- Email: [email protected]
Tooth infection and tonsillitis
THE LANCET
fulfilled the King’s criteria, were managed conservatively and recovered fully. The principal reasons for not transplanting these seven patients were that there was no evidence of rising intracranial pressure, and coagulopathy was manageable. Although our experience is quite limited, it does raise the question of the continued general applicability of the King’s criteria. Conservative management of patients with FHF has steadily improved, with the realisation of the benefit of N-Acetylcysteine given even as late as 36 hours after an overdose,3 improved techniques of intracranial pressure monitoring, and the recent emphasis on ensuring adequate cerebral blood flow and oxygenation. We feel that the King’s criteria provide a helpful indication of the severity of liver damage, but that they should not be accepted uncritically as the sole determinant of the need for a liver graft in a given patient. We have adopted a conservative approach in paracetamol-related FHF. We rely on careful continuing monitoring of coagulation profile, neurological status, and intracerebral pressure, with transplantation being reserved for those who have unmanageable coagulopathy or evidence of progressive cerebral oedema. Recent data from the King’s group presented at the British Society of Gastroenterology meeting in Manchester, UK, in September, 1996, encompassed the care of 129 patients with paracetamol-related FHF between 1990 and 1996 who met the King’s criteria. Of the 39 patients transplanted, 93% survived; of the 90 patients not transplanted, only 11% survived, suggesting that the King’s criteria were indeed appropriate. It should be noted, however, that the two groups were not comparable, since the latter contained all those patients who had deteriorated to the point where transplantation was deemed to be no longer worthwhile. Could it be that Australians’ livers are somehow more robust than their UK counterparts? We advocate a more carefully tailored approach to the individual patient when deciding the need for transplantation. It is important to prevent patients dying from FHF by giving them a new liver. It is arguably equally important to refrain from transplanting those who will recover. Paul J Gow, Peter W Angus, *Richard A Smallwood Liver Transplant Unit, Austin and Repatriation Medical Centre, Heidelberg 3084, Australia
1
Makin AJ, Wendon J, Williams R. A 7-year experience of severe acetaminophen-induced hepatotoxicity (1987–1993). Gastroenterology 1995; 109: 1907–16.
652
2
3
O’Grady JG, Alexander GJM, Hayllar KM, Williams R. Early indicators of prognosis in fulminant hepatic failure. Gastroenterology 1989; 97: 439–45. Harrison PM, Keays R, Bray GP, Alexander GJM, Williams R. Improved outcome of paracetamol induced fulminant hepatic failure by late administration of acetyl cysteine. Lancet 1990; 335: 1572–73.
Exposure to benzo[a]pyrene SIR—Myddelton (Dec 21/28, p 1744)1 seeks to compare the exposure of cigarette smokers and the general public to benzo[a]pyrene. The data provided on ambient concentrations are out of date. The annual average concentration of benzo[a]pyrene in London has fallen from 26–39 ng/m3 in 1962 to less than 1 ng/m3 in 1997. M L Williams, *R L Maynard Department of Environment, London; and *Department of Health, Skipton House, London SE1 6LW, UK
1 2
Myddelton G. Mutagen in cigarettes and foggy air. Lancet 1996; 348: 1744. Air Quality A to Z: a directory of air quality data for the UK in the 1990s. London: UK Meterological Office, 1995.
Disturbed consciousness and asthma SIR—Dimond and Palazzo (Jan 11, p 98)1 describe a case of severe acute asthma showing unconsciousness, dilation of the left pupil, and diffuse cerebral swelling on computed tomography. We report a case of severe acute asthma associated with disturbed consciousness, in which asthmainduced cerebral swelling was considered to be accompanied by neuronal damage after examination of cerebrospinal fluid. A 39-year-old woman was admitted with an acute exacerbation of asthma. On admission she was confused and widespread polyphonic wheezes were audible. Analysis of blood gas on admission revealed severe hypoxaemia (PaO2 45 mm Hg), but normal PaCO2 (36 mm Hg), and pH (7·45). Computed tomography of her head showed diffuse cerebral swelling. Cerebrospinal fluid was examined to exclude encephalitis, but results were all normal apart from an increased concentration of tau protein (84 pg/mL; normal range <40 pg/mL).2 She received oxygen inhalation and was treated with theophylline infusion, nebulised salbutamol, and dexamethasone. Her wheeze decreased and hypoxaemia was corrected. After 5 days, she became alert, diffuse cerebral swelling on computed-tomography scan
subsided, and the concentration of tau protein in cerebrospinal fluid returned to within the normal range (17 pg/mL). She made a full recovery with no detectable neurological deficit and was discharged 2 weeks later. Since the concentration of tau protein in cerebrospinal fluid is believed to originate from damaged or dying neurons within the central nervous system, latent brain damage could occur during severe asthma attack with disturbed consciousness. The consequence of transient brain damage is uncertain, but care should be taken to control asthma symptoms to keep to a minimum potential brain damage in such patients. Takashi Ohrui, Mutsuo Yamaya, Hiroyuki Arai, Kiyohisa Sekizawa, *Hidetada Sasaki Department of Geriatric Medicine, Tohoku University School of Medicine, Aoba-ku Seiryo-machi 1-1 Sendai 980, Japan
1
2
3
Dimond JP, Palazzo MGA. An unconscious man with asthma and a fixed, dilated pupil. Lancet 1997; 349: 98. Arai H, Terajima M, Miura M, et al. Tau in cerebrospinal fluid: a potential diagnostic marker in Alzheimer’s disease. Ann Neurol 1995; 386: 649–52. Trojanowski JQ, Clark CM, Schmidt ML, et al. Implications of tau-rich neurofibrillary lesions for the pathobiology and diagnosis of Alzheimer’s disease. In: Appel S, ed. Current neurology, vol 16. St Louis: Mosby Year Books, 1996: 93–113.
Tooth infection and tonsillitis SIR—Niessen (Dec 14, p 1602)1 discusses pericoronitis as one cause of tonsillitis. The organisms in pericoronitis may also perhaps, induce tonsillitis because of the proximity of anatomical structures, and throughflow of masticated bolus. Differentiation of the source of current tonsillar infection may be assisted by reference to the patient’s history of lower third molar or tonsillar inflammation. Between April, 1984, and December, 1995, we saw 656 patients (aged 16–30 years) with 1173 lower third molars affected by periconitis. None of these patients had both tonsillitis and pericoronitis as chronic conditions. Only one patient (a 23year-old man) developed peritonsillar abscess after pericoronitis in a partlyerupted mandibular third molar. 483 of our patients had partly erupted lower third molars, which may have had persistent local infection. Thus, the extension of pericoronitis to the peritonsillar space seems to be infrequent, and bacterial cultures from tonsillar swabs (identifying gramnegative pathogens that cause
Vol 349 • March 1, 1997
THE LANCET
pericoronitis) should establish or rule out a link between pericoronitis and tonsillitis. *Minoru Yamaoka, Kiyofumi Furusawa Oral and Maxillofacial Surgery Department II, Matsumoto Dental College, Shiojiri, Nagano 399-07, Japan
1
Niessen LC. Pericoronitis as a cause of tonsillitis. Lancet 1996; 348: 1602–03.
Should benznidazole be used in chronic Chagas’ disease? SIR—Andrade and associates (Nov 23, p 1407)1 report the beneficial effects of benznidazole in schoolchildren at the early stage of chronic Chagas’ disease. By performing a prospective, randomised, double-blind, placebocontrolled clinical trial, these workers were able to show a striking decrease in serum antibody concentrations by indirect immunofluorescence and indirect haemagglutination, as well as a higher rate of disappearance of antibodies by ELISA in the benznidazole group. They conclude that such results “justify the recommendation of treatment for seropositive children as public health policy”. I think that Andrade and colleagues’ recommendation should be regarded with caution for the following reasons. First, benznidazole has been associated with malignant neoplasms in both Chagas’ heart transplants2 and murine models of the disease.3 Since the duration of the follow-up was only 3 years, I think that a longer time is necessary to definitively rule out benznidazole-induced cancer in this subset of patients. Second, acute chagasic myocarditis is usually severe, but mortality is low. After 30 days of infection, untreated patients recover well; radiographic and resting electrocardiogram findings return to normal, but serological tests remain positive. The appearance of chronic cardiomyopathy is closely related to the severity of the acute stage. Parasites are not believed to have a pivotal role in the appearance of chronic cardiomyopathy.4,5 In this scenario, what is the clinical relevance of negative seroconversion or a decrease in serum antibody concentration induced by benznidazole in patients with chronic Chagas’ disease? Will treatment with this drug prevent schoolchildren chronically infected with Trypanosoma cruzi from developing Chagas’ cardiomyopathy? On the basis of the appearance of more new cases of chronic cardiomyopathy in the placebo group
Vol 349 • January 00, 1997
than in the benznidazole group, I suggest that Andrade and colleagues continue to follow their patients. Taking into account the high annual rate (7%) of cardiomyopathy in chronically infected schoolchildren and the number of patients enrolled in the trial, we might well see the efficacy of benznidazole in the prevention of cardiomyopathy in this subset of chagasic patients. For the time being, I believe that benznidazole should not be routinely given for patients with chronic Chagas’ disease even in the early stage of the disease. Reinaldo B Bestetti Serviço de Saúde da Universidade de São Paulo, Ribeirão Preto, 14049-900, Brazil
1
2
3
4
5
Andrade ALS, Zicker F, Oliveira RM, et al. Randomised trial of efficacy of benznidazole in treatment of early Trypanosoma cruzi infection. Lancet 1996; 348: 1407–13. Bocchi EA, Higushi ML, Fiorelli A, et al. Higher incidendce of malignant neoplasma after heart transplantation for treatment of Chagas’ heart disease (abstract). Eur Heart J 1994; 15: 179. Teixeira ARL, Calixto MA, Teixeira ML. Chagas’ disease: carcinogenic activity of the antitrypanosomal nitroarenes in mice. Mutation Res 1994; 305: 189–96. Rossi MA, Bestetti RB. The challenge of chagasic cardiomyopathy. Cardiology 1995; 86: 1–7. Bestetti RB. Role of parasites in the pathogenesis of Chagas’ cardiomyopathy. Lancet 1996; 347: 913–14.
Authors’ reply SIR—Bestetti is reluctant to accept our recommendation of the use of benznidazole as a public health treatment for Trypanosoma cruzi seropositive children. Chagas’ disease is clearly a public health priority in Latin America. More than 3 million disability-adjusted years of life are lost annually and 60% of the adult population is seropositive in some endemic regions.1 Chronic heart disease is expected to develop in about 30% of infected individuals. Benznidazole has been available for at least 20 years, and in use for the parasitological treatment of acute and congenital infections and no clinical evidence of disease enhancement or benznidazole-induced cancer has ever been reported. The experimental evidence of the carcinogenic effect of benznidazole is not consistent. No mutagenic effect was detected in serum and urine from guineapigs treated with 500 mg/kg (100 times the daily doses recommended in man). The drug seemed not to be metabolised by the mammalian host into stable mutagenic derivates, and the potential cancer risk for human being is small.2 No case of cancer has been reported in patients who have been followed-up for 5–18 years after
benznidazole chemotherapy.3 We are extending the follow-up of patients to evaluate the long-term effect of treatment on serology and disease evolution. We do not think, however, that we will be able to detect any potential benznidazole-induced cancer. Those events when present are extremely rare, and the number of patients enrolled would not be sufficient to detect any rare toxicity of the drug. The beneficial effect of the parasiticidal treatment in the chronic phase has been demonstrated in animals as well as in clinical trials. A regression in the inflammatory heart lesion and a decrease in the components of the interstitial matrix were recorded in treated compared with untreated mice.4 Patients observed for 8 years after treatment presented significantly fewer electrocardiographic changes and lower frequency of deterioration in their clinical conditions than did non-treated patients.5 We do believe that the treatment will prevent the development of chronic cardiopathy in children as initially shown in the trial. At this stage of scientific knowledge, not to offer benznidazole treatment to the placebo group would be unethical. The study was carried out in an area where the progression of the disease seemed to be very fast. After opening the codes, the children assigned to the placebo group were given the treatment. All the study children are now under periodical observation and we hope to show a significant reduction in the occurrence of electrocardiographic alterations. *Ana Lucia S Sgambatti de Andrade, Fabio Z icker *Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, Brazil; and Pan American Health Organization, Washington DC, USA
1
2
3
4
5
Andrade ALSS, Zicker F, Silva IG, Souza JMP, Martelli CMT. Risk factors for Trypanosoma cruzi infection among children in central Brazil: a case-control study in vector control settings. Am J Trop Med Hyg 1995; 92: 183–87. Ferreira RC, de-Melo ME, Moraes-Junior MA, Ferreira LC. Evaluation of genotoxic activity in the blood and urine of guinea pigs treated with nifurtimox and benznidazole. Braz J Med Biol Res 1988; 21: 1069–77. Ferreira HO. Tratamento da forma indeterminada da doença de Chagas com Nifurtimox e Benznidazol. Rev Soc Bras Med Trop 1990; 23: 209–11. Andrade SG, Stocker-Guerret S, Pimentel AS, Grimaldi JA. Reversibility of cardiac fibrosis in mice chronically infected with Trypanosoma cruzi under specific chemotherapy. Mem Inst Oswaldo Cruz 1991; 86: 187–200. Viotti R, Vigliano C, Armenti H, Segura E. Treatment of chronic Chagas’ disease with benznidazole: clinical and serological evolution of patients with long-term followup. Am Heart J 1994; 127: 151–62.
653
fulfilled the King’s criteria, were managed conservatively and recovered fully. The principal reasons for not transplanting these seven patients were that there was no evidence of rising intracranial pressure, and coagulopathy was manageable. Although our experience is quite limited, it does raise the question of the continued general applicability of the King’s criteria. Conservative management of patients with FHF has steadily improved, with the realisation of the benefit of N-Acetylcysteine given even as late as 36 hours after an overdose,3 improved techniques of intracranial pressure monitoring, and the recent emphasis on ensuring adequate cerebral blood flow and oxygenation. We feel that the King’s criteria provide a helpful indication of the severity of liver damage, but that they should not be accepted uncritically as the sole determinant of the need for a liver graft in a given patient. We have adopted a conservative approach in paracetamol-related FHF. We rely on careful continuing monitoring of coagulation profile, neurological status, and intracerebral pressure, with transplantation being reserved for those who have unmanageable coagulopathy or evidence of progressive cerebral oedema. Recent data from the King’s group presented at the British Society of Gastroenterology meeting in Manchester, UK, in September, 1996, encompassed the care of 129 patients with paracetamol-related FHF between 1990 and 1996 who met the King’s criteria. Of the 39 patients transplanted, 93% survived; of the 90 patients not transplanted, only 11% survived, suggesting that the King’s criteria were indeed appropriate. It should be noted, however, that the two groups were not comparable, since the latter contained all those patients who had deteriorated to the point where transplantation was deemed to be no longer worthwhile. Could it be that Australians’ livers are somehow more robust than their UK counterparts? We advocate a more carefully tailored approach to the individual patient when deciding the need for transplantation. It is important to prevent patients dying from FHF by giving them a new liver. It is arguably equally important to refrain from transplanting those who will recover. Paul J Gow, Peter W Angus, *Richard A Smallwood Liver Transplant Unit, Austin and Repatriation Medical Centre, Heidelberg 3084, Australia
1
Makin AJ, Wendon J, Williams R. A 7-year experience of severe acetaminophen-induced hepatotoxicity (1987–1993). Gastroenterology 1995; 109: 1907–16.
652
2
3
O’Grady JG, Alexander GJM, Hayllar KM, Williams R. Early indicators of prognosis in fulminant hepatic failure. Gastroenterology 1989; 97: 439–45. Harrison PM, Keays R, Bray GP, Alexander GJM, Williams R. Improved outcome of paracetamol induced fulminant hepatic failure by late administration of acetyl cysteine. Lancet 1990; 335: 1572–73.
Exposure to benzo[a]pyrene SIR—Myddelton (Dec 21/28, p 1744)1 seeks to compare the exposure of cigarette smokers and the general public to benzo[a]pyrene. The data provided on ambient concentrations are out of date. The annual average concentration of benzo[a]pyrene in London has fallen from 26–39 ng/m3 in 1962 to less than 1 ng/m3 in 1997. M L Williams, *R L Maynard Department of Environment, London; and *Department of Health, Skipton House, London SE1 6LW, UK
1 2
Myddelton G. Mutagen in cigarettes and foggy air. Lancet 1996; 348: 1744. Air Quality A to Z: a directory of air quality data for the UK in the 1990s. London: UK Meterological Office, 1995.
Disturbed consciousness and asthma SIR—Dimond and Palazzo (Jan 11, p 98)1 describe a case of severe acute asthma showing unconsciousness, dilation of the left pupil, and diffuse cerebral swelling on computed tomography. We report a case of severe acute asthma associated with disturbed consciousness, in which asthmainduced cerebral swelling was considered to be accompanied by neuronal damage after examination of cerebrospinal fluid. A 39-year-old woman was admitted with an acute exacerbation of asthma. On admission she was confused and widespread polyphonic wheezes were audible. Analysis of blood gas on admission revealed severe hypoxaemia (PaO2 45 mm Hg), but normal PaCO2 (36 mm Hg), and pH (7·45). Computed tomography of her head showed diffuse cerebral swelling. Cerebrospinal fluid was examined to exclude encephalitis, but results were all normal apart from an increased concentration of tau protein (84 pg/mL; normal range <40 pg/mL).2 She received oxygen inhalation and was treated with theophylline infusion, nebulised salbutamol, and dexamethasone. Her wheeze decreased and hypoxaemia was corrected. After 5 days, she became alert, diffuse cerebral swelling on computed-tomography scan
subsided, and the concentration of tau protein in cerebrospinal fluid returned to within the normal range (17 pg/mL). She made a full recovery with no detectable neurological deficit and was discharged 2 weeks later. Since the concentration of tau protein in cerebrospinal fluid is believed to originate from damaged or dying neurons within the central nervous system, latent brain damage could occur during severe asthma attack with disturbed consciousness. The consequence of transient brain damage is uncertain, but care should be taken to control asthma symptoms to keep to a minimum potential brain damage in such patients. Takashi Ohrui, Mutsuo Yamaya, Hiroyuki Arai, Kiyohisa Sekizawa, *Hidetada Sasaki Department of Geriatric Medicine, Tohoku University School of Medicine, Aoba-ku Seiryo-machi 1-1 Sendai 980, Japan
1
2
3
Dimond JP, Palazzo MGA. An unconscious man with asthma and a fixed, dilated pupil. Lancet 1997; 349: 98. Arai H, Terajima M, Miura M, et al. Tau in cerebrospinal fluid: a potential diagnostic marker in Alzheimer’s disease. Ann Neurol 1995; 386: 649–52. Trojanowski JQ, Clark CM, Schmidt ML, et al. Implications of tau-rich neurofibrillary lesions for the pathobiology and diagnosis of Alzheimer’s disease. In: Appel S, ed. Current neurology, vol 16. St Louis: Mosby Year Books, 1996: 93–113.
Tooth infection and tonsillitis SIR—Niessen (Dec 14, p 1602)1 discusses pericoronitis as one cause of tonsillitis. The organisms in pericoronitis may also perhaps, induce tonsillitis because of the proximity of anatomical structures, and throughflow of masticated bolus. Differentiation of the source of current tonsillar infection may be assisted by reference to the patient’s history of lower third molar or tonsillar inflammation. Between April, 1984, and December, 1995, we saw 656 patients (aged 16–30 years) with 1173 lower third molars affected by periconitis. None of these patients had both tonsillitis and pericoronitis as chronic conditions. Only one patient (a 23year-old man) developed peritonsillar abscess after pericoronitis in a partlyerupted mandibular third molar. 483 of our patients had partly erupted lower third molars, which may have had persistent local infection. Thus, the extension of pericoronitis to the peritonsillar space seems to be infrequent, and bacterial cultures from tonsillar swabs (identifying gramnegative pathogens that cause
Vol 349 • March 1, 1997
THE LANCET
pericoronitis) should establish or rule out a link between pericoronitis and tonsillitis. *Minoru Yamaoka, Kiyofumi Furusawa Oral and Maxillofacial Surgery Department II, Matsumoto Dental College, Shiojiri, Nagano 399-07, Japan
1
Niessen LC. Pericoronitis as a cause of tonsillitis. Lancet 1996; 348: 1602–03.
Should benznidazole be used in chronic Chagas’ disease? SIR—Andrade and associates (Nov 23, p 1407)1 report the beneficial effects of benznidazole in schoolchildren at the early stage of chronic Chagas’ disease. By performing a prospective, randomised, double-blind, placebocontrolled clinical trial, these workers were able to show a striking decrease in serum antibody concentrations by indirect immunofluorescence and indirect haemagglutination, as well as a higher rate of disappearance of antibodies by ELISA in the benznidazole group. They conclude that such results “justify the recommendation of treatment for seropositive children as public health policy”. I think that Andrade and colleagues’ recommendation should be regarded with caution for the following reasons. First, benznidazole has been associated with malignant neoplasms in both Chagas’ heart transplants2 and murine models of the disease.3 Since the duration of the follow-up was only 3 years, I think that a longer time is necessary to definitively rule out benznidazole-induced cancer in this subset of patients. Second, acute chagasic myocarditis is usually severe, but mortality is low. After 30 days of infection, untreated patients recover well; radiographic and resting electrocardiogram findings return to normal, but serological tests remain positive. The appearance of chronic cardiomyopathy is closely related to the severity of the acute stage. Parasites are not believed to have a pivotal role in the appearance of chronic cardiomyopathy.4,5 In this scenario, what is the clinical relevance of negative seroconversion or a decrease in serum antibody concentration induced by benznidazole in patients with chronic Chagas’ disease? Will treatment with this drug prevent schoolchildren chronically infected with Trypanosoma cruzi from developing Chagas’ cardiomyopathy? On the basis of the appearance of more new cases of chronic cardiomyopathy in the placebo group
Vol 349 • January 00, 1997
than in the benznidazole group, I suggest that Andrade and colleagues continue to follow their patients. Taking into account the high annual rate (7%) of cardiomyopathy in chronically infected schoolchildren and the number of patients enrolled in the trial, we might well see the efficacy of benznidazole in the prevention of cardiomyopathy in this subset of chagasic patients. For the time being, I believe that benznidazole should not be routinely given for patients with chronic Chagas’ disease even in the early stage of the disease. Reinaldo B Bestetti Serviço de Saúde da Universidade de São Paulo, Ribeirão Preto, 14049-900, Brazil
1
2
3
4
5
Andrade ALS, Zicker F, Oliveira RM, et al. Randomised trial of efficacy of benznidazole in treatment of early Trypanosoma cruzi infection. Lancet 1996; 348: 1407–13. Bocchi EA, Higushi ML, Fiorelli A, et al. Higher incidendce of malignant neoplasma after heart transplantation for treatment of Chagas’ heart disease (abstract). Eur Heart J 1994; 15: 179. Teixeira ARL, Calixto MA, Teixeira ML. Chagas’ disease: carcinogenic activity of the antitrypanosomal nitroarenes in mice. Mutation Res 1994; 305: 189–96. Rossi MA, Bestetti RB. The challenge of chagasic cardiomyopathy. Cardiology 1995; 86: 1–7. Bestetti RB. Role of parasites in the pathogenesis of Chagas’ cardiomyopathy. Lancet 1996; 347: 913–14.
Authors’ reply SIR—Bestetti is reluctant to accept our recommendation of the use of benznidazole as a public health treatment for Trypanosoma cruzi seropositive children. Chagas’ disease is clearly a public health priority in Latin America. More than 3 million disability-adjusted years of life are lost annually and 60% of the adult population is seropositive in some endemic regions.1 Chronic heart disease is expected to develop in about 30% of infected individuals. Benznidazole has been available for at least 20 years, and in use for the parasitological treatment of acute and congenital infections and no clinical evidence of disease enhancement or benznidazole-induced cancer has ever been reported. The experimental evidence of the carcinogenic effect of benznidazole is not consistent. No mutagenic effect was detected in serum and urine from guineapigs treated with 500 mg/kg (100 times the daily doses recommended in man). The drug seemed not to be metabolised by the mammalian host into stable mutagenic derivates, and the potential cancer risk for human being is small.2 No case of cancer has been reported in patients who have been followed-up for 5–18 years after
benznidazole chemotherapy.3 We are extending the follow-up of patients to evaluate the long-term effect of treatment on serology and disease evolution. We do not think, however, that we will be able to detect any potential benznidazole-induced cancer. Those events when present are extremely rare, and the number of patients enrolled would not be sufficient to detect any rare toxicity of the drug. The beneficial effect of the parasiticidal treatment in the chronic phase has been demonstrated in animals as well as in clinical trials. A regression in the inflammatory heart lesion and a decrease in the components of the interstitial matrix were recorded in treated compared with untreated mice.4 Patients observed for 8 years after treatment presented significantly fewer electrocardiographic changes and lower frequency of deterioration in their clinical conditions than did non-treated patients.5 We do believe that the treatment will prevent the development of chronic cardiopathy in children as initially shown in the trial. At this stage of scientific knowledge, not to offer benznidazole treatment to the placebo group would be unethical. The study was carried out in an area where the progression of the disease seemed to be very fast. After opening the codes, the children assigned to the placebo group were given the treatment. All the study children are now under periodical observation and we hope to show a significant reduction in the occurrence of electrocardiographic alterations. *Ana Lucia S Sgambatti de Andrade, Fabio Z icker *Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, Brazil; and Pan American Health Organization, Washington DC, USA
1
2
3
4
5
Andrade ALSS, Zicker F, Silva IG, Souza JMP, Martelli CMT. Risk factors for Trypanosoma cruzi infection among children in central Brazil: a case-control study in vector control settings. Am J Trop Med Hyg 1995; 92: 183–87. Ferreira RC, de-Melo ME, Moraes-Junior MA, Ferreira LC. Evaluation of genotoxic activity in the blood and urine of guinea pigs treated with nifurtimox and benznidazole. Braz J Med Biol Res 1988; 21: 1069–77. Ferreira HO. Tratamento da forma indeterminada da doença de Chagas com Nifurtimox e Benznidazol. Rev Soc Bras Med Trop 1990; 23: 209–11. Andrade SG, Stocker-Guerret S, Pimentel AS, Grimaldi JA. Reversibility of cardiac fibrosis in mice chronically infected with Trypanosoma cruzi under specific chemotherapy. Mem Inst Oswaldo Cruz 1991; 86: 187–200. Viotti R, Vigliano C, Armenti H, Segura E. Treatment of chronic Chagas’ disease with benznidazole: clinical and serological evolution of patients with long-term followup. Am Heart J 1994; 127: 151–62.
653