- Email: [email protected]
DNA light on the Tegernsee giant
1454
also showed that lowering the threshold for children 12 months and older improves sensitivity, and this is the basis for current WHO recommendations. For the 35 children 12 months and older with pneumonia in Harari’s study a cut-off of 50 would identify 19 (sensitivity 54%) while one of 40 would identify 25 (71%). This confirms previous studies, but because overall sensitivity increased by only 10%, Harari and colleagues conclude that a single cut-off (50) is adequate. An overall sensitivity of 63% is not acceptable for pneumonia, especially when it can easily be increased to 73% merely by changing the cut-off for older children. Maximising sensitivity is important even if older children with pneumonia are less likely to die than younger children. Insensitive clinical definitions, even if highly specific, are unlikely to be accepted by health workers or parents. Harari et al imply that training health-care workers to apply age-specific cut-offs would be too difficult. In Lesotho, where age-adjusted cut-offs consistent with WHO recommendations are used, we found that seventeen nurses trained 6-8 months earlier could correctly apply these case definitions to clinical histories of children with respiratory illness in 75% of cases (87% in those nurses who had received a supervisory visit, 63% in unsupervised
nurses). Harari et al show that a case definition combining rapid breathing with chest indrawing, either intercostal or subcostal, identifies more children with pneumonia than respiratory rate alone. WHO has recommended that chest indrawing be defmed only as subcostal indrawing’ and that it be used as a sign indicating severe pneumonia necessitating hospital referral. Few data are available to assess the value of this recommendation. Campbell et aP showed that intercostal indrawing was a valuable sign for detecting pneumonia in children over 12 months old, but did not distinguish more from less severe radiographic findings.’’ An analysis differentiating intercostal and subcostal indrawing and the relation of each to pneumonia and severe pneumonia could clarify this issue. Again the ease of teaching health-care workers to recognise different types of chest indrawing must be considered. Harari and colleagues’ study increases our understanding of the clinical presentation of pneumonia, but consideration of the above issues could add even more. In Lesotho, we found that nurses could apply age-specific cut-offs, and we cannot agree that Harari’s data should force a reconsideration of current WHO guidelines. International Health Program Office, Centers for Disease Control, Atlanta, Georgia 30333, USA
GERTRUDE THINYANE
tract infections m children: critena for selection of patients for antibiotic therapy and hospital admission. Bull WHO 1984, 62: 749-53. 2. Cherian T, John TJ, Simoes E, Steinhoff MC, John M. Evaluation of simple clinical signs for the diagnosis of acute lower respiratory tract infections Lancet 1988; ii. 125-28. 3. Campbell H, Byass P, Greenwood BM. Simple clinical signs for diagnosis of acute lower respiratory tract infections Lancet 1988; n: 742-43. 4. World Health Organisation. Acute respiratory infections in children: case management in small hospitals in developing countries (WHO/ARI/90.5). Geneva: WHO, 1990. 5. Campbell H, Byass P, Lamont AC, et al. Assessment of clinical criteria for identification of severe acute lower respiratory tract infections in children Lancet 1989; i. 297-99.
1. Shann
J. F. D. and M. H. N. G. thank the Wellcome Trust for financial support.
J. F. DOHERTY M. A. DIJKHUIZEN Tropical Metabolism Research Unit and Department of Radiology, University Hospital of the West Indies, Kingston 7, Jamaica
F. T. WIERINGA N. MOULE M. H. N. GOLDEN
SIR,-From their (weighted) data it appears that most of the children in Dr Harari and colleagues’ study with crepitations (the most consistent auscultatory sign of pneumonia) were classified as having "no pneumonia". There were 53 children with crepitations and 54 children with fast breathing or chest-wall indrawing in the "no pneumonia" group. Presumably many of the children with crepitations also had fast breathing or indrawing. How many children in these groups were in fact treated with antibiotics? If all children with crepitations were so treated, this large group should not have been classified as "no pneumonia", given that the objective is to determine which physical signs best predict the need for antibiotics in children presenting with cough or breathing
difficulty. We have done similar studies in the Philippines and Swaziland.’ However, to defme pneumonia we used the conclusion of a paediatrician after history, examination, and chest radiography because we have found that bronchopneumonia in young children often produces vague radiological signs, even in clinically severe cases. Nevertheless, our findings with respect to the sensitivity of respiratory rates as predictors of pneumonia were similar to those of Harari and colleagues:
STEPHEN C. REDD ANNE E. RODMAN
Ministry of Health, Maseru, Lesotho
6 patients had post-mortem findings consistent with pneumonia: 3 had no radiological evidence of pneumonia and 3 had radiographic changes consistent with the diagnosis. There were no false positives: the radiographs of all 8 patients without post-mortem evidence of pneumonia were all normal. The necropsy findings suggest that absence of radiological evidence does not rule out significant pulmonary infection in malnourished children. Harari et al make no reference to nutritional status. Any physician caring for children in developing countries should bear nutritional status in mind when interpreting a chest radiograph.
F, Hart K, Thomas D. Acute lower respiratory
possible
SIR,-Dr Harari and colleagues used radiographic evidence of pneumonia as their standard. We have retrospectively assessed the effect of malnutrition on the ability of the host to produce an inflammatory exudate in the presence of pneumonia by comparing ante-mortem chest radiographic evidence of pneumonia with necropsy findings in patients dying from severe malnutrition. Only necropsy reports specifically referring to pneumonia, as the principal cause of death or as an associated condition, were regarded as positive. Negative necropsies were those that specifically stated that the lungs were macroscopically normal. For 14 children with a post-mortem report and an ante-mortem chest radiograph, the radiographs were assessed "blind" by a radiologist (N. M.) who had no knowledge of the nature of the study. Radiographs were regarded as positive when the radiologist reported consolidation.
*50 in mfants, 40 in children 12 months of age or more The lower specificities found by Harari et al suggest that their definition of pneumonia identified a smaller subgroup of the population of children with cough. However, it is sensitivity that is important. A sensitivity of 68% means that 32% of children with pneumonia will not be treated, and this is unacceptable. The data of Harari and colleagues and our own suggest that to predict the need for antibiotics in children with cough or difficult breathing, it is preferable to use a respiratory rate of 50/min for children 2-12 months and 40/min for children 12 months to 5 years, as recommended by WHO. This will detect about 80 % of pneumonia cases.
MRC Laboratories, PO Box 273, Banjul, The Gambia
E. KIM MULHOLLAND
Department of Pediatrics, University of Colorado, Denver, Colorado, USA
ERIC A. F. SIMOES
1. Mulholland
EK, Simoes EAF, Costales MOD, McGrath EJ, Manalac EM, Gove S. Standardized diagnosis of pneumonia in developing countries. Pediatr Infect Dis J
(in press).
DNA
light on the Tegernsee giant
SIR,-On the basis of radiological and histological studies of the skeleton, Dr Nerlich and colleagues (Oct 5, p 886) suggest that the "Tegemsee giant", who died in 1876 at age 25, had both juvenile gigantism and polyostotic fibrous dysplasia. DNA research indicates that such an association is not unexpected.
1455
growth-hormone-secreting tumours of the anterior somatic mutations in the GNASI gene encoding the a-subunit of the stimulatory GTP-binding protein (G-protein) have been found as the presumed "cause". 1,2 One of these mutations results in a substitution of histidine (CAT) for arginine (CGT) as aminoacid residue 201This very mutation has been identified in a longtime patient at Johns Hopkins Hospital, who has severe polyostotic fibrous dysplasia and typical cutaneous changes of the McCune-Albright syndrome, besides a history of thyrotoxicosis.3 In this patient the mutation is present in mosaic form and presumably spared the pituitary acidophilic cells because gigantism is not present; indeed, the patient is only 1 -17 m tall. This case and four studied by Weinstein et al4 support Happle’s hypothesiss that polyostotic fibrous dysplasia is caused by a dominant lethal mutation that is compatible with survival only when present in mosaic state (resulting from postzygotic mutation). These "activating" mutations convert the gene into an oncogene, which Landis et a 12 termed gsp. They result in constitutive activation of adenylyl cyclase as the cause of McCune-Albright syndrome. The arginine at position 201 of the a-subunit seems to be functionally important. That residue is, for example, the site of ADP ribosylation by cholera toxin. Endocrinopathies, most often precocious puberty but also hyperthyroidism, are part of the McCune-Albright syndrome. The Tegernsee giant seems to have had a neoplastic endocrinopathy as part of his McCune-Albright In
some
pituitary,
syndrome. Mutations in the GNAS 1 gene that result in decreased function the cause of Albright hereditary osteodystrophy (pseudohypoparathyroidism type Ia).6’ Thus the two disorders described by Fuller Albright in 1937 and 1942 are due to opposite-type (plus and minus) mutations in the same gene. are
Johns
Hopkins Hospital,
Baltimore, Maryland 21205, USA
WILLIAM F. SCHWINDINGER CLAIR A. FRANCOMANO MICHAEL A. LEVINE VICTOR A. MCKUSICK
1. Vallar L, Spada A, Giannattasio G. Altered Gs and adenylate cyclase activity in human GH-secreting pituitary adenomas. Nature 1987; 330: 566-68. 2. Landis CA, Masters SB, Spada A, Pace AM, Bourne HR, Vallar L. GTPase inhibiting mutations activate the alpha chain of G(s) and stimulate adenylyl cyclase in human pituitary tumours. Nature 1989; 340: 692-96. 3. Schwindinger WF, Francomano CA, Levine MA. Identification of a mutation in the gene encoding the alpha subunit of the stimulatory G-protein of adenylyl cyclase in McCune-Albright syndrome. Proc Natl Acad Sci USA (in press). 4. Weinstein LS, Shenker A, Gejman PV, Merino MJ, Friedman E, Spiegel AM. Activating mutations of the stimulatory G protein in the McCune-Albright syndrome. N Engl J Med 1991; 325: 1688-95. 5. Happle R. The McCune-Albright syndrome. a lethal gene surviving by mosaicism. Chn Genet 1986; 29: 321-24. 6. Patten JL, Johns DR, Valle D, et al. Mutation of the gene encoding the stimulatory G protein of adenylate cyclase in Albright’s hereditary osteodystrophy. N Engl J Med
1990; 322: 1412-19. LS, Gejman PV, Friedman E, et al. Mutations of the Gs alpha-subunit in Albnght hereditary osteodystrophy detected by denaturing gradient gel electrophoresis. Proc Natl Acad Sci USA 1990; 87: 8287-90.
7. Weinstein
Ethnic differences in sleeping position and in risk of cot death the prone sleeping position in is associated with increased risk of sudden infant death syndrome (SIDS).lz The risk of SIDS among the Asian community seems to be lower than it is in the rest of Britain. 3-S In the Birmingham study’ the risk of SIDS in those of Asian ethnic background was roughly halved, independent of other known risk factors, including low birthweight and paternal unemployment. Sociocultural differences in child rearing are likely to be important, and data on sleeping position are therefore pertinent both to the ethnic variation issue and to the sleeping position hypothesis. This hospital serves an inner city community with a large Asian population, most of whom are Sikhs from northern India or Muslims from Pakistan. We have done a survey of Asian and white mothers attending our antenatal clinic to find out what proportion of mothers put their infants to sleep in the prone or supine positions. The study sample consisted of all Asian and white multigravidae attending the antenatal clinic on randomly selected days. A
Sip,—There is evidence that
infancy
questionnaire was administered by a medical student (S. F.), fluent in Punjabi, over a 6 week period in mid-winter. Of 180 women eligible for inclusion 179 agreed to participate (82 Asian, 97 white). The questions related to the sleeping position favoured for the youngest child over the first year of life, the mother’s age, duration of residence in the UK, sleeping arrangements in the home, and heating in the bedroom. Proportions were compared by binomial or X2 test for trend. The age distributions of the two groups of women were similar. Just over half the respondents put their infants to sleep on their sides (46% Asians, 58% whites). However, 31% of white mothers put their infants down in the prone sleeping compared with 16% of Asians (95% confidence interval [CI] for difference 14-265%; p=003). Asian mothers born outside the UK were least likely to report use of the prone position (12%, 7/57), compared with Asian mothers born in the UK (24%, 6/25) and white mothers (31 %, 30/97) (p=0009). Only 3% of white mothers used the supine position as against 22% of Asians (95% CI for difference 8’3-27’2%; p 0-0002).24% of white mothers had no opinion as to the best sleeping position in infancy, compared with 56% of Asian mothers, indicating that for Asian women the position tends not to reflect a conscious decision. 98 % of Asian infants slept in their parents’ room in the first year of life, 34% (28) in the same bed; 65% of white infants slept in their parents’ room. 44% of Asian women reported that the infant’s bedroom was "always" and 11 % "never" heated at night, compared with 13-5% and 36% of white women. While the study sample is not population based, it is likely to be representative of the hospital’s catchment area, an area with a high proportion of disadvantaged mothers. Asian infants are about seven times more likely to be placed to sleep on their back than white infants. In view of the lower incidence of SIDS in the Asian community in Britain, these data are consistent with the hypothesis that the supine sleeping position may be protective. Asian mothers born in the UK were more likely to favour the prone sleeping position than those born in the Indian sub-continent. It would be tragic if adoption of "western ways" promoted by health-care professionals were to place babies born in the Asian community in Britain at higher risk of SIDS. =
University Department of Medicine, Dudley Road Hospital, Birmingham B18 7QH, UK
SADAF FAROOQI
I. J. PERRY D. G. BEEVERS
et al. Interaction between bedding and sleeping position in the sudden infant death syndrome: a population based case control study. Br Med J 1990; 301: 85-89. 2. Dwyer T, Ponsonby AB, Newman NM, Gibbons LE. Prospective cohort study of prone sleeping position and sudden infant death syndrome. Lancet 1991; 337: 1244-47. 3. Balarajan R, Raleigh VS, Botting B. Sudden infant death syndrome and postneonatal mortality in immigrants in England and Wales. Br Med J 1989; 298: 716-20. 4 Kyle D, Sunderland R, Stonehouse M, Cummins C, Ross O. Ethnic differences in incidence of sudden infant death syndrome in Birmingham. Arch Dis Child 1990; 65: 830-33. 5. Editorial. Prone, hot, and dead. Lancet 1990; 336: 1104.
1.
Fleming PJ, Gilbert R, Azaz Y,
Oral
typhoid vaccine Ty21a
SiR,—The live attenuated, oral vaccine Salmonella typhi Ty2la has been licensed in many European countries, in Australia, and in the USA for prophylaxis against typhoid fever. The recommended regimen of three or four alternate daily doses of 109 viable organisms has been decided upon on the strength of field trials in Egypt,l Chile,z,3 and Indonesia (Dr Simanjuntak and colleagues, Oct 26, p 1055). The protective efficacies demonstrated in these trials have varied greatly, and these variations have largely been attributed to differences in formulation, vaccination schedule, and infection incidence rate. The Indonesian study increased the variables through the use of two different preparations and a dose schedule of three alternate weekly doses, such that at least the third dose would have been administered at the time of peak intestinal antibodyThis might well have resulted in the negation of the third dose, blocked by intestinal antibodies. There are few consistencies between the studies that permit any clear conclusion, except that S typhi Ty2la can induce an uncertain degree of immunity in typhoid endemic areas.
also showed that lowering the threshold for children 12 months and older improves sensitivity, and this is the basis for current WHO recommendations. For the 35 children 12 months and older with pneumonia in Harari’s study a cut-off of 50 would identify 19 (sensitivity 54%) while one of 40 would identify 25 (71%). This confirms previous studies, but because overall sensitivity increased by only 10%, Harari and colleagues conclude that a single cut-off (50) is adequate. An overall sensitivity of 63% is not acceptable for pneumonia, especially when it can easily be increased to 73% merely by changing the cut-off for older children. Maximising sensitivity is important even if older children with pneumonia are less likely to die than younger children. Insensitive clinical definitions, even if highly specific, are unlikely to be accepted by health workers or parents. Harari et al imply that training health-care workers to apply age-specific cut-offs would be too difficult. In Lesotho, where age-adjusted cut-offs consistent with WHO recommendations are used, we found that seventeen nurses trained 6-8 months earlier could correctly apply these case definitions to clinical histories of children with respiratory illness in 75% of cases (87% in those nurses who had received a supervisory visit, 63% in unsupervised
nurses). Harari et al show that a case definition combining rapid breathing with chest indrawing, either intercostal or subcostal, identifies more children with pneumonia than respiratory rate alone. WHO has recommended that chest indrawing be defmed only as subcostal indrawing’ and that it be used as a sign indicating severe pneumonia necessitating hospital referral. Few data are available to assess the value of this recommendation. Campbell et aP showed that intercostal indrawing was a valuable sign for detecting pneumonia in children over 12 months old, but did not distinguish more from less severe radiographic findings.’’ An analysis differentiating intercostal and subcostal indrawing and the relation of each to pneumonia and severe pneumonia could clarify this issue. Again the ease of teaching health-care workers to recognise different types of chest indrawing must be considered. Harari and colleagues’ study increases our understanding of the clinical presentation of pneumonia, but consideration of the above issues could add even more. In Lesotho, we found that nurses could apply age-specific cut-offs, and we cannot agree that Harari’s data should force a reconsideration of current WHO guidelines. International Health Program Office, Centers for Disease Control, Atlanta, Georgia 30333, USA
GERTRUDE THINYANE
tract infections m children: critena for selection of patients for antibiotic therapy and hospital admission. Bull WHO 1984, 62: 749-53. 2. Cherian T, John TJ, Simoes E, Steinhoff MC, John M. Evaluation of simple clinical signs for the diagnosis of acute lower respiratory tract infections Lancet 1988; ii. 125-28. 3. Campbell H, Byass P, Greenwood BM. Simple clinical signs for diagnosis of acute lower respiratory tract infections Lancet 1988; n: 742-43. 4. World Health Organisation. Acute respiratory infections in children: case management in small hospitals in developing countries (WHO/ARI/90.5). Geneva: WHO, 1990. 5. Campbell H, Byass P, Lamont AC, et al. Assessment of clinical criteria for identification of severe acute lower respiratory tract infections in children Lancet 1989; i. 297-99.
1. Shann
J. F. D. and M. H. N. G. thank the Wellcome Trust for financial support.
J. F. DOHERTY M. A. DIJKHUIZEN Tropical Metabolism Research Unit and Department of Radiology, University Hospital of the West Indies, Kingston 7, Jamaica
F. T. WIERINGA N. MOULE M. H. N. GOLDEN
SIR,-From their (weighted) data it appears that most of the children in Dr Harari and colleagues’ study with crepitations (the most consistent auscultatory sign of pneumonia) were classified as having "no pneumonia". There were 53 children with crepitations and 54 children with fast breathing or chest-wall indrawing in the "no pneumonia" group. Presumably many of the children with crepitations also had fast breathing or indrawing. How many children in these groups were in fact treated with antibiotics? If all children with crepitations were so treated, this large group should not have been classified as "no pneumonia", given that the objective is to determine which physical signs best predict the need for antibiotics in children presenting with cough or breathing
difficulty. We have done similar studies in the Philippines and Swaziland.’ However, to defme pneumonia we used the conclusion of a paediatrician after history, examination, and chest radiography because we have found that bronchopneumonia in young children often produces vague radiological signs, even in clinically severe cases. Nevertheless, our findings with respect to the sensitivity of respiratory rates as predictors of pneumonia were similar to those of Harari and colleagues:
STEPHEN C. REDD ANNE E. RODMAN
Ministry of Health, Maseru, Lesotho
6 patients had post-mortem findings consistent with pneumonia: 3 had no radiological evidence of pneumonia and 3 had radiographic changes consistent with the diagnosis. There were no false positives: the radiographs of all 8 patients without post-mortem evidence of pneumonia were all normal. The necropsy findings suggest that absence of radiological evidence does not rule out significant pulmonary infection in malnourished children. Harari et al make no reference to nutritional status. Any physician caring for children in developing countries should bear nutritional status in mind when interpreting a chest radiograph.
F, Hart K, Thomas D. Acute lower respiratory
possible
SIR,-Dr Harari and colleagues used radiographic evidence of pneumonia as their standard. We have retrospectively assessed the effect of malnutrition on the ability of the host to produce an inflammatory exudate in the presence of pneumonia by comparing ante-mortem chest radiographic evidence of pneumonia with necropsy findings in patients dying from severe malnutrition. Only necropsy reports specifically referring to pneumonia, as the principal cause of death or as an associated condition, were regarded as positive. Negative necropsies were those that specifically stated that the lungs were macroscopically normal. For 14 children with a post-mortem report and an ante-mortem chest radiograph, the radiographs were assessed "blind" by a radiologist (N. M.) who had no knowledge of the nature of the study. Radiographs were regarded as positive when the radiologist reported consolidation.
*50 in mfants, 40 in children 12 months of age or more The lower specificities found by Harari et al suggest that their definition of pneumonia identified a smaller subgroup of the population of children with cough. However, it is sensitivity that is important. A sensitivity of 68% means that 32% of children with pneumonia will not be treated, and this is unacceptable. The data of Harari and colleagues and our own suggest that to predict the need for antibiotics in children with cough or difficult breathing, it is preferable to use a respiratory rate of 50/min for children 2-12 months and 40/min for children 12 months to 5 years, as recommended by WHO. This will detect about 80 % of pneumonia cases.
MRC Laboratories, PO Box 273, Banjul, The Gambia
E. KIM MULHOLLAND
Department of Pediatrics, University of Colorado, Denver, Colorado, USA
ERIC A. F. SIMOES
1. Mulholland
EK, Simoes EAF, Costales MOD, McGrath EJ, Manalac EM, Gove S. Standardized diagnosis of pneumonia in developing countries. Pediatr Infect Dis J
(in press).
DNA
light on the Tegernsee giant
SIR,-On the basis of radiological and histological studies of the skeleton, Dr Nerlich and colleagues (Oct 5, p 886) suggest that the "Tegemsee giant", who died in 1876 at age 25, had both juvenile gigantism and polyostotic fibrous dysplasia. DNA research indicates that such an association is not unexpected.
1455
growth-hormone-secreting tumours of the anterior somatic mutations in the GNASI gene encoding the a-subunit of the stimulatory GTP-binding protein (G-protein) have been found as the presumed "cause". 1,2 One of these mutations results in a substitution of histidine (CAT) for arginine (CGT) as aminoacid residue 201This very mutation has been identified in a longtime patient at Johns Hopkins Hospital, who has severe polyostotic fibrous dysplasia and typical cutaneous changes of the McCune-Albright syndrome, besides a history of thyrotoxicosis.3 In this patient the mutation is present in mosaic form and presumably spared the pituitary acidophilic cells because gigantism is not present; indeed, the patient is only 1 -17 m tall. This case and four studied by Weinstein et al4 support Happle’s hypothesiss that polyostotic fibrous dysplasia is caused by a dominant lethal mutation that is compatible with survival only when present in mosaic state (resulting from postzygotic mutation). These "activating" mutations convert the gene into an oncogene, which Landis et a 12 termed gsp. They result in constitutive activation of adenylyl cyclase as the cause of McCune-Albright syndrome. The arginine at position 201 of the a-subunit seems to be functionally important. That residue is, for example, the site of ADP ribosylation by cholera toxin. Endocrinopathies, most often precocious puberty but also hyperthyroidism, are part of the McCune-Albright syndrome. The Tegernsee giant seems to have had a neoplastic endocrinopathy as part of his McCune-Albright In
some
pituitary,
syndrome. Mutations in the GNAS 1 gene that result in decreased function the cause of Albright hereditary osteodystrophy (pseudohypoparathyroidism type Ia).6’ Thus the two disorders described by Fuller Albright in 1937 and 1942 are due to opposite-type (plus and minus) mutations in the same gene. are
Johns
Hopkins Hospital,
Baltimore, Maryland 21205, USA
WILLIAM F. SCHWINDINGER CLAIR A. FRANCOMANO MICHAEL A. LEVINE VICTOR A. MCKUSICK
1. Vallar L, Spada A, Giannattasio G. Altered Gs and adenylate cyclase activity in human GH-secreting pituitary adenomas. Nature 1987; 330: 566-68. 2. Landis CA, Masters SB, Spada A, Pace AM, Bourne HR, Vallar L. GTPase inhibiting mutations activate the alpha chain of G(s) and stimulate adenylyl cyclase in human pituitary tumours. Nature 1989; 340: 692-96. 3. Schwindinger WF, Francomano CA, Levine MA. Identification of a mutation in the gene encoding the alpha subunit of the stimulatory G-protein of adenylyl cyclase in McCune-Albright syndrome. Proc Natl Acad Sci USA (in press). 4. Weinstein LS, Shenker A, Gejman PV, Merino MJ, Friedman E, Spiegel AM. Activating mutations of the stimulatory G protein in the McCune-Albright syndrome. N Engl J Med 1991; 325: 1688-95. 5. Happle R. The McCune-Albright syndrome. a lethal gene surviving by mosaicism. Chn Genet 1986; 29: 321-24. 6. Patten JL, Johns DR, Valle D, et al. Mutation of the gene encoding the stimulatory G protein of adenylate cyclase in Albright’s hereditary osteodystrophy. N Engl J Med
1990; 322: 1412-19. LS, Gejman PV, Friedman E, et al. Mutations of the Gs alpha-subunit in Albnght hereditary osteodystrophy detected by denaturing gradient gel electrophoresis. Proc Natl Acad Sci USA 1990; 87: 8287-90.
7. Weinstein
Ethnic differences in sleeping position and in risk of cot death the prone sleeping position in is associated with increased risk of sudden infant death syndrome (SIDS).lz The risk of SIDS among the Asian community seems to be lower than it is in the rest of Britain. 3-S In the Birmingham study’ the risk of SIDS in those of Asian ethnic background was roughly halved, independent of other known risk factors, including low birthweight and paternal unemployment. Sociocultural differences in child rearing are likely to be important, and data on sleeping position are therefore pertinent both to the ethnic variation issue and to the sleeping position hypothesis. This hospital serves an inner city community with a large Asian population, most of whom are Sikhs from northern India or Muslims from Pakistan. We have done a survey of Asian and white mothers attending our antenatal clinic to find out what proportion of mothers put their infants to sleep in the prone or supine positions. The study sample consisted of all Asian and white multigravidae attending the antenatal clinic on randomly selected days. A
Sip,—There is evidence that
infancy
questionnaire was administered by a medical student (S. F.), fluent in Punjabi, over a 6 week period in mid-winter. Of 180 women eligible for inclusion 179 agreed to participate (82 Asian, 97 white). The questions related to the sleeping position favoured for the youngest child over the first year of life, the mother’s age, duration of residence in the UK, sleeping arrangements in the home, and heating in the bedroom. Proportions were compared by binomial or X2 test for trend. The age distributions of the two groups of women were similar. Just over half the respondents put their infants to sleep on their sides (46% Asians, 58% whites). However, 31% of white mothers put their infants down in the prone sleeping compared with 16% of Asians (95% confidence interval [CI] for difference 14-265%; p=003). Asian mothers born outside the UK were least likely to report use of the prone position (12%, 7/57), compared with Asian mothers born in the UK (24%, 6/25) and white mothers (31 %, 30/97) (p=0009). Only 3% of white mothers used the supine position as against 22% of Asians (95% CI for difference 8’3-27’2%; p 0-0002).24% of white mothers had no opinion as to the best sleeping position in infancy, compared with 56% of Asian mothers, indicating that for Asian women the position tends not to reflect a conscious decision. 98 % of Asian infants slept in their parents’ room in the first year of life, 34% (28) in the same bed; 65% of white infants slept in their parents’ room. 44% of Asian women reported that the infant’s bedroom was "always" and 11 % "never" heated at night, compared with 13-5% and 36% of white women. While the study sample is not population based, it is likely to be representative of the hospital’s catchment area, an area with a high proportion of disadvantaged mothers. Asian infants are about seven times more likely to be placed to sleep on their back than white infants. In view of the lower incidence of SIDS in the Asian community in Britain, these data are consistent with the hypothesis that the supine sleeping position may be protective. Asian mothers born in the UK were more likely to favour the prone sleeping position than those born in the Indian sub-continent. It would be tragic if adoption of "western ways" promoted by health-care professionals were to place babies born in the Asian community in Britain at higher risk of SIDS. =
University Department of Medicine, Dudley Road Hospital, Birmingham B18 7QH, UK
SADAF FAROOQI
I. J. PERRY D. G. BEEVERS
et al. Interaction between bedding and sleeping position in the sudden infant death syndrome: a population based case control study. Br Med J 1990; 301: 85-89. 2. Dwyer T, Ponsonby AB, Newman NM, Gibbons LE. Prospective cohort study of prone sleeping position and sudden infant death syndrome. Lancet 1991; 337: 1244-47. 3. Balarajan R, Raleigh VS, Botting B. Sudden infant death syndrome and postneonatal mortality in immigrants in England and Wales. Br Med J 1989; 298: 716-20. 4 Kyle D, Sunderland R, Stonehouse M, Cummins C, Ross O. Ethnic differences in incidence of sudden infant death syndrome in Birmingham. Arch Dis Child 1990; 65: 830-33. 5. Editorial. Prone, hot, and dead. Lancet 1990; 336: 1104.
1.
Fleming PJ, Gilbert R, Azaz Y,
Oral
typhoid vaccine Ty21a
SiR,—The live attenuated, oral vaccine Salmonella typhi Ty2la has been licensed in many European countries, in Australia, and in the USA for prophylaxis against typhoid fever. The recommended regimen of three or four alternate daily doses of 109 viable organisms has been decided upon on the strength of field trials in Egypt,l Chile,z,3 and Indonesia (Dr Simanjuntak and colleagues, Oct 26, p 1055). The protective efficacies demonstrated in these trials have varied greatly, and these variations have largely been attributed to differences in formulation, vaccination schedule, and infection incidence rate. The Indonesian study increased the variables through the use of two different preparations and a dose schedule of three alternate weekly doses, such that at least the third dose would have been administered at the time of peak intestinal antibodyThis might well have resulted in the negation of the third dose, blocked by intestinal antibodies. There are few consistencies between the studies that permit any clear conclusion, except that S typhi Ty2la can induce an uncertain degree of immunity in typhoid endemic areas.