MANAGEMENT STRATEGIES FOR HIV IN OBSTETRICS

656 FINGER CLUBBING

SIR,-Professor Dickinson and Dr Martin (Dec 19, p 1434) megakaryocytes and platelet clumps are the cause of finger clubbing. Several questions arise, however. Why are more babies not born with clubbing, given the greater chance for megakaryocytes to pass into the limb arteries before birth? Why is clubbing not rarer in taller people if distance be the reason for more clubbing in the hands than feet? Why does unilateral clubbing occur? Why is clubbing uncommon in peripheral vascular disease given the high incidence of platelet clumps in these patients? We feel that the concept of vasodilator acting on the uniquely sensitive digitial microvasculature remains the most plausible explanation for clubbing, although experimental evidence is still lacking. 1,2 Raynaud’s disease demonstrates that the microvasculature of hands and feet behave differently. A closer study of the long-term response of Sucquet-Hoyer canals to vasoactive peptides may bring a fuller understanding of both Raynaud’s disease and clubbing. propose that

Department of Histopathology, Foothills Hospital, Calgary, Alberta T2N 2T9, Canada

B. GALLAGHER E. COSGROVE

Digital clubbing and hypertrophic osteoarthropathy the underlying mechanisms. Br J Dis Chest 1981; 75: 113-31. 2 Martinez-Lavin M. Digital clubbing and hypertrophic osteoarthropathy: a unifying hypothesis. J Rheumatol 1987; 14: 68 1. Shneerson JM.

ANTI-PRE-S2 AS ONLY SERUM HBV MARKER: POSSIBLE RELATION TO HBV-2 INFECTION

S1R,-Dr Coursaget and colleagues (Dec 12, p 1354) report a new type of virus infection in a man in Senegal. The new virus, named HBV-2, is supposed to share only a few envelope epitopes with the conventional hepatitis B virus (HBV), and the nucleocapsid of HBV-2 does not seem to cross-react with HBV nucleocapsid antigens (hepatitis B core [HBcAg] and e antigen [HBeAg]), since the new infection is characterised by the lack of antibodies to HBcAg (anti-HBc) and by no cross-protection by antibodies to

HBsAg (anti-HBs). The putative "new virus", although similar to HBV, has some features different from previously recognised hepadnaviruses. The cross-reaction of nucleocapsid antigens would be expected, considering the close relation between HBV and HBV-2, as serological cross-reactivity of viral nucleocapsid antigens occurs in viruses which are philogenetically related while their envelope components undergo antigenic variation. The core antigens of hepadnaviruses cross-react to a different extent. However, despite a 72% aminoacid sequence homology between woodchuck hepatitis virus core antigen (WHcAg) and HBcAg and an apparent cross-reactivity in combination radioimmunoassays, the commercial assay for anti-HBc (’Corab’, Abbott) failed to detect antibodies to WHcAg in most infected woodchucks.’ Therefore the absence of anti-HBc in sera of HBV-2 infected patients requires further investigation. Moreover, even if there is no homology at the nucleotide and aminoacid sequence level within the pre-S region of hepadnaviruses,2 the "new virus" seems to cross-react with HBV by the pre-Sz encoded determinants. In 1985 we tested 74 serum samples collected from acute hepatitis cases in the Ivory Coast for HBV markers, including pre-Sz and anti-pre-Sz by immunoassay.3.. In 53 sera we found markers of HBV infection, but in 10 of these 53 anti-pre-Sz was the only HBV marker. The anti-pre-S, response was directed against both pre-Sza and pre-Szb epitopes of the pre-S, sequence, previously defined by two non-overlapping monoclonal anti-pre-S, antibodies F124 and F376 .3 ’ The anti-pre-S, titre in these sera ranged up to 106 and, what is unusual for HBV infection in Europe, anti-pre-Sz antibodies were not accompanied either by anti-HBc or anti-HBs. With the immunocapture assay we determined that anti-pre-S, antibodies in these sera were of both the IgG and IgM isotype. Coursaget and colleagues report the reactivity of HBV-2 with F124, a monoclonal antibody which specifically recognises the pre-S2 sequence of HBV.-’ This finding and our data suggest the cross-reactivity of the "new virus" (found in two countries of West Africa) with conventional HBV by the pre-S2 determinants of the

viral envelope. Therefore the "new virus" seems to be a variant of conventional HBV, rather than the new member of the hepadnavirus group. Screening for pre-Sz antigen and anti-pre-S2 antibodies might help to identify potential HBV-2 carriers who are seronegative for anti-HBc. Unité d’Immunologie Microbienne, Institut Pasteur, 75724 Pans Cedex 15, France, Hôpital Antoine Béclère,

AGATA BUDKOWSKA PASCAL DUBREUIL

Clamart, France; and Unité d’Immunochimie, Institute Pasteur de Cote d’Ivoire, Ivory Coast

ANTOINE OUATARRA

JACQUES PILLOT

1 Ponzetto A, Cote PJ, Ford EC, et al Radioimmunoassay and characterisaton of woodchuck hepatitis virus core antigen and antibody. Virus Res 1985; 2: 301-15 2 Tiollais P, Wait-Hobson S Molecular genetics of the hepatitis B virus. In Chisari F, ed Advances in hepatitis research New York Mason, 1984 9-20 3 Budkowska A, Dubreuil P, Riottot MM, et al. A monoclonal antibody enzyme immunoassay for the detection of epitopes encoded by the pre-S2 region of the hepatitis B virus genome J Immunol Meth 1987; 102: 77-85 4 Budkowska A, Dubreuil P, Pillot J. Detection of antibodies to pre-S2 encoded epitopes

of hepatitis B virus by monoclonal antibody enzyme immunoassay J Immunol Meth 1987, 102: 85-92 5 Budkowska A, Riottot MM, Dubreuil P, et al Monoclonal antibody recognizing pre-S2 epitope of hepatitis B virus Characterization of pre-S2 epitope and anti-pre-S2 antibody J Med Virol 1986, 20: 111-15

POSSIBLE CASE OF HBV-2 INFECTION

SIR,-Dr Coursaget and colleagues (Dec 12, p 1354) describe 38 patients in whom a positive reaction in serum for hepatitis B surface antigen (HBsAg) was not accompanied by the presence of antibodies to hepatitis B core antigen (anti-HBc). They tentatively classified these

cases as

HBV-2 infections.

LABORATORY DETAILS OF PATIENT TENTATIVELY CLASSIFIED AS

HBv-2

In 1982 we saw a patient in Los Angeles with similar discrepancy between HBsAg positivity and serum anti-HBc. This patient was a 27-year-old black woman who presented with an acute icteric illness compatible with acute viral hepatitis (table). On each of the first three clinic visits, she was HBsAg positive by radioimmunoassay (RIA). However, on those dates and on five subsequent clinic visits, anti-HBs (RIA) was consistently negative. HBsAg then became negative about three weeks into her clinical illness. HBV-DNA determined by dot-blot hybridisation on serum obtained on Jan 21, 1982, was negative. Testing for antibodies to HBsAg (RIA) at 2 and 3,1months after HBsAg clearance showed only weak positivity (9-1and 9-5 units, respectively). In all serological aspects tested, this patient was similar to those reported by Coursaget and colleagues, and could thus also be classified as HBV-2. Liver Unit, University of Southern California, Downey, California 90242, USA

ALLAN G. REDEKER SUGANTHA GOVINDARAJAN

MANAGEMENT STRATEGIES FOR HIV IN OBSTETRICS

SIR,-The long-awaited report of the Royal College of Obstetricians and Gynaecologists (RCOG) AIDS sub-committee, to which Mr Hudson and colleagues refer (Jan 30, p 239), presents pragmatic guidelines on the management of HIV in obstetrics, gynaecology, and paediatrics in an abbreviated style, similar to the DHSS instructions on AIDS in other areas of medicine, which were circulated to all doctors in 1986-87. The findings do not differ

657

much from those of a review published over twelve months ago.’ To implement these recommendations effectively (allocate local resources, define a rational screening policy, educate all grades of staff, organise adequate antenatal counselling facilities, and coordinate community psychiatric support) we need to be aware of the arguments upon which proposals were based--considerable elaboration is therefore required. Apart from this report, there has been little serious discussion of the obstetric implications of HIV infection in England and Wales, as clinicians in most centres remain isolated from the problem.2 Local strategy must be flexible enough to accommodate changes in expert advice based on the latest knowledge, such as the finding that infants who are seropositive at birth may remain HIV antigen positive regardless of their subsequent antibody status. The amount of experience of antenatal intravenous drug abuse in centres such as New York,4 Milan,s Dublin,3 and Edinburgh6 could fill a tome such as the RCOG report on pre-clinical neoplasia of the cervix.’ In this, expert discussion of each aspect of the subject was recorded, summarised, and referenced in detail, before the recommendations were presented. The time is right for an enlargement of work of the RCOG AID S subcommittee.8 The collected thoughts of an international group of experts would help us manage obstetric HIV problems in England and Wales, as we might expect a lag of three to four years behind the situation in America and Scotland: forewarned is forearmed. If the predicted heterosexual HIV explosion fails to materialise, because of the biology of the virus, control of drug abuse, or changing sexual practice, then obstetricians will be none the worse for having studied the arguments in full. Departments of Gynaecology and Genitourinary Medicine, Royal Northern Hospital, London N7 6LD

PETER GREENHOUSE

Br J Hosp Med 1986, 36: 342-46 2. Greenhouse P, Palmer P. AIDS and health-care workers. Lancet 1987, i 223-24 3 Kelly G HIV infection in the Republic of Ireland. Presented at MSSVD meeting, 1 Forbes PB The significance of AIDS in obstetncs practice.

London, 1987

Fikrig S. Pregnancies resulting in infants with acquired immunodeficiency syndrome or AIDS-related complex Obstet Gynecol

4. Minkoff H, Nanda D, Menez R,

1987, 69: 285-87 5.

6 7

Semprini AE, Vucetich A, Pardi G, Cossu MM. HIV infection and AIDS in newborn babies of mothers positive for HIV antibody. Br Med 1987, J 294: 610. Johnstone F, MacCallum L, Brettle R, Inglis J, Peutherer J Does infection with HIV affect the outcome of pregnancy? Br Med J 1988, 296: 467. Jordan JA, Sharp F, Singer A, eds. Pre-clinical neoplasia of the cervix. London Royal College of Obstetricians and Gynaecologists, 1982

8 Minkoff H, Schwarz RH AIDS Time for obstetricians Gynecol 1986; 68: 267-68.

to

over a litre of urine; no laboratory or blood gas results available from the referring hospital. Passage of a nasogastric tube produced copious amounts of coffee-ground fluid. The patient was intubated and hyperventilated. Emergency carotid angiography revealed no filling of the internal carotid or its branches beyond the dura due to raised intracranial pressure. A large right parasagittal meningioma was removed but brain swelling prevented closure of the bone flap. The patient did not regain consciousness or make any respiratory efforts. Brainstem death was confirmed 24 hours later. In retrospect it is easy to link the mental deterioration with a slow-growing meningioma. However, the diagnosis of senile dementia seems especially unfortunate in this case. More active management in the referring hospital might not have affected the outcome, but early reduction of intracranial pressure is recommended. There are other lessons in this case. Any comatose patient being transferred should have airway protection with a cuffed tube, especially if there is raised intracranial pressure.2 Such patients should also be ventilated and given nasogastric intubation and dexamethasone and/or mannitol, with careful management of fluid balance. This requires an intravenous infusion and urinary catheterisation, and all comatose patients should have a medical escort in the ambulance. Craniotomy was done too late and the outcome was inevitableindeed in some countries the carotid angiogram would have been a criterion for brainstem death.3 In such cases it is easy to look back and identify points at which alternative management might have influenced events. Besides more aggressive management on admission to hospital, earlier diagnosis of the meningioma would have led to earlier surgery. An intracranial mass must be borne in mind whenever a diagnosis of senile dementia is proposed, especially when the symptoms are

produced were

rapidly progressive. I thank Prof Lindsay

SIR,-A 68-year-old man was admitted to hospital having been found unconscious in bed after becoming increasingly drowsy over 24 hours. During the previous 2 years he had complained of increasing loss of memory, mental slowing, irritability, and anxiety, a condition diagnosed as senile dementia by his general practitioner. Over the 2 weeks before his admission his condition had worsened, with increasing drowsiness, confusion, and headaches. 3 days before being found comatose he had been seen by three hospital psychiatrists who confirmed senile dementia. The day before admission to hospital, with the patient complaining of severe headache and drowsiness, and being difficult to arouse, the general practitioner diagnosed a chest infection and prescribed antibiotics. On admission to hospital the patient was deeply unconscious with fixed dilated pupils, blood pressure 220/100 mm Hg, pulse 100/min, and spontaneous breathing,and he was reported to be protecting his own airway. A computerised tomographic scan showed a large anterior fossa mass with midline shift. He was treated conservatively with dexamethasone, surgery to be considered only if his clinical condition improved. 12 hours later he was transferred to a neurosurgical centre. He arrived by ambulance without medical escort, unintubated and breathing spontaneously; he was hypoxic (POZ 74 mm Hg) and dehydrated (haematocrit 057, plasma osmolarity 315 mosmol/1). Although reported to have been anuric for 24 h catheterisation

PAUL R. HOWELL*

London WC1

1. Marshall M. Control of intracranial pressure. In Neuro-anaesthesia. (Curr Topics in Anaesth 3). 1979. 2 Robinson N, Macleod KGA. Airway management m the transfer of the unconscious patient Ann R Coll Surg Engl 1983; 65: 372-73. 3. Pallis C. ABC of brain stem death: the position in the USA and elsewhere. Br Med J 1983; 286: 209-10

*Present address

get involved Obstet

MENINGIOMA MISDIAGNOSED AS SENILE DEMENTIA

Symon for permission to report his case.

Department of Anaesthesia, National Hospital for Nervous Diseases,

Charing Cross Hospital, London SW6

PENICILLIN-INSENSITIVE MENINGOCOCCI IN THE UK from patients with meningitis or which had reduced susceptibility to benzylpenicillin (minimum inhibitory concentration [MIC] C’2-0’4 fJg/ml) but were not p-lactamase producers, were isolated more frequently in Spain during 1986. Another was recognised in South Africa by Dr Botha (Jan 2/9, p 54), together with two P-lactamase-producing isolates. These P-lactamase-producing isolates were the first reported from patients with meningitis, the only other being apparently from the urogenital tract.3 Conjugal transfer of P-lactamase plasmids from 3 of 20 gonococci to 4 different meningococci, in vitro, has been reported .4 During the past 2 years, penicillin-insensitive meningococci have also occurred more often among isolates referred to the Public Health Laboratory, Manchester (reference centre for England and Wales), both from infected patients and carriers (table i), but none were p-lactamase producers. Those from infected patients were serogroups B or C, including a variety of different serotypes. They were sent from many laboratories in different places and only once did two of the same type come from the same source, and that was within a 10 day period. As yet, no penicillin-insensitive serogroup A isolates have been encountered by us or otherwise reported. Sensitivities to penicillin G are shown in table 11. 61 % were additionally resistant to sulphonamide but none was resistant to

SIR,-Meningococci,

bacteraemia

and

rifampicin, aminoglycosides, erythromycin, tetracycline, chloramphenicol.

or