Documenti di Didattica
Documenti di Professioni
Documenti di Cultura
ABSTRACT Publication of the WHO monograph, “Interactions of Nutrition and Infection,” in 1968 by Scrimshaw,
Taylor and Gordon stimulated many scientists to pursue further research on these issues. With regard to the
relationships between diarrhea and malnutrition, the research conducted since 1968 can be categorized in one of
three major areas: 1) the impact of diarrhea on nutritional status, particularly in young children; 2) nutritional risk
factors for diarrhea; and 3) appropriate dietary therapy for patients during and after enteric infections. The results
of these studies have prompted a number of changes in the clinical treatment of patients with diarrhea and in public
health policies regarding its prevention. J. Nutr. 133: 328S–332S, 2003.
It is personally very gratifying to be able to contribute to Thus began my personal and professional odyssey in quest of
this symposium, which revisits the 1968 treatise by Scrimshaw, greater knowledge on these topics.
Taylor and Gordon entitled, “Interactions of Nutrition and The comprehensive monograph “Interactions of Nutri-
Infection” (1), because this publication had a major impact on tion and Infection” stimulated many scientists to pursue
my own thinking and career development. For individuals like further research on these issues, and in this presentation I
me who were U.S. university students at the time, the year will highlight some of the resulting studies on diarrhea and
1968 was notable for the growing distrust of the “military– nutrition. In general, the research conducted on this topic
industrial complex,” the widespread resistance to the war in since 1968 can be categorized in one of three major areas:
Vietnam, and the reawakened social concern for disenfran- 1) the impact of diarrhea on nutritional status, particularly
chised peoples, both in the United States and elsewhere. At in young children; 2) nutritional risk factors for diarrhea;
the same time, Timothy Leary was counseling students and and 3) appropriate dietary therapy for patients during and
other members of the love generation to “turn on, tune in, and after enteric infections. Notably, the results of these studies
drop out” (2); and the hippie movement was reaching its peak. prompted a number of changes in the clinical management
As a graduating senior confronting these competing claims on of patients with diarrhea and in public health policies
my attention, and as the recipient of a lottery number from the
regarding its prevention. For lack of time, and because of
U.S. Selective Service Board that all but ensured my inscrip-
my own personal interests and experience, my comments
tion into the U.S. Army immediately after graduation unless
other options were pursued, I chose instead to enroll in med- will focus primarily on epidemiological and clinical studies
ical school until I could decide what I really wanted to do with that were conducted in humans. I will not attempt to
my life. Because I had originally hoped to join the Peace Corps provide a comprehensive treatment of the literature; rather,
after finishing my undergraduate studies, once in medical I will highlight those studies that I believe have exerted the
school I began to explore opportunities for practicing medicine greatest influence on current thinking.
and/or conducting biomedical research in the developing
world; and I soon discovered the series of publications by
Scrimshaw, Gordon and colleagues on “weanling diarrhea” (3) Overview of diarrhea and nutrition
and the interactions between infection and nutrition (4,5).
As articulated by Scrimshaw, Taylor and Gordon in their
1
1968 review, the relationship between infection and malnu-
Presented as part of the symposium “Nutrition and Infection, Prologue and
Progress Since 1968” given at the 2002 Experimental Biology meeting on April 23,
trition is bidirectional (Fig. 1). Infection adversely affects
2002, New Orleans, LA. The symposium was sponsored by The American Society nutritional status through reductions in dietary intake and
for Nutritional Sciences. The proceedings are published as a supplement to The intestinal absorption, increased catabolism and sequestration
Journal of Nutrition. Guest editors were Nevin S. Scrimshaw, Massachusetts
Institute of Technology, Cambridge, MA, and Food and Nutrition Programme, of nutrients that are required for tissue synthesis and growth.
United Nations University, Tokyo, Japan, and William R. Beisel, Department of On the other hand, malnutrition can predispose to infection
Microbiology and Immunology, Johns Hopkins School of Hygiene and Public because of its negative impact on the barrier protection af-
Health, Baltimore, MD.
2
To whom correspondence should be addressed. forded by the skin and mucous membranes and by inducing
E-mail: khbrown@ucdavis.edu. alterations in host immune function.
328S
(and other infections) compared with infants who either re- covered that clinic visits and hospital admissions for diarrhea
ceived other foods or liquids along with breast milk or were were decreased in vitamin A–supplemented children, even
fully weaned from the breast (21,22); and similar results have though diarrheal incidence rates remained unchanged (27).
been published more recently from more industrialized settings Thus, it appeared that vitamin A reduced the severity of
(23). illness without affecting the overall attack rate.
During the 1980s and 1990s researchers began to question More recently, several groups of investigators have pursued
whether deficiencies of specific micronutrients might also af- studies of the effect of zinc supplementation on the risk of
fect the risk of diarrhea. Studies were beginning to emerge that diarrhea (28,29). These and other studies, which have been
indicated that the risk of mortality was reduced in children summarized in a recently published pooled analysis (30), dem-
who had received large doses of vitamin A (24). Because most onstrate an impressive reduction in diarrheal incidence of
childhood deaths in low income settings are attributable to nearly 20% among zinc-supplemented children.
infection, it was reasonable to assume that this effect of vita-
min A might be attributable to a reduced incidence of infec-
tions. Despite the apparent logic of this assumption, most Dietary management of patients with diarrhea
studies of this relationship found no effect of vitamin A In response to the growing recognition that diarrhea un-
supplementation on the incidence of diarrhea (25,26). How- dermines nutritional status, a number of investigators began to
ever, researchers in Ghana clarified this issue when they dis- reexamine the prevailing approaches to the dietary manage-
ment of these patients, as summarized in Figure 5. As early as
1924, Parks stated that, “The habit of starving an infant just
because he has frequent stools is fallacious and gives rise to
disastrous results.” In 1948 Chung and Viscorova found that
children who were fed continuously during diarrhea gained
weight more rapidly and did not differ with regard to diarrheal
duration or treatment failure rates compared with those who
were starved during the first 24 – 48 h of hospital-based treat-
ment (31). Despite these observations, pediatrics textbooks
published during the 1960s and 1970s continued to advise
“bowel rest” for 12– 48 h followed by several days of gradual
refeeding (32,33), and in 1979 the 3rd edition of the Pediatric
Nutrition Handbook of the American Academy of Pediatrics
remained silent on the issue of appropriate dietary therapy
during acute diarrhea (34).
In 1988 researchers from Peru published the results of a
randomized, clinical trial to assess the optimal approach for
the initial dietary management of children with acute diarrhea
and dehydration (35). Immediately after several hours of re-
FIGURE 4 Summary of the research on nutritional risk factors for hydration therapy, the patients were assigned to receive one of
diarrhea. four different dietary regimens for 48 h: 1) a nutritionally
Downloaded from https://academic.oup.com/jn/article-abstract/133/1/328S/4687565
by guest
on 26 July 2018
DIARRHEA AND MALNUTRITION 331S
LITERATURE CITED
1. Scrimshaw, N. S., Taylor, C. E. & Gordon, A.J.E. (1968) Interactions of
Nutrition and Infection. WHO monograph series no. 57. World Health Organiza-
tion, Geneva, Switzerland.
2. Leary, T. (1965) The Politics of Ecstasy. Putnam, New York, NY.
3. Gordon, J. E., Chitkara, I. D. & Wyon, J. B. (1963) Weanling diarrhea.
Am. J. Med. Sci. 245: 129 –160.
4. Scrimshaw, N. S., Guzman, M. A. & Gordon, J. E. (1967) Nutrition and
infection field study in Guatemalan villages, 1959 –1964. I. Study plan and exper-
imental design. Arch. Environ. Health 14: 657– 662.
5. Gordon, J. E., Ascoli, W., Mata, L. J., Guzman, M. A. & Scrimshaw, N. S.
(1968) Nutrition and infection field study in Guatemalan villages, 1959 –1964. VI.
Acute diarrheal disease and nutritional disorders in general disease incidence.
Arch. Environ. Health 16: 424 – 437.
6. Mata, L. J., Kronmal, R. A., Garcia, B., Butler, W., Urrutia, J. J. & Murillo,
S. (1976) Breast-feeding, weaning and the diarrhoeal syndrome in a Guate-
malan Indian village. Acute diarrhoea in childhood. Ciba Found. Symp. 42: 311–
338.
7. Martorell, R., Habicht, J.-P., Yarbrough, C., Lechtig, A., Klein, R. E. &
Western, K. A. (1975) Acute morbidity and physical growth in rural Guatemala
FIGURE 5 Summary of research on dietary management of diar- children. Am. J. Dis. Child. 129: 1296 –1301.
rhea. 8. Rowland, M.G.M., Cole, T. J. & Whitehead, R. G. (1977) A quantitative
study into the role of infection in determining nutritional status in Gambian village ern Ghana: effects on clinic attendances, hospital admissions, and child mortality.
children. Br. J. Nutr. 37: 441– 450. Lancet 342: 7–12.
9. Black, R. E., Brown, K. H. & Becker, S. (1984) Effects of diarrhea 28. Sazawal, S., Black, R. E., Bhan, M. K., Jalla, S., Sinha, A. & Bhandari, N.
associated with specific enteropathogens on the growth of children in rural (1997) Efficacy of zinc supplementation in reducing the incidence and preva-
Bangladesh. Pediatrics 73: 799 – 805. lence of acute diarrhea—a community-based, double-blind, controlled trial.
10. Martorell, R., Yarbrough, C. & Klein, R. E. (1980) The impact of Am. J. Clin. Nutr. 66: 413– 418.
ordinary illnesses on the dietray intakes of malnourished children. Am. J. Clin. 29. Ruel, M. T., Rivera, J. A., Santizo, M.-C., Lönnerdal, B. & Brown, K. H.
Nutr. 33: 345–350. (1997) Impact of zinc supplementation on morbidity from diarrhea and respira-
11. Brown, K. H., Black, R. E., Robertson, A. D. & Becker, S. (1985) Effects tory infections among rural Guatemalan children. Pediatrics 99: 808 – 813.
of season and illness on the dietary intake of weanlings during longitudinal studies 30. Zinc Investigators’ Collaborative Group (Bhutta, Z. A., Black, R. E.,
in rural Bangladesh. Am. J. Clin. Nutr. 41: 343–355. Brown, K. H., Meeks-Gardner, J., Gorem, S., Hidayat, A., Khatun, F., Martorell, R.,
12. Brown, K. H., Stallings, R. Y., Creed de Kanashiro, H., Lopez de Romaña, Ninh, N. X., Penny, M. E., Rosado, J. L., Roy, S. K., Ruel, M., Sazawal, S. &
G. & Black, R. E. (1990) Effects of common illnesses on infants’ energy intakes Shankar, A.). (1999) Prevention of diarrhea and pneumonia by zinc supple-
from breast milk and other foods during longitudinal community-based studies in mentation in children in developing countries: pooled analysis of randomized
Huascar (Lima), Peru. Am. J. Clin. Nutr. 52: 1005–1013. controlled trials. J. Pediatr. 135: 689 – 697.
13. Rowland, M.G.M., Rowland, S.G.J.G. & Cole, T. J. (1988) Impact of 31. Chung, A. W. & Viscorova, B. (1948) The effect of early oral feeding
infection on the growth of children from 0 to 2 years in an urban West African versus early oral starvation on the course of infantile diarrhea. J. Pediatr. 33:
community. Am. J. Clin. Nutr. 47: 134 –138. 14 –22.
14. Lutter, C. K., Mora, J. O., Habicht, J.-P., Rasmussen, K. M., Robson, D. S. 32. Arena, J. M. (1969) Davison’s Compleat Pediatrician, 9th ed. Lea &
& Sellers, S. G. (1989) Nutritional supplementation: effects on child stunting Febiger, Philadelphia, PA.
associated with diarrhea. Am. J. Clin. Nutr. 50: 1– 8. 33. Forfar, J. O. & Arneil, G. C. (1973) Textbook of Paediatrics. Churchill
15. Castillo-Duran, C., Vial, P. & Uauy, R. (1988) Trace mineral balance Livingstone, Edinburgh, UK.
during acute diarrhea in infants. J. Pediatr. 113: 452– 457. 34. Committee on Nutrition, American Academy of Pediatrics. (1979) Pe-
16. James, J. W. (1972) Longitudinal study of the morbidity of diarrheal diatric Nutrition Handbook, 3rd ed. American Academy of Pediatrics, Elk Grove
and respiratory infections in malnourished children. Am. J. Clin. Nutr. 25: 690 – Village, IL.
694. 35. Brown, K. H., Gastañaduy, A. S., Saavedra, J. M., Lembcke, J., Rivas, D.,
17. Sepulveda, J., Willett, W. & Munoz, A. (1988) Malnutrition and diar- Robertson, A. D., Yolken, R. & Sack, R. B. (1988) Effect of continued oral
rhea: a longitudinal study among urban Mexican children. Am. J. Epidemiol. 127: feeding on clinical and nutritional outcomes of acute diarrhea in children. J. Pe-
365–376. diatr. 112: 191–200.
18. Black, R. E., Brown, K. H. & Becker, S. (1984) Malnutrition is a 36. Sadhu, B. K., Isolauri, E., Walker-Smith, J. A., Banchini, G., Van Caillie-
determining factor in diarrheal duration, but not incidence, among young children Bertrand, M., Dias, J. A., Guandalini, S., Hoekstra, J. H., Juntunen, M., Kolacek,
in a longitudinal study in rural Bangladesh. Am. J. Clin. Nutr. 39: 87–94. S., Marx, D., Micetic-Turk, D., Razenberg, M.C.A.C., Szajewska, H., Tarminiau, J.,
19. Palmer, D. L., Koster, F. T., Alam, A.K.M.J. & Islam, M. R. (1976) Weizman, Z., Zanacca, C. & Zetterstrom, R. (1997) Early feeding in childhood
Nutritional status: a determinant of severity of diarrhea in patients with cholera. gastroenteritis. J. Pediatr. Gastroenterol. Nutr. 24: 522–527.
J. Infect. Dis. 134: 8 –14. 37. Committee on Nutrition, American Academy of Pediatrics. (1998) Pe-
20. Samadi, A., Chowdhury, A. I., Huq, M. I. & Shahid, N. S. (1985) Risk diatric Nutrition Handbook, 4th ed. American Academy of Pediatrics, Elk Grove
factors for death in complicated diarrhoea of children. Br. Med. J. 290: 1615– Village, IL.
1617. 38. Sutton, R. E. & Hamilton, J. R. (1968) Tolerance of young children with
21. Brown, K. H., Black, R. E., Lopez de Romaña, G. & Kanashiro, H. C. severe gastroenteritis to dietary lactose: a controlled study. Can. Med. Assoc. J.
(1989) Infant-feeding practices and their relationship with diarrheal and other 99: 980 –982.
diseases in Huascar (Lima), Peru. Pediatrics 83: 31– 40. 39. Chew, F., Penna, F. J., Peret Filho, L. A., Quan, C., Lopes, M. C., Mota,
22. Popkin, B. M., Adair, L., Akin, J. S., Black, R., Briscoe, J. & Flieger, W. J. A. & Fontaine, O. (1993) Is dilution of cows’ milk formula necessary for
(1990) Breast-feeding and diarrheal morbidity. Pediatrics 86: 874 – 882. dietary management of acute diarrhoea in infants aged less than 6 months?
23. Kramer, M. S., Chalmers, B., Hodnett, E. D., Sevkovskaya, Z., Dzikovich, Lancet 341: 194 –197.
I., Shapiro, S., Collet, J. P., Vanilovich, I., Mezen, I., Ducruet, T., Shishko, G., 40. Brown, K. H., Peerson, J. M. & Fontaine, O. (1994) Use of nonhuman
Zubovich, V., Mknuik, D., Gluchanina, E., Dombrovskiy, V., Ustinovitch, A., Kot, milks in the dietary management of young children with acute diarrhea: a meta-
T., Bogdanovich, N., Ovchinikova, L., Helsing, E. & PROBIT Study Group (Pro- analysis of clinical trials. Pediatrics 93: 17–27.
motion of Breastfeeding Intervention Trial). (2001) Promotion of Breastfeeding 41. Brown, K. H. (1994) Dietary management of acute diarrheal disease:
Intervention Trial (PROBIT): a randomized trial in the Republic of Belarus. J. Am. contemporary scientific issues. J. Nutr. 124: 1455S–1460S.
Med. Assoc. 285: 413– 412. 42. Brown, K. H., Perez, F., Peerson, J. M., Fadel, J., Brunsgaard, G., Ostrom,
24. Sommer, A., Tarwotjo, I., Djunaedi, E., West, K. P., Jr., Loeden, A. A., K. M. & MacLean, W. C., Jr. (1993) Effect of dietary fiber (soy polysaccharide)
Tilden, R., Mele, L. & Aceh Study Group. (1986) Impact of vitamin A supple- on the severity, duration, and nutritional outcome of acute, watery diarrhea in
mentation on childhood mortality. A randomised controlled community trial. Lan- children. Pediatrics 92: 241–247.
cet 1: 1169 –1173. 43. Bhandari, N., Bahl, R., Sazawal, S. & Bhan, M. K. (1997) Breast-
25. Rahmathullah, L., Underwood, B. A., Thulasiraj, R. D. & Milton, R. C. feeding status alters the effect of vitamin A treatment during acute diarrhea in
(1991) Diarrhea, respiratory infections, and growth are not affected by a weekly children. J. Nutr. 127: 59 – 63.
low-dose vitamin A supplement: a masked, controlled field trial in children in 44. Zinc Investigators’ Collaborative Group (Bhutta, Z. A., Bird, S. M., Black,
southern India. Am. J. Clin. Nutr. 54: 568 –577. R. E., Brown, K. H., Gardner, J. M., Hidayat, A., Khatun, F., Martorell, R., Ninh,
26. Dibley, M. J., Sadjimin, T., Kjolhede, C. L. & Moulton, L. H. (1996) N. X., Penny, M. E., Rosado, J. L., Roy, S. K., Ruel, M., Sazawal, S. & Shankar, A.).
Vitamin A supplementation fails to reduce incidence of acute respiratory illness (2000) Therapeutic effects of oral zinc in acute and persistent diarrhea in
and diarrhea in preschool-age Indonesian children. J. Nutr. 126: 434 – 442. children in developing countries: pooled analysis of randomized controlled trials.
27. Ghana VAST Study Team. (1993) Vitamin A supplementation in north- Am. J. Clin. Nutr. 72: 1516 –1522.