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occupying 449 cm3. The standard liver volume for the patient, as calculated by body size, was 880 cm3. The father’s left lobe was calculated to be large enough to provide about half the standard liver volume of the patient,2 and therefore was chosen as the graft. On Aug 28, a left lobectomy, including the middle and left hepatic veins, was done on the father, and the resected segment was transplanted orthotopically. The transplantation technique has been reported.3 The patient was treated by plasmapheresis while in grade 4 hepatic coma, which improved to grade 2-3 just before he entered the operating room. Postoperative recovery was remarkable, and the patient could walk on day 3. He was discharged on day 58, and is now leading a normal life. Nine living-related liver transplantations have been done at our university since 1990. All were done electively except for the present case. An essential prerequisite is donor hepatectomy with minimum risk.3 In our case, there was little time available between the initial consultation and transplantation, because the life of the recipient was in danger and no alternative treatment was available. Although the amount of self-blood stored preoperatively was less than usual, no banked blood was transfused into the donor, who made an uneventful recovery. Another unique feature of this case was intensive plasmapheresis before transplantation, which provided valuable time for surgical preparation and enabled the patient to be given the transplant while in a grade 2-3 hepatic coma, rather than in a worse condition. With living-related liver transplantation, the volume of the graft is insufficient for metabolic reduction of hyperbilirubinaemia in the recipient because of the limited size of the graft harvested from the living donor. Therefore, for the patient to tolerate the post-transplantation period, he should be in the best possible condition before surgery. First Department of Surgery, Shinshu University School of Medicine, Matsumoto 390, Japan, Department of Paediatrics, Nakano General Hospital, Department of Paediatric Surgery, University of Tokyo; and Department of Surgery, National Cancer Center,

Tokyo

HIDETOSHI MATSUNAMI MASATOSHI MAKUUCHI SEIJI KAWASAKI SHINPACHI ISHIZONE YOUICHI MIZUSAWA HIDEO KAWARASAKI TADATOSHI TAKAYAMA

We chose to calculate relative risk on the basis of the cumulative number of tuberculosis patients (potential source cases) since, owing to the large difference recorded (85 HIV-positive vs 1079 HIV-negative patients), this is a more reliable measure of the risk of the two conditions investigated. By relying on crude incidence values of tuberculosis in HCWs caring for HIV-positive (0-86 cases/year per 100 HCWs) and HIV-negative patients (0-3 cases/year per 100 HCWs), while ignoring the huge difference with respect to magnitude of exposure, we would have lost important

information.

Finally, we did not have microbiologial evidence (Mycobacterium tuberculosis strain typing was not done) that tuberculosis in HCWs originated from the hospital cases, nor were purified-proteinderivative conversion studies feasible (HCWs receive BCG vaccination at enrolment) to see whether tuberculosis in these workers was the result of reactivation of latent infection or of recent exposure. However, it seems highly probable that tuberculosis was acquired in hospital, in view of the chronological features of events and the lack of any evidence of latent disease developing in these HCWs. Furthermore, the yearly incidence of tuberculosis in these HCWs (0-86 cases/year per 100 HCWs) is much higher than that in the general population (0-033 cases/year per 100 persons).’ The cases are thus unlikely to have the disease as a result of reactivation of latent tuberculous infections. More data are needed to clarify fully the occupational threat of personnel assisting AIDS patients, but nevertheless our findings and those of others1.2 are of some concern in view of the worldwide resurgence of tuberculosis. Institute of Immunology and Infectious Diseases, and Bronchoscopy, University of Verona, Ospedale Civile Maggiore, 37126 Verona, Italy, and 1st Clinic of Infectious Diseases, University of Genova

GIOVANNI DI PERRI ANGELO CAZZADORI ERCOLE CONCIA DANTE BASSETTI

Schultze-Werninghaus G, Helm EB. Tuberkulosegefahrdung des Pflegerpersonals durch AIDS-Patienten. First German Congress for Infections and Tropical Medicine. Berlin, March, 1991, abstr 122.

1. Brodt HR,

2. Franchini

D, Hewlett D, Alfalla C, et al. Tuberculin skin test conversions among 64

at an urban hospital associated with an inpatient AIDS unit. 32nd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) Anheim, California, October, 1992, abstr 1197.

employees

PH, Wendon JA, Gimson AES, et al. Improvement by acetylcysteine of hemodynamics and oxygen transport in fulminant hepatic failure. N Engl J Med 1991; 324: 1852-57. 2. Kawasaki S, Makuuchi M, Ishizone S, et al. Liver regeneration in recipient and donors after transplantation. Lancet 1992; 339: 580-81. 3. Makuuchi M, Kawasaki S, Noguchi T, et al. Donor hepatectomy for living related partial liver transplantation. Surgery (in press). 1. Harrison

Transmission of HIV-associated tuberculosis to health-care workers SIR,-Dr Castro and colleagues (Oct 24, p 1043) raise several issues about our retrospective comparative investigation (Sept 12, p 682) on tuberculosis (TB) as an occupational hazard in wards having both HIV infected and uninfected patients with active tuberculosis. None of the health-care workers (HCWs) who cared for patients with HIV infection and tuberculosis had HIV infection or any other predisposing condition. All HCWs in the Italian national health system undergo periodic medical checks; HIV testing is not part of this check-up but those working in the three AIDS units were repeatedly tested (on a voluntary basis) for HIV antibodies during the investigation, with a coverage of about 90%. More importantly, HIV-antibody testing was again done with negative results in the seven HCWs who developed tuberculosis. Infection control measures differed between the infectious diseases and respiratory medicine wards investigated, with more rigorous precautions in the former. National guidelines have been produced by the Ministry of Health to protect personnel assisting HIV-infected subjects. These include the use of face masks and gloves, which are only occasionally used in respiratory medicine wards. Care given to tuberculosis patients does not substantially differ in the two types of wards, and ventilation control measures are of the same standard: the recirculated air is not filtered and there are no systems generating differential air pressures.

Spurious malarial antibodies in HIV infection SIR,-In addition to voluntary named testing, HIV infection in being monitored by surveys of unlinked anonymised specimens.’ In the survey by the Public Health Laboratory Service (PHLS) of women attending antenatal clinics, the only personal information retained with the specimen is age group. Several studies, including that of the PHLS, have identified antenatal clinics in the London area with HIV prevalence rates substantially above average, which may be due to attendence by women from African countries where the prevalence of HIV in the heterosexual population is high. Chrystie et aP reported ethnic origin of 2931 of 4099 patients at the antenatal clinic at St Thomas’ Hospital, London, linked to HIV test results. The prevalence (2%) of HIV in women reported as African was ten times more than that in women reported as European. They also examined the malarial antibody status of HIV-positive patients with an enzyme immunoassay (EIA, Launch Diagnostics). High proportions of African patients with (90%) and without (75%) HIV infection had malarial antibodies whereas only 1 of 3 HIV-positive and 1 of 96 HIV-negative European women had malarial antibodies. Chrystie and colleagues attributed the presence of malarial antibodies to having "lately visited or been resident in tropical Africa". We have also been seeking serological markers of likely travel or residence in regions where HIV is hyperendemic. We examined sera from two groups of patients (table), who had voluntary HIV tests, for the presence of malarial antibody. The first group comprised patients who had lived in, or travelled to, Africa. They were either resident in East Africa or lived in the UK and reported the UK is

1413

ASSOCIATION OF MALARIAL ANTIBODIES WITH ANTI-HIV-1 SEROSTATUS

’Serum samples collected m UK from patients who requested HIV testing and reported previous residence m, or travel to, Africa

previous residence or travel in Africa. The second group comprised subjects with no such history. 37 of the African residents

(97%)

and 68 of those

reporting

previous time in Africa (72%) had malarial antibodies. However, we also found that the presence of anti-HIV in the serum was associated with a positive malaria EIA in individuals without a history of time spent in Africa. Except in African residents, the proportion of HIV-1infected patients whose serum gave a positive reaction in the malaria EIA was far in excess of that in HIV-1 uninfected subjects. We know of no reason why patients not known to have travelled to Africa who were infected with HIV would be more likely to be exposed to malaria than those who were uninfected, and so we believe that many of the malaria antibody reactions in their serum specimens were false. Because we found large overlaps (data not presented) in the strength of antibody reactivity between the groups, it does not seem that true and false reactivity can be distinguished. In 1986 Biggar et aP suggested that reports then of high prevalences of HIV infection in Africa were probably due to sera from patients with malaria giving false-positive anti-HIV EIA reactions; improved EIA avoided this difficulty. The two agents might share a common antigenic site which has been eliminated from the antigen in modern anti-HIV kits, but remains in the antigen in the malaria EIA. The detection of malarial antibodies in HIV positive individuals, at least by the Launch EIA, cannot be used as a marker of acquisition of HIV infection in Africa or other regions where malaria is hyperendemic. Our fmdings should not seriously detract from the intended application of this EIA to screening blood donations for the potential to transmit malaria.

PHLS Virus Reference Division, Central Public Health Laboratory, and Communicable Disease Surveillance Centre, 61 Colindale Avenue, London NW9 5HT, UK

JOHN V. PARRY JOAN RICHMOND NATASHA EDWARDS AHILYA NOONE

1. Anon. The unlinked anonymous HIV prevalence monitoring programme in England and Wales. preliminary results. CDR 1991; 1: R69-76. 2. Chrystie IL, Palmer SJ, Kennedy A, Banatvala JE. HIV seroprevalence among women attending antenatal clinics in London. Lancet 1991; 339: 364. 3 Biggar RJ, Saxinger C, Sarin P, Blattner WA. Non-specificity of HTLV III reactivity in sera from rural Kenya and eastern Zaire. East Afr Med J 1986; 63: 683-84.

Neuronal loss in symptom-free HIV infection SIR,—There is significant neocortical neuronal loss in the frontal cortex

of patients who die of AIDS without cerebral

opportunistic

infections or neoplasms, which is not related to the presence of HIV

encephalitis.lDecline in neuronal number is a potential indicator of HiV-associated dementiawhich characteristically develops during advanced HIV disease. However, the clinical significance of

neuronal fallout is inconclusive because earlier reports correlated the degree of dementia with the severity of HIV encephalitis3 and it is not known whether the loss occurs only in patients with symptoms when clinical cognitive impairments develop. When neuronal loss evolves is difficult to clarify because symptom-free HIV-infected individuals rarely come to necropsy. We describe such a series. Neuronal density’ was estimated in the superior frontal gyrus of 14 HIV-infected patients and 15 HIV-negative controls (mean [SD] ages 29-8 [5.0] and 27-4 [5’7]; 8 M/6 F and 13 M/2 F, respectively). All were intravenous drug users and none had HIV-associated neuropathology.4 20 um paraffm-embedded sections were stained with cresyl violet and coded for assessment blind to diagnosis. The mean neuronal numerical density (x lOZ/mm3) for the HIV group was 488 (94) compared with 479 (78) for the controls (not significantly different). The numerical densities were not significantly related to age in either the HIV group (Pearson’s r= -0-02, p=0-95) or the controls (r=0-2,

p = 0-48). Contrary to findings in AIDS patients, the neuronal numerical density in HIV-infected symptom-free individuals did not differ from that in controls. Neuronal numerical density is a function of nerve-cell number and tissue volume. While in principle cell density could remain constant in the face of neuronal loss due to parallel tissue shrinkage, this seems unlikely. Our investigation is consistent with the fmdings that clinical cognitive abnormalities are very rare in symptom-free HIV-infected patients.s When such abnormalities are found, they are often subclinical and do not predict progression to clinical dementia. Similarly, neuroimaging results have not shown cerebral atrophy at such an early stage. This is in contrast to patients with AIDS who have cerebral atrophy on neuroimaging6 and neuronal loss on magnetic resonance spectroscopy,’ which we have corroborated in quantitative studies of patients who died of AIDS.1 The demonstration that neuronal loss only develops late during HIV infection provides a clinical rationale for developing drugs to prevent neurotoxicity in symptom-free individuals. Explanations of the mechanism of neuronal loss in AIDSinclude a neurotoxic effect envelope glycoprotein gp 120, which is thought to be effected through activation of calcium channels linked to the N-methyl-Dasparate (NMDA) receptor, and possibly neuronal vasoactive intestinal polypeptide receptors.8 Rise in intracellular calcium is followed by neuronal death and in-vitro calcium entry can be blocked by calcium channel antagonists.9 Similarly, quinolinic acid is an endogenous NMDA toxic agonist which is raised in cerebrospinal fluid of patients with HIV-associated cognitive and motor abnormalities.10 on the

IAN EVERALL Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK, and Hospital Raymond Poincare, Garches, France

F. H. M. P. P.

GRAY BARNES DURIGON LUTHERT LANTOS

IP, Luthert PJ, Lanton PL. Neuronal loss in the frontal cortex in HIV infection Lancet 1991; 337: 1119-21. 2. American Academy of Neurology AIDS Task Force. Nomenclature and research case definitions for neurologic manifestations of human immunodeficiency virus-type 1 (HIV-1) infection. Neurology 1991; 41: 778-85. 3. Navia BA, Cho ES, Petito CK, Price RW. The AIDS dementia complex II. neuropathology. Ann Neurol 1986; 19: 525-35. 4. Gray F, Gherardi R, Keohane C, Favolini M, Sobels A, Poirer J. Pathology of the central nervous system in 40 cases of acquired immune deficiency syndrome (AIDS). Neuropathol Appl Neurobiol 1988; 14: 365-80. 5. McArthur JC, Cohen BA, Selnes OA, et al Low prevalence of neurological and neuropsychological abnormalities in otherwise healthy HIV-1infected individuals: results from the multicenter AIDS cohort study Ann Neurol 1989; 26: 601-11. 6. Post J, Tate L, Quencer R, et al CT, MR and pathology in HIV encephalitis and 1. Everall

meningitis. AJR 1988; 151: 373-80. DK, Baudouin D, Tomlinson D, Hoyle C. Proton MR spectroscopy and imaging of the brain in AIDS. evidence of neuronal loss in regions that appear normal with imaging. J Comput Assist Tomog 1990; 14: 882-85 8. Lipton SA. HIV-related neurotoxicity Brain Pathol 1991, 1: 193-99. 9. Dreyer EB, Kaiser PK, Offermann JT, Lipton SA. HIV-1 coat protein neurotoxicity prevented by calcium channel antagonists. Science 1990; 248: 364-67. 10. Heyes MP, Brew BJ, Martin A, et al. Quinolinic acid in cerebrospinal fluid and serum in HIV-1 infection relationship to clinical and neurological status. Ann Neurol 1991; 29: 202-89. 7. Menon