848
AT-111-deficient kindreds. In Italy in 1981 only 0-3% of all deaths were directly attributed to venous thromboembolism. National Bureau of Statistics data, based on death certificates, are probably underestimates: in necropsy studies pulmonary embolism regarded as fatal was found in 9% of cases, but in only 0-8-2-4% of patients was this not associated with some other terminal illness.s,6 Information obtained from published reports is subject to bias because in recent years familial AT III quantitative deficiency will not have had the same attention as formerly and kindreds with more unfavourble clinical courses will have been diagnosed and published more frequently. However, kindreds with severe clinical expression of AT III deficiency do exist and long-term prophylaxis with oral anticoagulants needs to be carefully evaluated in all members of these kindreds, whether they have symptoms or not. The necessity of life-long prophylaxis in those who have had a thrombosis is supported by our observation that a recurrent episode probably accounted for half the deaths from venous thromboembolism. A main target of long-term prophylaxis in AT III deficiency should be the prevention of morbidity from venous thromboembolism and of its sequelae, besides the prevention of mortality. AT-III-deficient individuals have the highest risk of first thrombosis between 15 and 50 years,4 and in our opinion the use of anticoagulants in such symptomless individuals, who as a rule have no indication for prophylaxis, should be reconsidered. A complete list of references available from the authors. Istituto di Semeiotica Medica, Catholic University, 00168 Rome, Italy
on
the AT-III-deficient families
analysed is
VALERIO DE STEFANO GIUSEPPE LEONE
1. Leone G, De Stefano V, Di Donfrancesco A, Ferrelli R, Traisci G, Bizzi B. Antithrombin III Pescara: a defective AT III variant with no alterations of plasma crossed immunoelectrophoresis; but with an abnormal crossed immunoelectrofocusing pattern. Br J Haematol 1987; 65: 187-91. 2. Finazzi G, Caccia R, Barbui T. Different prevalence of thromboembolism in the subtypes of congenital antithrombin III deficiency: review of 404 cases. Thromb Haemostas 1987; 58: 1094. 3. De Stefano V, Leone G. Antithrombin III congenital defects: revising classificaton system. Thromb Haemostas 1989; 62: 820-21. 4. Hirsh J, Piovella F, Pini M. Congenital anrithrombin III deficiency: incidence and clinical features. Am J Med 1989; 87 (suppl 3B): 34S-38S. 5. Macintyre IMC, Ruckley CV. Pulmonary embolism: a clinical and autopsy study. Scot Med J 1974; 19: 20-24. 6. Nielsen HK, Bechgaard P, Nielsen PF, Husted SE, Geday E. 178 fatal cases of pulmonary embolism in a medical department. Acta Med Scand 1981; 209: 351-55.
Helicobacter pylori infection in children
cohabiting
SiR,—The association between Helicobacterpylori in the stomach and histologically proven gastritis is well recognised. However, little is known about the sources, potential reservoirs, and routes of transmission of this bacterium. Since Hpylori has been isolated only from human gastric mucosa and is endemic throughout the world human beings are the most likely natural reservoir.’ Person-toperson transmission would be predicted and H pylori antibodies are found in household contacts of infected patients;2 saliva may be the route of transmission. Identification of the same strain of H pylori in cohabiting subjects would provide further confirmatory evidence of this view. We examined Hpylori isolates from areas of gastritis in 5 mentally handicapped children, who lived in close contact, by restriction endonuclease DNA analysis. All children (3 boys and 2 girls) aged 4-12 years were living in the same long-term care facility for several years. Samples were cultured at 37°C for up to five days under microaerophilic conditions on both selective and unselective media. H pylori colonies were subcultured from unselective medium and DNA was extracted by sodium dodecylsulphate alkaline lysis, as previously described.4 Dual restriction endonuclease analysis was completed with 10 units of Hind III for 1 h and 10 units of Bst EII for 1 h at 37°C and 60°C, respectively, in appropriate buffer as described by the manufacturer (Gibco BRL, Cergy-Pontoise, France). DNA fragments were separated by horizontal 7% agarose gel electrophoresis and photographed with an ’MP-4 Land’ camera
(Polaroid).
isolates, digested bacterial DNA samples were in electrophoresed the same gel with other H pylori strains from unrelated patients. Some had indistinguishable restriction patterns. Two children had identical patterns, as did two others. No overlap with other strains was observed. Our study shows that two individuals with infectious gastritis can be infected by the same strain. Contamination is unlikely because the endoscope was disinfected and the grip changed before each procedure, the linked children were not endoscoped on the same day, and bacterial counts were high. Many epidemiological studies have shown that living conditions may influence the communicability of H pylori. In our study, the living conditions suggest that person-to-person transmission was likely and that there was a common source of infection. The importance of saliva remains uncertain but some studies suggest that the mouth could be a reservoir’ and that oro-oral transmission could take place. To compare
Bacteriology Laboratory A, Faculty of Medicine, 59 045 Lille, France; and Paediatric Service, CHR de Lille, and CPIJ, Vendin-le-Viel
P. VINCENT F. GOTTRAND P. PERNES M. A. HUSSON A. BEJU H. LECLERC J. P. FARRIAUX
1. Graham DY, Adam E, Klein PD, et al. Epidemiology of Campylobacter pylon infection. Gastroenterol Clin Biol 1989; 13: 84B-89B 2. Graham DY, Malatty HM, Klein PD, Evans DG, Evans DJ, Adam E. Helicobacter pylon infection clusters in family. Rev Esp Enferm Apar Dig 1990; 78: 26. 3. Albenque M, Tall F, Dabis F, Megraud F. Epidemiological study of Helicobacter pylori transmission from mother to child in Africa Rev Esp Enferm Apar Dig 1990, 78: 48 4. Beji A, Izard D, Gaviny F, Leclerc H, Leseine-Delstanche M, Krembel J. A rapid chemical procedure for isolation and purification of chromosomal DNA from Gram-negative bacilli. Ann Biochem 1987; 162: 18-23 5. Krajden S, Fuksa M, Anderson J, et al. Examination of human stomach biopsies, saliva and dental plaque for Campylobacter pylori.J Clin Microbiol 1989; 27: 1397-98
Transmission of Brucella melitensis SIR,-Dr Ruben and colleagues (Jan 5, p 14) report person-toperson transmission of Brucella melitensis. The following case provides further evidence of between-person transmission of brucellosis. A 35-year-old Swedish man and his 30-year-old girlfriend spent two weeks in the south of Spain in June, 1989. They shared accommodation and meals with three other people. No-one had symptoms during the stay. The man had respiratory tract symptoms and remittent fever 14 weeks after leaving Spain. 4 weeks later swelling of the right knee developed and 8 weeks after this (December, 1989) he had a right-sided epididymitis. He was given amoxycillin and cefadroxil for airway symptoms, diclofenac for arthritis, and ciprofloxacin for epididymitis. Faecal and blood cultures were negative, but the latter were not taken until after antibiotics were begun. In December he had titres of 640 against Yersinia enterocolitica type 9 and 320 against Brucella abortus. He eventually recovered uneventfully and was believed to have had
yersinia infection. Stored serum samples were sent to the state bacteriological laboratory, Solna, Sweden, for analysis by ELISA. A rising IgG titre (peak 850) and decreasing IgM titre (peak > 1500) compatible with brucella infection were recorded. This patient’s girlfriend became ill in April, 1990-9 months after the stay in Spain-with sudden fever, sweating, headache, and leucopenia. Repeated blood cultures grew B melitensis. Serum agglutinin titre to B abortus was 320 and to Y enterocolitica type 9 160. Peak antibody titres to brucella measured with ELISA were IgM over 1500 and IgG 850. She was given doxycycline and rifampicin and recovered without complications. Although the diagnosis of the man was not verified by culture, the clinical picture as well as the serological findings are, in retrospect, compatible with brucellosis. There is serological crossreactivity between brucella and yersinia antigens, which may account for the serological reactivity that confused the diagnosis. The disease started in the
woman
9 months after
possible
exposure. This exceeds the maximum recorded incubation time of 7 months.1,2 It therefore seems unlikely that both patients were
infected in Spain. The fact that the three individuals with whom they shared accommodation at that time were not infected and had
AT-111-deficient kindreds. In Italy in 1981 only 0-3% of all deaths were directly attributed to venous thromboembolism. National Bureau of Statistics data, based on death certificates, are probably underestimates: in necropsy studies pulmonary embolism regarded as fatal was found in 9% of cases, but in only 0-8-2-4% of patients was this not associated with some other terminal illness.s,6 Information obtained from published reports is subject to bias because in recent years familial AT III quantitative deficiency will not have had the same attention as formerly and kindreds with more unfavourble clinical courses will have been diagnosed and published more frequently. However, kindreds with severe clinical expression of AT III deficiency do exist and long-term prophylaxis with oral anticoagulants needs to be carefully evaluated in all members of these kindreds, whether they have symptoms or not. The necessity of life-long prophylaxis in those who have had a thrombosis is supported by our observation that a recurrent episode probably accounted for half the deaths from venous thromboembolism. A main target of long-term prophylaxis in AT III deficiency should be the prevention of morbidity from venous thromboembolism and of its sequelae, besides the prevention of mortality. AT-III-deficient individuals have the highest risk of first thrombosis between 15 and 50 years,4 and in our opinion the use of anticoagulants in such symptomless individuals, who as a rule have no indication for prophylaxis, should be reconsidered. A complete list of references available from the authors. Istituto di Semeiotica Medica, Catholic University, 00168 Rome, Italy
on
the AT-III-deficient families
analysed is
VALERIO DE STEFANO GIUSEPPE LEONE
1. Leone G, De Stefano V, Di Donfrancesco A, Ferrelli R, Traisci G, Bizzi B. Antithrombin III Pescara: a defective AT III variant with no alterations of plasma crossed immunoelectrophoresis; but with an abnormal crossed immunoelectrofocusing pattern. Br J Haematol 1987; 65: 187-91. 2. Finazzi G, Caccia R, Barbui T. Different prevalence of thromboembolism in the subtypes of congenital antithrombin III deficiency: review of 404 cases. Thromb Haemostas 1987; 58: 1094. 3. De Stefano V, Leone G. Antithrombin III congenital defects: revising classificaton system. Thromb Haemostas 1989; 62: 820-21. 4. Hirsh J, Piovella F, Pini M. Congenital anrithrombin III deficiency: incidence and clinical features. Am J Med 1989; 87 (suppl 3B): 34S-38S. 5. Macintyre IMC, Ruckley CV. Pulmonary embolism: a clinical and autopsy study. Scot Med J 1974; 19: 20-24. 6. Nielsen HK, Bechgaard P, Nielsen PF, Husted SE, Geday E. 178 fatal cases of pulmonary embolism in a medical department. Acta Med Scand 1981; 209: 351-55.
Helicobacter pylori infection in children
cohabiting
SiR,—The association between Helicobacterpylori in the stomach and histologically proven gastritis is well recognised. However, little is known about the sources, potential reservoirs, and routes of transmission of this bacterium. Since Hpylori has been isolated only from human gastric mucosa and is endemic throughout the world human beings are the most likely natural reservoir.’ Person-toperson transmission would be predicted and H pylori antibodies are found in household contacts of infected patients;2 saliva may be the route of transmission. Identification of the same strain of H pylori in cohabiting subjects would provide further confirmatory evidence of this view. We examined Hpylori isolates from areas of gastritis in 5 mentally handicapped children, who lived in close contact, by restriction endonuclease DNA analysis. All children (3 boys and 2 girls) aged 4-12 years were living in the same long-term care facility for several years. Samples were cultured at 37°C for up to five days under microaerophilic conditions on both selective and unselective media. H pylori colonies were subcultured from unselective medium and DNA was extracted by sodium dodecylsulphate alkaline lysis, as previously described.4 Dual restriction endonuclease analysis was completed with 10 units of Hind III for 1 h and 10 units of Bst EII for 1 h at 37°C and 60°C, respectively, in appropriate buffer as described by the manufacturer (Gibco BRL, Cergy-Pontoise, France). DNA fragments were separated by horizontal 7% agarose gel electrophoresis and photographed with an ’MP-4 Land’ camera
(Polaroid).
isolates, digested bacterial DNA samples were in electrophoresed the same gel with other H pylori strains from unrelated patients. Some had indistinguishable restriction patterns. Two children had identical patterns, as did two others. No overlap with other strains was observed. Our study shows that two individuals with infectious gastritis can be infected by the same strain. Contamination is unlikely because the endoscope was disinfected and the grip changed before each procedure, the linked children were not endoscoped on the same day, and bacterial counts were high. Many epidemiological studies have shown that living conditions may influence the communicability of H pylori. In our study, the living conditions suggest that person-to-person transmission was likely and that there was a common source of infection. The importance of saliva remains uncertain but some studies suggest that the mouth could be a reservoir’ and that oro-oral transmission could take place. To compare
Bacteriology Laboratory A, Faculty of Medicine, 59 045 Lille, France; and Paediatric Service, CHR de Lille, and CPIJ, Vendin-le-Viel
P. VINCENT F. GOTTRAND P. PERNES M. A. HUSSON A. BEJU H. LECLERC J. P. FARRIAUX
1. Graham DY, Adam E, Klein PD, et al. Epidemiology of Campylobacter pylon infection. Gastroenterol Clin Biol 1989; 13: 84B-89B 2. Graham DY, Malatty HM, Klein PD, Evans DG, Evans DJ, Adam E. Helicobacter pylon infection clusters in family. Rev Esp Enferm Apar Dig 1990; 78: 26. 3. Albenque M, Tall F, Dabis F, Megraud F. Epidemiological study of Helicobacter pylori transmission from mother to child in Africa Rev Esp Enferm Apar Dig 1990, 78: 48 4. Beji A, Izard D, Gaviny F, Leclerc H, Leseine-Delstanche M, Krembel J. A rapid chemical procedure for isolation and purification of chromosomal DNA from Gram-negative bacilli. Ann Biochem 1987; 162: 18-23 5. Krajden S, Fuksa M, Anderson J, et al. Examination of human stomach biopsies, saliva and dental plaque for Campylobacter pylori.J Clin Microbiol 1989; 27: 1397-98
Transmission of Brucella melitensis SIR,-Dr Ruben and colleagues (Jan 5, p 14) report person-toperson transmission of Brucella melitensis. The following case provides further evidence of between-person transmission of brucellosis. A 35-year-old Swedish man and his 30-year-old girlfriend spent two weeks in the south of Spain in June, 1989. They shared accommodation and meals with three other people. No-one had symptoms during the stay. The man had respiratory tract symptoms and remittent fever 14 weeks after leaving Spain. 4 weeks later swelling of the right knee developed and 8 weeks after this (December, 1989) he had a right-sided epididymitis. He was given amoxycillin and cefadroxil for airway symptoms, diclofenac for arthritis, and ciprofloxacin for epididymitis. Faecal and blood cultures were negative, but the latter were not taken until after antibiotics were begun. In December he had titres of 640 against Yersinia enterocolitica type 9 and 320 against Brucella abortus. He eventually recovered uneventfully and was believed to have had
yersinia infection. Stored serum samples were sent to the state bacteriological laboratory, Solna, Sweden, for analysis by ELISA. A rising IgG titre (peak 850) and decreasing IgM titre (peak > 1500) compatible with brucella infection were recorded. This patient’s girlfriend became ill in April, 1990-9 months after the stay in Spain-with sudden fever, sweating, headache, and leucopenia. Repeated blood cultures grew B melitensis. Serum agglutinin titre to B abortus was 320 and to Y enterocolitica type 9 160. Peak antibody titres to brucella measured with ELISA were IgM over 1500 and IgG 850. She was given doxycycline and rifampicin and recovered without complications. Although the diagnosis of the man was not verified by culture, the clinical picture as well as the serological findings are, in retrospect, compatible with brucellosis. There is serological crossreactivity between brucella and yersinia antigens, which may account for the serological reactivity that confused the diagnosis. The disease started in the
woman
9 months after
possible
exposure. This exceeds the maximum recorded incubation time of 7 months.1,2 It therefore seems unlikely that both patients were
infected in Spain. The fact that the three individuals with whom they shared accommodation at that time were not infected and had
