- Email: [email protected]
Borrelia seropositive with no symptoms of Lyme disease
most
likely
due
to recurrent
chromogenic activity assay. The tPA antigen method used by Ridker and colleagues is likely to measure both free (active) tPA and tPA bound to PAI-1 as an inactive tPA/PAI-1 complex. The findings in their studies may have been a reflection of PAI-1 at least as much as of tPA.
malaria. Given with folinic
acid, pyrimethamine caused no notable toxicity. This regimen, therefore, seems advisable for treatment of HMSS, least in other African areas where chloroquine-resistant falciparum strains are widespread. The duration of pyrimethamine administration is relatively short and the number of patients who would need the drug is limited compared with the general population. Thus, from an epidemiological point of view, it is unlikely that such therapy could stimulate the appearance and the spread of the resistance of plasmodia to pyrimethamine-sulphonamide combinations used for the treatment of acute malaria in several endemic areas. at
P
Franco Manenti, Eliana Porta, Roberto
T W Meade, D J Howarth, J
1
2
Esposito, Spinello Antinori
2
3
4
5
Crane GG. Hyperreactive malarious splenomegaly (tropical splenomegaly syndrome). Parasitol Today 1986; 2: 4-9. Hoffman SL, Piessens WF, Ratiwayanto S, et al. Reduction of suppressor T lymphocytes in the tropical splenomegaly syndrome. N Engl J Med 1984; 310: 337-41. World Health Organization. Terminology of malaria and of malaria eradication. Monograph Series No 13. Geneva: World Health Organization, 1963. Sagoe A-S. Tropical splenomegaly syndrome: long-term proguanil therapy correlated with spleen size, serum IgM, and lymphocyte transformation. BMJ 1970; 3: 378-82. Fakunle YM. Tropical splenomegaly, part I: tropical Africa, Clin Haematol 1981; 10: 963-75.
Fibrinolytic activity and arterial disease SiR-Ridker and colleagues (April 16, p 940) add a clear relation of high tissue plasminogen activator (tPA) antigen with risk of stroke to their earlier report of a similar relation with myocardial infarction.’ These findings are- counter to the anticipated association of low fibrinolytic activity with the incidence of arterial disease. The explanation could lie in the difference between antigen and activity assays for components of the fibrinolytic system. We reported an independent association between low fibrinolytic activity and increased risk of ischaemic heart disease (IHD) in younger men in the Northwick Park Heart Study (NPHS), with the dilute clot lysis time (DCLT).2 We have now measured activity levels of tPA and of plasminogen activator inhibitor (PAI-1) in 28 patients (12 men, 16 women) aged between 21 and 58 (mean 43) years attending a thrombosis clinic either because they were at high risk or following clinical episodes (in the latter group at least several weeks after the event). None were taking agents to modify fibrinolysis. Both tPA activity and PAI-1 activity were measured with modifications of the chromogenic assay Coatest PAI (substrate S 2403, Chromogenix, Sweden). Mean values have been used for the 23 patients investigated on more than one occasion, the total number of samples being 81. Findings were similar in men and women. The correlation between tPA and DCLT was -0-51 (p=0006). The correlation between PAI-1 and DCLT was 0-71 Partial correlation coefficients with DCLT were (p<0001). calculated to allow for the association between tPA and PAI-1 (r-0-48, p=0001) and were -0-21 (p=029) for tPA and 0-59 (p=0001) for PAI-1. The correlation between DCLT and PAI-1 is strong, especially in view of the considerable within-person and laboratory variation in DCLT,3 and DCLT seems to be an index mainly of inhibition rather than activation of fibrinolysis. The association between low fibrinolytic activity and IHD in NPHS is probably mainly attributable to high PAI-1values in those who developed IHD and complements the relation between raised PAI-1 values and recurrent IHD in younger patientsalso based on a 1442
Ridker PM,
Vaughan DE, Stampfer MJ, Manson JE, Hennekens CH. Endogenous tissue-type plasminogen activator and risk of myocardial infarction. Lancet 1993; 341: 165-68. Meade TW, Ruddock V, Stirling Y, Chakrabarti R, Miller GJ. F brinolytic activity, clotting factors, and long-term incidence of ischaemic heart disease in the Northwick Park Heart Study. Lancet
1993; 342: 1076-79. Thompson SG, Martin JC, Meade TW. Sources of variability in coagulation factor assays. Thromb Haem 1987; 31: 685-92. 4 Hamsten A, Walldius G, Szamosi A, et al. Plasminogen activator inhibitor in plasma: risk factor for recurrent myocardial infarction. Lancet 1987; 2: 3-9. 5 Walker I, Davidson JF. Assessment of fibrinolysis. In: Bloom AL, Forbes CD, Thomas DP, Tuddenham EGD, eds. Haemostasis and
Mugana Hospital, Bukoba, Tanzania; and Clinic of Infectious Diseases, University of Parma and University of Milan, Via GB Grassi 74, 20157 Milan, Italy 1
Cooper, P K MacCallum, Y Stirling
MRC Epidemiology and Medical Care Unit, Wolfson Institute of Preventive Medicine, The Medical College of St Bartholomew’s Hospital, London EC1M 6BQ, UK
3
Thrombosis. London: Churchill
Livingstone,
Borrelia seropositive with Lyme disease
no
1994: 618.
symptoms of
SiR-Weber and Pfister’s review (April 23, p 1017) did not address management of the seropositive symptomless individual. Although there are significant numbers of falsepositive serological assays for Lyme borreliosis, more specific western blots are available,’ and the correct approach to a symptom-free seropositive individual who has no history of erythema migrans, arthritis, or other compatible complaints and who has been in an endemic area is unclear. It can be argued that such a person should be managed similarly to an individual who has a positive serological test for syphilis-ie, with a suitable antimicrobial agent. Syphilis and Lyme borreliosis resemble each other in some ways (spirochaetal aetiology, an initial cutaneous [or mucous membrane] inoculation, and a multistage illness with a primary cutaneous stage, a secondary multisystem stage, and late disease which can be difficult to cure). Additionally, late disease may occur without recognition of the earlier stages, and asymptomatic periods, sometimes long, can occur between stages. Routine antibiotic treatment is recommended for individuals with late latent syphilis2 in an effort to prevent progression to tertiary disease of the central nervous or cardiovascular systems. This recommendation appears based on the follow-up of untreated patients in the Tuskegee3 and Oslo. studies, both on patients with early syphilis. I am not aware, however, of similar data on seropositive individuals not known to have had clinical syphilis. A well-designed study of the history of asymptomatic Lyme seropositivity with and without treatment would be welcome.
Larry I Lutwick Infectious Diseases Division, Maimonides Medical Center and SUNY Health Science Center, Brooklyn, NY 11219, USA
1
Huycke MM, D’Alessio DD, Marx JJ. Prevalence of antibody to Borrelia burgdorferi by indirect fluorescent antibody assay, ELISA, and Western immunoblot in healthy adults in Wisconsin and Arizona. J Infect Dis 1992; 165: 1133-37.
2 3
Centers for Disease Control and Prevention. 1993 sexually transmitted disease treatment guidelines. MMWR 1993; 42 (RR-14): 1-102. Rockwell DG, Yobs AR, Moore MB. The Tuskegee study of untreated syphilis: the 30th year of observation. Arch Intern Med 1964; 114: 792-98.
4
Gjestland T. The Oslo study of untreated syphilis. Acta Dermatovener 1955; 35 (suppl 34): 1-368.
likely
due
to recurrent
chromogenic activity assay. The tPA antigen method used by Ridker and colleagues is likely to measure both free (active) tPA and tPA bound to PAI-1 as an inactive tPA/PAI-1 complex. The findings in their studies may have been a reflection of PAI-1 at least as much as of tPA.
malaria. Given with folinic
acid, pyrimethamine caused no notable toxicity. This regimen, therefore, seems advisable for treatment of HMSS, least in other African areas where chloroquine-resistant falciparum strains are widespread. The duration of pyrimethamine administration is relatively short and the number of patients who would need the drug is limited compared with the general population. Thus, from an epidemiological point of view, it is unlikely that such therapy could stimulate the appearance and the spread of the resistance of plasmodia to pyrimethamine-sulphonamide combinations used for the treatment of acute malaria in several endemic areas. at
P
Franco Manenti, Eliana Porta, Roberto
T W Meade, D J Howarth, J
1
2
Esposito, Spinello Antinori
2
3
4
5
Crane GG. Hyperreactive malarious splenomegaly (tropical splenomegaly syndrome). Parasitol Today 1986; 2: 4-9. Hoffman SL, Piessens WF, Ratiwayanto S, et al. Reduction of suppressor T lymphocytes in the tropical splenomegaly syndrome. N Engl J Med 1984; 310: 337-41. World Health Organization. Terminology of malaria and of malaria eradication. Monograph Series No 13. Geneva: World Health Organization, 1963. Sagoe A-S. Tropical splenomegaly syndrome: long-term proguanil therapy correlated with spleen size, serum IgM, and lymphocyte transformation. BMJ 1970; 3: 378-82. Fakunle YM. Tropical splenomegaly, part I: tropical Africa, Clin Haematol 1981; 10: 963-75.
Fibrinolytic activity and arterial disease SiR-Ridker and colleagues (April 16, p 940) add a clear relation of high tissue plasminogen activator (tPA) antigen with risk of stroke to their earlier report of a similar relation with myocardial infarction.’ These findings are- counter to the anticipated association of low fibrinolytic activity with the incidence of arterial disease. The explanation could lie in the difference between antigen and activity assays for components of the fibrinolytic system. We reported an independent association between low fibrinolytic activity and increased risk of ischaemic heart disease (IHD) in younger men in the Northwick Park Heart Study (NPHS), with the dilute clot lysis time (DCLT).2 We have now measured activity levels of tPA and of plasminogen activator inhibitor (PAI-1) in 28 patients (12 men, 16 women) aged between 21 and 58 (mean 43) years attending a thrombosis clinic either because they were at high risk or following clinical episodes (in the latter group at least several weeks after the event). None were taking agents to modify fibrinolysis. Both tPA activity and PAI-1 activity were measured with modifications of the chromogenic assay Coatest PAI (substrate S 2403, Chromogenix, Sweden). Mean values have been used for the 23 patients investigated on more than one occasion, the total number of samples being 81. Findings were similar in men and women. The correlation between tPA and DCLT was -0-51 (p=0006). The correlation between PAI-1 and DCLT was 0-71 Partial correlation coefficients with DCLT were (p<0001). calculated to allow for the association between tPA and PAI-1 (r-0-48, p=0001) and were -0-21 (p=029) for tPA and 0-59 (p=0001) for PAI-1. The correlation between DCLT and PAI-1 is strong, especially in view of the considerable within-person and laboratory variation in DCLT,3 and DCLT seems to be an index mainly of inhibition rather than activation of fibrinolysis. The association between low fibrinolytic activity and IHD in NPHS is probably mainly attributable to high PAI-1values in those who developed IHD and complements the relation between raised PAI-1 values and recurrent IHD in younger patientsalso based on a 1442
Ridker PM,
Vaughan DE, Stampfer MJ, Manson JE, Hennekens CH. Endogenous tissue-type plasminogen activator and risk of myocardial infarction. Lancet 1993; 341: 165-68. Meade TW, Ruddock V, Stirling Y, Chakrabarti R, Miller GJ. F brinolytic activity, clotting factors, and long-term incidence of ischaemic heart disease in the Northwick Park Heart Study. Lancet
1993; 342: 1076-79. Thompson SG, Martin JC, Meade TW. Sources of variability in coagulation factor assays. Thromb Haem 1987; 31: 685-92. 4 Hamsten A, Walldius G, Szamosi A, et al. Plasminogen activator inhibitor in plasma: risk factor for recurrent myocardial infarction. Lancet 1987; 2: 3-9. 5 Walker I, Davidson JF. Assessment of fibrinolysis. In: Bloom AL, Forbes CD, Thomas DP, Tuddenham EGD, eds. Haemostasis and
Mugana Hospital, Bukoba, Tanzania; and Clinic of Infectious Diseases, University of Parma and University of Milan, Via GB Grassi 74, 20157 Milan, Italy 1
Cooper, P K MacCallum, Y Stirling
MRC Epidemiology and Medical Care Unit, Wolfson Institute of Preventive Medicine, The Medical College of St Bartholomew’s Hospital, London EC1M 6BQ, UK
3
Thrombosis. London: Churchill
Livingstone,
Borrelia seropositive with Lyme disease
no
1994: 618.
symptoms of
SiR-Weber and Pfister’s review (April 23, p 1017) did not address management of the seropositive symptomless individual. Although there are significant numbers of falsepositive serological assays for Lyme borreliosis, more specific western blots are available,’ and the correct approach to a symptom-free seropositive individual who has no history of erythema migrans, arthritis, or other compatible complaints and who has been in an endemic area is unclear. It can be argued that such a person should be managed similarly to an individual who has a positive serological test for syphilis-ie, with a suitable antimicrobial agent. Syphilis and Lyme borreliosis resemble each other in some ways (spirochaetal aetiology, an initial cutaneous [or mucous membrane] inoculation, and a multistage illness with a primary cutaneous stage, a secondary multisystem stage, and late disease which can be difficult to cure). Additionally, late disease may occur without recognition of the earlier stages, and asymptomatic periods, sometimes long, can occur between stages. Routine antibiotic treatment is recommended for individuals with late latent syphilis2 in an effort to prevent progression to tertiary disease of the central nervous or cardiovascular systems. This recommendation appears based on the follow-up of untreated patients in the Tuskegee3 and Oslo. studies, both on patients with early syphilis. I am not aware, however, of similar data on seropositive individuals not known to have had clinical syphilis. A well-designed study of the history of asymptomatic Lyme seropositivity with and without treatment would be welcome.
Larry I Lutwick Infectious Diseases Division, Maimonides Medical Center and SUNY Health Science Center, Brooklyn, NY 11219, USA
1
Huycke MM, D’Alessio DD, Marx JJ. Prevalence of antibody to Borrelia burgdorferi by indirect fluorescent antibody assay, ELISA, and Western immunoblot in healthy adults in Wisconsin and Arizona. J Infect Dis 1992; 165: 1133-37.
2 3
Centers for Disease Control and Prevention. 1993 sexually transmitted disease treatment guidelines. MMWR 1993; 42 (RR-14): 1-102. Rockwell DG, Yobs AR, Moore MB. The Tuskegee study of untreated syphilis: the 30th year of observation. Arch Intern Med 1964; 114: 792-98.
4
Gjestland T. The Oslo study of untreated syphilis. Acta Dermatovener 1955; 35 (suppl 34): 1-368.