- Email: [email protected]
Typhoid fever in children
2
Misiewicz JJ, Lennard Jones JE, Connell AM, Baron JH, Avery Jones F. Controlled trial of sulphasalazine in maintenance therapy for ulcerative colitis. Lancet 1965; i: 185–88. 3 Dissanayake AS, Truelove SC. A controlled therapeutic trial of long term maintenance treatment in ulcerative colitis with sulphasalazine (Salazopyrine). Gut 1973; 14: 923–26. 4 Fockens P, Mulder CJJ, Tytgat GNJ, Blok P, Ferwerda J, Dutch Pentasa Study Group. Comparison of the efficacy and safety of 1·5 compared with 3·0 g oral slowrelease mesalazine (Pentasa) in the maintenance treatment of ulcerative colitis. Eur J Gastroenterol Hepatol 1995; 7: 1025–30. 5 Mulder CJJ, Tytgat GNJ, Weterman IT, et al. Double blinded comparison of slowrelease 5-aminosalicylate and sulfasalazine in remission maintenance in ulcerative colitis. Gastroenterology 1988; 95: 1449–53.
Authors’ reply Sir—M J S Langman and R N Allan underscore the high relapse rates in our study, which is an important point that we discussed at length. A systematic review from the Cochrane database found that 5-aminosalicylic acid was significantly more effective than placebo, but that there was no difference in efficacy between different formulations or doses.1 Despite this finding, studies have reported a wide range of relapse rates, with different aminosalicylates, which may differ by a factor of five between different studies.2–5 Because there is no evidence that the use of different formulations or doses is responsible for the wide variation in relapse rates, there must be alternative explanations. When we reviewed published studies, we found that previous studies had recruited patients at variable durations of remission and then reviewed them at a few fixed timepoints during the year, commonly in different hospitals and by different physicians. The risk of relapse may be lowest when patients are recruited into trials during a long period of remission and highest when they are recruited soon after an exacerbation. To reduce bias we chose to recruit patients at the same timepoint (ie, during the active stage of disease), and then followed them prospectively into remission and relapse. Furthermore, patients were given the contact number of a single physician who reviewed them in our open-access clinic. Our approach reduces bias by standardising the population, and encourages patients to report changes in symptoms at an early stage. We believe that our results accurately reflect the high risk of relapse in these patients. Langman and Allan question the wording of our summary. Even “the
THE LANCET • Vol 354 • December 4, 1999
unwary reader” should have noted that it was clearly stated (on two occasions) and discussed that all patients with active disease received standard medical therapy, and that our suggestion of an equivalent effect of non-pathogenic E coli referred only to the maintenance of remission. *B J Rembacken, A M Snelling, P M Hawkey, D M Chalmers, A T R Axon *Centre for Digestive Diseases, General Infirmary at Leeds, Leeds LS1 3EX, UK; and Department of Microbiology, University of Leeds, Leeds 1
Sutherland L, Roth D, Beck P, May G, Makiyama K. The use of oral 5aminosalicylic acid for maintenance of remission in ulcerative colitis. In: Cochrane Library [CDROM and online]. Cochrane Collaboration; issue 3. Oxford: Update Software, 1997. 2 Rijk MC, van Lier HJ, van Tongeren JH. Relapse-preventing effect and safety of sulfasalazine and olsalazine in patients with ulcerative colitis in remission: a prospective, double-blind, randomised multicenter study. Am J Gastroenterol 1992; 87: 438–42. 3 Kiilerich S, Ladefoged K, Rannem T, Ranlov PJ. Prophylactic effects of olsalazine vs sulphasalazine during 12 months maintenance treatment of ulcerative colitis. Gut 1992; 33: 252–55. 4 Riley SA. What dose of 5-aminosalicylic acid (mesalazine) in ulcerative colitis? Gut 1998; 42: 761–63. 5 Riley SA, Mani V, Goodman MJ, Herd ME, Dutt S, Turnberg LA. Comparison of delayed-release 5-aminosalicylic acid (Mesalazine) and sulfasalazine as maintenance treatment for patients with ulcerative colitis. Gastroenterology 1988; 94: 1383–89.
investigation through carefully controlled studies in endemic areas. Any potential effectiveness of typhoid vaccine should be pursued in view of a possible future increase in resistance of the organism to safe oral drugs such as ciprofloxacin. Such resistance leads to the need for expensive parenteral therapy and hospital admission. Madhur Dev Bhattarai Department of Medicine, Bir Hospital, PO Box 3245, Kathmandu, Nepal (e-mail: [email protected]) 1
2
Sinha A, Sazawal S, Kumar R, et al. Typhoid fever in children aged less than 5 years. Lancet 1999; 354: 734–37. Griffin GE. Typhoid fever and childhood vaccine strategies. Lancet 1999; 354: 698–99.
Sir—Anju Sinha and colleagues1 did not observe any case of typhoid fever in children aged less than 1 year probably because of passive immunity from their mothers in a population in which typhoid fever is endemic. A sharp contrast in frequency of typhoid fever between age-groups in this population (27·3% aged <5 years, 11·7% 5–19 years, and 1·1% ⭓19 years) could indicate early exposure to typhoid, and therefore strong immunity in older agegroups. The investigators should have checked antibody titre to Salmonella typhi in blood samples that were obtained to show this supposition (this could still be done if serum samples are available). In an epidemic in Ankara, Turkey, 24 children with typhoid fever were admitted to Ihsan Dog ramaci Children’s Hospital during 2 months.2 Only two patients were aged less than 5 years and 14 were aged 5–9 years, which might indicate that typhoid fever is not common in children aged less than 5 years outside endemic areas, even in less-developed countries. The investigators should also have done leucocyte counts and differential diagnoses of patients who presented with typhoid because granulocytopenia is not expected in children aged less than 10 years. v
Typhoid fever in children Sir—Anju Sinha and colleagues (Aug 28, p 734)1 report that typhoid fever is a common and important cause of morbidity in children aged 1–5 years. They argue that the age at which typhoid vaccine is given and the choice of vaccines need to be re-examined. In his Aug 28 commentary,2 George Griffin discusses the difficulties in the incorporation of typhoid vaccine into the paediatric vaccination schedule. In particular, he focuses on effectiveness of available vaccines, route of vaccination, and difficulty in the introduction of new vaccines in existing schedules. Regular mass vaccination is not recommended even for adults in endemic areas of lessdeveloped countries. Many patients have recurrent typhoid fever for years. One attack of typhoid fever does not seem to confer longlasting protection. Any person with typhoid fever is at high risk of subsequent exposure in endemic areas. Thus, typhoid vaccine, even with present effectiveness, is likely to be costeffective if given selectively to such people. This possibility deserved further
Sinasi Özsoylu 5
Fatih University Medical Faculty, Çiftlik cad, Number 57, 06510 Emek, Ankara, Turkey 1
Sinha A, Sazawal S, Kumar R, et al. Typhoid fever in children aged less than 5 years. Lancet 1999; 354: 734–37. ~ MK, Özsoylu S, Kanra G. Relative 2 Çaglar granulocytous in childhood typhoid fever. J Pediatr 1983; 102: 603–04. 5
Sir—Anju Sinha and colleagues1 report clinical and epidemiological data for typhoid fever in children and conclude that typhoid fever is a common and significant cause of morbidity between 1 and 5 years of age. We have some different views on these points.
2001
Misiewicz JJ, Lennard Jones JE, Connell AM, Baron JH, Avery Jones F. Controlled trial of sulphasalazine in maintenance therapy for ulcerative colitis. Lancet 1965; i: 185–88. 3 Dissanayake AS, Truelove SC. A controlled therapeutic trial of long term maintenance treatment in ulcerative colitis with sulphasalazine (Salazopyrine). Gut 1973; 14: 923–26. 4 Fockens P, Mulder CJJ, Tytgat GNJ, Blok P, Ferwerda J, Dutch Pentasa Study Group. Comparison of the efficacy and safety of 1·5 compared with 3·0 g oral slowrelease mesalazine (Pentasa) in the maintenance treatment of ulcerative colitis. Eur J Gastroenterol Hepatol 1995; 7: 1025–30. 5 Mulder CJJ, Tytgat GNJ, Weterman IT, et al. Double blinded comparison of slowrelease 5-aminosalicylate and sulfasalazine in remission maintenance in ulcerative colitis. Gastroenterology 1988; 95: 1449–53.
Authors’ reply Sir—M J S Langman and R N Allan underscore the high relapse rates in our study, which is an important point that we discussed at length. A systematic review from the Cochrane database found that 5-aminosalicylic acid was significantly more effective than placebo, but that there was no difference in efficacy between different formulations or doses.1 Despite this finding, studies have reported a wide range of relapse rates, with different aminosalicylates, which may differ by a factor of five between different studies.2–5 Because there is no evidence that the use of different formulations or doses is responsible for the wide variation in relapse rates, there must be alternative explanations. When we reviewed published studies, we found that previous studies had recruited patients at variable durations of remission and then reviewed them at a few fixed timepoints during the year, commonly in different hospitals and by different physicians. The risk of relapse may be lowest when patients are recruited into trials during a long period of remission and highest when they are recruited soon after an exacerbation. To reduce bias we chose to recruit patients at the same timepoint (ie, during the active stage of disease), and then followed them prospectively into remission and relapse. Furthermore, patients were given the contact number of a single physician who reviewed them in our open-access clinic. Our approach reduces bias by standardising the population, and encourages patients to report changes in symptoms at an early stage. We believe that our results accurately reflect the high risk of relapse in these patients. Langman and Allan question the wording of our summary. Even “the
THE LANCET • Vol 354 • December 4, 1999
unwary reader” should have noted that it was clearly stated (on two occasions) and discussed that all patients with active disease received standard medical therapy, and that our suggestion of an equivalent effect of non-pathogenic E coli referred only to the maintenance of remission. *B J Rembacken, A M Snelling, P M Hawkey, D M Chalmers, A T R Axon *Centre for Digestive Diseases, General Infirmary at Leeds, Leeds LS1 3EX, UK; and Department of Microbiology, University of Leeds, Leeds 1
Sutherland L, Roth D, Beck P, May G, Makiyama K. The use of oral 5aminosalicylic acid for maintenance of remission in ulcerative colitis. In: Cochrane Library [CDROM and online]. Cochrane Collaboration; issue 3. Oxford: Update Software, 1997. 2 Rijk MC, van Lier HJ, van Tongeren JH. Relapse-preventing effect and safety of sulfasalazine and olsalazine in patients with ulcerative colitis in remission: a prospective, double-blind, randomised multicenter study. Am J Gastroenterol 1992; 87: 438–42. 3 Kiilerich S, Ladefoged K, Rannem T, Ranlov PJ. Prophylactic effects of olsalazine vs sulphasalazine during 12 months maintenance treatment of ulcerative colitis. Gut 1992; 33: 252–55. 4 Riley SA. What dose of 5-aminosalicylic acid (mesalazine) in ulcerative colitis? Gut 1998; 42: 761–63. 5 Riley SA, Mani V, Goodman MJ, Herd ME, Dutt S, Turnberg LA. Comparison of delayed-release 5-aminosalicylic acid (Mesalazine) and sulfasalazine as maintenance treatment for patients with ulcerative colitis. Gastroenterology 1988; 94: 1383–89.
investigation through carefully controlled studies in endemic areas. Any potential effectiveness of typhoid vaccine should be pursued in view of a possible future increase in resistance of the organism to safe oral drugs such as ciprofloxacin. Such resistance leads to the need for expensive parenteral therapy and hospital admission. Madhur Dev Bhattarai Department of Medicine, Bir Hospital, PO Box 3245, Kathmandu, Nepal (e-mail: [email protected]) 1
2
Sinha A, Sazawal S, Kumar R, et al. Typhoid fever in children aged less than 5 years. Lancet 1999; 354: 734–37. Griffin GE. Typhoid fever and childhood vaccine strategies. Lancet 1999; 354: 698–99.
Sir—Anju Sinha and colleagues1 did not observe any case of typhoid fever in children aged less than 1 year probably because of passive immunity from their mothers in a population in which typhoid fever is endemic. A sharp contrast in frequency of typhoid fever between age-groups in this population (27·3% aged <5 years, 11·7% 5–19 years, and 1·1% ⭓19 years) could indicate early exposure to typhoid, and therefore strong immunity in older agegroups. The investigators should have checked antibody titre to Salmonella typhi in blood samples that were obtained to show this supposition (this could still be done if serum samples are available). In an epidemic in Ankara, Turkey, 24 children with typhoid fever were admitted to Ihsan Dog ramaci Children’s Hospital during 2 months.2 Only two patients were aged less than 5 years and 14 were aged 5–9 years, which might indicate that typhoid fever is not common in children aged less than 5 years outside endemic areas, even in less-developed countries. The investigators should also have done leucocyte counts and differential diagnoses of patients who presented with typhoid because granulocytopenia is not expected in children aged less than 10 years. v
Typhoid fever in children Sir—Anju Sinha and colleagues (Aug 28, p 734)1 report that typhoid fever is a common and important cause of morbidity in children aged 1–5 years. They argue that the age at which typhoid vaccine is given and the choice of vaccines need to be re-examined. In his Aug 28 commentary,2 George Griffin discusses the difficulties in the incorporation of typhoid vaccine into the paediatric vaccination schedule. In particular, he focuses on effectiveness of available vaccines, route of vaccination, and difficulty in the introduction of new vaccines in existing schedules. Regular mass vaccination is not recommended even for adults in endemic areas of lessdeveloped countries. Many patients have recurrent typhoid fever for years. One attack of typhoid fever does not seem to confer longlasting protection. Any person with typhoid fever is at high risk of subsequent exposure in endemic areas. Thus, typhoid vaccine, even with present effectiveness, is likely to be costeffective if given selectively to such people. This possibility deserved further
Sinasi Özsoylu 5
Fatih University Medical Faculty, Çiftlik cad, Number 57, 06510 Emek, Ankara, Turkey 1
Sinha A, Sazawal S, Kumar R, et al. Typhoid fever in children aged less than 5 years. Lancet 1999; 354: 734–37. ~ MK, Özsoylu S, Kanra G. Relative 2 Çaglar granulocytous in childhood typhoid fever. J Pediatr 1983; 102: 603–04. 5
Sir—Anju Sinha and colleagues1 report clinical and epidemiological data for typhoid fever in children and conclude that typhoid fever is a common and significant cause of morbidity between 1 and 5 years of age. We have some different views on these points.
2001