316 define the toxicological requirements for any new substance intended for use in cosmetics. These toxicological data should be evaluated more critically than they are at present: the mixture of MCI and MI is allowed in the EEC up to a concentration of 30 ppm, and a few years ago even 50 ppm. EEC legislation should also require cosmetic manufacturers to declare all ingredients on the product or the label. Ingredient labelling (introduced in the USA 10 years ago) would (i) enable dermatologists to adequately investigate their patients suffering from cosmetic allergy; (ii) enable patients to buy products that do not contain the substances to which they are allergic; (iii) ensure that the detection of new sensitisers is not delayed (which has been the cause with kathon CG); and (iv) boost scientific investigation into the allergens in cosmetics. Ultimately the cosmetic industry will benefit, since the scientific data that will emerge from ingredient labelling can be used to improve the safety profile of their products.
3. Kathon CG—product information sheet. Philadelphia; Rohm & Haas, 1983. 4. Hjorth N, Roed-Petersen J. Patch test sensitivity to Kathon CG. Contact Dermatitis 1986; 14: 155-57. 5. Menne T, Hjorth N. Kathon CG reactivity in 1396 consecutively patch tested patients m the Copenhagen area. Contact Dermatitis 1988; 19: 260-62 6. Shaw S, Wilkinson JD. Kathon CG—a perspective. Data presented at 8th
Symposium on Contact Dermatitis, Cambridge, March 20-22, 1986 S, Spiro J. Measurement of risk of sensitisation and its application to kathon Contact Dermatitis. 1987; 17: 299-302. 8. Hannuksela M. Rapid increase in contact allergy to Kathon CG in Finland. Contact Dermatitis 1986; 15: 211-14. 9. Fuchs T. Aktuelle Kontaktallergene und ihre Perspektiven. Med Welt 1986; 37: International
7. Shuster
1305-07. 10. Frosch P, Schulze-Dirks A. Kontaktallergie auf Kathon CG. Hautarzt 1987, 38: 422-25. 1 1. de Groot AC. Adverse reactions to cosmetics. Thesis. State University of Groningen,
Netherlands, 1988. 12. Cronin E, Hannuksela M, Lachapelle
J-M, Maibach HI, Malten KE, Meneghini CL Frequency of sensitisation to the preservative Kathon CG Contact Dermatitis 1988; 18: 274-79. 13. Meneghini CL, Angelini G, Vena GA. Contact allergy to Kathon CG. Contact Dermatitis 1987, 17: 247-49. 14. Tosti A. Prevalence and sources of Kathon CG sensitization in Italy Contact Dermatitis 1988; 18: 173-74. 15. Bjorkner B, Bruze M, Dahlquist I, Fregert S. Gruvberger B, Persson K. Contact allergy to the preservative Kathon CG. Contact Dermatitis 1986; 14: 85-90 16 Fransway AF. Sensitivity to Kathon CG findings m 365 consecutive patients. Contact Dermatitis 1988, 19: 342-47.
We thank Prof Sigfrid
Fregert (Lund, Sweden) for helpful
Correspondence should be addressed to A.
comments.
C. de G.
JD, van Joost Th, van der Meeren HLM, Jagtman BA, Weyland JW. The allergens in cosmetics. Arch Dermatol 1988, 124: 1525-29 18. Chan PK, Baldwin RC, Parsons RD, Moss JN, Stiratelli R, Smith JM, Hayes AW Kathon biocide Manifestation of delayed contact dermatitis in guinea pigs is dependent on the concentration for induction and challenge. J Invest Derm 1983, 17. de Groot AC, Bruynzeel DP, Bos
81: 409-11.
M, Fregert S, Gruvberger B, Persson K. Contact allergy to the active ingredients of Kathon CG in the guinea pig. Acta Derm Venereol 1987; 67: 315-20 Maibach HI Diagnostic patch test concentration for Kathon CG Contact Dermatitis 1985; 13: 242-45. Expert Panel of the Cosmetic Ingredient Review. Tentative report of the safety assessment of methylisothiazolinone and methylchloroisothiazolinone Washington DC: Cosmetic, Toiletry and Fragrance Association, 1988.
19. Bruze
REFERENCES
1. Grattan CEH, Harman RRM, Tan RSH Milk recorder dermatitis. Contact Dermatitis 1986; 14: 217-20. 2 Pilger C, Nethercott JR, Weksberg F Allergic contact dermatitis due to a biocide containing 5-chloro-2-methyl-4-isothiazolin-3-one Contact Dermatitis 1986; 14: 201-04.
20. 21
Communicable Disease
BACKGROUND
BETWEEN Thursday, Dec 31, 1987, and Monday, Jan 4, 1988, about 200 people visited a hotel and leisure complex in
LOCHGOILHEAD FEVER: OUTBREAK OF NON-PNEUMONIC LEGIONELLOSIS DUE TO LEGIONELLA MICDADEI DAVID J. GOLDBERG1 PETER W. COLLIER RONALD J. FALLON2 THOMAS M. MCKAY4 TERENCE A. MARKWICK4
JOHN G. WRENCH1 JOHN A. EMSLIE1 GERALD I. FORBES3 AGNES C. MACPHERSON5 DANIEL REID1
Communicable Diseases ( Scotland) Unit1 and Department of Laboratory Medicine,2 Ruchill Hospital, Glasgow; Scottish Home and Health Department, Edinburgh;3 Environmental Health Department of Argyll and Bute District Council, Lochgilphead;4 and Argyll and Clyde Health Board, Paisley5
Analysis of case histories from
people who had visited a hotel and leisure complex in Lochgoilhead, a village on the west coast of Scotland, indicated that 170 had had an acute illness characterised by headache, fatigue, arthralgia, myalgia, cough, and Summary
187
breathlessness. These symptoms were consistent with Pontiac fever-like illness. Legionella micdadei was isolated from the leisure complex whirlpool spa at the time that 60 of 72 individuals with symptoms seroconverted to L micdadei antigen. This outbreak is thought to be the first of a Pontiac fever-like illness ascribed to L micdadei and the first large-scale outbreak of its kind to have occurred outside North America. Whirlpool spas can be a major reservoir of legionella organisms; they must therefore be properly maintained and operated to prevent outbreaks of infection.
Lochgoilhead, a village on the west coast of Scotland. The complex consists of a 12 bedroomed hotel with chalets and caravans in its grounds. An adjoining leisure centre has facilities for curling, swimming, and social functions. Most visitors came from Lochgoilhead or from other parts of Scotland, but some had travelled from England, the Netherlands, and the USA. Over the New Year weekend most participated in indoor leisure pursuits and evening social events. The first notification of an outbreak of an influenza-like illness, affecting 10 hotel visitors, was made on Wednesday, Jan 6, 1988. This event prompted an investigation by the Environmental Health Department of Argyll and Bute District Council, the Communicable Diseases (Scotland) Unit, and the Department of Laboratory Medicine, Ruchill
Hospital, Glasgow. INVESTIGATION
The Illness Because the leisure centre did not record day visitors, details of the outbreak had to be elicited by face-to-face and telephone interviews with a snowball survey technique (extension of investigations by asking those interviewed if they knew of other people who had attended the complex over the same period). A preliminary questionnaire inquiry of 50 ill people indicated that all had been present at the leisure centre and that Pontiac fever (non-pneumonic legionellosis) was a likely diagnosis. The clirucal presentation was that of an influenza-like illness, with an apparent high attack rate, short incubation period, and absence of secondary spread. In addition, 1 person with a pneumonic illness suggestive of legionellosis had been admitted to hospital. The source of infection
317
seemed
to
be within the leisure centre, since the centre featured as the principal environment in the complex all individuals with symptoms.
epidemiologically visited by
The Environment The large, modem leisure centre consists of a spacious lounge/ function room which looks onto and communicates with the curling rink and swimming pool. These three areas are separated by glazed partitions to ceiling level. At one end of the pool area is a large de-humidifier and a sauna, and at the other is a whirlpool spa 3 metres from the door leading to the lounge. Moist air in the pool area is drawn through the de-humidifier, reheated, and then recirculated through vents in the ceiling, sited above the glazed partition separating the pool from the curling rink. Despite this recirculation, the bathing environment consistently remains warm and humid because of negligible air change. Possible sources of aerosol production were thought to be the swimming pool, the whirlpool spa, the changing room showers, and condensation on poolside windows. The private water supply to the complex is from two mountain streams which provide untreated, unfiltered water to the hotel and leisure centre, respectively. Samples were taken from these sources and numerous water outlets within the complex. On Thursday, Jan 14, all water systems, condensers, and de-humidifiers in the hotel and leisure centre were disinfected with sodium hypochlorite, and following this treatment no further cases were identified.
Fig 2-Frequency of symptoms in 170 ill subjects.
Serology 72 of the 170 individuals with symptoms had tests for antibodies to Legionella spp. 12 (17%) were negative (titre 16 or less), 17 (23%) had antibody titres to L micdadei of 64 or 128, and 43 (60%) had a fourfold change in titre or a single titre of 256 or more. Subjects were judged to have had recent infection with L micdadei if they showed a fourfold change in titre on serial testing or a single titre of 256 or more. Probable infection was defined as a titre of 64 or 128 on either single or serial testing. 14 of the 17 subjects without symptoms had blood tests, 2 (15%) were serologically negative; 9 (64%) had titres to L micdadei of 64 or 128, and 3 (21 %) had titres of 256 or more or a fourfold change in titre. A control group of 31 Lochgoilhead residents, who claimed never to have visited the complex, had tests four weeks after the acute outbreak for legionella antibodies-all were negative.
Environment RESULTS
Epidemiology Preliminary analysis of case histories for 187 people who had visited the complex during late December, 1987, and 170 had had symptoms-an overall attack rate of 91 %. Most patients became unwell between Jan 3 and Jan 9, although sporadic cases occurred from Dec 14 onwards (fig 1). The incubation period was calculated as the difference in time between the date of first visit to the complex and the date of onset of symptoms. The median incubation period was 2 days (range, less than 1 to 9). Most of those who were ill had influenza-like symptoms (fig 2) lasting a few days. The median duration of acute illness was 3 days (range, less than 1 to 14). Symptoms were prolonged and recurrent in some cases, and a separate inquiry is underway to establish the proportion of subjects with long-lasting features. No similar illness was reported by Lochgoilhead residents who had not visited the hotel during the same period. Of the 170 ill individuals, 83 (49%) were male and 87 (51 %) were female. Of those not ill, 8 (47%) were male and 9 (53%) were female. Fig 3 shows the age distribution of the subjects. The median age for those ill was 32 years (range 2-72) and for those not ill was 23 years (range 7-55). Attack rates did not differ with respect to use of individual facilities at the complex.
Indirect fluorescent antibody tests indicated the likely presence of L micdadei in water from the whirlpool spa and in swabs from the de-humidifier ducting. L micdadei was
early January, 1988, indicated that
Fig 3-Age distribution of 170 ill subjects (.)and 17 ([]) who had visited the hotel and leisure complex.
well
subjects
318
subsequently
grown in co-cultivation with Acanthamoebea
polyphaga in Leeds. Also in Leeds, and subsequently in Glasgow, direct culture of the whirlpool water yielded L micdadei. At the time of initial investigation on Jan 9, 1988,
Dogma Disputed
recorded levels of chlorination from the manually dosed swimming pool were suspect. Records of bromination for the whirlpool were not kept, although it was dosed and monitored by an automated system. Bromine levels could not be measured at the time of inspection but later examination of the system’s chemical monitoring device showed 20% of readings were inaccurate.
GENDER, LIPOPROTEINS, DIET, AND
recent
CARDIOVASCULAR RISK Sauce for the goose may not be
JOHN R. CROUSE
preliminary report records the clinical and epidemiological characteristics of this outbreak, which were closely similar to those first described for Pontiac fever in 1978.1 However, we identified atypical features such as breathlessness and long-lasting illness in some cases. The high proportion of individuals with antibodies to L micdadei and the isolation of this organism from whirlpool spa water, indicate that L micdadei was the causative agent. The outbreak we report is the first of a Pontiac fever-like illness ascribed to L micdadei. Only L pneumophila serogroups 1 and 6 and L feelei serogroup 1 have been implicated in previous outbreaks.2-6 It is the second largest recorded outbreak of non-pneumonic legionellosis and is thought to be the first large-scale outbreak to have occurred outside the USA and Canada. Other important features include the presence of infected symptom-free individuals and the occurrence of illness in children; the latter has not been described in previous outbreaks. We believe that the faulty bromination system allowed the accumulation of L micdadei in the whirlpool water system. The most likely explanation for the outbreak is that an aerosol containing L rnicdadei disseminated throughout the enclosed pool area and through the frequently opened door to the lounge, which was visited by all 187 individuals. Whirlpool spas have previously been associated with outbreaks of legionellosis, including those of Pontiac fever in Michigan and Vermont, USA/’*’and that of Legionnaires’ disease in Brighton, UK (unpublished, Public Health Laboratory Service, Communicable Disease Surveillance Centre). With the ever increasing popularity of whirlpool spas they will almost certainly continue to contribute towards legionella infection unless they are properly and regularly maintained. FIeld bn’estlgatlOll Team: Argyll and Bute District Council: Mr Beveridge, Mr G. Garrett, Mr T. Henry, Mr G. Linney, Mr T. McKay, Mr T. Markwick, Mr A. Morrison, Mr R. Murray. Argyll and Clyde Health Board: Dr A. Macpherson, Dr Dr F. Russell, Dr M. Wertheim. Communicable Diseases (Scotland) Unit: Mr P. Collier, Dr J. Emslie, Dr D. Goldberg, Mr C. Guthne, Dr D. Reid, Dr J. Wrench. Greater Glasgow Health Board: Mr W. Abraham, Dr R. Fallon, Dr S. T. Green, Dr D. Kennedy, Dr E. McCruden. Scottish Home and Health Department: Dr G. Forbes. Strathclyde Regional Council: Dr C. Benton. Public Health Laboratory, Leeds: Dr T. Rowbotham. We thank the following people for their help in the investigation: Dr J. Holms and Dr G. Findlay, general practitioners in Lochgoilhead; Dr D A. Donald, general practitioner in Edinburgh; Mr A. Millar, audiovisual technician, Communicable Diseases (Scotland) Unit, Glasgow; Mr A. Miles, computer consultant; Dr C. Bartlett and Dr M. O’Mahoney, Communicable Disease Surveillance Centre, London; Dr C. Love, consultant in infectious diseases, Ruchill Hospital, Glasgow; Dr C. McSharry, department of bacteriology and immunology, Western Infirmary, Glasgow.
Correspondence should be addressed to D. J. G., Communicable Diseases (Scotland) Unit, Ruchill Hospital, Bilsland Drive, Glasgow G20 9NB.
for the gander
III
Department of Medicine, Bowman Gray School of Medicine, 300 South Hawthorne Road, Winston-Salem, North Carolina 27103, USA
DISCUSSION
This
sauce
POPULATION-BASED studies have shown that the risk of cardiovascular disease is directly related to the plasma concentration of low density lipoprotein (LDL) cholesterol, and inversely related to high density lipoprotein (HDL) cholestero1.1 However, these results are heavily biased by observations in men. Cardiovascular risk is greater in men than women and, in early studies, LDL was thought to be a more appropriate target for risk reduction than HDLj therefore in the first successful clinical trial of a lipidlowering agent the investigators used a drug to reduce LDL in hyperlipidaemic men.2 The relation between lipoproteins and risk is generally assumed to be similar for men and women, and so results of this trial were extrapolated to include women and to justify dietary modification of LDL.3 A subsequent clinical trial (also in men) confirmed the importance of lowering LDL for risk reduction, but also suggested that raising HDL may give additional protection against cardiovascular disease.4 Although the roles of LDL and HDL in risk reduction may be equal in men, there is less evidence that this is true in women. Very high LDL concentrations carry the same poor prognosis in both sexes: men and women who are homozygous for familial hypercholesterolaemia have a similarly increased risk for coronary heart disease.’ However, women who are heterozygous for familial hypercholesterolaemia have a lower risk attributable to LDL compared with heterozygous men/ this finding may be due to the higher HDL in women. For the general population, where plasma concentrations of LDL and HDL are more nearly normal, but which includes the vast majority of those at risk, inferences from genetic models of high LDL may not be accurate. In one population-based study, high total cholesterol had no adverse effect in women in the presence of raised HDL.’ The only prospective population-based data on the relation of LDL and HDL cholesterol to risk in women are found in the Donolo-Tel Aviv study,’ in the Lipid Research Clinics (LRC) follow-up study,8.9 and in later data from Framingham.’,"" Results of
D
J GOLDBERG AND OTHERS. REFERENCES
TJ Isolation of Legionella pneumophila from clinical specimens via amoebae and the interaction of those and other isolates with amoebae. J Clin Pathol 1983, 36: 978-86 2. Glick TH, Gregg MB, Berman B, et al Pontiac fever: an epidemic of unknown aetiology in a health department, I. clinical and epidemiologic aspects AmJ 1 Rowbotham
Epidemiol 1978, 107: 149-60 S, Spitalny KC, Barbaree J, et al. Pontiac fever outbreak associated with cooling tower. Am J Public Health 1987; 77: 568-71 Herwaldt LA, German GW, McGrath T, et al. A new Legionella species, Legionella feeleii species nova, causes pontiac fever in an automobile plant. Ann Intern Med
3. Friedman 4.
1984; 100: 333-38 5.
6
Mangione EJ, Remis RS, Tait KA, et al An outbreak of Pontiac fever related to whirlpool use, Michigan 1982. JAMA 1985, 253: 535-39 Spitalny KC, Vogt RL, Orciari LA, et al Pontiac fever associated with a whirlpool spa Am J Epidemiol 1984, 120: 809-17.