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EEG revealed a mild diffuse abnormality, with a few irregular slow

temporal and frontal regions. The findings suggested encephalopathy. Nerve conduction studies were consistent with a polyneuropathy. Over the ensuing week he became more confused, with visual hallucinations and inappropriate behaviour; the EEG now revealed episodic slow waves which were more frequent and greater in amplitude than before; and there was evidence of significant intellectual impairment. Gold-induced neuroencephalopathy was diagnosed and on chelation therapy with dimercaprol (150 mg four time a day for 2 days, 150 mg twice daily for 2 days, 150 mg daily for 6 days) he rapidly improved, regaining his appetite and reporting insight into the previous hallucinations. After 10 days he was discharged, alert and oriented. His CSF gold concentration fell from 25 ug/1 before chelation therapy to 5 ug/1 after 10 days. At follow-up 4 months, clinical examination and psychometric testing were normal. Nerve conduction studies were much improved but the EEG remained slightly abnormal. Reports of psychiatric and neurological complications of gold appeared in early French and German reports;l,2 and cases of Guillian-Barre polyneuropathy,3peripheral neuropathy without encephalopathy,4 and encephalopathy without peripheral neuropathyS have been reported by others. Perry et al6 described a similar patient, who also responded dramatically to chelation therapy. In a further case of neuropathy and encephalopathy’I treatment with steroids, without chelation therapy, failed to produce a complete cure, despite stopping of gold treatment. We suggest that paraesthesiae, fasciculation, or behavioural changes in a patient on aurotherapy should be an indication to discontinue gold and initiate chelation therapy. waves over

the left

We thank Mr B. Sampson and Dr A. Taylor for the gold assays; Dr Marta Etian for the EEGs and electrophysiology, and the department of psychiatry, Charing Cross Hospital, for the psychometry.

Regional Neurosciences Centre, Charing Cross Hospital,

M. N. DUBOWITZ P. J. HUGHES* R. J. M. LANE

London W6, UK

J. P. H. WADE

*

Present address:

Lymington Hospital, Lymington SO41 9ZH, UK.

advocates of this treatment for septicaemic shock-organisms and inflammatory mediators are removed from the circulation. This therapy failed in septicaemic shock. Since the clinical effects of severe malaria are due to schizont sequestration, the removal of early malarial trophozoites from the circulation during exchange transfusion might also be expected to have limited benefit only. Coppetts Wood Unit, Royal Free Hospital, Department of Infectious and Tropical Diseases, London N10 1UN, UK

1. Warrell DA, Molyneux ME, Beales PF. Pharmacology of antimalarial drugs in severe and complicated falciparum malaria Trans R Soc Trop Med Hyg 1990; 84 (suppl 2): 25-31.

Frequency of twinning in paediatric HIV infection SiR,—Two reports have shown a high frequency of twinning in children with AIDS and in children born to women with HIV infection and enrolled in a foster-care programmes In Los Angeles (LA) County, California, where community-based active surveillance for paediatric (children under 13 years) HIV infection has been undertaken since March, 1988, we have also found a high

twinning rate. Since Nov 30,1990, we have had birth information for 201 of 215 perinatally HIV-exposed infants and children diagnosed in LA county (including uninfected seroreverters to HIV-antibody negative). Nine sets of twins were recorded-a twinning rate of 4-7% for all HIV-exposed births (9/192) (table). This rate was 6-5% inblacks,4-l% in hispanics, and 2,6% in whites. For LA county the overall twinning rate is 1-0% (blacks 1-3%, hispanics 09%, and whites 12%). Of the 47 AIDS cases (defined by the Centers for Disease Control, CDC, criteria)4 5 were twins (three twin sets). Maternal age at birth was 19-35 years for twins. Among the nine twin sets, 4 infants were less than 15 months old and of indeterminate HIV status. Among the remaining five sets, three (60%) were discordant for HIV infection, and of these three sets,1 infected twin had AIDS and 2 had symptoms without AIDS: Twin sets

goldehandlung der chronsshen arthritis unter besonderer berucksichtingung der Komplikationen. Acta Med Scand 1941; 117 (suppl): 1-291. 2. Endtz LJ. Complications nerveuses du traitement aurique. Revue Neurol 1958; 99: 1. Sundelin F

Die

395-410. D, Raman D. The Guillan Barré syndrome

following gold therapy. Scand J Rheumatol 1982; 11: 119-20. 4. Katrak SM, et al. Clinical and morphological features of gold neuropathy. Brain 1980; 3. Dick

103: 671-93. 5. McAudley DLF,

Lecky BRF, Earl CJ. Gold encephalopathy. J Neurol Neurosurg Psychiatry 1977; 40: 1021-22. 6. Perry RP, Jacobsen ES. Gold induced encephalopathy: case report. J Rheumatol 1984; 11: 233-34. 7. Gotten M, Day

CP, Day JL. Acute disseminated encephalomyelitis as a complication of treatment with gold. Br Med J 1985; 290: 1179.

Treating cerebral malaria S!R,—DrWyler(Feb 16, p 433) criticises our case-report (Jan 12, 115) about the long-term neurological sequelae after cerebral malaria on the grounds that other conditions, such as seizures, were not excluded. We completed extensive investigations to exclude other microbial and biochemical causes. Computed tomography and lumbar puncture were normal. Prophylactic treatment with anticonvulsant agents and careful monitoring of this patient make unrecognised seizures or hypoxia after admission unlikely. Such events may have taken place before admission, but would not alter our contention that changes induced by cerebral malaria are not always reversible. We agree with much of Dr Hall’s (Feb 16, p 433) comments about malaria management. However, his concerns about quinine toxicity at serum concentrations above 10 mg/1 are not supported by Warrell et al,l who provide evidence that the increased protein binding of this drug in severe malaria prevents adverse effects up to a concentration of 20 mg/1. The arguments for exchange transfusion in severe malaria are similar to those previously advanced by p

M. G. BROOK W. R. C. WEIR B. A. BANNISTER

PO/PO PO/PI PO/SR P2/SR P2/P2

No 2 1 1 3 2 9

rio) (22)

(11) (11) (33) (22) Total (100) Among the two concordant sets, both twins had AIDS and3 of the 4 children have died; both sets were male/female pairs. Maternal intravenous (iv) drug use was reported in five (56%) twin sets and 56 (31 %) of the singletons. 78% of twin mothers vs 40% of singleton mothers reported using drugs, including "crack" and non-iv drugs (p < 005). Among blacks, 100% of twin mothers vs 49% of singleton mothers reported drug use (p = 0-06). Mean age at AIDS diagnosis was 12 and 14 months for twins and singletons, respectively. Case-fatality rates were equal for both groups. Among children classified Pl and P2, 63% of twins and 47% of singletons had AIDS, with a median age at last medical contact of 21 and 24 months, respectively. Among the children classified PO-P2, mean age at first HIV evaluation was 3 and 10 months for the twins and singletons, respectively (not significant). Because of low birthweight and high prematurity rates, twins may BIRTH TYPE BY CDC CLASSIFICATION

852

receive medical attention and be reported more frequently than singleton babies. Among children with known HIV status no association between birth type and risk of mother-to-infant HIV transmission was noted. 33% of both twins and singletons were uninfected, although reporting may be more complete for the twins than for singletons. Whether HIV-infected women have higher twinning rates, and whether twins are more frequently reported to a surveillance system, is best addressed by newborn heelstick HIV-seroprevalence studies to test every newborn baby. However, to maintain confidentiality, twinning information is generally unavailable. Further prospective studies of perinatally HIV-exposed infants investigating the effect of drug use and other factors will further elucidate the relation between HIV infection and twinning. Pediatric AIDS Surveillance Study, Los Angeles County Department of Health Services,

(313 no Figueroa, room 203), Los Angeles, California 90012,

USA

TONI FREDERICK LAURENE MASCOLA

1. Thomas

P, Ralston S, Bernard M, et al. Pediatric acquired immunodeficiency syndrome: an unusually high incidence of twinning. Pediatrics 1990; 86: 774-76. 2. Greene M, Gurdin P, Bolasogno P. Maternal HIV infection and drug use associated with an increased incidence of twin gestation. (Presented at the 6th International Conference on AIDS, San Francisco, June, 1990: abstract 2158). 3. 1988 Vital Statistics of Los Angeles County. Los Angeles: Department of Health Services, 1988. 4. Centers for Disease Control. Classification system for human immunodeficiency virus (HIV) infection in children under 13 years of age. MMWR 1987; 36: 225-30, 235.

Emergence of drug-resistant Mycobacterium tuberculosis in HIV-infected patients SIR,-Standard antituberculosis drugs are reported to be highly

Mycobacterium tuberculosis infection in anti-HIV positive patients.1-3The recommended regimen in adults is isoniazid (INH) up to 300 mg daily, rifampicin up to 600 mg daily, and pyrazinamide (20-30 mg/kg body weight per day).4 Ethambutol (15-25 mg/kg) may also be added when central nervous system (CNS) involvement or disseminated disease is suspected.4 With this regimen, we verified the failure of antituberculosis treatment in 10 of 23 HIV-seropositive patients in whom acid-fast bacilli were identified and who had symptomatic illness consistent with mycobacterial disease. We therefore reviewed data on antibiotic susceptibility of mycobacterium tuberculosis isolates from 12 patients who had never received antituberculosis drugs. All patients were admitted to our clinic between February, 1986, and November, 1990. All were caucasian, intravenous drug abusers, and anti-HIV positive, and met Center for Disease Control (CDC) criteria for HIV infection. In 4 patients AID S preceded diagnosis of tuberculosis. In these patients the presenting AIDS diagnoses were Kaposi’s sarcoma, Pneumocystis carinii pneumonia, cryptococcal meningitis, and oesophageal candidiasis, respectively. 3 had pulmonary M tuberculosis disease and in 1 patient pulmonary localisation was associated with CNS involvement. In 8 patients AID S and tuberculosis were diagnosed concurrently since all had at least one documented extrapulmonary acid-fast bacilli site of infection. The sites of extrapulmonary involvement were CNS (3 patients), musculoskeletal (1), urogenital (1), lymphatic (4), bone marrow or blood (2), and peritoneum plus pericardium (1). No patient showed evidence of other simultaneous opportunistic infection. The table shows drug susceptibility of isolates. As shown beforewe found a higher than expected frequency of resistance to rifampicin and isoniazid (25% and 8-3%, respectively). Surprisingly 4 isolates (2 from CSF) were resistant to ethambutol, and a high degree of resistance was also seen with streptomycin (33%) and ofloxacin 5 ug/ml (50%). Furthermore, 7 of the 12 isolates (58%) were resistant to more than one drug. These data were in accordance with clinical findings since 6 patients did not improve clinically, radiographically, and microbiologically after standard treatment, whereas rifabutine (450 mg daily) which is generally restricted to atypical mycobacteriosis4 seemed to be clinically effective. Our results emphasise the trend of mycobacterial drug resistance from 1980 to 1987 in HIV-negative subjects in our areaand effective for

DRUG SUSCEPTIBILITY OF M TUBERCULOSIS ISOLATES FROM 12 AIDS PATIENTS I

I

I

I

S=sensltlve, R=resistant, INH=isoniazid (02 2 g/ml). RFP=rifampicin (20 g/m!), STR=streptomycin (5 g/m!), ETB=ethambutol (3 g/mi), CYC=cyclosenne (30 g/ml), OFX= ofloxacln (*1 and 5 pg/ml on left and nghtof column, respectively), I node=lymph node

suggest that such resistance results from epidemiological factors rather than HIV-related conditions. The emergence of drug-resistance strains of M tuberculosis both in anti-HIV-positive subjects and in the general population is very alarming. Tuberculosis is more likely to develop and be more severe in HIV-seropositive individuals because of their immunity impairment than in the general population. Moreover, such individuals in Italy,’ as well as in other European countries, are mainly intravenous drug addicts who often live in confined environments (prison, therapeutic communities) where tuberculosis spread could be a real hazard. If tuberculosis becomes even more common in HIV-infected patients than at present the incidence of tuberculosis in the general population could soon begin to rise. Our data suggest that such infection would be resistant to standard drugs, at least in some areas. Clinic of Infectious Diseases, and Institute of Hygiene, University of Bari, 70124, Bari, Italy

L. MONNO G. ANGARANO S. CARBONARA S. COPPOLA D. COSTA M. QUARTO G. PASTORE

RE, Schecter GF, Theuer CP, et al. Tuberculosis m patients with acquired immunodeficiency syndrome. Am Rev Respir Dis 1987; 136: 570-74. 2. Theuer CP, Hopewell PC, Elias D, et al. Human immunodeficiency virus infection in tuberculosis patients. J Infect Dis 1990; 162: 8-12. 3. Chaisson RE, Slutkin G. Tuberculosis and human immunodeficiency virus infection J Infect Dis 1989; 159: 96-100. 4. US Department of Health and Human Services. Diagnosis and management of mycobacterial infection and disease in persons with human immunodeficiency 1. Chaisson

virus infection. Ann Intern Med 1987; 106: 254-56. 5. Pitchenik AE, Burr J, Laufer M, et al. Outbreaks of drug-resistant tuberculosis at AIDS centre. Lancet 1990; 336: 440-41. 6. Zubiani M. Present aspect of bacteriological diagnosis of tuberculous and nontuberculous mycobacteria Riv Tuberc Mal App Respir 1989; 21: 97-118. 7. Angarano G, Pastore G, Monno L, Santantonio T, Luchena N, Schiraldi O. Rapid spread of HTLV-III infection among drug addicts in Italy. Lancet 1985, ii:1302

Neuropathological evidence that zidovudine reduces incidence of HIV infection of brain SiR,—There is clinical and biological evidence that zidovudine reduce the incidence or improve features of HIV encephalopathy.1-3 We have studied the brains of 135 adults who died from AID S between August, 1982, and December, 1990, and can

have found further evidence for this view. In 43 cases (group 1) zidovudine had been administered for over 1 month and continued until death. Group 2 were patients not given zidovudine (77 cases), treated for less than 1 month (10), or having their treatment stopped because of myelotoxicity 3 months or more before death (5). At least twenty paraffin-embedded blocks from several regions and six large sections from the cerebral hemispheres and whole brainstem and cerebellum were examined. HIV infection of the brain was assessed by the presence of multinucleated giant cells (MGC), which are seen as the hallmark of productive HIV infection of the brain.4 MGC were found in 52 brains (11group 1, 41 group 2), and in these cases MGC or macrophages expressed HIV proteins gp41,