Characterisation of acyclovir-resistant and -sensitive clinical herpes simplex virus isolates from an immunocompromised patient.

A detailed study was made of herpes simplex virus type 1 (HSV-1) isolates from an immunocompromised patient whose infection became resistant to acyclovir (ACV) during a prolonged course of oral treatment. Three HSV isolates and 33 virus clones derived from them were characterised. The development of clinical resistance correlated with the emergence of thymidine kinase (TK) defective strains. The ACV-sensitive strains studied contained a small proportion of insensitive virus. The resistant isolate contained 0.6% of TK-positive virus which was sensitive to a relatively low concentration of ACV.

Clinical resistance to acyclovir of herpes simplex virus infections in immunocompromised patients.

Herpes simplex virus strains, isolated from three immunocompromised patients whose infections showed clinical resistance to acyclovir, were studied as treatment progressed. Virus isolated from two patients remained sensitive to acyclovir throughout. Isolates from the third patient, who had received a prolonged course of oral acyclovir, showed a sharp decrease in drug sensitivity which corresponded to loss of thymidine kinase activity. No changes in restriction endonuclease profiles were observed in isolates from the same patient as treatment with acyclovir progressed.

Detection of HSV1 DNA by in situ hybridisation in human brain after immunosuppression.

Human brain cells were examined for the presence of herpes simplex virus type 1 (HSV1) DNA sequences by in situ hybridisation. Viral genome was detected in immunosuppressed patients with virological evidence of past HSV infection but not in immunosuppressed patients with no such evidence. In patients who had not been immunosuppressed, no HSV DNA sequences were detectable.

Virus infections in immunocompromised patients: their importance and their management.

Opportunistic viral infections were investigated in 156 adult patients admitted over one year to a medical oncology service: 35% of the total group and 65% of those with acute leukaemia experienced viral infections, 79% of which were with viruses of the herpes group. Surprisingly few enteric viruses were recovered. Reactivation of herpes simplex virus in the brains of these immunosuppressed patients was suggested by the demonstration by nucleic acid hybridization of herpes simplex virus DNA sequences in neurones and endothelial cells in patients with evidence of past infection with virus. Acyclovir was effective in therapy and prophylaxis. Twenty-three strains from 7 patients were tested for sensitivity to this antiviral: in 3 instances clinical resistance was observed but the strains were fully sensitive in vitro, as were all other strains tested.

Oral acyclovir prophylaxis against herpes simplex virus in non-Hodgkin lymphoma and acute lymphoblastic leukaemia patients receiving remission induction chemotherapy. A randomised double blind, placebo controlled trial.

Forty-one patients receiving remission induction chemotherapy with vincristine, adriamycin and prednisolone (VAP) for high grade lymphoma or acute lymphoblastic leukaemia were entered into a double blind, placebo controlled trial of oral acyclovir prophylaxis against herpes simplex virus (HSV) infection. The dose of acyclovir was 200 mg four times daily for the duration of chemotherapy (six weeks). Of the 40 evaluable patients, 20 were randomised to each arm. Prophylactic oral acyclovir significantly reduced the incidence of clinical HSV infection from 60% on placebo to 5% acyclovir (P less than 0.001), and the incidence of viral isolates from 70% on placebo to 5% on acyclovir (P less than 0.001).

Epidemic outbreaks of adenovirus 7 with special reference to the pathogenicity of adenovirus genome type 7b.

Adenovirus type 7 (Ad 7) is the serotype among the 36 recognized adenovirus types which most frequently has been associated with severe illness. Three different epidemic patterns of Ad 7 infection can be distinguished: 1) the first appears during the winter among infants with median age below two years, has characteristic symptoms of high fever and pneumonia and an outcome that may be fatal: 2) the second appears in the fall among children with median age seven years, has characteristic symptoms of high fever, pneumonia, abdominal symptoms and meningism and an outcome that is favorable; 3) and the third has been seen as acute respiratory disease among military recruits. In the United States, the last mentioned outbreaks require prophylaxis in the form of a live enteric-coated vaccine. DNA restriction site mapping demonstrated the occurrence of three distinct viral entities of Ad 7, which have been designated Ad 7 prototype, Ad 7a (the vaccine strain) and the Ad 7b genome type. In the present study, 36 isolates obtained from outbreaks with the first and the second epidemic patterns were analyzed by restriction endonucleases Bam HI and Sma I. All were identified as the newly recognized Ad 7b genome type. It is concluded that this genome type is responsible for a large portion of the severe infections caused by Ad 7. The epidemic nature of Ad 7 and the severe illness noted among infants indicate that vaccination of institutionalized infants could be considered during years when Ad 7 epidemics appear.

Detection of herpes-simplex viral genome in brain tissue.

Herpes-simplex virus type (HSV-1) nucleic-acid sequences were detected by in-situ hybridisation in thin sections of brains from mice which had been inoculated 24 weeks previously with HSV-1. These mice were not ill, and infectious virus could not be recovered from them. HSV-1 sequences were also present in brain smears from 3 of 4 elderly patients who had died with chronic psychiatric illness and neuropathological changes but not in smears from 2 patients who had had acute psychotic episodes and minimum abnormal histology. Adenovirus type 7 nucleic-acid sequences were not detected in these human specimens.

Slow viruses and chronic disease of the central nervous system.

Although recognized since the 1930s, slow infections have only recently received considerable attention. There are three types, group A (related to the type C RNA viruses), group B (bizarre agents such as scrapie and kuru) and group C (viruses such as measles which normally produce acute infections but which are behaving here in an unusual fashion). These viruses are only united in that they produce disease with excessively long incubation periods. Many slow infections result in neurological diseases and these will be discussed, together with some possible explanations of their action.