473
She had been to an endemic malaria area (the Kruger Park in 1984) only once during her time in Africa. However, her flight to London from Johannesburg stopped at night in Abidjan, Ivory Coast, for one hour for refuelling. She did not leave her seat during the stopover but noted that the aeroplane doors remained open and the cabin was sprayed before take-off. We surmise that our patient acquired severe falciparum malaria en route from one non-endemic area to another by a mosquito bite on a runway in Abidjan. Without a detailed travel history, she was misdiagnosed twice before admission. It is clearly important to consider imported malaria in all ill travellers and to ask not only "Where have you been?" but also "How did you return home?" Infectious Disease Unit, Nuffield Department of Medicine, John Radcliffe Hospital, Oxford OX3 9DU, UK
CHRISTOPHER P. CONLON ANTHONY R. BERENDT KENNETH DAWSON TIMOTHY E. A. PETO
Blister calendar packs for treatment of tuberculosis SIR,-Blister calendar or bubble packs (BCPs) of drugs have been widely used with considerable success. BCPs of a combination of drugs for the treatment of tuberculosis have also been available for several years, but, in contrast with those for leprosy,l-3 their potential value, notably in the improvement of compliance, has attracted little attention. After successful studies in the Philippines and India BCP multiple drug therapy for leprosy4,5 began on a national scale. In the Philippines about 116 100 new cases of tuberculosis are recorded yearly. The drug regimen consists of twice-weekly streptomycin with daily isoniazid for twelve months. Regular intramuscular injections of streptomycin are difficult to organise in this scattered island population and patients often find them painful; in 1985 the completion rate in patients treated with this standard regimen was just over 41 %. Through the World Health Organisation, drugs are obtained for a six-month regimen of daily rifampicin 450 mg, isoniazid 300 mg, and pyrazinamide 1 g for the first two months (phase 1), followed by daily rifampicin 450 mg and isoniazid 300 mg for the remaining four months (phase 2)--all to be taken unsupervised by the patient at home. In the Philippines body weight of adults presenting with tuberculosis is between 40-50 kg. The additional packaging for this project adds about 5% to the total cost of drugs. The patient attends the government health centre every week for supply of drugs and to check compliance and any toxic effects. Contraindications to the use of this regimen include jaundice, known hepatitis or cirrhosis, alcoholism, drug addiction, mental defect and psychosis, renal disease, gout, the use of steroids for more than six months, and pregnancy during the first four months. Between September, 1986, and September, 1989, 261 116 patients had had this regimen, and 151 107 (58%) of these have completed treatment; 76 179 (29%) are still under treatment and 33 830 (13%) have either dropped out or been lost to follow-up. 6% had adverse reactions, 2% died,1 % have been transferred from the programme area to another, and 0-7% refused treatment. Toxic reactions consisted mainly of jaundice. Nausea, vomiting, and arthralgia or the influenza syndrome were also seen, but did not usually necessitate withdrawal. All deaths were attributable to tuberculosis, the patients having had far-advanced disease at the outset. The completion rate so far, based on attendance and return of empty packs, is over 80%. On the basis of sputum tests, there is a 91 % conversion from positive to negative in those who completed the course. To our knowledge, this is the first report of the use of BCPs in a national tuberculosis programme in such a population. However, the pace of implementation has outstripped objective assessment of their value, notably in improving compliance. Steps are being taken to do urine spot-checks for isoniazid and the presence of the characteristic orange/brown colour imparted after ingestion of rifampicin. There have also been occasional lapses in the systematic
distribution of drugs. Nevertheless, the BCPs described here have proved highly acceptable to patients and staff and seem to have administrative, operational, and logistic advantages. Department of Health, Tuberculosis Control Service, Manila, Republic of the Philippines
F. S. VALEZA
Department of Dermatology, Slade Hospital, Oxford
A. C. MCDOUGALL
Georgiev GD, McDougall AC. Blister calendar packs: potential for improvement in the supply and utilization of multiple drug therapy in leprosy control programmes. Int J Lepr Other Mycobact Dis 1988; 56: 603-10. 2. Winsley BE, McDougall AC, Brown KE. Chemotherapy of leprosy: "bubble" or "calendar" packs for the administration of rifampin, dapsone, clofazimine or prothionamide/ethionamide. Int J Lepr Other Mycobact Dis 1983; 51: 592-94. 3. WHO. Chemotherapy of leprosy for control programmes: report of a WHO Study Group. Tech Rep Ser WHO 1982; no 675. 4. Editorial. A new approach to multidrug therapy for leprosy. Africa Health 1989, April/May (suppl): 5-6. 5. Revankar CR, Sorensen BH, Kielstrup RW. Delivery of MDT through blister calendar packs in leprosy eradication programmes: a multicentre field trial (phase 1). Lepr Rev 1989; 60: 135-38. 1.
Amphotericin-resistant invasive hepatosplenic candidiasis controlled by fluconazole SIR,-In March, 1988, Philadelphia-positive chronic granulocytic (250 x 109 white blood cells [WBC] per litre) was in a 23-year-old woman. A suitable donor for bone diagnosed marrow transplantation (BMT) could not be found. Cytostatic chemotherapy was instituted and WBC counts were reduced to 9 x 109/1 (March, 1989). In April, 1989, BMT was done with her father as the donor (3/4 identical for HLA, mixed lymphocyte culture negative) without preceding total body irradiation and following our mitobronitol/ cytarabine/cyclophosphamide conditioning protocol.1 The patient was barrier nursed, without laminar air flow. She received oral sulphonamide/trimethoprim, oral amphotericin, intravenous methotrexate, oral cyclosporin, and immunoglobulin every two leukaemia
weeks. From
day 7 post-transplant, sepsis became apparent. No pathogens could be grown. Despite treatment with several antibiotic combinations, her body temperature remained above 38°C and her clinical condition worsened gradually. Anti-candida haemagglutination titre, which was 1 in 160 on day 10, became 1 in 5120 on day 36; Aspergillus was not detected. Systemic amphotericin B was instituted, and escalating doses of up to 1 mg/kg body weight daily were given. Despite this treatment at day 55 disseminated hepatosplenic foci were detected, consisting of 5-16 mm large mainly solid, but occasionally cystic, units. Candida was not isolated from the one abscess biopsied. Nevertheless, Candida albicans spores and exceptional injured segmented forms were identified cytologically. By contrast with other transplanted patients, her WBC count reached 1
x
109/1
on
day
55. Graft-versus-host
disease,
or
other
transplant-related complications were absent. At day 82 the total intravenous amphotericin dose was 2-17 g. Her sepsis-associated fever, rarely over 39°C, did not diminish, and weight loss was about 20 kg. The size of hepatosplenic foci did not change. At this stage, she had direct intrahepatic/intravascular amphotericin via the truncus coeliacus. The daily dose was 25 mg. A total of 425 mg was infused into the liver up to day 98 post-transplant without any clinical amelioration or sonographic improvement. The anti-candida titre was 1 in 20 480. On day 99, amphotericin was withdrawn and fluconazole was instituted, 400 mg per day intravenously for the first two weeks, and 200 mg daily orally thereafter. On day 4 post-fluconazole her temperature began to diminish. For 9 days the patient was subfebrile, and from the third week post-fluconazole her temperature was almost normal and hepatosplenic foci diminished. At day 113 post-transplant the patient was discharged, having gained 7 kg in weight. Two months after fluconazole, the anti-candida titre was 1 in 1260. The patient is symptom-free and afebrile. 100 days post-fluconazole hepatosplenic
She had been to an endemic malaria area (the Kruger Park in 1984) only once during her time in Africa. However, her flight to London from Johannesburg stopped at night in Abidjan, Ivory Coast, for one hour for refuelling. She did not leave her seat during the stopover but noted that the aeroplane doors remained open and the cabin was sprayed before take-off. We surmise that our patient acquired severe falciparum malaria en route from one non-endemic area to another by a mosquito bite on a runway in Abidjan. Without a detailed travel history, she was misdiagnosed twice before admission. It is clearly important to consider imported malaria in all ill travellers and to ask not only "Where have you been?" but also "How did you return home?" Infectious Disease Unit, Nuffield Department of Medicine, John Radcliffe Hospital, Oxford OX3 9DU, UK
CHRISTOPHER P. CONLON ANTHONY R. BERENDT KENNETH DAWSON TIMOTHY E. A. PETO
Blister calendar packs for treatment of tuberculosis SIR,-Blister calendar or bubble packs (BCPs) of drugs have been widely used with considerable success. BCPs of a combination of drugs for the treatment of tuberculosis have also been available for several years, but, in contrast with those for leprosy,l-3 their potential value, notably in the improvement of compliance, has attracted little attention. After successful studies in the Philippines and India BCP multiple drug therapy for leprosy4,5 began on a national scale. In the Philippines about 116 100 new cases of tuberculosis are recorded yearly. The drug regimen consists of twice-weekly streptomycin with daily isoniazid for twelve months. Regular intramuscular injections of streptomycin are difficult to organise in this scattered island population and patients often find them painful; in 1985 the completion rate in patients treated with this standard regimen was just over 41 %. Through the World Health Organisation, drugs are obtained for a six-month regimen of daily rifampicin 450 mg, isoniazid 300 mg, and pyrazinamide 1 g for the first two months (phase 1), followed by daily rifampicin 450 mg and isoniazid 300 mg for the remaining four months (phase 2)--all to be taken unsupervised by the patient at home. In the Philippines body weight of adults presenting with tuberculosis is between 40-50 kg. The additional packaging for this project adds about 5% to the total cost of drugs. The patient attends the government health centre every week for supply of drugs and to check compliance and any toxic effects. Contraindications to the use of this regimen include jaundice, known hepatitis or cirrhosis, alcoholism, drug addiction, mental defect and psychosis, renal disease, gout, the use of steroids for more than six months, and pregnancy during the first four months. Between September, 1986, and September, 1989, 261 116 patients had had this regimen, and 151 107 (58%) of these have completed treatment; 76 179 (29%) are still under treatment and 33 830 (13%) have either dropped out or been lost to follow-up. 6% had adverse reactions, 2% died,1 % have been transferred from the programme area to another, and 0-7% refused treatment. Toxic reactions consisted mainly of jaundice. Nausea, vomiting, and arthralgia or the influenza syndrome were also seen, but did not usually necessitate withdrawal. All deaths were attributable to tuberculosis, the patients having had far-advanced disease at the outset. The completion rate so far, based on attendance and return of empty packs, is over 80%. On the basis of sputum tests, there is a 91 % conversion from positive to negative in those who completed the course. To our knowledge, this is the first report of the use of BCPs in a national tuberculosis programme in such a population. However, the pace of implementation has outstripped objective assessment of their value, notably in improving compliance. Steps are being taken to do urine spot-checks for isoniazid and the presence of the characteristic orange/brown colour imparted after ingestion of rifampicin. There have also been occasional lapses in the systematic
distribution of drugs. Nevertheless, the BCPs described here have proved highly acceptable to patients and staff and seem to have administrative, operational, and logistic advantages. Department of Health, Tuberculosis Control Service, Manila, Republic of the Philippines
F. S. VALEZA
Department of Dermatology, Slade Hospital, Oxford
A. C. MCDOUGALL
Georgiev GD, McDougall AC. Blister calendar packs: potential for improvement in the supply and utilization of multiple drug therapy in leprosy control programmes. Int J Lepr Other Mycobact Dis 1988; 56: 603-10. 2. Winsley BE, McDougall AC, Brown KE. Chemotherapy of leprosy: "bubble" or "calendar" packs for the administration of rifampin, dapsone, clofazimine or prothionamide/ethionamide. Int J Lepr Other Mycobact Dis 1983; 51: 592-94. 3. WHO. Chemotherapy of leprosy for control programmes: report of a WHO Study Group. Tech Rep Ser WHO 1982; no 675. 4. Editorial. A new approach to multidrug therapy for leprosy. Africa Health 1989, April/May (suppl): 5-6. 5. Revankar CR, Sorensen BH, Kielstrup RW. Delivery of MDT through blister calendar packs in leprosy eradication programmes: a multicentre field trial (phase 1). Lepr Rev 1989; 60: 135-38. 1.
Amphotericin-resistant invasive hepatosplenic candidiasis controlled by fluconazole SIR,-In March, 1988, Philadelphia-positive chronic granulocytic (250 x 109 white blood cells [WBC] per litre) was in a 23-year-old woman. A suitable donor for bone diagnosed marrow transplantation (BMT) could not be found. Cytostatic chemotherapy was instituted and WBC counts were reduced to 9 x 109/1 (March, 1989). In April, 1989, BMT was done with her father as the donor (3/4 identical for HLA, mixed lymphocyte culture negative) without preceding total body irradiation and following our mitobronitol/ cytarabine/cyclophosphamide conditioning protocol.1 The patient was barrier nursed, without laminar air flow. She received oral sulphonamide/trimethoprim, oral amphotericin, intravenous methotrexate, oral cyclosporin, and immunoglobulin every two leukaemia
weeks. From
day 7 post-transplant, sepsis became apparent. No pathogens could be grown. Despite treatment with several antibiotic combinations, her body temperature remained above 38°C and her clinical condition worsened gradually. Anti-candida haemagglutination titre, which was 1 in 160 on day 10, became 1 in 5120 on day 36; Aspergillus was not detected. Systemic amphotericin B was instituted, and escalating doses of up to 1 mg/kg body weight daily were given. Despite this treatment at day 55 disseminated hepatosplenic foci were detected, consisting of 5-16 mm large mainly solid, but occasionally cystic, units. Candida was not isolated from the one abscess biopsied. Nevertheless, Candida albicans spores and exceptional injured segmented forms were identified cytologically. By contrast with other transplanted patients, her WBC count reached 1
x
109/1
on
day
55. Graft-versus-host
disease,
or
other
transplant-related complications were absent. At day 82 the total intravenous amphotericin dose was 2-17 g. Her sepsis-associated fever, rarely over 39°C, did not diminish, and weight loss was about 20 kg. The size of hepatosplenic foci did not change. At this stage, she had direct intrahepatic/intravascular amphotericin via the truncus coeliacus. The daily dose was 25 mg. A total of 425 mg was infused into the liver up to day 98 post-transplant without any clinical amelioration or sonographic improvement. The anti-candida titre was 1 in 20 480. On day 99, amphotericin was withdrawn and fluconazole was instituted, 400 mg per day intravenously for the first two weeks, and 200 mg daily orally thereafter. On day 4 post-fluconazole her temperature began to diminish. For 9 days the patient was subfebrile, and from the third week post-fluconazole her temperature was almost normal and hepatosplenic foci diminished. At day 113 post-transplant the patient was discharged, having gained 7 kg in weight. Two months after fluconazole, the anti-candida titre was 1 in 1260. The patient is symptom-free and afebrile. 100 days post-fluconazole hepatosplenic
