and according to CDC recommendations.2,3 Food, water, and stool specimens were cultured. The kitchen, water supply, and chlorinating system of the ship were examined. We proceeded, using epidemiological methods, to identify the source of the infection. 191 (14%) passengers were interviewed with a standardised questionnaire that probed for information about symptoms, exposure to drinking water, or consumption of specific food from the ship’s menu; 71 (37%) of these passengers were ill and 120 (63%) symptomfree. A case-control study was undertaken on the ship. Cultures from food and water specimens did not yield the microorganism responsible. We did not find any leakage of the ship’s waste products into the water supply. All stool specimens cultured (n=26) yielded Shigella dysenteriae type A1. Analysis of the data showed that the main symptoms were diarrhoea, fever, and headache. We concluded that the probable transmission vectors were smoked swordfish with salted cod. Control measures for the passengers and crew members were instituted before the ship’s departure.
Several factors may account for these findings of C botulinum in mascarpone, including lack of maximum limits for spore numbers in raw milk, and an insufficient ultrafiltration procedure. The heating milk-cream process2 was inadequate to inactivate the spores of C botulinum type A.3 Moreover, the pH, aw, and redox potential (Eh) of the final product were conducive for the viability of the pathogen. Growth of proteolytic neurotoxic clostridia occurs at 10ºC. The evidence suggests that raised storage temperature of the mascarpone at some point along the distribution chain favoured the production of botulinum toxin. This outbreak of botulism underlines the necessity to apply HACCP principles to the manufacturing process of all dairy products, and the importance of not relying solely on refrigeration for controlling the growth of C botulinum.
*Achilleas Gikas, John Pediaditis, Z oi Giti, John Papadakis, Yiannis Tselentis
Department of Clinical Bacteriology, Parasitology, Z oonoses, and Geographical Medicine, University of Crete, WHO Collaborating Centre, Iraklion, Crete, Greece
*Paolo Aureli, Giovanna Franciosa, Manoochehr Pourshaban National Reference Centre of Botulism, Food Microbiology Laboratory, Istituto Superiore della Sanita, 00161 Rome, Italy
3 1 2
Simini B. Shigellosis strikes Italian cruise ship passengers. Lancet 1996; 348: 742. Koo D, Maloney K, Tauxe R. Epidemiology of diarrheal disease outbreaks on cruise ships,, 1986 through 1993. JAMA 1996; 275: 545–47. Addiss DG, Yashuk JC, Clapp DE, et al. Outbreaks of diarrhoeal illness on passenger cruise ships, 1975–85. Epidemiol Infect 1989; 103: 63–72.
Foodborne botulism in Italy SIR—Foodborne botulism is a neuroparalytic disease caused by ingestion of toxin produced by Clostridium botulinum in contaminated food. Dairy products have seldom been associated with botulism; indeed, only seven outbreaks have been reported worldwide in the past 50 years, all caused by type A and B serotypes. As Simini reports (Sept 21, p 813),1 episodes of botulism in four southern Italy cities were brought to our attention: eight people were affected (six male, two female, ages 6–24 years). All the patients had consumed commercial acidified dairy cream (mascarpone cheese), either alone or as an ingredient of a home-prepared dessert, tiramisù, 12–24 h before onset of their symptoms. All the patients recalled that the mascarpone was malodorous. Their first symptoms (nausea, cephalagia, vomiting) were rapidly followed by neurological signs. All patients were supported by artificial ventilation and treated with trivalent antiserum. One patient died, and six were still in hospital at the time of writing (mid-October). Botulinum toxin type A was detected in two of four serum samples and two of seven rectal swabs; C botulinum type A was isolated from the faeces of all eight patients. Two brands of mascarpone, purchased in the same local stores, contained type A botulinum toxin (1866 LD50/g) and spores of C botulinum type A (>105/g). Tiramisù consumed by two of the patients, and an unopened package of mascarpone from the same grocery shop at which the cream for the dessert had been purchased, contained type A toxin and C botulinum spores: 125 LD50/g and 100 000 spores/g (tiramisù) and 2495 LD50/g and greater than 100 000 spores/g (mascarpone), respectively. Several samples of mascarpone from different production lots, and collected from the grocery and from the manufacturing plant, were contaminated with about four spores of C botulinum type A (per gram of product).
Simini B. Outbreak of foodborne botulism continues in Italy. Lancet 1996; 348: 813. UNI-Ente Nazionale Italiano di Unificazione. Progetto di norma U59092140 (Mascarpone cheese: definition of specificity, composition, characteristics), 1996. Hauschild AHW. Clostridium botulinum. In: Doyle MP, ed. Foodborne bacterial pathogens. New York: Marcel Dekker, 1989: 111.
Haemorrhagic fever with renal syndrome and chronic renal failure SIR—Some patients with chronic renal failure (CRF) have a history of haemorrhagic fever with renal syndrome (HFRS),1,2 a disease with high morbidity in Penza region (Central Volga). HFRS is caused by Puumala virus. Rodents are the primary reservoir and the bank vole (Clethrionomys glareolus) has been closely linked to infection. Seroprevalence studies have detected antibodies to hantaviruses in 4·9% of people in Penza region.3 However, only 1% of seropositive men have had clinical manifestations of HFRS.4 To clarify the impact of HFRS on rates of CRF, we analysed morbidity due to HFRS and CRF in 28 agricultural Penza regions with a population of 931 700. Cases in towns with a population above 100 000 were not analysed. We divided the territory of Penza region into two provinces, depending on vegetation. Forest province lies to the east of the region and consists mostly of oak, lime, and pine trees, which provide good conditions for C glareolus. Steppe province lies to the west of the region and has cultivated land. To the northwest of the steppe area lies a forest. One administrative region is located there. This territory was not included. The ratio of forest to steppe territories is 1:1·6. In the forest province there are eight regions and more than half the territory borders five administrative regions. The rest of the 14 regions are situated on the steppe provinces territory. The mean annual morbidity rate for HFRS from January, 1991, to December, 1995, in forest province was 15·6 (median 17; range 6·3–21·1) cases per 100 000 of population compared with 2·8 (median 2·4; range 2·2–3·6) per 100 000 in steppe province. Diagnosis was confirmed by antibody to hantavirus in serum by indirect immunofluorescence. Information about 80 patients with CRF (serum creatinine level above 200 µmol/L) was analysed. The mean age was 46·2 years (median 45; range 15–76); 49 (61%) patients were men. They were observed in territorial hospitals and did not need haemodialysis. The dialysis population is not included because many patients move when haemodialysis starts. On
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Jan 1, 1995, the prevalence of CRF in forest province (13·6 per 100 000) was more than in steppe province (5·1 per 100 000). Thus morbidity from HFRS is directly connected to landscape, and there is a relation between the prevalence of HFRS and CRF. Our results suggest that HFRS contributes to CRF in endemic regions. *Alexandre Shutov, Emilia Maximova, Kira Potrashkova, Olga Bruzgacheva
that the haemodynamic state of the donor is central to the occurrence of these lesions.4 In both studies, they have not been shown to have a functional impact on kidney graft function. *Coronel Bernard, Mercatello Alain, Colon Simone, Martin Xavier, Moskovtchenko Jean-François *Intensive Care and Continuous Immunotherapy Units, Pathology Laboratory, and Urology and Renal Transplantation Department, Hôpital E Herriot, 69437 Lyon, France
*Department of Nephrology, Burdenco Regional Hospital, 440026 Penza, Russia; and Department of Epidemiology, Regional Centre of Epidemiology, Penza
Yan PS, Lin YF, Wang BY, Lin J, Yi KF, Yang BS. Pathological renal changes in epidemic hemorrhagic fever accompanied by chronic renal failure in one case. Chin Med J 1986; 99: 503–06. Glass GE, Watson AJ, LeDuc JW, Kelen GD, Quinn TC, Childs JE. Infection with a ratborne hantavirus in US residents is consistently associated with hypertensive renal disease. J Infect Dis 1993; 167: 614–20. Malkin AE, Myasnikov YuA, Ryltseva EV, Tkachenko EA. Landscape districting of the natural HFRS foci in Russia. Med Parasitol 1996; 2: 27–32. Drozdov SG, Tkachenco EA. Hemorrhagic fever with renal syndrome. In: Lvov DR, Klimenko SM, Gaidamovich SI, eds. Arboviruses and arbovirus infections. Moscow: Meditsina, 1989: 289–307
Hydroxyethylstarch and osmotic nephrosislike lesions in kidney transplants SIR—Patients with absence of brainstem functions can require infusion of plasma expanders to avoid arterial hypotension and to compensate for volume changes due to polyuria. The most widely used volume expander was albumin until the appearance of solutions based on hydroxyethylstarch (HES). 1 An increased frequency of osmotic-nephrosis-like lesions (ON) (from 14% in 1990 to 80% in 1992), described in a retrospective study, may be related to use of HES.2 We analysed 24 renal-transplant biopsy specimens taken 15 min after kidney reperfusion, for which the donors’ care, organ harvest, and transplantation were all carried out in our centre between May 1, 1993, and Jan 31, 1994. They were classified without any information about the donors’ care as ON negative or ON positive.3 Donors were also classified into two groups according to use of HES: no HES infusion (HES –) or with HES infusion (HES+) during donor intensive care. Between ON – and ON+ groups, there was no difference in the use of HES in the donors (table). However, donor urinary output was significantly lower in the ON+ group. It is noteworthy that HES+ donors were also those who required more dopamine (mean 4 [SD 4] vs 16  µg kg–1 min–1) to maintain an adequate haemodynamic state. Despite this, donor urinary output was lower in the HES+ group (1001  vs 2097  mL). Serum creatinine levels were similar in the ON – and ON + groups, and in those with kidneys from the HES – and HES+ groups at 1, 3, and 6 months after transplantation. In this study, the osmotic nephrosis-like lesions were less frequent (25%) than reported by Legendre et al2 and there is no reason to input them to HES. However, the lower urinary output in the HES+ and ON + groups and the higher vasopressive amine requirement in the HES+ group indicate Donors
HES– HES+ (n) HES+ (mL) Urinary output (mL)
6 12 1444 (1280) 1655 (1348)
2 4 2000 (1581) 501 (428)*
Coronel B, Laurent V, Mercatello A, et al. Can hydroxyethylamidon be used during intensive care of brain-dead organ donors? Ann Fr Anesth Réanim 1994; 13: 10–16. Legendre C, Thervet E, Page B, Percheron A, Noël L, Kreis H. Hydroxyethylstarch and osmotic-nephrosis-like lesions in kidney transplantation. Lancet 1993; 342: 248–49. Heptinstall R. Tubular disorders. In: Heptinstall R, ed. Pathology of the kidney. 4th ed. Boston: Little Brown, 1992: 1990–93. Walaszewski J, Rowinski W, Zawadzki A, Chmura A, Kowalczyk J. The influence of preagonal hemodynamic disturbances in the donor on
Reversible thyroid dysfunction with filgrastim SIR—Haemopoietic growth factors are being increasingly used to accelerate myeloid recovery after bone-marrow transplantation and chemotherapy. Granulocyte colonystimulating factor (G-CSF) stimulates the differentation and growth of neutrophil progenitors by signalling through its receptor (G-CSFR). Filgrastim is usually well tolerated but adverse effects have been reported (glomerulonephritis, vasculitis, osteoporosis, hypersplenism), and there may be a potential leukaemogenic risk.1 We report a new adverse effect. The patient was a 40-year-old woman with breast cancer, and no family history of thyroid disease who had normal thyroid function (table). She received doxorubicin 90 mg/m2 and cyclophosphamide 1000 mg/m2 intravenously every 3 weeks. Filgrastim (Roche) was given at a dose of 10 µg/kg subcutaneously every day from days 3 to 13 of each cycle. During the third cycle she developed a goitre and the titres of thyroid microsomal and thyroglobulin antibodies rose. Symptoms of clinical hypothyroidism (cold intolerance, constipation, somnolence) developed after three cycles of therapy. No antibodies to thyrotropin receptors were found. She required thyroxine therapy for 2 months. Thyroid function and antibodies returned to normal within 10 weeks of the last dose of G-CSF. Chemotherapeutic drugs were not thought to be contributing to this patient’s thyroid dysfunction as she continued with new chemotherapy cycles without G-CSF, without effect on thyroid function and antibodies. G-CSF induced reversible thyroid dysfunction in this patient with prevously normal thyroid function. Autoimmune thyroiditis has been observed after treatment with interferonalfa, interleukin-2, and granulocyte-macrophage CSF in patients with pre-existing thyroid antibodies.2 G-CSF has no effect on thyroid function and autoimmunity in a previous study.3 Our patient with normal thyroid function and with no Cycle
ThyroidTri-iodostimulating thyronine hormone (nmol/L) (mU/L)
Thyroglobulin antibodies (IU/L)
Microsomal antibodies (IU/L)
Pretreatment Post 1 Post 2 Post 3 10 weeks post 3
3·8 3·9 4·1 45 3·7
120 110 111 15 122
0 0 40 200 0
0 0 200 600 0
1·9 1·8 1·6 0·2 1·9
Number or mean (SD). χ2 and U tests as appropriate, *p<0·05 ON⫺vs ON+.
Normal values: 0·5–5, 50–150, 1·1–2·8, <20, and <80, respectively.
Table: ON – and ON+ groups: HES infusion and urinary output
Table: Thyroid function
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