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Shigellosis strikes Italian cruise ship passengers
THE LANCET
SCIENCE AND MEDICINE
Two candidates for a live AIDS vaccine emerge wo research groups have independently developed similar attenuated and inactivatable strains of HIV-1, and put them forward as models for live AIDS vaccines. In both cases, the nef gene of HIV-1 has been deleted and the thymidine kinase (tk) gene from herpes simplex virus has been inserted into the HIV-1 genome. The latest of these reports is published this month in the Proceedings of the National Academy of Sciences USA by Chakrabarti and colleagues (1996; 93: 9810–15)—the other group published their results in July (Smith et al, Proc Natl Acad Sci USA 1996; 93: 7955–60). HIV-1 vaccines based on peptides from the virus have not yet proven effective, so scientists have been investigating the possibility of making a safe but live HIV-1 vaccine instead. There is good evidence that deletion of nef attenuates HIV-1. For example, some long-term non-progressors infected with HIV-1 carry nef-minus viruses, and nef-minus viruses replicate poorly in human cells in culture. nef-minus simian immunodeficiency virus (SIV) can act as an effective vaccine in adult rhesus macaques but not in newborn monkeys where it is highly pathogenic. There are additional safety con-
T
cerns about using live retroviruses as vaccines, including the risk of insertional mutagenesis. The inclusion of the tk gene into the attenuated HIV1 virus is designed to make it a safer retrovirus. Expression of the herpes simplex tk gene in a cell makes the cell sensitive to the acyclic nucleoside analogue ganciclovir. Both Chakrabarti and Smith have demonstrated that ganciclovir can eliminate their recombinant HIV-1 from human cells in vitro. Smith and co-workers have also demonstrated the elimination of their virus in a small animal model (severe combined immune deficiency mice populated with human peripheral blood mononuclear cells). Both groups acknowledge that the problem of escape mutants that have lost the tk gene remains, and that there may be some (correctable) sequences in the herpesvirus tk that could contribute to its loss during viral replication. However, Chakrabarti and colleagues say that the tk gene was remarkably stable, even in cells cultured in low levels of ganciclovir. And in Smith’s report combined treatment with zidovidine and ganciclovir eliminated all tk escape mutants in culture. Paul M Rowe
Shigellosis strikes Italian cruise ship passengers idespread, sensationalist— somewhat inaccurate—media coverage was devoted last week in Italy to an outbreak of acute gastroenteritis on an Italian ship which had left Venice for a week’s cruise in the eastern Mediterranean. The aetiological agent has now been identified as Shigella dysenteriae type 1. One third of the cruise ship’s 1300-plus passengers developed symptoms of bacillary dysentery (fever, colicky abdominal pain, and watery diarrhoea) while sailing from the Greek island of Corfu towards Crete. About 10% of the 450 or so affected passengers reported seeing gross blood in their stools (haemorrhagic colitis). Although 12 patients were kept in the ship’s infirmary and eight were briefly hospitalised in Heraklion (Crete), the disease was self-limiting in all cases and no-one died. All the patients (aged between 1 and 77 years) had eaten raw smoked fish with a Venetian cod
W
742
sauce (baccalà mantecato), whereas passengers who had not eaten this delicacy remained unaffected. None of the ship’s 650 crew members was affected—presumably the crew was fed a different cuisine, less elaborate, but seemingly healthier. Outbreaks of shigellosis are usually caused by food contaminated by infected faeces. Convalescent or symptomless carriers are the only recognised reservoir of this microorganism. Prof Alberto Origone, president of the Genoa-based Italian Association of Ship Doctors, who joined the ship in Heraklion and coordinated the medical management of the outbreak, said that, in agreement with Italian health regulations, screening of the foodstuffs and of the staff handling them is underway in order to identify the origin of the outbreak. Bruno Simini
Signs, symptoms, and psychiatric diagnoses
A
10-year follow-up of patients with neurological conversion symptoms identified several factors associated with a poor outcome. 73 of 79 patients identified in 1985 at the National Hospital for Neurology, London, as having a non-organic or hysterical symptom after detailed neurological and psychiatric investigation were traced (Br J Psychiatry 1996; 169: 282-88). C J Mace and M R Trimble found that an improvement in symptoms was related to psychiatric status. Patients with an affective disorder, anxiety or depression, were most likely to improve (24/30), patients with no psychiatric diagnosis were less likely to do so (14/26), whereas individuals with a personality dis order had the worst prognosis (5/17 improved) of all (p=0·0026 between groups). Non-improvement was also associated with age, length of previous history, and the use of non-psychotropic medication. In 11 patients, an organic basis was blamed for the symptom. The median number of signs was greater in these patients (3 vs 1) and a provisional neurological diagnosis had been recorded in six patients. The authors note that “multiple signs on examination of the nervous system should raise suspicions of undiagnosed neurological disease, whatever their nature”. K D Hopkins
Phototoxic celery
P
atients experiencing unexpected phototoxic reactions during standard psoralen and ultraviolet A (PUVA) treatment should be asked about their recent meals, suggest three Manchester-based clinicians (Br J Dermatol 1996; 135: 330–45). A patient with life-long atopic eczema who had been successfully treated with PUVA for 9 months unexpectedly developed a phototoxic reaction. When questioned, she said that she had eaten home-made soup containing celery, parsnip, and parsley the previous evening and again 2 hours before treatment. Celery, parsnip, and parsley all contain psoralens, and the authors suggest that the patient’s phototoxicity was due to the additive effects of the psoralens in the soup and the prescribed drug.
Vol 348 • September 14, 1996
SCIENCE AND MEDICINE
Two candidates for a live AIDS vaccine emerge wo research groups have independently developed similar attenuated and inactivatable strains of HIV-1, and put them forward as models for live AIDS vaccines. In both cases, the nef gene of HIV-1 has been deleted and the thymidine kinase (tk) gene from herpes simplex virus has been inserted into the HIV-1 genome. The latest of these reports is published this month in the Proceedings of the National Academy of Sciences USA by Chakrabarti and colleagues (1996; 93: 9810–15)—the other group published their results in July (Smith et al, Proc Natl Acad Sci USA 1996; 93: 7955–60). HIV-1 vaccines based on peptides from the virus have not yet proven effective, so scientists have been investigating the possibility of making a safe but live HIV-1 vaccine instead. There is good evidence that deletion of nef attenuates HIV-1. For example, some long-term non-progressors infected with HIV-1 carry nef-minus viruses, and nef-minus viruses replicate poorly in human cells in culture. nef-minus simian immunodeficiency virus (SIV) can act as an effective vaccine in adult rhesus macaques but not in newborn monkeys where it is highly pathogenic. There are additional safety con-
T
cerns about using live retroviruses as vaccines, including the risk of insertional mutagenesis. The inclusion of the tk gene into the attenuated HIV1 virus is designed to make it a safer retrovirus. Expression of the herpes simplex tk gene in a cell makes the cell sensitive to the acyclic nucleoside analogue ganciclovir. Both Chakrabarti and Smith have demonstrated that ganciclovir can eliminate their recombinant HIV-1 from human cells in vitro. Smith and co-workers have also demonstrated the elimination of their virus in a small animal model (severe combined immune deficiency mice populated with human peripheral blood mononuclear cells). Both groups acknowledge that the problem of escape mutants that have lost the tk gene remains, and that there may be some (correctable) sequences in the herpesvirus tk that could contribute to its loss during viral replication. However, Chakrabarti and colleagues say that the tk gene was remarkably stable, even in cells cultured in low levels of ganciclovir. And in Smith’s report combined treatment with zidovidine and ganciclovir eliminated all tk escape mutants in culture. Paul M Rowe
Shigellosis strikes Italian cruise ship passengers idespread, sensationalist— somewhat inaccurate—media coverage was devoted last week in Italy to an outbreak of acute gastroenteritis on an Italian ship which had left Venice for a week’s cruise in the eastern Mediterranean. The aetiological agent has now been identified as Shigella dysenteriae type 1. One third of the cruise ship’s 1300-plus passengers developed symptoms of bacillary dysentery (fever, colicky abdominal pain, and watery diarrhoea) while sailing from the Greek island of Corfu towards Crete. About 10% of the 450 or so affected passengers reported seeing gross blood in their stools (haemorrhagic colitis). Although 12 patients were kept in the ship’s infirmary and eight were briefly hospitalised in Heraklion (Crete), the disease was self-limiting in all cases and no-one died. All the patients (aged between 1 and 77 years) had eaten raw smoked fish with a Venetian cod
W
742
sauce (baccalà mantecato), whereas passengers who had not eaten this delicacy remained unaffected. None of the ship’s 650 crew members was affected—presumably the crew was fed a different cuisine, less elaborate, but seemingly healthier. Outbreaks of shigellosis are usually caused by food contaminated by infected faeces. Convalescent or symptomless carriers are the only recognised reservoir of this microorganism. Prof Alberto Origone, president of the Genoa-based Italian Association of Ship Doctors, who joined the ship in Heraklion and coordinated the medical management of the outbreak, said that, in agreement with Italian health regulations, screening of the foodstuffs and of the staff handling them is underway in order to identify the origin of the outbreak. Bruno Simini
Signs, symptoms, and psychiatric diagnoses
A
10-year follow-up of patients with neurological conversion symptoms identified several factors associated with a poor outcome. 73 of 79 patients identified in 1985 at the National Hospital for Neurology, London, as having a non-organic or hysterical symptom after detailed neurological and psychiatric investigation were traced (Br J Psychiatry 1996; 169: 282-88). C J Mace and M R Trimble found that an improvement in symptoms was related to psychiatric status. Patients with an affective disorder, anxiety or depression, were most likely to improve (24/30), patients with no psychiatric diagnosis were less likely to do so (14/26), whereas individuals with a personality dis order had the worst prognosis (5/17 improved) of all (p=0·0026 between groups). Non-improvement was also associated with age, length of previous history, and the use of non-psychotropic medication. In 11 patients, an organic basis was blamed for the symptom. The median number of signs was greater in these patients (3 vs 1) and a provisional neurological diagnosis had been recorded in six patients. The authors note that “multiple signs on examination of the nervous system should raise suspicions of undiagnosed neurological disease, whatever their nature”. K D Hopkins
Phototoxic celery
P
atients experiencing unexpected phototoxic reactions during standard psoralen and ultraviolet A (PUVA) treatment should be asked about their recent meals, suggest three Manchester-based clinicians (Br J Dermatol 1996; 135: 330–45). A patient with life-long atopic eczema who had been successfully treated with PUVA for 9 months unexpectedly developed a phototoxic reaction. When questioned, she said that she had eaten home-made soup containing celery, parsnip, and parsley the previous evening and again 2 hours before treatment. Celery, parsnip, and parsley all contain psoralens, and the authors suggest that the patient’s phototoxicity was due to the additive effects of the psoralens in the soup and the prescribed drug.
Vol 348 • September 14, 1996