Lyme borreliosis

Lyme borreliosis

Within the past four months an attempt by the World in Action television team to interview districts who sought to restrict clozapine was met with sto...

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Within the past four months an attempt by the World in Action television team to interview districts who sought to restrict clozapine was met with stony silence. Indeed only this week I offered the family of a severely tortured schizophrenic the opportunity to try clozapine, which had been denied to him in his home district. His purchasing authority threatened to report me to my Trust board because dealing with families was not in the NHS regulations. Although Kerwin’s statement that "the prospects for schizophrenia research are looking up" is undoubtedly true, I am less sure about the prospects for schizophrenics, as long as we continue to be seen to support covert restrictions based on rather primitive economic notions.

EIAs based on synthetic peptides derived from the V3 loop of the envelope proteins representing group 0 (ANT70 and MVP5180) were used to screen the 62 seropositive samples. No group 0 reactivity (ANT70-like or MVP5180-like) was found. *Abinbola J Dada, Yetunde M Olumide, Denis R Henrard, Bruce Phelps, Chou-Pong Pau, Thomas C Quinn, Robert J Biggar, Thomas R O’Brien, William A Blattner *Viral Epidemiology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD20852, USA; STD/Dermatology Clinic, Lagos University Teaching Hospital, Lagos, Nigeria; Retrovirus Medical Research, Abbott Laboratories, Chicago, USA; Division of HIV/AIDS, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta; and Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH

Mike Launer Burnley

General

Hospital, Casterton Avenue, Burnley BB10 2PQ, UK

Search for HIV-1 group 0 infection in

Gurtler LG, Hauser PH, Eberle J, et al. A new subtype of human immunodeficiency virus type 1 (MVP-5180) from Cameroon. J Virol

2

De Lays R, Van der Borght B, Van den Heasevelde M, et al. Isolation and partial characterization of an unusual human immunodeficiency retrovirus from two persons of West Central African origin. J Virol

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Schable C, Zekeng L, Chou-Pong P, et al. Sensitivity of United States HIV antibody tests for detection of HIV-1 group O infections. Lancet

4

Nkengasong JNB, Peeters M, Van den Haesevelde M, et al. Antigenic

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evidence of the presence of the aberrant HIV-1 ANT70 virus in Cameroon and Gabon. AIDS 1993; 7: 1536-38. Candal DH, Pau C-P, Kai M, et al. Search for HIV-1 group O infections by peptide serology. ASTPHLD meeting (Reno, Nevada) March 6-9, 1995.

149; 68: 1581-85.

Nigeria

SIR—Among the HIV-1strains is the immunologically and genetically divergent group O1,2 which is thought to represent separate introduction of HIV-1 infection into man. HIV-1 group 0 (ANT70 and MVP5180) was first isolated in 1989;’ it has distinct serological behaviour in that some licensed HIV antibody screening assays failed to detect some individuals infected with this strain.Geographically, most infections with HIV-1 group 0 strains have been reported among people from Cameroon and Gabon.3-5 The proximity of Nigeria (which borders Cameroon) to the epicentre of HIV-1 group 0 infection and the strategic locale of Lagos as a large commercial centre along the transcontinental route from Cameroon to West Africa, coupled with the increasing prevalence of HIV-1, makes Lagos a useful sentinel for HIV1 group 0 detection. From a total population of 2000 commercial sex workers and patients seen at clinics for sexually transmitted disease, between 1990-91 and 1994, we selected 248 serum samples on the basis of their reactivity in a standard viral-lysate a

enzyme-linked immunoassay (EIA) (Genetic Systems, Seattle). Of 182 reactive specimens, 61 were HIV westernblot positive, 73 were indeterminate, and 48 were negative (no bands). The remaining 66 were EIA negative but had varying numbers of reactive bands. The samples were then sent to Abbott Laboratories, Chicago, and also the US Centers for Disease Control and Prevention, Atlanta, for HIV-1 group 0 testing. The 248 samples were tested at Abbott Laboratories by the Clonatech HIV (1 +2) EIA. This assay was introduced as a peptide-based diagnostic screen for all HIV strains but is typically non-reactive with group 0, so reactivity in the viral lysate EIA but not in the Clonatech assay might indicate antibody to HIV-1 group O. 94 samples had negative Clonatech results, including 2 that were western-blot positive. The remaining 92 were negative or indeterminate on western blot. 40 of the 94 sampled (including the 2 western blot-positives) were further evaluated for type 0 reactivity using "consensus" group 0 specific peptides for the gp41 region of HIV-1. None of the Clonatech negative samples had group 0 peptide reactivity. No further testing or characterisation was attempted. At a later date, an additional 19 samples from patients referred to the STD/Dermatology Clinic of Lagos University Teaching Hospital in July and August, 1994, were screened. 12 of these patients lived in the eastern region of Nigeria directly bordering Cameroon and 7 came from Cameroon itself. None of the 19 samples had peptide reactivity consistent with type 0 infection. At CDC all 248 samples were tested by Genetic HIV 1/2 EIA, and 62 samples were screened HIV 1436

1

Systems positive.

1990; 64: 1207-216.

1994; 344: 1333-34.

Lyme borreliosis SIR—Vartiovaara (April 1, p 842) describes his experience of living with lyme disease. We wish to make the following comments.

One of us (JVSL) (hereinafter referred to as "the patient") has been living with lyme since the spring of 1988, and has chronic neurological, cardiac, and osteomusculoarticular problems.’ Until the patient was diagnosed three and a half years after being bitten by an arthropod, he had been regarded as a depressive neurotic, despite his efforts to convince his doctor that his illness was organic and serious. Lyme borreliosis is diagnosed clinically,2 which underlines the importance of listening to the patient, investigating, understanding, and evaluating each one of the symptoms and signs, and searching for an organic cause. Like Vartiovaara, he had no erythema migrans, but had a lump near the site of the bite (back) and was seronegative. These findings delayed antibiotic treatment until his illness became life-threatening. We think that in seronegative patients the immune system should be evaluated and that antibiotics are needed. Our patient received during 2 years seven short-term antibotic treatments, achieving transitory improvements. Nonetheless, his condition greatly deteriorated. In October, 1993, he started a different antibiotic regimen (ceftriaxone, 2 g per day intravenously for 12 months, oral roxithromycin 150 mg per day for 2 months, and oral ciprofloxacin, 500 mg per 12 hours for 2 months). After ceftriaxone he has continued with oral minocycline, 100 mg per 12 hours for 7 months. His quality of life has greatly improved and the treatment is more tolerable than the borreliosis. Perhaps Vartiovaara’s problems are caused by autoimmune events since his PCR for Borrelia burgdorferi was negative. There is controversy about the value of such techniques.3,4 We agree with Vartiovaara’s comment that "When the whole picture leans towards Lyme borreliosis it is both ethically and medically right to treat". We add, however, in accord with the advice of others3,5 that

antibiotics should be continued in the long term, until achieve cure or delay the progression of the disease.

we

*Josep Ferris i Tortajada, Juan A López Andreu, José Salcede Vivó, Jesús V Sala Lizarraga Departments of

*Paediatrics and Clinical Biopathology, Hospital Infantil "La Fe". Valencia 46009, Spain; and Rehabilitation Service, Hospital General Universitario, Val

1 López-Andreu JA, Ferns J, Canosa CA, Sala-Lizarraga JA. Treatment of late Lyme disease: a challenge to accept. J Clin Microbiol 1994; 32: 1415-16. 2 Burrascano J Jr.

Managing Lyme disease: late-stage Lyme disease: options and guidelines. Int Med Spec 1989; 10: 102-07. Pachner AR, Delaney E. The polymerase chain reaction in the diagnosis of Lyme neuroborreliosis. Ann Neurol 1993; 34: 544-49. Liegner KB. Lyme disease: the sensible pursuit of answers. J Clin Microbiol 1993; 31: 1961-63. treatment

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SIR-I share Vartiovaara’s concern about the diagnosis of Lyme borreliosis, but the patient and his physician often confront the difficulties together. Antibody tests sometimes remain negative even in patients with persistent cultureproven infection with B burgdorferi. However, problems are usually not far away even if the antibody test is positive. It is the doctor’s responsibility to decide whether the symptoms and antibody positivity are related. Antibodies against B burgdorferi can be positive for years in a symptom-free patient without any evidence of living spirochaetes. Clinically, it is therefore useful to gather additional information before making the decision to treat with antibiotics or merely follow the patient. If DNA of the spirochaete is found in the patient, the doctor will know that he is not dealing with a patient with "post-Lyme syndrome" old "serological scars" years after infection. or with Theoretically, patients with positive PCR results are those who most probably will benefit from treatment or retreatment. Without doubt, PCR has opened a new era in infectious disease. Vartiovaara states that it is too expensive for routine use. It is noteworthy that in our laboratory, PCR for B burgdorferi is not expensive-it costs £30. laboratories in many other countries are restricted laws concerning PCR and its use.

However,

by patent

Jarmo Oksi Department of Medical Microbiology, Turku University, FIN-20520 Turku, Finland; and Department of Medicine, Turku University Central Hospital

Thromboembolism and the combined oral

contraceptive pill SIR—There has long been concern about the potential thrombotic risks associated with the use of the combined oral contraceptive pill, which has again been focused upon in recent UK press reports (Sunday Times, May 7, 1995). Indeed package inserts contain a warning of this risk. Although obesity, age, and smoking are well recognised risk factors these might not be the most important factors predisposing to thrombosis. The media reporting of this issue may be missing an important and fundamental pointnamely, the high prevalence of APC (activated protein C) resistance in the general population. APC resistance might underlie the thrombotic tendency seen in many women. APC resistance (factor V Leiden) is now recognised to be the single commonest inherited prothrombotic disorder and can be present in up to 7% of a caucasian population.’ In the heterozygous form the risk of thrombosis is estimated to be increased eight-fold above that of a comparable control population, whereas in heterozygous women using the combined oral contraceptive pill it is raised more than 30fold. More strikingly, in the homozygous form the risk rises

least 50-fold and more than 100-fold in homozygous using the combined oral contraceptive pill.2 Although this argument is equally applicable to other prothrombotic states such as antithrombin, protein C, and protein S deficiency, these disorders are rare in the general population. By contrast, the high background prevalence of APC resistance substantially increases the number of women potentially placed at increased risk by use of the oral contraceptive pill. With the present level of concern this factor alone could merit screening for such a defect before use of the combined oral contraceptive pill. Such screening would be a major undertaking with important cost implications. However, it has the potential to reduce morbidity from thromboembolism seen in association with use of the combined oral contraceptive pill and to provide a degree of reassurance to the women concerned. In addition, knowledge of APC resistance status would enable appropriate counselling of the women identified to be at increased risk with respect to the relative benefits and risks of the combined oral contraceptive pill.

to at

women

*K J Pasi, D J Perry, C A Lee Haemophilia Centre and Haemostasis Unit, Department of Haematology, Royal Free Hospital and School of Medicine, London SW3 2QG, UK Svensson PJ, Dahlback B. Resistance to activated protein C as a basis for venous thrombosis. New Engl J Med 1994; 330: 517-22. Vanderbroucke JP, Koster T, Briet E, Reitsma P, Bertine R, Rosendaal F. Increased risk of venous thrombosis in oral contraceptive users who are carriers of factor V Leiden mutation. Lancet 1994; 344: 1453-57.

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Temporal doppler-flow studies for suspected giant-cell arteritis SIR—Schmidt and colleagues (April 1, p 866) report the value of colour doppler sonography as a so-called new method for the diagnosis of temporal arteritis. They suggest that further studies are necessary to estimate the sensitivity and specificity of the method and whether it is suitable for replacing temporal artery biopsy. We describe our experience of more than ten years of superficial temporal doppler-flow studies (DFS) in suspected giant-cell arteritis. Giant-cell arteritis is characterised by a predisposition for the cranial arteries. The assumption that these arteries are not affected by atheromatous disease and that therefore flow abnormalities could indicate giant-cell arteritis led in 1981 to the first use of temporal blood-flow study by continuouswave doppler in diagnosis of this condition.’ Nevertheless, when restricted to the temporal arteries, the results of DFS were unremarkable in a high proportion of patients with histologically proven giant-cell arteritis. To improve the diagnostic value of DFS, we also examined with ultrasonography ophthalmic and facial arteries. We developed a diagnostic score from 0 to 10, which was the sum of the various isolated findings as follows: Score

Arteries/finding Temporal arteries (maximum 4) Stenosis or no putse Irregularity or decreased flow Ophthalmic arteries (maximum 4) No pulse or asymmetry >50% Moderate decreased flow Facial arteries (maximum No pulse

DFS

2 1 1 1

2) 1

was regarded as positive when the score was 2 or greater. A prospective study was then undertaken to validate this diagnostic score in 80 patients with clinically suspected giant-cell arteritis.2 The patients underwent temporal, ophthalmic, and facial DFS and then temporal artery biopsy.