Meningococci with reduced susceptibility to penicillin

863

ALT data in infant with liver

Fig 2-Amplified HHV-6

DNA in brain

(a) and liver (b).

Positive bands with 776 base-pairs indicated M=molecular weight marker of À.phage DNA.

by square markers.

progression from drowsiness to coma in this patient can be explained by hepatic encephalopathy but HHV-6 invasion of the brain might have contributed. Department of Paediatrics, Fujita Health University School of Medicine, Toyoake, Aichi 470-11, Japan

Department of Virology, Research Institute for Microbial Diseases, Osaka University

YOSHIZO ASANO TETSUSHI YOSHIKAWA SADAO SUGA TAKEHIKO YAZAKI

KAZUHIRO KONDO KOICHI YAMANISHI

K, Okuno T, Shiraki K, et al. Identification of human herpesvirus-6 as a causal agent for exanthem subitum. Lancet 1988; i: 1065-67. 2. Asano Y, Yoshikawa T, Suga S, et al. Viremia and neutralizing antibody response m infants with exanthem subitum. J Pediatr 1989; 114: 535-39. 3 Suga S, Yoshikawa T, Asano Y, Yazaki T, Hirata S. Human herpesvirus-6 infection (exanthem subitum) without rash. Pediatrics 1989; 83: 1003-06. 4. Kondo K, Hayakawa Y, Mori H, et al. Detection of human herpesvirus 6 (HHV-6) DNA in peripheral blood of exanthem subitum patients by polymerase chain reaction DNA amplification. J Clin Microbiol (in press). 5. Downing RG, Sewankambo N, Serwadda D, et al. Isolation of human lymphotropic herpesviruses from Uganda. Lancet 1987; ii: 390 1. Yamanishi

Human

herpesvirus-6 infection with liver injury in neonatal hepatitis

SIR,-We report a case of hepatitis in an infant who had an episode of liver injury associated with human herpesvirus-6 (HHV-6) infection. A 2-month-old baby was referred to this hospital for investigation of cholestasis. Neonatal hepatitis was diagnosed, and giant cell transformation was revealed by needle biopsy at 3 months of age. Hepatitis B surface antigen, hepatitis A virus, Toxoplasma gondii, rubella virus, cytomegalovirus, and herpes simplex virus were ruled out and his serum oq-antitrypsin was normal. The cholestasis gradually disappeared but alanine aminotransferase activities remained high, with one episode of acute exacerbation of liver dysfunction (figure). He was discharged at 5 months of age on a Chinese herbal medicine (Shosaikoto) alone. At his discharge his serum aspartate aminotransferase was 84 IU/1 and his serum alanine aminotransferase (ALT) was 148 IU/1. He had an uneventful clinical course after discharge, and his serum ALT remained around 148 IU/1 until 7 months of age when liver function deteriorated (figure). An episode of vomiting on Dec 10 was followed by moderate degree of fever lasting 4 days. On Dec 14, red maculopapular eruptions appeared on his back and abdomen, and his serum ALT had risen to 467 IU/1. He was

damage and HHV-6 infection.

admitted for investigation. HHV-6 was isolatedl from peripheral blood mononuclear cells obtained on Dec 14. An HHV-6 antibody test, which had been negative before this episode, was positive on

Jan 10. Roseola infantum due to HHV-6, superimposed upon neonatal hepatitis, exacerbated liver damage in this patient. Although the agent responsible for the initial hepatitis has not been identified, the later exacerbation of hepatitis was probably associated with HHV-6. HHV-6 has a T-cell tropism,2 which might modulate an interaction between host immunity and hepatotropic viruses such as hepatitis B virus.

Department of Paediatrics, Osaka University Hospital, Fukushima 553 Osaka, Japan

H. TAJIRI O. NOSE K. BABA S. OKADA

K, Okuno T, Shiraki K, et al. Identification of human herpesvirus-6 as a causal agent for exanthem subitum. Lancet 1988; i: 1065-67. 2. Takahashi K, Sonoda S, Higashi K, et al. Predominant CD4 T-lymphocyte trophism of human herpesvirus 6-related virus. J Virol 1989; 63: 3161-63. 1. Yamanishi

Meningococci with reduced susceptibility to penicillin SIR,-When we reportedl on the prevalence of meningococci from meningitis or septicaemia with a reduced susceptibility to benzylpenicillin (minimum inhibitory concentration 0 16-1-28 mg/1) it appeared that the incidence of such strains was increasing. However, since 1987, despite an increase in the prevalence of meningococcal infection throughout the UK, the proportion of strains relatively insensitive to penicillin has remained about the same (table). These strains continue to be a mixture of group B and group C serotypes with no particular phenotype predominating. These strains have an altered penicillin-binding protein, the result of the incorporation of genetic material coding for this from a non-pathogenic species, Neisseria flavescens.2 At present, therefore, about 3% of infections may be caused by strains of meningococci showing some diminution in susceptibility to penicillin but we had not heard of any problems arising from the therapeutic use of penicillin until the report by Dr Turner and SUSCEPTIBILITY TO PENICILLIN G OF MENINGOCOCCI FROM CLINICAL CASES IN ENGLAND AND WALES 1985-89

864

colleagues (March 24, p 732). The dosage of penicillin used for the treatment of their patient, regarded as adequate in the past, was ineffective. Penicillin should still be regarded as first choice in the treatment of meningococcal infection with these strains, but in the light of this report the rather larger doses (eg, 1-2 MU 4-hourly) that are commonly used are probably essential. Manchester Regional Public Health Laboratory, Withington Hospital, Manchester M20 8LR, UK

D. M. JONES E. M. SUTCLIFFE

1. Sutcliffe EM, Jones DM, El-Sheikh S, Percival A. Penicillin-insensitive meningococci in the UK. Lancet 1988; i: 657-58. 2. Spratt BG, Qian-Yun Zhang, Jones DM, Hutchison A. Brannigan JA, Dowson CG. Recruitment of a penicillin-binding protein gene from Neisseria flavescens during the emergence of penicillin resistance m Neisseria meningitidis. Proc Natl Acad Sci

(USA) 1989; 86: 8988-992.

Prescribing smokable drugs SIR,-Drug dependency clinics see many clients who wish to stop using injectable drugs, but not to stop using drugs. Unfortunately, clients see no acceptable alternatives because often methadone syrup is all that is offered, usually as a reduction course. Methadone syrup has many advantages. It has a long half-life and can be given once in a daily dose that suppresses craving and provides stability throughout a 24 hour period, staving off any withdrawal symptoms. One of the drawbacks of the syrup is that, since it does not induce a "buzz", addicts will resort to black market supplies for their "entertainment", using the syrup only to keep themselves stable. In addition, methadone is very addictive and addicts have withdrawal effects long after stopping the drug. Many users complain of nausea, vomiting, tooth decay, and weight gain from long-term use and feel left with little alternative but to continue to take their drugs intravenously, either prescribed or from the black market. However careful and sterile the injection practices of the user may be, this is still by far the most hazardous route of administration. Widnes drug dependency clinic, with the approval of the Home Office drugs branch, has been prescribing an alternative to methadone mixture for clients who wish to try to stop injecting. It had been observed that several clients who had been prescribed only methadone mixture to try to curtail their intravenous drug use had returned to injectable drugs because they could not cope on methadone alone. Reefers—cigarettes—injected with 60 mg of diamorphine, 40 mg cocaine, or 20 mg amphetamine have been prescribed separately or in conjunction with methadone syrup and the injection practices of clients have been monitored. So far, this experiment has produced some encouraging results with respect to the reduction of intravenous use. Widnes has 30 clients, all of whom have long histories of intravenous drug use and are now maintained on either reefers or reefers and methadone syrup. They are monitored regularly for signs of intravenous use and urine samples are taken randomly to check that no other drugs are being used. The table shows the reduction of intravenous use since the introduction of reefers:

All clients seem to be coping well and none has returned to intravenous use. Their health has improved, relationships are now much more stable, and partners and families are relieved that worries about intravenous drug use have ceased. Several have found employment and, as a result of being freed from black market supplies, are no longer in trouble with the authorities and are away from the dangers of adulterated drugs. The main advantage of the reefers is that they provide an acceptable alternative to intravenous use and associated health risks.

The reefers also provide the buzz the user craves in a safer, more controlled format. Finally they are less addictive than methadone syrup and, therefore, easier to withdraw from. It is worth mentioning that clients registered at the Widnes clinic who have received prescriptions of injectable drugs for over ten years are exchanging ampoules for reefers on a trial basis. No pressure is placed on them to stop injecting in favour of reefers (such pressure may be misconstrued) and, if a client wishes, he or she may return to intravenous use.

J. A. MARKS

Drug Dependency Clinic, Widnes, Cheshire, WA8 7RP, UK

A. PALOMBELLA

Evening primrose oil

in

atopic eczema

SIR,-Dr Sharpe and Dr Farr (March 17, p 667) conclude that published trials of ’Epogam’ (evening primrose oil) in atopic eczema do not show a significant advantage over placebo. They claim that 311 patients entered trials but that information on only 128 had been published. However, the results on the 286 patients who completed the trials have appeared in the form of a meta-analysis. The claim that "no published trial yields a significant advantage of epogam over placebo" is also wrong. Wright and Burton2 stated, "the doctor’s assessment also showed a beneficial effect of the active treatment on the overall severity of the condition (p<0-002)". Schalin-Karrila et aP allowed patients to vary their use of steroids according to need, and those on placebo used more than three times as much steroid as did those on epogam, a significant difference and one that is clinically important. Despite using only one-third of the amount of steroid, the patients on epogam assessed their itch as improving significantly more than did those on placebo. Most dermatologists would be very pleased if they could reduce steroid use in eczema patients by two-thirds. Bordoni et aI,4 describing a trial of evening primrose oil in very young children, stated that eczema in the treated children "significantly improved in comparison with that of the placebo-treated children

(p < 0.01)". Meta-analysis

or overview analysis combines data from several trials to increase the reliability of conclusions drawn from individual studies. As Peto has pointed out,5 "Overviews of trials are sometimes portrayed as machines for generating positive results. This is not true: overviews of treatments that do not work produce ’null’ results... Overviews are not machines for generating positive results: they are machines for generating accurate results". The meta-analysis of trials on epogam in atopic eczema, accepted by the UK Department of Health and by the British Journal of

Dermatology,l showed that the effects of epogam were significantly better than those of placebo (2p 0.04 to 0.0001). Improvements in patients on epogam, who were already receiving the best available conventional treatments, were 22-25%. Most patients would describe such an improvement, over and above the best that can be achieved by conventional therapy, as substantial. In Bamford and colleagues’ study there was no difference between the effects of epogam and placebo6 but it is almost certain that patients in both groups received active treatment since in both groups plasma concentrations of dihomogammalinolenic acid, a =

marker for epogam treatment, increased.1 Even if Bamford’s results are included in the overall analysis, epogam remains significantly better than placebo on both itch and clinician’s global assessment.1 We agree with Sharpe and Farr that double-blind, randomised, placebo-controlled trials are best for the evaluation of therapy in any chronic relapsing disease, and we would argue that in such a chronic disease the trials should continue for a long time. This is why we did such trials, in all of which (except those in very young children) active treatment lasted for 8-12 weeks.1 Hundreds of preparations are used for the management of atopic eczema, including topical and oral steroids, emollients, and the sedating antihistamines. If your correspondents were to do their own literature search on published, randomised, double-blind, placebo-controlled trials of these agents in atopic eczema they would be surprised by the outcome. There are no placebocontrolled trials of any emollient. We found only one placebocontrolled trial of a sedating antihistamine in atopic eczema, and this showed no benefit.7 Only four topical steroid preparations have