment and receive antibiotics before the results of diagnostic studies become available. Yet antibiotics seem to work in only 5–15% of our patients; in 85–95% of cases, the pathogen is unknown, or the antibiotic has no effect on a known pathogen. The indiscriminate use of antibiotics may result in undesirable side effects, including diarrhea, and chronic use can lead to the development of bacterial resistance (7). Lactobacillus GG, a probiotic, may prove useful for treating diarrheal disease. In controlled trials, this agent has shown safety and efficacy in diarrhea associated with travel (9) and relapsing Clostridium difficile (10). A recent placebo-controlled study in Peru demonstrated that LGG may be useful in the prevention of diarrhea in malnourished children (11). Preliminary results with LP299v and LGG in northeast Brazil suggest that, with widespread use, reductions in duration of pediatric diarrheal episodes and in new cases of diarrhea may be possible (12). With a reduction in diarrheal disease incidence, total antibiotic consumption and the rate of hospitalization may also decline.
THE ROLE OF EDUCATION Many healthcare workers in northeastern Brazil have been trained to diagnose and treat childhood diarrhea, but costly complications persist. One issue is the lack of a universally accepted standard for assessing diarrhea and dehydration status, which applies as much in developed nations as it does in Brazil. Recently, we have been attempting to implement a uniform system to assess cases and to classify patients. Even with a diagnostic system, however, the most effective measures for interrupting the spread of infections that cause diarrhea seem to be matters of basic hygiene. In earlier work (13), we showed that only 1% of trained health workers provide correct advice to the caretaker on preven-
Diarrheal Disease in a Developing Nation
S15
tion and home care aspects of diarrheal diseases. Thus, in nearly all cases, caregivers and patients are released from our healthcare facilities without any education, which allows a single episode of diarrhea to develop in many cases into more serious or recurrent disease.
CONCLUSIONS The problem of diarrhea in infants and young children remains serious in many developing nations, including northeast Brazil. Associated morbidity is high, and our research suggests that an effective approach for preventing diarrheal disease or reducing the rate of hospitalization could have a significant impact on the total problem and merits consideration. Probiotics may represent a viable new approach in many cases. With diarrheal episodes and hospital days ranging in the millions per year in the northeast region alone, this new therapy deserves full investigation. Reprint requests and correspondence: Hugo Ribeiro, Jr., M.D., Pediatric University Hospital of Bahia, Diarrheal Diseases Research Unit, Rua Padre Feijo 29, Canela, Salvador, Bahia, Brazil. Received Mar. 17, 1999; accepted Sep. 7, 1999.
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;60:605–13. 2. Kapikian AX, Kim H, Wyatt R, et al. Human reovirus-like agent as the major pathogen associated with “winter” gastroenteritis in hospitalized infants and young children. N Engl J Med 1976;294:965–72. 3. Ho MS, Glass RI, Pinsky PF, et al. Diarrheal deaths in American children: Are they preventable? JAMA 1988;260:3281– 4. 4. Brasil, Ministerio de Sau´de, Fundac¸a¯o Nacional de Sau´de, Centro Nacional de Epidemiologia. Bullet 82 n Semanal. Brasilia: Ministerio de Sau´de, 3 June 1993. 5. United Nations Children’s Fund. Child mortality since the 1960s. New York: UNICEF, 1992:57– 62. 6. Victora C, Barros F. Diarrheal diseases among children under five years in the Americas, 1980 –1992. New York: UNICEF, 1993. 7. Soriano-Brucher H, Avendano P, O’Ryan M, et al. Bismuth subsalicylate in the treatment of acute diarrhea in children: A clinical study. Pediatrics 1991;87:18 –27. 8. Victora CG, Olinto MT, Barros FC, et al. Falling diarrhoea mortality in Northeastern Brazil: Did ORT play a role? Health Policy Plan 1996;11:132– 41. 9. Oksanen PJ, Salminen S, Saxelin M, et al. Prevention of diarrhea by Lactobacillus GG. Ann Med 1990;22:53– 6. 10. Gorbach SL, Chang TW, Goldin B. Successful treatment of relapsing Clostridium difficile colitis with Lactobacillus GG. Lancet 1987;2:1519 (letter). 11. Oberhelman RA, Gilman RH, Sheen P, et al. A placebocontrolled trial of Lactobacillus GG to prevent diarrhea in undernourished Peruvian children. J Pediatr 1999;134:15–20. 12. Ribeiro H, Vanderhoof JA. Reduction of diarrheal illness following administration of Lactobacillus plantarum 299v in a daycare facility. J Pediatr Gastroenterol Nutr 1998;26:561. 13. Ribeiro HC Jr, Drasbek CJ. Correct case management of childhood diarrhea: A survey of nine state capitals in northeast Brazil. Bull Pan Am Health Organ 1995;29:237– 49.
Vol. 95, No. 1, Suppl., 2000 ISSN 0002-9270/00/$20.00 PII S0002-9270(99)00810-2
Diarrheal Disease in a Developing Nation Hugo Ribeiro, Jr., M.D. Diarrheal Diseases Research Unit, Pediatric University Hospital of Bahia, Salvador, Bahia, Brazil
ABSTRACT Infants and young children from many developing nations face a serious public health threat from diarrhea. In the northeast region of Brazil, diarrheal disease causes significant morbidity and mortality. Although diarrheal deaths in this region have been declining since the early 1980s, the hospitalization rate remains high. Diarrhea may account for 25% of total healthcare costs in northeast Brazil. Many patients become ill because of poor environmental conditions and because their caregivers lack awareness of basic hygiene. Many also return to the hospital after initial treatment because health workers do not provide appropriate preventive and home care instruction to patients in 99% of cases. Antibiotics have no effect in 85–95% of pediatric diarrheal cases in the region. Improvement of preventive home care management in association with probiotic bacteria, which have been effective against several forms of diarrhea in developing nations, may be useful in managing diarrheal disease in infants. (Am J Gastroenterol 2000;95(Suppl.): S14 –S15. © 2000 by Am. Coll. of Gastroenterology)
INTRODUCTION Diarrheal diseases are a serious, worldwide health problem. A 1980 World Health Organization (WHO) report found that the number of deaths worldwide from diarrhea ranged from 5 to 10 million per year, with 0.7–1 billion acute episodes occurring annually in children younger than 5 yr of age (1). Recent global estimates suggest that diarrhea kills about 3.2 million young children every year (almost a third of all infant deaths in developing countries), with a per-child average of three to four acute episodes per year. Lifethreatening diarrhea is generally more common in developing nations, but it is not exclusive to them. Gastroenteritis with diarrhea has been cited as a major cause of hospitalization of children in the United States (2). In 1988, the Centers for Disease Control reported that “diarrheal deaths constitute an important and preventable fraction of postneonatal mortality in the United States.” (3) This report focuses on the current situation for pediatric diarrheal disease in Brazil, specifically in the northeastern state of Bahia. In recent years, education and the widespread use of oral rehydration therapy (ORT) have reduced the number of diarrheal deaths in northeastern Brazil. However, the rate of hospitalization for diarrhea remains high, placing an enormous burden on the healthcare system. Morbidity and hospitalization rates might be substantially reduced with improved case management and an increased emphasis on
patient education. New therapies would be welcome, as the vast majority of patients who require medical therapy do not respond to antibiotics. A probiotic strain, Lactobacillus GG (LGG), which has shown efficacy in preventing and treating various forms of diarrhea in developed nations, may provide benefits to many Brazilian children.
EPIDEMIOLOGY Most pediatric patients in Brazil experience frequent acute diarrheal episodes of short duration. In the northeast region, we average three to five cases of diarrhea per child per year. Although the duration of each episode is short, when one considers episode frequency over the course of a year, children in northeastern Brazil have diarrhea approximately 30% of the time. Diarrheal disease causes morbidity and mortality throughout Brazil, but the problem is most pronounced in the northeast (4). For example, more than half of all diarrheal deaths among Brazilian children younger than 5 yr occurred in the northeast region between 1980 and 1992 (5). Although the majority of deaths today occur in children younger than age 2 yr, diarrhea still kills more children from northeastern Brazil in their first year than any other illness (4). Diarrheal disease also contributes to high rates of malnutrition among those who survive (4). Despite the high concentration of disease, however, there were signs of improvement over the same period. Infant deaths attributed to diarrhea fell from 41% in 1980 to 25% in 1989; similar decreases were seen among children aged 1– 4 yr (6).
BURDEN OF ILLNESS The significant reduction in total diarrheal deaths has not been matched by a similar decline in the proportion of cases hospitalized, and healthcare costs associated with this failure strain limited public health resources. Work done in the Public Health Institute at the Federal University of Bahia showed that from 1992 to 1996, the duration of an average hospital stay for diarrheal disease remained at about 6 days. The per-case cost of hospitalization increased slightly, but most of this increase can be traced to price corrections and inflation, not to a more expensive case management approach. We estimate that diarrhea accounts for approximately 20 –25% of total hospitalization costs in Brazil, or about $19 million per year; with the present state of healthcare, avoiding one diarrheal death costs about $15,000.
AJG – January, Suppl., 2000
Many patients seeking emergency treatment for diarrhea are hospitalized, and many of them end up dying. An admission rate of about 5% of patients presenting with diarrhea might be expected, but ⬎43% of patients younger than age 4 yr who seek emergency treatment for diarrhea are admitted to our hospitals. The rate of death after hospitalization for diarrhea is about 80% among young children in the northeast region.
TREATMENT The high incidence of infectious diarrhea among children in northeast Brazil has led to a range of interventions. Perhaps the most important of these has been the introduction of ORT. ORT has become the global treatment of choice for acute childhood diarrhea, regardless of etiology, and its use has resulted in a dramatic decrease in diarrhea-related morbidity and mortality in developing countries (7). In northeastern Brazil, Victora and coworkers concluded that ORT has a significant impact after finding an inverse relationship between ORT use and infant diarrhea mortality (8). However, ORT can neither prevent diarrheal episodes nor reduce their duration. In addition, many patients require immediate treatment and receive antibiotics before the results of diagnostic studies become available. Yet antibiotics seem to work in only 5–15% of our patients; in 85–95% of cases, the pathogen is unknown, or the antibiotic has no effect on a known pathogen. The indiscriminate use of antibiotics may result in undesirable side effects, including diarrhea, and chronic use can lead to the development of bacterial resistance (7). Lactobacillus GG, a probiotic, may prove useful for treating diarrheal disease. In controlled trials, this agent has shown safety and efficacy in diarrhea associated with travel (9) and relapsing Clostridium difficile (10). A recent placebo-controlled study in Peru demonstrated that LGG may be useful in the prevention of diarrhea in malnourished children (11). Preliminary results with LP299v and LGG in northeast Brazil suggest that, with widespread use, reductions in duration of pediatric diarrheal episodes and in new cases of diarrhea may be possible (12). With a reduction in diarrheal disease incidence, total antibiotic consumption and the rate of hospitalization may also decline.
THE ROLE OF EDUCATION Many healthcare workers in northeastern Brazil have been trained to diagnose and treat childhood diarrhea, but costly complications persist. One issue is the lack of a universally accepted standard for assessing diarrhea and dehydration status, which applies as much in developed nations as it does in Brazil. Recently, we have been attempting to implement a uniform system to assess cases and to classify patients. Even with a diagnostic system, however, the most effective measures for interrupting the spread of infections that cause diarrhea seem to be matters of basic hygiene. In earlier work (13), we showed that only 1% of trained health workers provide correct advice to the caretaker on preven-
Diarrheal Disease in a Developing Nation
S15
tion and home care aspects of diarrheal diseases. Thus, in nearly all cases, caregivers and patients are released from our healthcare facilities without any education, which allows a single episode of diarrhea to develop in many cases into more serious or recurrent disease.
CONCLUSIONS The problem of diarrhea in infants and young children remains serious in many developing nations, including northeast Brazil. Associated morbidity is high, and our research suggests that an effective approach for preventing diarrheal disease or reducing the rate of hospitalization could have a significant impact on the total problem and merits consideration. Probiotics may represent a viable new approach in many cases. With diarrheal episodes and hospital days ranging in the millions per year in the northeast region alone, this new therapy deserves full investigation. Reprint requests and correspondence: Hugo Ribeiro, Jr., M.D., Pediatric University Hospital of Bahia, Diarrheal Diseases Research Unit, Rua Padre Feijo 29, Canela, Salvador, Bahia, Brazil. Received Mar. 17, 1999; accepted Sep. 7, 1999.
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;60:605–13. 2. Kapikian AX, Kim H, Wyatt R, et al. Human reovirus-like agent as the major pathogen associated with “winter” gastroenteritis in hospitalized infants and young children. N Engl J Med 1976;294:965–72. 3. Ho MS, Glass RI, Pinsky PF, et al. Diarrheal deaths in American children: Are they preventable? JAMA 1988;260:3281– 4. 4. Brasil, Ministerio de Sau´de, Fundac¸a¯o Nacional de Sau´de, Centro Nacional de Epidemiologia. Bullet 82 n Semanal. Brasilia: Ministerio de Sau´de, 3 June 1993. 5. United Nations Children’s Fund. Child mortality since the 1960s. New York: UNICEF, 1992:57– 62. 6. Victora C, Barros F. Diarrheal diseases among children under five years in the Americas, 1980 –1992. New York: UNICEF, 1993. 7. Soriano-Brucher H, Avendano P, O’Ryan M, et al. Bismuth subsalicylate in the treatment of acute diarrhea in children: A clinical study. Pediatrics 1991;87:18 –27. 8. Victora CG, Olinto MT, Barros FC, et al. Falling diarrhoea mortality in Northeastern Brazil: Did ORT play a role? Health Policy Plan 1996;11:132– 41. 9. Oksanen PJ, Salminen S, Saxelin M, et al. Prevention of diarrhea by Lactobacillus GG. Ann Med 1990;22:53– 6. 10. Gorbach SL, Chang TW, Goldin B. Successful treatment of relapsing Clostridium difficile colitis with Lactobacillus GG. Lancet 1987;2:1519 (letter). 11. Oberhelman RA, Gilman RH, Sheen P, et al. A placebocontrolled trial of Lactobacillus GG to prevent diarrhea in undernourished Peruvian children. J Pediatr 1999;134:15–20. 12. Ribeiro H, Vanderhoof JA. Reduction of diarrheal illness following administration of Lactobacillus plantarum 299v in a daycare facility. J Pediatr Gastroenterol Nutr 1998;26:561. 13. Ribeiro HC Jr, Drasbek CJ. Correct case management of childhood diarrhea: A survey of nine state capitals in northeast Brazil. Bull Pan Am Health Organ 1995;29:237– 49.