972
ECMO should lead us to reconsider some aspects of our conventional management of patients with severe ARDS.9 Experience has demonstrated the safety and feasibility of transporting even the most critically ill to centres specialising in ECMO. In the UK ECMO should be available in a few centres capable of meeting a need of between two and five cases per million population per year. Our cardiothoracic unit with the support of the university department of surgery has been staffed, equipped, and funded by charitable donations to provide an ECMO service. To date we have treated four children, all referred with a 100% predicted mortality, in whom ECMO was used as a last resort. Two children survived; the other two died of complications unrelated to ECMO. Regional Cardiothoracic Unit, Groby Road Hospital,
A. W. SOSNOWSKI T. R. GRAHAM R. K. FIRMIN
Leicester LE3 9QE, UK, and Department of Surgery, University of Leicester
1. Editorial. Persistent fetal circulation and extracorporeal membrane oxygenation. Lancet 1988, ii: 1289-91. 2. Anon. ELSO registry report. Ann Arbor, Michigan: University of Michigan, 1990. 3. Lillehei C, O’Rourke P, Vacanti J, Crone R. Role of ECMO in selected pediatric respiratory problems. J Thoracic Cardiovasc Surg 1989; 98: 968-71. 4. Zwischenberger J, Toomasian J, Drake K, Andrews A, Kolobow T, Bartlett R Total
respiratory support with single lumen cannula veno-venous ECMO: double lumen continuous flow vs single lumen tidal flow. Am Soc Artif Intern Organs 1985; 31: 610-15. 5. Weinhaus L, Canter C, Noetzel M, McAlister W, Spray T. ECMO for circulatory support after repair of congenital heart defects Am Thoracic Surg 1989; 48: 206-12. 6. Egan T, Duffin J, Glynn M, et al. Ten year experience with ECMO for severe respiratory failure. Chest 1988; 94: 681-87. 7. Hickling K. Extra corporeal CO2 removal in severe adult respiratory distress syndrome. Anæsth Intens Care 1989; 14: 46-53. 8. Gattinoni L, Pesenti A, Mascheroni D, et al. Low frequency positive-pressure ventilation with extra corporeal CO2 removal of severe acute respiratory failure.
JAMA 1986; 256: 257-62. 9. Editorial. ARDS time. Lancet
1989; i: 140.
Mefloguine prophylaxis SiR,-Neurological reactions, ranging from dizziness and inability to concentrate to psychotic reactions," after mefloquine treatment and prophylaxis have raised the question of the risks of mefloquine prophylaxis. This is of special concern to doctors who have to recommend prophylaxis for those travelling to regions with multiply resistant Plasmodium falciparum. We report our experience with mefloquine prophylaxis in US soldiers training in Thailand for 6 weeks in 1988. We conducted a double-blind, placebo-controlled study comparing the effect on diarrhoeal disease of prophylaxis with daily
doxycycline
100 mg or weekly mefloquine hydrochloride 250 mg. 119 soldiers were randomised to receive doxycycline and 134 to receive mefloquine. All were healthy men aged 18-40 years (mean age 24). At the end of the fourth and sixth weeks of medication, the soldiers were interviewed for side-effects and blood was obtained serum doxycycline or mefloquine determinations by highperformance liquid chromatography. The frequencies of side-effects were not significantly different between the two groups (table). Nausea and vomiting were reported more frequently by those taking doxycycline, and headache was reported more often with mefloquine; only 1 soldier thought that his symptom (nausea) was attributable to mefloquine. No soldier needed to discontinue mefloquine prophylaxis because of perceived
for
adverse side-effects. The mean serum mefloquine level was 450 ng/ml (95% confidence interval 417-484) after the fourth weekly dose and 437 REPORTED SIDE-EFFECTS OF MALARIA PROPHYLAXIS
after the sixth dose. Reported side-effects could be related to raised mefloquine levels. 15 soldiers taking doxycycline were potentially non-compliant with their prophylaxis regimen by week 6, as indicated by doxycycline levels or refusal to have blood drawn. Only 7 soldiers were potentially non-compliant with mefloquine (p=0’04); all reported for the side-effect interview but 4 refused to have their blood drawn and 3 had mefloquine levels less than 2 SD below the mean. 4 of the 7 reported diarrhoea; all had confirmed infection with enterotoxigenic Escherichia coli; 2 of the 7 reported no side-effects; and the remaining soldier reported diarrhoea and headache but no causative agent was identified. This is the largest group of US nationals reported to date in whom mefloquine malaria prophylaxis was studied in the tropics. That more soldiers were potentially non-compliant with the doxycycline regimen than the mefloquine regimen, and that no soldier failed to perform during the demanding training period because of what might have been a neurological reaction, indicate that neurological reactions to weekly mefloquine prophylaxis that impair individual performance must be unusual. We are confident that no serious neurological reactions occurred from the weekly mefloquine malaria prophylaxis, although our study was not designed to detect infrequent and subtle neurological events.
ng/ml (404-470) not
JAMES D. ARTHUR Armed Forces Institute of Medical Sciences, Bangkok 10400, Thailand
G. DENNIS SHANKS PETER ECHEVERRIA
1. Rouveix
B, Bricaire F, Michon C, Franssen G, Lebras J, Bernard J. Mefloquine and brain syndrome. Ann Intern Med 1989; 110: 577-78. 2. Stuiver PC, Ligthelm RJ, Goud ThJLM. Acute psychosis after mefloquine. Lancet 1989; ii. 282 3 Patchen LC, Campbell CC, Williams SB. Neurologic reactions after a therapeutic dose of mefloquine. N Engl J Med 1989; 321: 1415-16. 4. Bjorkman A. Acute psychosis following mefloquine prophylaxis. Lancet 1989; ii: 865 an acute
Further
experience with Japanese encephalitis vaccine
SiR,—Formalin-inactivated Japanese encephalitis vaccine has been shown to be effective in Thai children and has been recommended in the United States for use in certain travellers visiting the Orient.1,2 However, efficacy data in Thailand were derived in a population heavily exposed to flaviviruses (dengue and Japanese encephalitis) which may not be representative of most travellers. To learn about the safety and immunogenicity of the vaccine in a more representative population, we evaluated it in US soldiers. Soldiers were immunised with two doses of monovalent vaccine (NakayamaNIH strain; Biken, Osaka, Japan). Between May, 1987, and August, 1989, 4034 Department of Defense personnel were evaluated. Two doses 1 week apart were given; a small number received a third dose about 6 months later. Soldiers were briefed on the investigational nature of the vaccine and expected side-effects. Questionnaires asking about arm soreness, redness at injection site, febrile episodes, headaches, and rashes were given to all vaccinees 1 to 4 weeks after vaccination and the forms were completed within a week of each dose. 3573 (89%) vaccinees submitted completed forms. No severe adverse reactions occurred. Arm soreness occurred in about one-fifth of vaccinees (table!); this was mild, lasting no more than a few hours, and was not associated with significant swelling, erythema, or limitation of function. Headaches were significantly (p
ECMO should lead us to reconsider some aspects of our conventional management of patients with severe ARDS.9 Experience has demonstrated the safety and feasibility of transporting even the most critically ill to centres specialising in ECMO. In the UK ECMO should be available in a few centres capable of meeting a need of between two and five cases per million population per year. Our cardiothoracic unit with the support of the university department of surgery has been staffed, equipped, and funded by charitable donations to provide an ECMO service. To date we have treated four children, all referred with a 100% predicted mortality, in whom ECMO was used as a last resort. Two children survived; the other two died of complications unrelated to ECMO. Regional Cardiothoracic Unit, Groby Road Hospital,
A. W. SOSNOWSKI T. R. GRAHAM R. K. FIRMIN
Leicester LE3 9QE, UK, and Department of Surgery, University of Leicester
1. Editorial. Persistent fetal circulation and extracorporeal membrane oxygenation. Lancet 1988, ii: 1289-91. 2. Anon. ELSO registry report. Ann Arbor, Michigan: University of Michigan, 1990. 3. Lillehei C, O’Rourke P, Vacanti J, Crone R. Role of ECMO in selected pediatric respiratory problems. J Thoracic Cardiovasc Surg 1989; 98: 968-71. 4. Zwischenberger J, Toomasian J, Drake K, Andrews A, Kolobow T, Bartlett R Total
respiratory support with single lumen cannula veno-venous ECMO: double lumen continuous flow vs single lumen tidal flow. Am Soc Artif Intern Organs 1985; 31: 610-15. 5. Weinhaus L, Canter C, Noetzel M, McAlister W, Spray T. ECMO for circulatory support after repair of congenital heart defects Am Thoracic Surg 1989; 48: 206-12. 6. Egan T, Duffin J, Glynn M, et al. Ten year experience with ECMO for severe respiratory failure. Chest 1988; 94: 681-87. 7. Hickling K. Extra corporeal CO2 removal in severe adult respiratory distress syndrome. Anæsth Intens Care 1989; 14: 46-53. 8. Gattinoni L, Pesenti A, Mascheroni D, et al. Low frequency positive-pressure ventilation with extra corporeal CO2 removal of severe acute respiratory failure.
JAMA 1986; 256: 257-62. 9. Editorial. ARDS time. Lancet
1989; i: 140.
Mefloguine prophylaxis SiR,-Neurological reactions, ranging from dizziness and inability to concentrate to psychotic reactions," after mefloquine treatment and prophylaxis have raised the question of the risks of mefloquine prophylaxis. This is of special concern to doctors who have to recommend prophylaxis for those travelling to regions with multiply resistant Plasmodium falciparum. We report our experience with mefloquine prophylaxis in US soldiers training in Thailand for 6 weeks in 1988. We conducted a double-blind, placebo-controlled study comparing the effect on diarrhoeal disease of prophylaxis with daily
doxycycline
100 mg or weekly mefloquine hydrochloride 250 mg. 119 soldiers were randomised to receive doxycycline and 134 to receive mefloquine. All were healthy men aged 18-40 years (mean age 24). At the end of the fourth and sixth weeks of medication, the soldiers were interviewed for side-effects and blood was obtained serum doxycycline or mefloquine determinations by highperformance liquid chromatography. The frequencies of side-effects were not significantly different between the two groups (table). Nausea and vomiting were reported more frequently by those taking doxycycline, and headache was reported more often with mefloquine; only 1 soldier thought that his symptom (nausea) was attributable to mefloquine. No soldier needed to discontinue mefloquine prophylaxis because of perceived
for
adverse side-effects. The mean serum mefloquine level was 450 ng/ml (95% confidence interval 417-484) after the fourth weekly dose and 437 REPORTED SIDE-EFFECTS OF MALARIA PROPHYLAXIS
after the sixth dose. Reported side-effects could be related to raised mefloquine levels. 15 soldiers taking doxycycline were potentially non-compliant with their prophylaxis regimen by week 6, as indicated by doxycycline levels or refusal to have blood drawn. Only 7 soldiers were potentially non-compliant with mefloquine (p=0’04); all reported for the side-effect interview but 4 refused to have their blood drawn and 3 had mefloquine levels less than 2 SD below the mean. 4 of the 7 reported diarrhoea; all had confirmed infection with enterotoxigenic Escherichia coli; 2 of the 7 reported no side-effects; and the remaining soldier reported diarrhoea and headache but no causative agent was identified. This is the largest group of US nationals reported to date in whom mefloquine malaria prophylaxis was studied in the tropics. That more soldiers were potentially non-compliant with the doxycycline regimen than the mefloquine regimen, and that no soldier failed to perform during the demanding training period because of what might have been a neurological reaction, indicate that neurological reactions to weekly mefloquine prophylaxis that impair individual performance must be unusual. We are confident that no serious neurological reactions occurred from the weekly mefloquine malaria prophylaxis, although our study was not designed to detect infrequent and subtle neurological events.
ng/ml (404-470) not
JAMES D. ARTHUR Armed Forces Institute of Medical Sciences, Bangkok 10400, Thailand
G. DENNIS SHANKS PETER ECHEVERRIA
1. Rouveix
B, Bricaire F, Michon C, Franssen G, Lebras J, Bernard J. Mefloquine and brain syndrome. Ann Intern Med 1989; 110: 577-78. 2. Stuiver PC, Ligthelm RJ, Goud ThJLM. Acute psychosis after mefloquine. Lancet 1989; ii. 282 3 Patchen LC, Campbell CC, Williams SB. Neurologic reactions after a therapeutic dose of mefloquine. N Engl J Med 1989; 321: 1415-16. 4. Bjorkman A. Acute psychosis following mefloquine prophylaxis. Lancet 1989; ii: 865 an acute
Further
experience with Japanese encephalitis vaccine
SiR,—Formalin-inactivated Japanese encephalitis vaccine has been shown to be effective in Thai children and has been recommended in the United States for use in certain travellers visiting the Orient.1,2 However, efficacy data in Thailand were derived in a population heavily exposed to flaviviruses (dengue and Japanese encephalitis) which may not be representative of most travellers. To learn about the safety and immunogenicity of the vaccine in a more representative population, we evaluated it in US soldiers. Soldiers were immunised with two doses of monovalent vaccine (NakayamaNIH strain; Biken, Osaka, Japan). Between May, 1987, and August, 1989, 4034 Department of Defense personnel were evaluated. Two doses 1 week apart were given; a small number received a third dose about 6 months later. Soldiers were briefed on the investigational nature of the vaccine and expected side-effects. Questionnaires asking about arm soreness, redness at injection site, febrile episodes, headaches, and rashes were given to all vaccinees 1 to 4 weeks after vaccination and the forms were completed within a week of each dose. 3573 (89%) vaccinees submitted completed forms. No severe adverse reactions occurred. Arm soreness occurred in about one-fifth of vaccinees (table!); this was mild, lasting no more than a few hours, and was not associated with significant swelling, erythema, or limitation of function. Headaches were significantly (p
