- Email: [email protected]
BCG, tuberculosis, and leprosy
304
prophylaxis.7 Our technique should also be applicable to other protozoan parasites found in blood and to human genetic studies.8 Supported by WHO/UNDP/World Bank special programme and by Overseas Development Administration. F.M.A.E.K. is supported by the British Council and the Sir Halley Stewart Trust and is in receipt of an ORS award. We thank John Frean for help in developing the malaria PCR protocol. PHLS Malaria Reference Laboratory and Department of Medical Parasitology, London School of Hygiene and Tropical Medicine, London W1 E 7HT, UK
D. C. WARHURST F. M. AWAD EL KARIEM M. A. MILES
1. Anon. DNA diagnosis and the polymerase chain reaction. Lancet 1988; i: 1372-73. 2. Wilson CM, Serrano AE, Wasley A, et al. Amplification of a gene related to mammalian mdr genes in drug-resistant Plasmodium falciparum. Science 1989; 244: 1184-86. 3. Foote SJ, Thompson JK, Cowman AF, Kemp DJ. Amplification of the multidrug resistance gene in some chloroquine-resistant isolates of Plasmodium falciparum. Cell 1989; 57: 921-30. 4. Mercier B, Gaucher C, Feugeas O, Mazurier C. Direct PCR from whole blood, without DNA extraction. Nucl Acids Res 1990; 18: 5908. 5. Desjardins RE, Canfield CJ, Haynes JD, Chulay JD. Quantitative assessment of antimalarial activity in vitro by a semi-automated microdilution technique. Antimicrob Ag Chemother 1979; 16: 710-18. 6. Dowling MAC, Shute GT. A comparative study of thick and thin blood films in the diagnosis of scanty malaria parasitaemia. Bull WHO 1966; 34: 249-67. 7. Warhurst DC. Diagnosis of malaria. Lancet 1990; 335: 472. 8. Nelson PV, Carey WF, Moms CP. Gene amplification directly from Guthrie blood spots. Lancet 1990; 336: 1451-52.
and adverse reactions to treatment in Onchocerca volvulus-infected British expatriates treated with ivermectin. We report here our experience in American expatriates. Since 1988, the Centers for Disease Control has monitored the release of ivermectin for the treatment of patients with onchocerciasis in the United States. 27 US citizens have been treated for 0 volvulus infections. 14 patients were male, and the median age was 33. Most were in occupations necessitating long stays in onchocerciasis-endemic areas of West and Central Africa; 9 were field scientists, 8 were Peace Corps volunteers, and 8 were missionaries or their family members. Lengths of stay in these areas ranged from 3 months to 8 years, with a median of 2 years. Onchocerciasis was confirmed in 25 by skin snip, nodulectomy, and/or slit-lamp examination of the ocular anterior chamber. The other two patients had compatible clinical symptoms and exposure history. All were treated as outpatients with a standard oral dose of ivermectin 150 Ixg/kg. 10 patients who had recurrent or persistent symptoms after 6 months or more were re-treated with the same dose; all responded favourably. Adverse reactions were noted at a frequency similar to that recorded in British expatriates except that localised oedema was less common in the Americans and none reported fever. All reactions were mild and transient: Reaction Pruritus Rash
Fatigue Localised oedema Headache Chills
BCG, tuberculosis, and leprosy SIR,-Abel and colleagues1 confirm the results of othersz in their case-control study that showed the protective efficacy of BCG against the non-lepromatous form of leprosy in southern Vietnam. These findings may reflect defective cellular immunity against mycobacteria in lepromatous patients. We have reanalysed our data on risk factors for leprosy3.4 to fmd if there was a negative association between tuberculosis and tuberculoid leprosy. 116 patients with lepromatous leprosy (LL) and 73 patients with tuberculoid leprosy (TT) were studied who were seen as outpatients at the Center for Hansen’s disease in Athens. Only cases with either of the two polar types of leprosy were included. 382 patients of low socioeconomic class, admitted to nearby hospitals for other reasons, acted as a control group. All subjects were of caucasian origin, a unique feature of this study. For patients with LL and TT, 10 (8-6%) and 0 subjects had a history of tuberculosis, respectively (=6-64, p=0-01). The frequency of tuberculosis among control patients was 10%. We conclude that there is a negative correlation between tuberculosis and the TT form of leprosy, which is not found in the LL form. These data support the evidence emerging from efficacy studies of BCG vaccination for leprosy prevention, which suggest that cellular immune responses, probably linked to major histocompatibility complex alleles, are important modifiers of the clinical expression of leprosy. 3,4 University of Athens Medical School, 115 27 Goudi, Athens, Greece
EVANGELIA KAKLAMANI YVONNI KOUMANDAKI KLEA KATSOUYANNI
Department of Epidemiology, Harvard School of Public Health, USA
DIMITRIOS TRICHOPOULOS
1. Abel L, Cua VV, Oberti J, et al. Leprosy and BCG in southern Vietnam. Lancet 1990; i: 1536. 2. Fine PEM. BCG vaccination against tuberculosis and leprosy Br Med Bull 1988; 44: 691-703. 3. Papaioannou DJ, Kaklamani EP, Parissis NG, Koumantaki IG, Karalis DT, Trichopoulos DR. Hepatitis B virus (HBV) serum markers in Greek leprosy patients. Int J Lepr 1986; 54: 245-51. 4. Koumantaki IG, Katsouyanni KM, Kaklamani EP, et al. An investigation of family size and birth order as risk factors in leprosy. Int J Lepr 1987; 55: 463-67.
Expatriates treated with ivermectin we are rapidly gaining experience in the of onchocerciasis in residents of Africa and Latin America, little is known about the effects of this disease or its treatment on visitors to onchocerciasis-endemic regions.1,2 Dr Davidson and colleagues (Oct 20, p 1005) describe initial symptoms
SIR,-Although
treatment
No 6 3 3 3 2 2
Reaction Hives Nausea Dizzmess
Myalgia Groin pain
Limbitis/lens opacities
No 1 1 1 1 1 1
This
experience shows that individuals in certain occupational groups who spend more than 3 months in onchocerciasis-endemic areas are at risk for the disease and should be considered for targeted prevention. Adverse reactions to ivermectin are common in 0 volvulus-infected expatriates but in this series the reactions were not severe and are generally well-tolerated by outpatients. Parasitic Diseases Branch, Division of Parasitic Diseases, and Clinical Medicine Branch, Division of Immunologic, Oncologic, and Hematologic Diseases, Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia 30333, USA
RALPH T. BRYAN SUSAN L. STOKES HARRISON C. SPENCER
Pacque M, Munoz B, Greene BM, et al. Safety and compliance with communitybased ivermectin therapy. Lancet 1990; 335: 1377-80 2. Taylor HR, Greene BM. The status of ivermectin in the treatment of human onchocerciasis. Am J Trop Med Hyg 1989; 41: 460-66. 1.
Sudden infant death in Thailand and Alaska S;R,—Dr Wilson (Nov 10, p 1199) questions why sudden infant death syndrome (SIDS) is so uncommon or virtually unknown in south China whereas there is a high frequency in native Indians of Alberta, Canada. The same question could be raised about North Americans of Chinese ancestry, who have a low frequency of SIDS, and Alaska native infants, who have one of the highest rates. In 1990 we visited forensic facilities in Thailand and gathered information about SIDS. In a heavily populated north-west province, a medical examiner who had trained in forensic pathology in the USA could not recall an infant death diagnosed as SIDS during the past several years. In a north-eastern province, a forensic pathologist participating in a government collaborative study on sudden unexplained death in adults (SUDS) could recall only one medical examiner’s case being diagnosed as SIDS. In other provinces the general consensus by medical examiners is that Thai infants are at near zero risk of SIDS. Despite the difficulties of basic sanitation in this developing country, infants may be at less risk for injury in Thailand than those in Western countries. When a Thai mother is occupied with housework, grandparents may attend the infant and provide extra care. In addition, it is culturally unacceptable for Thai (or Chinese) mothers to consume alcohol while nursing or bedsharing with their infants. Fetal alcohol syndrome is not a health problem in Thai or Chinese infants, unlike native North American infants.
prophylaxis.7 Our technique should also be applicable to other protozoan parasites found in blood and to human genetic studies.8 Supported by WHO/UNDP/World Bank special programme and by Overseas Development Administration. F.M.A.E.K. is supported by the British Council and the Sir Halley Stewart Trust and is in receipt of an ORS award. We thank John Frean for help in developing the malaria PCR protocol. PHLS Malaria Reference Laboratory and Department of Medical Parasitology, London School of Hygiene and Tropical Medicine, London W1 E 7HT, UK
D. C. WARHURST F. M. AWAD EL KARIEM M. A. MILES
1. Anon. DNA diagnosis and the polymerase chain reaction. Lancet 1988; i: 1372-73. 2. Wilson CM, Serrano AE, Wasley A, et al. Amplification of a gene related to mammalian mdr genes in drug-resistant Plasmodium falciparum. Science 1989; 244: 1184-86. 3. Foote SJ, Thompson JK, Cowman AF, Kemp DJ. Amplification of the multidrug resistance gene in some chloroquine-resistant isolates of Plasmodium falciparum. Cell 1989; 57: 921-30. 4. Mercier B, Gaucher C, Feugeas O, Mazurier C. Direct PCR from whole blood, without DNA extraction. Nucl Acids Res 1990; 18: 5908. 5. Desjardins RE, Canfield CJ, Haynes JD, Chulay JD. Quantitative assessment of antimalarial activity in vitro by a semi-automated microdilution technique. Antimicrob Ag Chemother 1979; 16: 710-18. 6. Dowling MAC, Shute GT. A comparative study of thick and thin blood films in the diagnosis of scanty malaria parasitaemia. Bull WHO 1966; 34: 249-67. 7. Warhurst DC. Diagnosis of malaria. Lancet 1990; 335: 472. 8. Nelson PV, Carey WF, Moms CP. Gene amplification directly from Guthrie blood spots. Lancet 1990; 336: 1451-52.
and adverse reactions to treatment in Onchocerca volvulus-infected British expatriates treated with ivermectin. We report here our experience in American expatriates. Since 1988, the Centers for Disease Control has monitored the release of ivermectin for the treatment of patients with onchocerciasis in the United States. 27 US citizens have been treated for 0 volvulus infections. 14 patients were male, and the median age was 33. Most were in occupations necessitating long stays in onchocerciasis-endemic areas of West and Central Africa; 9 were field scientists, 8 were Peace Corps volunteers, and 8 were missionaries or their family members. Lengths of stay in these areas ranged from 3 months to 8 years, with a median of 2 years. Onchocerciasis was confirmed in 25 by skin snip, nodulectomy, and/or slit-lamp examination of the ocular anterior chamber. The other two patients had compatible clinical symptoms and exposure history. All were treated as outpatients with a standard oral dose of ivermectin 150 Ixg/kg. 10 patients who had recurrent or persistent symptoms after 6 months or more were re-treated with the same dose; all responded favourably. Adverse reactions were noted at a frequency similar to that recorded in British expatriates except that localised oedema was less common in the Americans and none reported fever. All reactions were mild and transient: Reaction Pruritus Rash
Fatigue Localised oedema Headache Chills
BCG, tuberculosis, and leprosy SIR,-Abel and colleagues1 confirm the results of othersz in their case-control study that showed the protective efficacy of BCG against the non-lepromatous form of leprosy in southern Vietnam. These findings may reflect defective cellular immunity against mycobacteria in lepromatous patients. We have reanalysed our data on risk factors for leprosy3.4 to fmd if there was a negative association between tuberculosis and tuberculoid leprosy. 116 patients with lepromatous leprosy (LL) and 73 patients with tuberculoid leprosy (TT) were studied who were seen as outpatients at the Center for Hansen’s disease in Athens. Only cases with either of the two polar types of leprosy were included. 382 patients of low socioeconomic class, admitted to nearby hospitals for other reasons, acted as a control group. All subjects were of caucasian origin, a unique feature of this study. For patients with LL and TT, 10 (8-6%) and 0 subjects had a history of tuberculosis, respectively (=6-64, p=0-01). The frequency of tuberculosis among control patients was 10%. We conclude that there is a negative correlation between tuberculosis and the TT form of leprosy, which is not found in the LL form. These data support the evidence emerging from efficacy studies of BCG vaccination for leprosy prevention, which suggest that cellular immune responses, probably linked to major histocompatibility complex alleles, are important modifiers of the clinical expression of leprosy. 3,4 University of Athens Medical School, 115 27 Goudi, Athens, Greece
EVANGELIA KAKLAMANI YVONNI KOUMANDAKI KLEA KATSOUYANNI
Department of Epidemiology, Harvard School of Public Health, USA
DIMITRIOS TRICHOPOULOS
1. Abel L, Cua VV, Oberti J, et al. Leprosy and BCG in southern Vietnam. Lancet 1990; i: 1536. 2. Fine PEM. BCG vaccination against tuberculosis and leprosy Br Med Bull 1988; 44: 691-703. 3. Papaioannou DJ, Kaklamani EP, Parissis NG, Koumantaki IG, Karalis DT, Trichopoulos DR. Hepatitis B virus (HBV) serum markers in Greek leprosy patients. Int J Lepr 1986; 54: 245-51. 4. Koumantaki IG, Katsouyanni KM, Kaklamani EP, et al. An investigation of family size and birth order as risk factors in leprosy. Int J Lepr 1987; 55: 463-67.
Expatriates treated with ivermectin we are rapidly gaining experience in the of onchocerciasis in residents of Africa and Latin America, little is known about the effects of this disease or its treatment on visitors to onchocerciasis-endemic regions.1,2 Dr Davidson and colleagues (Oct 20, p 1005) describe initial symptoms
SIR,-Although
treatment
No 6 3 3 3 2 2
Reaction Hives Nausea Dizzmess
Myalgia Groin pain
Limbitis/lens opacities
No 1 1 1 1 1 1
This
experience shows that individuals in certain occupational groups who spend more than 3 months in onchocerciasis-endemic areas are at risk for the disease and should be considered for targeted prevention. Adverse reactions to ivermectin are common in 0 volvulus-infected expatriates but in this series the reactions were not severe and are generally well-tolerated by outpatients. Parasitic Diseases Branch, Division of Parasitic Diseases, and Clinical Medicine Branch, Division of Immunologic, Oncologic, and Hematologic Diseases, Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia 30333, USA
RALPH T. BRYAN SUSAN L. STOKES HARRISON C. SPENCER
Pacque M, Munoz B, Greene BM, et al. Safety and compliance with communitybased ivermectin therapy. Lancet 1990; 335: 1377-80 2. Taylor HR, Greene BM. The status of ivermectin in the treatment of human onchocerciasis. Am J Trop Med Hyg 1989; 41: 460-66. 1.
Sudden infant death in Thailand and Alaska S;R,—Dr Wilson (Nov 10, p 1199) questions why sudden infant death syndrome (SIDS) is so uncommon or virtually unknown in south China whereas there is a high frequency in native Indians of Alberta, Canada. The same question could be raised about North Americans of Chinese ancestry, who have a low frequency of SIDS, and Alaska native infants, who have one of the highest rates. In 1990 we visited forensic facilities in Thailand and gathered information about SIDS. In a heavily populated north-west province, a medical examiner who had trained in forensic pathology in the USA could not recall an infant death diagnosed as SIDS during the past several years. In a north-eastern province, a forensic pathologist participating in a government collaborative study on sudden unexplained death in adults (SUDS) could recall only one medical examiner’s case being diagnosed as SIDS. In other provinces the general consensus by medical examiners is that Thai infants are at near zero risk of SIDS. Despite the difficulties of basic sanitation in this developing country, infants may be at less risk for injury in Thailand than those in Western countries. When a Thai mother is occupied with housework, grandparents may attend the infant and provide extra care. In addition, it is culturally unacceptable for Thai (or Chinese) mothers to consume alcohol while nursing or bedsharing with their infants. Fetal alcohol syndrome is not a health problem in Thai or Chinese infants, unlike native North American infants.