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Treatment of children with malnutrition and diarrhoea
Barr virus within epithelial cells of oral “hairy”leukoplakia, an AIDSassociated lesion. N Engl J Med 1985; 313: 1564–71. 5 Niedobitek G,Young LS. Epstein-Barr virus persistence and virusassociated tumours. Lancet 1994; 343: 333–35. 6 Faulkner GC, Burrows SR, Khanna R, Moss DJ, Bird AG,Crawford DH. X-linked agammaglobulinemia patients are not infected with Epstein-Barr virus:implications for the biology of the virus. JVirol 1999; 73: 155–64. 7 Babcock GJ, Decker LL, Volk M, Thorley-Lawson DA. EBV persistence in memory B cells in vivo. Immunity 1998; 9: 395–404. 8 Sugawara Y, Mizugaki Y, Uchida T, et al. Detection of Epstein-Barr virus in hepatocellular carcinoma tissue: a novel EBV latency characterized by the absence of EBV-encoded small RNA expression. Virology 1999; 256: 196–202. 9 Bonnet M, Guinbretiere J-M, Kremmer E, et al. Detection of EpsteinBarr virus in invasive breast cancers. J Natl Cancer Inst 1999; 91: 1376–81.
Treatment of children with malnutrition and diarrhoea Case-fatality rates for severe protein-energy malnutrition (PEM) have changed little over 50 years.1 Because such rates have been attributed to faulty case-management, Tahmeed Ahmed and colleagues2 examined the value of a standardised protocol for the management of severely malnourished children with diarrhoea at the International Centre for Diarrhoeal Diseases Research (ICDDR) in Dhaka, Bangladesh. The researchers, rightly, thought that random allotment of cases to standardised or unstandardised treatment was unethical, so they followed the standardised protocol for all children admitted in the first 6 months of 1997 and compared the effects with those of non-standardised treatment given to children admitted in the first half of 1996. Both groups were very large (about 300 children), had the same median age (6 months), and were severely stunted as well as wasted. The duration of previous diarrhoea was the same (median 6 days), and so was the prevalence of dehydration (about 40%), pneumonia (about 60%), and septicaemia (about 30%). The only significant difference at baseline was a higher prevalence of oedema among the test group. In both groups the median duration of stay in hospital was only 4 days. So the playing field was level, but there were highly significant differences in outcome.The mortality was 9% in the test group, compared with 17% in the controls. The most important contribution to this difference was probably the better management of dehydration. Only 40% of children in the test group received intravenous infusions, compared with 70% of the controls, and the volume infused and the duration of infusion were lower for the test group. However, whether the mere existence of a standardised protocol imposes more discipline, more attention to detail, and less freedom of choice for the clinician, including freedom to make mistakes, cannot be ruled out. Severe PEM is usually complicated by infection, and in this study the infectious element seemed to predominate. Nevertheless, the relation between mortality and the nature and amount of intravenous therapy suggests that the deaths were due primarily to malnourishment.That malnourished babies differ from normal babies in their response to intravenous infusion has long been recognised.The severely malnourished infant has an excess of water and sodium, even in the absence of clinical oedema, and is deficient in potassium. More than 30 years ago Smith3 recorded pulmonary oedema at necropsy in the majority of babies dying of malnutrition, and attributed it, probably correctly, to over-enthusiatic intravenous therapy. Another point that has not yet been settled is the best composition of oral 1142
rehydration fluid for malnourished children. The group working in Jamaica4 have recommended, for the reasons given above, that the sodium content should be reduced to a half or even a third of that of the standard WHO/ UNICEF oral rehydration solution; on the other hand, extra potassium should be given, as should extra glucose, to prevent hypoglycaemia.5 The ICDDR plans to carry out a comparative trial of the effectiveness of this formulation. The treatment of severe PEM has long been a neglected area. When I presented a paper to the UN Subcommittee on Nutrition some 20 years ago emphasising this deplorable waste of children’s lives, the official response was that resources could not be diverted from prevention to cure. In the past decade the picture has changed, perhaps because of the increasing number of malnourished refugees. WHO has recently produced a comprehensive manual6 on the management of severe malnutrition. This manual covers, in a simple and readable way, all the three conventional phases of treatment—the initial phase, as described in the ICDDR paper, lasting 4–7 days; the maintenance phase, lasting perhaps another week; and the phase of recuperation. In the first phase the priorities are rehydration, treatment of infection, and provision of essential trace elements (magnesium, zinc, and copper). The guidelines are in full agreement with the conclusions of the ICDDR study: to avoid intravenous therapy where possible and to use the low-sodium rehydration solution mentioned above. The manual puts the seal of its approval on the somewhat contentious policy of routinely giving antibiotics to all children, in case there is an undiagnosed infection. For the second phase, the advice on daily requirements is not more than 80–100 kcal/kg of energy and about 1 g protein/kg. The rationale of this regimen, which seemed to be very effective in Jamaica,4 is to avoid overloading the body’s depleted enzyme systems. The final phase begins when appetite has been restored, and highenergy feeds with reasonable amounts of protein can be given without risk. This manual should be widely disseminated in developing countries, perhaps backed up by training for paediatricians and nurses. Feedback is also essential. The next step for WHO is to support schemes to investigate how far the manual’s guidelines can be applied in poor district hospitals, where equipment and staff are in short supply. For the guidelines to be followed in such places requires a definition of the minimum resources needed for the handling of a given number of patients, and also ways of using the resources most effectively. All this may require changes in the traditional attitudes of doctors, nurses and administrators. John Waterlow Department of Public Health and P olicy, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK 1
2
3 4
5 6
Schofield C, Ashworth A .W hy have mortality rates for severe malnutrition remained so high? Bull World Health Organ 1996; 74: 223–29. Ahmed T, Ali M, Ullah MM, et al. Mortality in severely malnourished children with diarrhoea and use of a standardised management protocol. Lancet 1999; 353: 1919–22. Smith R. Hyponatraemia in infantile malnutrition. Lancet 1 9 6 3 ;i : 771–72. Waterlow JC, Golden MHN, Patrick S. Protein-energy malnutrition: treatment.In:Dickerson JWT, Lee HA, eds. Nutrition in the clinical management of disease. London:Edward Arnold,1978:49–71. Waterlow JC. Protein energy malnutrition.London:Edward Arnold, 1992. WHO. Management of severe malnutrition: a manual for physicians and other senior health workers. Geneva:WHO, 1999.
THE LANCET • Vol 354 • October 2, 1999
Treatment of children with malnutrition and diarrhoea Case-fatality rates for severe protein-energy malnutrition (PEM) have changed little over 50 years.1 Because such rates have been attributed to faulty case-management, Tahmeed Ahmed and colleagues2 examined the value of a standardised protocol for the management of severely malnourished children with diarrhoea at the International Centre for Diarrhoeal Diseases Research (ICDDR) in Dhaka, Bangladesh. The researchers, rightly, thought that random allotment of cases to standardised or unstandardised treatment was unethical, so they followed the standardised protocol for all children admitted in the first 6 months of 1997 and compared the effects with those of non-standardised treatment given to children admitted in the first half of 1996. Both groups were very large (about 300 children), had the same median age (6 months), and were severely stunted as well as wasted. The duration of previous diarrhoea was the same (median 6 days), and so was the prevalence of dehydration (about 40%), pneumonia (about 60%), and septicaemia (about 30%). The only significant difference at baseline was a higher prevalence of oedema among the test group. In both groups the median duration of stay in hospital was only 4 days. So the playing field was level, but there were highly significant differences in outcome.The mortality was 9% in the test group, compared with 17% in the controls. The most important contribution to this difference was probably the better management of dehydration. Only 40% of children in the test group received intravenous infusions, compared with 70% of the controls, and the volume infused and the duration of infusion were lower for the test group. However, whether the mere existence of a standardised protocol imposes more discipline, more attention to detail, and less freedom of choice for the clinician, including freedom to make mistakes, cannot be ruled out. Severe PEM is usually complicated by infection, and in this study the infectious element seemed to predominate. Nevertheless, the relation between mortality and the nature and amount of intravenous therapy suggests that the deaths were due primarily to malnourishment.That malnourished babies differ from normal babies in their response to intravenous infusion has long been recognised.The severely malnourished infant has an excess of water and sodium, even in the absence of clinical oedema, and is deficient in potassium. More than 30 years ago Smith3 recorded pulmonary oedema at necropsy in the majority of babies dying of malnutrition, and attributed it, probably correctly, to over-enthusiatic intravenous therapy. Another point that has not yet been settled is the best composition of oral 1142
rehydration fluid for malnourished children. The group working in Jamaica4 have recommended, for the reasons given above, that the sodium content should be reduced to a half or even a third of that of the standard WHO/ UNICEF oral rehydration solution; on the other hand, extra potassium should be given, as should extra glucose, to prevent hypoglycaemia.5 The ICDDR plans to carry out a comparative trial of the effectiveness of this formulation. The treatment of severe PEM has long been a neglected area. When I presented a paper to the UN Subcommittee on Nutrition some 20 years ago emphasising this deplorable waste of children’s lives, the official response was that resources could not be diverted from prevention to cure. In the past decade the picture has changed, perhaps because of the increasing number of malnourished refugees. WHO has recently produced a comprehensive manual6 on the management of severe malnutrition. This manual covers, in a simple and readable way, all the three conventional phases of treatment—the initial phase, as described in the ICDDR paper, lasting 4–7 days; the maintenance phase, lasting perhaps another week; and the phase of recuperation. In the first phase the priorities are rehydration, treatment of infection, and provision of essential trace elements (magnesium, zinc, and copper). The guidelines are in full agreement with the conclusions of the ICDDR study: to avoid intravenous therapy where possible and to use the low-sodium rehydration solution mentioned above. The manual puts the seal of its approval on the somewhat contentious policy of routinely giving antibiotics to all children, in case there is an undiagnosed infection. For the second phase, the advice on daily requirements is not more than 80–100 kcal/kg of energy and about 1 g protein/kg. The rationale of this regimen, which seemed to be very effective in Jamaica,4 is to avoid overloading the body’s depleted enzyme systems. The final phase begins when appetite has been restored, and highenergy feeds with reasonable amounts of protein can be given without risk. This manual should be widely disseminated in developing countries, perhaps backed up by training for paediatricians and nurses. Feedback is also essential. The next step for WHO is to support schemes to investigate how far the manual’s guidelines can be applied in poor district hospitals, where equipment and staff are in short supply. For the guidelines to be followed in such places requires a definition of the minimum resources needed for the handling of a given number of patients, and also ways of using the resources most effectively. All this may require changes in the traditional attitudes of doctors, nurses and administrators. John Waterlow Department of Public Health and P olicy, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK 1
2
3 4
5 6
Schofield C, Ashworth A .W hy have mortality rates for severe malnutrition remained so high? Bull World Health Organ 1996; 74: 223–29. Ahmed T, Ali M, Ullah MM, et al. Mortality in severely malnourished children with diarrhoea and use of a standardised management protocol. Lancet 1999; 353: 1919–22. Smith R. Hyponatraemia in infantile malnutrition. Lancet 1 9 6 3 ;i : 771–72. Waterlow JC, Golden MHN, Patrick S. Protein-energy malnutrition: treatment.In:Dickerson JWT, Lee HA, eds. Nutrition in the clinical management of disease. London:Edward Arnold,1978:49–71. Waterlow JC. Protein energy malnutrition.London:Edward Arnold, 1992. WHO. Management of severe malnutrition: a manual for physicians and other senior health workers. Geneva:WHO, 1999.
THE LANCET • Vol 354 • October 2, 1999