- Email: [email protected]
TTP
CORRESPONDENCE
Pathological and therapeutic distinctions in HUS/TTP Sir—S Dundas and colleagues (Oct 16, p 1327)1 report that in a survey of 22 adults with haemolytic-uraemic syndrome (HUS)/thrombotic thrombocytopenic purpura (TTP) associated with E coli O157, a significant benefit for plasma exchange was not found. However, while correctly noting that the value of plasma exchange “needs to be shown definitively in a multicentre, randomised controlled trial”, they persist in recommending this procedure for such patients as “a promising treatment”. I disagree. The theoretical basis for their recommendation includes the fact that plasma exchange is highly effective in idiopathic HUS/TTP as well as HIV and ticlopidine-linked disease.2,3 The researchers then draw parallels between the microangiography and increased concentrations of circulating von Willebrand factor (vWF) multimers seen in HUS/TTP, and E coli O157associated disease. These parallels are, I believe, unwarranted. HUS/TTP associated with chemotherapy, malignancy, and the shiga toxins, which are elaborated by E coli O157, are pathologically quite distinct from those forms of HUS/TTP in which plasma exchange is known to be effective.2 The main lesion in all forms of HUS/TTP is a thrombotic angiopathy. However, in the forms associated with shiga toxin and malignancy, fibrin thrombi predominate and can occur in the microvasculature as well as the larger vessels of all organs, including the lungs.2 This latter point was well illustrated by the prominent pulmonary disease seen in 14 of the 22 patients reported. Dundas and colleagues1 report that lesions are accompanied by necrosis and inflammation. In clear contrast, lesions in idiopathic, HIV, and ticlopidine-associated HUS/TTP are restricted to the microvasculature.2,4 The lesions involve endothelial cell and platelet plugging of vessels more than fibrin thrombi, never involve large vessels nor the pulmonary microvasculature, and show endothelial cell apoptosis, not inflammation or necrosis. Also, ultra-high molecular weight vWF multimers are characteristic of idiopathic, HIV, and ticlopidineassociated HUS/TTP but are not, as Dundas and colleagues assert, typically seen in the other forms.5 These in-vivo changes are paralleled by apoptosis induced in vitro by plasma from patients with acute idiopathic and HIV-associated HUS/TTP in primary
THE LANCET • Vol 355 • February 5, 2000
human endothelial cells of the microvasculature of all tissues except the lung.2 After plasmapheresis, patient plasma no longer induces such apoptosis. Plasma from patients with shiga toxin or cancer-associated HUS/TTP does not cause such apoptosis. The distinct pathology and pathophysiology of the various forms of HUS/TTP tell us that despite similar clinical patterns, they are very different diseases. The fact that plasma infusions, even without plasma exchange, have proven so effective in the idiopathic, HIV, and ticlopidine-associated forms, but remain of no documented value in the other types, is not surprising. Jeffrey Laurence Laboratory for AIDS Virus Research, Weill Medical College of Cornell University, New York, NY 10021, USA 1
2
3
4
5
Dundas S, Murphy J, Soutar RL, Jones GA, Hutchinson SJ, Todd WTA. Effectiveness of therapeutic plasma exchange in the 1996 Lanarkshire Escherichia coli O157:H7 outbreak. Lancet 1999; 354: 1327–30. Laurence J, Mitra D. Apoptosis of microvascular endothelial cells in the pathophysiology of thrombotic thrombocytopenic purpura/sporadic hemolytic uremic syndrome. Sem Hematol 1997; 34: 98–105. Bennett CL, Weinberg PD, Rozenberg-Ben-Dror K, Kwann HC, Green D. Thrombotic thrombocytopenic purpura associated with ticlopidine. Ann Intern Med 1998; 128: 541–44. Dang CT, Magid MS, Weksler B, Chadburn A, Laurence J. Enhanced endothelial cell apoptosis in splenic tissues of patients with thrombotic thrombocytopenic purpura. Blood 1999; 93: 1264–70. Furlan M, Robles R, Galbusera M, et al. von Willebrand factor-cleaving protease in thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome. N Engl J Med 1998; 339: 1578–84.
Sir—We disagree with the statement by S Dundas and colleagues1 that there is “just one potentially beneficial treatment option” in haemolytic uraemic syndrome (HUS)/thrombotic thrombocytopenic purpura (TTP) induced by Escherichia coli 0157:H7, which is plasma exchange. Plasma infusion is another reasonable first-line therapy in HUS/TTP. There is a general consensus supporting the use of plasma exchange instead of plasma infusion in the management of HUS/TTP. However, this consensus is based on the results of one prospective study2 that shows that plasma exchange is more efficacious than plasma infusion in HUS/TTP. The validity of the results of this study can be questioned because the two groups of patients who underwent exchange or infusion differed in terms of total plasma volume infused and duration of therapy. So, the superiority
of plasma exchange over plasma infusion in HUS/TTP has not been proven. Plasma infusion is a reasonable alternative to expensive and timeconsuming plasma exchange, particularly in HUS/TTP induced by E coli 0157:H7. Fadi Fakhouri, François Vincent, Christophe Legendre Service de Néphrologie, Hôpital Saint-Louis, 75010 Paris, France 1
2
Dundas S, Murphy J, Soutar RL, Jones GA, Hutchinson SJ, Todd WTA. Effectiveness of therapeutic plasma exchange in the 1996 Lanarkshire Escherichia coli O157:H7 outbreak. Lancet 1999; 354: 1327–30. Rock GA, Shumak KH, Buskard NE, et al. Comparison of plasma exchange with plasma infusion in the treatment of thrombotic thrombocytopenia purpura. N Engl J Med 1991; 325: 393–97.
Authors’ reply Sir—We thank Jeffrey Laurence for an update of his work on the pathogenesis of sporadic haemolytic uraemic syndrome (HUS)/thrombotic thrombocytopenic purpura (TTP). He highlights a pathological distinction between sporadic HUS/TTP and Escherichia coli O157 associated HUS/TTP and is specifically concerned about apoptosis and von Willebrand factor (vWF) multimer concentrations. The articles referred to present very little evidence on the pathogenesis of HUS/TTP associated with E coli O157. There is reference to plasma from one child with diarrhoea that failed to induce apoptosis. Others found verotoxin induced apoptosis in human microvascular endothelial cells preexposed to tumour-necrosis factor TNF-.1,2 There is no consensus that apoptosis is fundamental to the pathological process in HUS/TTP or that the effectiveness of therapeutic plasma exchange (TPE) is dependent on its ability to reverse apoptosis. Unusually large vWF multimeric forms have been shown to occur in plasma in HUS/TTP associated with E coli O157.3 The most recent reference cited by Laurence does not discuss vWF multimer concentrations in E coli O157 disease. The extended clinical features of HUS/TTP associated with E coli O157 also do not allow pathological distinction. HUS/TTP in this context is associated with gastrointestinal disease and striking hypoalbuminaemia, which may be an alternative explanation for frequent pulmonary oedema. Laurence’s work raises interesting questions about the pathogenesis of HUS/TTP but presents no definitive evidence that aetiological distinction is linked to pathological distinction and therefore response to TPE.
497
CORRESPONDENCE
To date TPE has not been subjected to clinical trials in HUS/TTP associated with E coli O157. We used TPE to treat E coli O157 associated HUS/TTP in adults, a condition with a recorded mortality rate close to 90%. We think TPE was clinically effective. TPE was not used to treat macrovascular disease (pulmonary oedema), but renal and cerebral disease, which were predominant and life threatening. The clinical efficacy, or otherwise, of TPE in E coli O157associated HUS/TTP needs to be defined. Certainly, there is no convincing evidence from the pathogenesis referred to that TPE could not be effective. In the absence of clinical evidence that TPE is ineffective or dangerous in adult E coli O157associated HUS/TTP, it is difficult to withhold this treatment in a disease with such a high mortbidity and mortality. Fadi Fakhouri and colleagues question the benefit of TPE over plasma infusion in the treatment of HUS/TTP. We concede that it is still unclear whether the benefit of TPE is a result of the removal of an injurious factor or the infusion of a factor deficient in the recipient that is contained in the donor fresh frozen plasma, or both. Our decision to use TPE as opposed to plasma infusion alone was governed by two elements: the consensus remains that TPE is superior to plasma infusion;4,5 and in elderly people with E coli O157associated HUS/TTP, the incidence of pulmonary oedema is high. We believed that it would be unsafe to give large volumes of fresh frozen plasma to patients predisposed to pulmonary oedema without removing an equivalent volume. We believe that if the role of TPE in E coli O157associated HUS/TTP is to be established definitively, patients should be offered what is currently regarded to be the most effective and safe treatment. Stephanie Dundas, *W T Andrew Todd, Richard L Soutar, John Murphy, Gwenyth A Jones, Sharon J Hutchinson Departments of *Infectious Diseases and Haematology, Monklands Hospital, Airdrie, Lanarkshire ML6 0JS, UK (e-mail: [email protected]) 1
2
3
Van de Kar NCAJ, Monnens LAH. Hemolytic uremic syndrome in childhood. Ball Clin Haematol 1998; 11: 498–507. Mahan JD, McAllister C, Karmali M, Verotoxin 1 (VT-1) induction of apoptosis in human glomerular capillary endothelial cells (GCEC) in vitro is dependant on cytokines, cell confluence and cell cyle. J Am Soc Nephrol 1996; 7: 11161. Moake JL. Haemolytic-uremic syndrome: basic science. Lancet 1994; 343: 393–97.
498
4
5
Bell WR. Thrombotic thrombocytpenic purpura/hemolytic uremic syndrome relapse: frequency, pathogenesis and meaning. Semin Haematol 1997; 325: 398–403. Remuzzi G, Ruggenenti P. The haemolytic uremic syndrome. Kidney Int 1995; 47: 2–19.
1
2
3
Where is the mother in maternal and child health? Sir—Abhay Bang and colleagues (Dec 4, p 1955)1 describe the impact on neonatal mortality of a programme to detect and treat neonatal sepsis—an important study in a neglected area. People planning such programmes should also tackle prevention of neonatal sepsis. In a study of village births in the Wosera, Papua New Guinea, we found an unexpected number of septic infants, associated with umbilical-cord infections.2 Tetanus had previously killed 200 of 1000 neonates in the area in which we were working.3 Maternal vaccination had eliminated the disease, but delivery practices leading to cord contamination had not changed. We were struck by the appearance of the infected cords, which were identical to descriptions from the last century.4 Strategies to prevent bacterial access to the umbilicus seem obvious, but there is not a single randomised trial that tests or compared interventions in a developing country.5 WHO and other organisations recommend ties, but their advice is based on history and simplicity rather than any scientific research. In the Wosera we decided against WHO policy, because the huts were dark and ties would lead to increase handling and contamination of the cord. Instead, we supplied commercial plastic clamps, which were more expensive. We still do not know whether our choice was the most effective or appropriate. Organisations such as WHO and UNICEF, which promote cord care, should test the alternatives through large, pragmatic trials, with neonatal death as the primary outcome. These trials should be set up to assess whether cord-carepromotion programmes targeted at birth attendants for village deliveries are effective; compare clamps with ties; and compare routine antiseptics with topical antibiotics. Such information will help those planning comprehensive strategies to prevent and treat neonatal sepsis in developing countries. *Paul Garner, Manesseh Baea *International Health Division, Liverpool School of Tropical Medicine, Liverpool L3 5QA, UK; Papua New Guinea Institute of Medical Research, Maprik, Papua New Guinea
4
5
Bang AT, Bang RA, Reddy MH, Deshmukh MD. Effect of home-based neonatal care and management of sepsis on neonatal mortality: a field trial in rural India. Lancet 1999; 354: 1955–61. Garner P, Lai D, Baea M, Edwards K, Heywood P. Avoiding neonatal death: an intervention study of umbilical cord care. J Trop Paediatr 1994; 40: 24–28. Schofield FD, Tucker VM, Westbrook GR. Neonatal tetanus in New Guinea: effect of active immunisation in pregnancy. BMJ 1961; 2: 785–89. Cullen TS. Embryology, anatomy and diseases of the umbilicus. Philadelphia: WB Saunders, 1916. Zupan J, Garner P. Topical umbilical cord care at birth (Cochrane review). Oxford: Update Software, 1999.
Sir—Bang and colleagues1 report that home-based diagnosis and treatment of neonatal sepsis in rural India by village health workers reduced neonatal and infant mortality by nearly 50%. Assistance by trained traditional birth attendants, health education, and fortnightly supervisory visits were also provided. This is an important finding, especially as policy makers seem to have shifted attention from community-based health care to basic health services.2 A similar reduction in neonatal mortality rates has been achieved in the Farafenni MRC demographic and health surveillance area in rural Gambia during 1982–96 (a decline from 60 per 1000 live births to close to 20/1000).3 Gambia’s primary-healthcare system offered, as part of antenatal care, tetanus toxoid immunisation (coverage 98%). This intervention is thought to have made an important contribution to the reduction of neonatal mortality in many developing countries.4 Also, in Gambia trained traditional birth attendants have improved delivery practices, and care of the umbilical stump. However, an improved healthy start for the child seems to be at the cost of the mother. We interviewed 623 (93%) of 670 women who delivered between Oct, 1997, and Sept, 1998, in the Farafenni surveillance area. Only 11 (2%) of the women were told during pregnancy or delivery to have a post-partum check on their health. 442 (71%) women had been visited by a traditional birth attendant within 5 days of delivery, but the birth attendant checked the health of the mother in only six instances. 503 (94%) women had attended a motherand-child clinic within 30 days of delivery (median 14 days), but only 185 (30%) reported having been examined. 584 (94%) of the women reported their child receiving a vaccination at the first clinic visit, but
THE LANCET • Vol 355 • February 5, 2000
Pathological and therapeutic distinctions in HUS/TTP Sir—S Dundas and colleagues (Oct 16, p 1327)1 report that in a survey of 22 adults with haemolytic-uraemic syndrome (HUS)/thrombotic thrombocytopenic purpura (TTP) associated with E coli O157, a significant benefit for plasma exchange was not found. However, while correctly noting that the value of plasma exchange “needs to be shown definitively in a multicentre, randomised controlled trial”, they persist in recommending this procedure for such patients as “a promising treatment”. I disagree. The theoretical basis for their recommendation includes the fact that plasma exchange is highly effective in idiopathic HUS/TTP as well as HIV and ticlopidine-linked disease.2,3 The researchers then draw parallels between the microangiography and increased concentrations of circulating von Willebrand factor (vWF) multimers seen in HUS/TTP, and E coli O157associated disease. These parallels are, I believe, unwarranted. HUS/TTP associated with chemotherapy, malignancy, and the shiga toxins, which are elaborated by E coli O157, are pathologically quite distinct from those forms of HUS/TTP in which plasma exchange is known to be effective.2 The main lesion in all forms of HUS/TTP is a thrombotic angiopathy. However, in the forms associated with shiga toxin and malignancy, fibrin thrombi predominate and can occur in the microvasculature as well as the larger vessels of all organs, including the lungs.2 This latter point was well illustrated by the prominent pulmonary disease seen in 14 of the 22 patients reported. Dundas and colleagues1 report that lesions are accompanied by necrosis and inflammation. In clear contrast, lesions in idiopathic, HIV, and ticlopidine-associated HUS/TTP are restricted to the microvasculature.2,4 The lesions involve endothelial cell and platelet plugging of vessels more than fibrin thrombi, never involve large vessels nor the pulmonary microvasculature, and show endothelial cell apoptosis, not inflammation or necrosis. Also, ultra-high molecular weight vWF multimers are characteristic of idiopathic, HIV, and ticlopidineassociated HUS/TTP but are not, as Dundas and colleagues assert, typically seen in the other forms.5 These in-vivo changes are paralleled by apoptosis induced in vitro by plasma from patients with acute idiopathic and HIV-associated HUS/TTP in primary
THE LANCET • Vol 355 • February 5, 2000
human endothelial cells of the microvasculature of all tissues except the lung.2 After plasmapheresis, patient plasma no longer induces such apoptosis. Plasma from patients with shiga toxin or cancer-associated HUS/TTP does not cause such apoptosis. The distinct pathology and pathophysiology of the various forms of HUS/TTP tell us that despite similar clinical patterns, they are very different diseases. The fact that plasma infusions, even without plasma exchange, have proven so effective in the idiopathic, HIV, and ticlopidine-associated forms, but remain of no documented value in the other types, is not surprising. Jeffrey Laurence Laboratory for AIDS Virus Research, Weill Medical College of Cornell University, New York, NY 10021, USA 1
2
3
4
5
Dundas S, Murphy J, Soutar RL, Jones GA, Hutchinson SJ, Todd WTA. Effectiveness of therapeutic plasma exchange in the 1996 Lanarkshire Escherichia coli O157:H7 outbreak. Lancet 1999; 354: 1327–30. Laurence J, Mitra D. Apoptosis of microvascular endothelial cells in the pathophysiology of thrombotic thrombocytopenic purpura/sporadic hemolytic uremic syndrome. Sem Hematol 1997; 34: 98–105. Bennett CL, Weinberg PD, Rozenberg-Ben-Dror K, Kwann HC, Green D. Thrombotic thrombocytopenic purpura associated with ticlopidine. Ann Intern Med 1998; 128: 541–44. Dang CT, Magid MS, Weksler B, Chadburn A, Laurence J. Enhanced endothelial cell apoptosis in splenic tissues of patients with thrombotic thrombocytopenic purpura. Blood 1999; 93: 1264–70. Furlan M, Robles R, Galbusera M, et al. von Willebrand factor-cleaving protease in thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome. N Engl J Med 1998; 339: 1578–84.
Sir—We disagree with the statement by S Dundas and colleagues1 that there is “just one potentially beneficial treatment option” in haemolytic uraemic syndrome (HUS)/thrombotic thrombocytopenic purpura (TTP) induced by Escherichia coli 0157:H7, which is plasma exchange. Plasma infusion is another reasonable first-line therapy in HUS/TTP. There is a general consensus supporting the use of plasma exchange instead of plasma infusion in the management of HUS/TTP. However, this consensus is based on the results of one prospective study2 that shows that plasma exchange is more efficacious than plasma infusion in HUS/TTP. The validity of the results of this study can be questioned because the two groups of patients who underwent exchange or infusion differed in terms of total plasma volume infused and duration of therapy. So, the superiority
of plasma exchange over plasma infusion in HUS/TTP has not been proven. Plasma infusion is a reasonable alternative to expensive and timeconsuming plasma exchange, particularly in HUS/TTP induced by E coli 0157:H7. Fadi Fakhouri, François Vincent, Christophe Legendre Service de Néphrologie, Hôpital Saint-Louis, 75010 Paris, France 1
2
Dundas S, Murphy J, Soutar RL, Jones GA, Hutchinson SJ, Todd WTA. Effectiveness of therapeutic plasma exchange in the 1996 Lanarkshire Escherichia coli O157:H7 outbreak. Lancet 1999; 354: 1327–30. Rock GA, Shumak KH, Buskard NE, et al. Comparison of plasma exchange with plasma infusion in the treatment of thrombotic thrombocytopenia purpura. N Engl J Med 1991; 325: 393–97.
Authors’ reply Sir—We thank Jeffrey Laurence for an update of his work on the pathogenesis of sporadic haemolytic uraemic syndrome (HUS)/thrombotic thrombocytopenic purpura (TTP). He highlights a pathological distinction between sporadic HUS/TTP and Escherichia coli O157 associated HUS/TTP and is specifically concerned about apoptosis and von Willebrand factor (vWF) multimer concentrations. The articles referred to present very little evidence on the pathogenesis of HUS/TTP associated with E coli O157. There is reference to plasma from one child with diarrhoea that failed to induce apoptosis. Others found verotoxin induced apoptosis in human microvascular endothelial cells preexposed to tumour-necrosis factor TNF-.1,2 There is no consensus that apoptosis is fundamental to the pathological process in HUS/TTP or that the effectiveness of therapeutic plasma exchange (TPE) is dependent on its ability to reverse apoptosis. Unusually large vWF multimeric forms have been shown to occur in plasma in HUS/TTP associated with E coli O157.3 The most recent reference cited by Laurence does not discuss vWF multimer concentrations in E coli O157 disease. The extended clinical features of HUS/TTP associated with E coli O157 also do not allow pathological distinction. HUS/TTP in this context is associated with gastrointestinal disease and striking hypoalbuminaemia, which may be an alternative explanation for frequent pulmonary oedema. Laurence’s work raises interesting questions about the pathogenesis of HUS/TTP but presents no definitive evidence that aetiological distinction is linked to pathological distinction and therefore response to TPE.
497
CORRESPONDENCE
To date TPE has not been subjected to clinical trials in HUS/TTP associated with E coli O157. We used TPE to treat E coli O157 associated HUS/TTP in adults, a condition with a recorded mortality rate close to 90%. We think TPE was clinically effective. TPE was not used to treat macrovascular disease (pulmonary oedema), but renal and cerebral disease, which were predominant and life threatening. The clinical efficacy, or otherwise, of TPE in E coli O157associated HUS/TTP needs to be defined. Certainly, there is no convincing evidence from the pathogenesis referred to that TPE could not be effective. In the absence of clinical evidence that TPE is ineffective or dangerous in adult E coli O157associated HUS/TTP, it is difficult to withhold this treatment in a disease with such a high mortbidity and mortality. Fadi Fakhouri and colleagues question the benefit of TPE over plasma infusion in the treatment of HUS/TTP. We concede that it is still unclear whether the benefit of TPE is a result of the removal of an injurious factor or the infusion of a factor deficient in the recipient that is contained in the donor fresh frozen plasma, or both. Our decision to use TPE as opposed to plasma infusion alone was governed by two elements: the consensus remains that TPE is superior to plasma infusion;4,5 and in elderly people with E coli O157associated HUS/TTP, the incidence of pulmonary oedema is high. We believed that it would be unsafe to give large volumes of fresh frozen plasma to patients predisposed to pulmonary oedema without removing an equivalent volume. We believe that if the role of TPE in E coli O157associated HUS/TTP is to be established definitively, patients should be offered what is currently regarded to be the most effective and safe treatment. Stephanie Dundas, *W T Andrew Todd, Richard L Soutar, John Murphy, Gwenyth A Jones, Sharon J Hutchinson Departments of *Infectious Diseases and Haematology, Monklands Hospital, Airdrie, Lanarkshire ML6 0JS, UK (e-mail: [email protected]) 1
2
3
Van de Kar NCAJ, Monnens LAH. Hemolytic uremic syndrome in childhood. Ball Clin Haematol 1998; 11: 498–507. Mahan JD, McAllister C, Karmali M, Verotoxin 1 (VT-1) induction of apoptosis in human glomerular capillary endothelial cells (GCEC) in vitro is dependant on cytokines, cell confluence and cell cyle. J Am Soc Nephrol 1996; 7: 11161. Moake JL. Haemolytic-uremic syndrome: basic science. Lancet 1994; 343: 393–97.
498
4
5
Bell WR. Thrombotic thrombocytpenic purpura/hemolytic uremic syndrome relapse: frequency, pathogenesis and meaning. Semin Haematol 1997; 325: 398–403. Remuzzi G, Ruggenenti P. The haemolytic uremic syndrome. Kidney Int 1995; 47: 2–19.
1
2
3
Where is the mother in maternal and child health? Sir—Abhay Bang and colleagues (Dec 4, p 1955)1 describe the impact on neonatal mortality of a programme to detect and treat neonatal sepsis—an important study in a neglected area. People planning such programmes should also tackle prevention of neonatal sepsis. In a study of village births in the Wosera, Papua New Guinea, we found an unexpected number of septic infants, associated with umbilical-cord infections.2 Tetanus had previously killed 200 of 1000 neonates in the area in which we were working.3 Maternal vaccination had eliminated the disease, but delivery practices leading to cord contamination had not changed. We were struck by the appearance of the infected cords, which were identical to descriptions from the last century.4 Strategies to prevent bacterial access to the umbilicus seem obvious, but there is not a single randomised trial that tests or compared interventions in a developing country.5 WHO and other organisations recommend ties, but their advice is based on history and simplicity rather than any scientific research. In the Wosera we decided against WHO policy, because the huts were dark and ties would lead to increase handling and contamination of the cord. Instead, we supplied commercial plastic clamps, which were more expensive. We still do not know whether our choice was the most effective or appropriate. Organisations such as WHO and UNICEF, which promote cord care, should test the alternatives through large, pragmatic trials, with neonatal death as the primary outcome. These trials should be set up to assess whether cord-carepromotion programmes targeted at birth attendants for village deliveries are effective; compare clamps with ties; and compare routine antiseptics with topical antibiotics. Such information will help those planning comprehensive strategies to prevent and treat neonatal sepsis in developing countries. *Paul Garner, Manesseh Baea *International Health Division, Liverpool School of Tropical Medicine, Liverpool L3 5QA, UK; Papua New Guinea Institute of Medical Research, Maprik, Papua New Guinea
4
5
Bang AT, Bang RA, Reddy MH, Deshmukh MD. Effect of home-based neonatal care and management of sepsis on neonatal mortality: a field trial in rural India. Lancet 1999; 354: 1955–61. Garner P, Lai D, Baea M, Edwards K, Heywood P. Avoiding neonatal death: an intervention study of umbilical cord care. J Trop Paediatr 1994; 40: 24–28. Schofield FD, Tucker VM, Westbrook GR. Neonatal tetanus in New Guinea: effect of active immunisation in pregnancy. BMJ 1961; 2: 785–89. Cullen TS. Embryology, anatomy and diseases of the umbilicus. Philadelphia: WB Saunders, 1916. Zupan J, Garner P. Topical umbilical cord care at birth (Cochrane review). Oxford: Update Software, 1999.
Sir—Bang and colleagues1 report that home-based diagnosis and treatment of neonatal sepsis in rural India by village health workers reduced neonatal and infant mortality by nearly 50%. Assistance by trained traditional birth attendants, health education, and fortnightly supervisory visits were also provided. This is an important finding, especially as policy makers seem to have shifted attention from community-based health care to basic health services.2 A similar reduction in neonatal mortality rates has been achieved in the Farafenni MRC demographic and health surveillance area in rural Gambia during 1982–96 (a decline from 60 per 1000 live births to close to 20/1000).3 Gambia’s primary-healthcare system offered, as part of antenatal care, tetanus toxoid immunisation (coverage 98%). This intervention is thought to have made an important contribution to the reduction of neonatal mortality in many developing countries.4 Also, in Gambia trained traditional birth attendants have improved delivery practices, and care of the umbilical stump. However, an improved healthy start for the child seems to be at the cost of the mother. We interviewed 623 (93%) of 670 women who delivered between Oct, 1997, and Sept, 1998, in the Farafenni surveillance area. Only 11 (2%) of the women were told during pregnancy or delivery to have a post-partum check on their health. 442 (71%) women had been visited by a traditional birth attendant within 5 days of delivery, but the birth attendant checked the health of the mother in only six instances. 503 (94%) women had attended a motherand-child clinic within 30 days of delivery (median 14 days), but only 185 (30%) reported having been examined. 584 (94%) of the women reported their child receiving a vaccination at the first clinic visit, but
THE LANCET • Vol 355 • February 5, 2000