Isolation rooms for highly infectious diseases: an inventory of capabilities in European countries.

Isolation of patients with highly infectious diseases (HIDs) in hospital rooms with adequate technical facilities is essential to reduce the risk of spreading disease. The European Network for Infectious Diseases (EUNID), a project co-funded by European Commission and involving 16 European Union member states, performed an inventory of high level isolation rooms (HIRs, hospital rooms with negative pressure and anteroom). In participating countries, HIRs are available in at least 211 hospitals, with at least 1789 hospital beds. The adequacy of this number is not known and will depend on prevailing circumstances. Sporadic HID cases can be managed in the available HIRs. HIRs could also have a role in the initial phases of an influenza pandemic. However, large outbreaks due to natural or to bioterrorist events will need management strategies involving healthcare facilities other than HIRs.

Epidemiology and clinical features of vivax malaria imported to Europe: sentinel surveillance data from TropNetEurop.

BACKGROUND: Plasmodium vivax is the second most common species among malaria patients diagnosed in Europe, but epidemiological and clinical data on imported P. vivax malaria are limited. The TropNetEurop surveillance network has monitored the importation of vivax malaria into Europe since 1999. OBJECTIVES: To present epidemiological and clinical data on imported P. vivax malaria collected at European level. MATERIAL AND METHODS: Data of primary cases of P. vivax malaria reported between January 1999 and September 2003 were analysed, focusing on disease frequency, patient characteristics, place of infection, course of disease, treatment and differences between network-member countries. RESULTS: Within the surveillance period 4,801 cases of imported malaria were reported. 618 (12.9%) were attributed to P. vivax. European travellers and immigrants were the largest patient groups, but their proportion varied among the reporting countries. The main regions of infection in descending order were the Indian subcontinent, Indonesia, South America and Western and Eastern Africa, as a group accounting for more than 60% of the cases. Regular use of malaria chemoprophylaxis was reported by 118 patients. With 86 (inter-quartile range 41-158) versus 31 days (inter-quartile range 4-133) the median symptom onset was significantly delayed in patients with chemoprophylaxis (p < 0.0001). Common complaints were fever, headache, fatigue, and musculo-skeletal symptoms. All patients survived and severe clinical complications were rare. Hospitalization was provided for 60% and primaquine treatment administered to 83.8% of the patients, but frequencies varied strongly among reporting countries. CONCLUSIONS: TropNetEurop data can contribute to the harmonization of European treatment policies.

Changing epidemiology of HBV infection in Danish children.

Hepatitis B continues to be a worldwide threat to human health, especially if infection occurs in childhood. Universal vaccination is recommended by WHO, but has not been implemented in the Scandinavian countries, Holland and UK, because of a low incidence rate. However, clinically overt infections are rare in childhood. We therefore performed a nation wide serosurvey for HBV markers in 2428 children aged primarily 6-16 years from 16 primary schools in Denmark. Anti-HBc was found in altogether 20 children (0.8%), 12 of whom were among 144 immigrant children (8.3%) compared to 8 (0.4%) in those born in Denmark. Three of the children, all immigrants, were HBsAg positive indicating chronic infection. At school level no relation of anti-HBc in Danish born children was found to schools with high number of immigrant children or schools with HBsAg positive children indicating a low risk of Hepatitis B transmission in this setting. The results do not support implementation of general vaccination, but stress the need for HBV screening in immigrants as it provides a mean for immunization of close contacts at risk and information on prevention.

Twenty-year survey of the epidemiology of hepatitis B in Denmark: effect of immigration.

Implementation of hepatitis B virus (HBV) vaccination is being considered in Denmark. Therefore, a 20 y survey on the epidemiology of HBV infection was performed. All notified cases of acute HBV infection in Denmark from 1982 to 2002 were reviewed retrospectively and all available data from 1970 to 2001 on the prevalence of hepatitis B surface antigen (HBsAg) in different groups of the Danish population were studied. The notified annual incidence of acute HBV infection has declined from more than 200 cases to fewer than 50 cases in 2001. In the indigenous population there has been a similar decline in prevalence of HBsAg carriers, from 0.15 to 0.03%, but owing to immigration of new HBsAg carriers from developing countries the overall number of carriers has not changed. The small effect of immigration on the incidence of acute HBV infections as well as the decreasing prevalence of HBsAg carriers among Danes should be taken into account when planning new vaccination strategies in Denmark.

Imported schistosomiasis in Europe: sentinel surveillance data from TropNetEurop.

BACKGROUND: Schistosomiasis is a major parasitic disease, increasingly imported into temperate climates by immigrants from and travelers to endemic areas. METHOD: To generate valid data on imported infectious diseases to Europe and to recognize trends over time, the European Network on Imported Infectious Diseases Surveillance (TropNetEurop) was founded in 1999. Three hundred and thirty-three reports of schistosomiasis were analyzed for epidemiologic and clinical features. RESULTS: Male patients accounted for 64% of all cases. The average age of all patients was 29.5 years. The majority of patients were of European origin (53%). Europeans traveled predominantly for tourism (52%). Main reasons for travel for people from endemic areas were immigration and refuge (51%) and visits to relatives and friends (28%). The majority of infections were acquired in Africa; 92 infections were clearly attributable to Schistosoma haematobium, 130 to Schistosoma mansoni, and 4 to Schistosoma intercalatum. Praziquantel was the only treatment used. No deaths were recorded. CONCLUSION: TropNetEurop sentinel provides valuable epidemiologic and clinical data on imported schistosomiasis to Europe.

Age as a risk factor for severe manifestations and fatal outcome of falciparum malaria in European patients: observations from TropNetEurop and SIMPID Surveillance Data.

Previous studies have indicated that age is a risk factor for severe falciparum malaria in nonimmune patients. The objectives of this study were to reevaluate previous findings with a larger sample and to find out how strongly clinical outcomes for elderly patients differ from those for younger patients. Results of adjusted analyses indicated that the risks of death due to falciparum malaria, of experiencing cerebral or severe disease in general, and of hospitalization increased significantly with each decade of life. The case-fatality rate was almost 6 times greater among elderly patients than among younger patients, and cerebral complications occurred 3 times more often among elderly patients. Antimalarial chemoprophylaxis was significantly associated with a lower case-fatality rate and a lower frequency of cerebral complications. Women were more susceptible to cerebral complications than were men. Our study provides evidence that falciparum malaria is more serious in older patients and demonstrates that clinical surveillance networks are capable of providing quality data for investigation of rare events or diseases.

Epidemiology and clinical features of imported dengue fever in Europe: sentinel surveillance data from TropNetEurop.

Travelers have the potential both to acquire and to spread dengue virus infection. The incidence of dengue fever (DF) among European travelers certainly is underestimated, because few centers use standardized diagnostic procedures for febrile patients. In addition, DF is currently not reported in most European public health systems. Surveillance has commenced within the framework of a European Network on Imported Infectious Disease Surveillance (TropNetEurop) to gain information on the quantity and severity of cases of dengue imported into Europe. Descriptions of 294 patients with DF were analyzed for epidemiological information and clinical features. By far the most infections were imported from Asia, which suggests a high risk of DF for travelers to that region. Dengue hemorrhagic fever occurred in 7 patients (2.4%) all of whom recovered. Data reported by member sites of the TropNetEurop can contribute to understanding the epidemiology and clinical characteristics of imported DF.

A 2-dose regimen of a recombinant hepatitis B vaccine with the immune stimulant AS04 compared with the standard 3-dose regimen of Engerix-B in healthy young adults.

An open-label randomized study was undertaken to compare a 2-dose regimen (Months 0 and 6) of hepatitis B surface antigen (HBsAg) vaccine formulated with a novel adjuvant (HBsAg/AS04) with a standard 3-dose regimen (Months 0, 1 and 6) of licensed recombinant HBsAg vaccine in terms of immunogenicity and reactogenicity when administered to healthy subjects aged between 15 and 40 y. At 1 and 6 months after the full vaccination course there was a 100% seroprotection rate (anti-HBs > or = 10 mIU/ml) with the HBsAg/AS04 vaccine, compared with a 99% response rate with the licensed vaccine. The corresponding geometric mean titres were significantly higher for the novel vaccine compared to the standard vaccine: 15,468 and 2,745 mIU/ml at Months 7 and 12 vs. 6,274 and 1,883 mIU/ml, respectively. There was a higher prevalence of local symptoms with the adjuvant vaccine (90% of doses) than with the standard vaccine (48% of doses). However, these symptoms (pain, swelling and redness) were predominantly of mild-to-moderate intensity and resolved rapidly without treatment. A 2-dose regimen of the new HBsAg/AS04 adjuvant vaccine therefore compared favourably to the standard regimen in healthy young adults. It is anticipated that the simplified vaccination schedule may improve compliance and reduce costs.

Imported Falciparum malaria in Europe: sentinel surveillance data from the European network on surveillance of imported infectious diseases.

Malaria continues to have a high morbidity rate associated among European travelers. Thorough recording of epidemiological and clinical aspects of imported malaria has been helpful in the detection of new outbreaks and areas of developing drug resistance. Sentinel surveillance of data collected prospectively since 1999 has begun within TropNetEurop, a European network focusing on imported infectious diseases. TropNetEurop appears to cover approximately 10% of all patients with malaria seen in Europe. Reports of 1659 immigrants and European patients with Plasmodium falciparum malaria were analyzed for epidemiological information and data on clinical features. Regional data were quite diverse, reflecting local patterns of immigration and international travel. By far, the most infections were imported from West Africa. Europeans had more clinical complications; consequently, all deaths occurred in this group. Compared with European standards, the mortality rate was low (0.6% in Europeans). Data from TropNetEurop member sites can contribute to our understanding of the epidemiological and clinical findings regarding imported falciparum malaria.

[Malaria. An evaluation of 127 patients treated in Rigshospitalet in 1999 and 2000]. / Malaria. Opgørelse over 127 patienter behandlet på Rigshospitalet i 1999 og 2000.

INTRODUCTION: The incidence of malaria has increased globally to 500 million cases a year. Imported malaria in travellers comprises only a small fraction, but the disease has become a serious problem in Europe and the United States. The aim of the present study was to elucidate the epidemiological and clinical aspects of patients with imported malaria in Denmark. MATERIAL AND METHODS: All patients treated for malaria at the Department of Infectious Diseases, Rigshospitalet, in 1999-2000 were evaluated retrospectively. Age, sex, nationality, destination, chemoprophylaxis, symptoms, duration of symptoms, parasitaemia, treatment, and complications were registered. RESULTS: Seventy per cent of the patients had falciparum malaria. Of these, 95% had been infected in Africa and 46% of these patients were Africans living in Denmark. Only 50% of all patients had been taking chemoprophylaxis and of these only half had been compliant. Chloroquine and proguanile were most commonly used. Seven patients had parasitaemia above 5%, but only one of these developed complicated malaria. DISCUSSION: The risk of complicated malaria in this series was low and seems to be related to lack of chemoprophylaxis, advanced age, and duration of symptoms.

[Travel prophylaxis among immigrants]. / Rejseprofylakse hos indvandrere.

A female immigrant and her child acquired Plasmodium falciparum infection during a visit to her home country. They did not receive chemoprophylaxis during or after the journey. Immigrants comprise a high risk group for malaria as well as typhoid fever and hepatitis A. Increased attention towards this group of travellers is recommended.

Dependency of cerebral blood flow on mean arterial pressure in patients with acute bacterial meningitis.

OBJECTIVE: Patients with acute bacterial meningitis are often treated with sympathomimetics to maintain an adequate mean arterial pressure (MAP). We studied the influence of such therapy on cerebral blood flow (CBF). DESIGN: Prospective physiologic trial. SETTING: The Department of Infectious Diseases, Copenhagen University Hospital, Denmark. PATIENTS: Sixteen adult patients with acute bacterial meningitis. INTERVENTION: Infusion of norepinephrine to increase MAP. MEASUREMENTS: During a rise in MAP induced by norepinephrine infusion, we measured relative changes in CBF by transcranial Doppler ultrasonography of the middle cerebral artery, recording mean flow velocity (Vmean), and by the arterial to jugular oxygen saturation difference. In 10 out of 16 patients, serial measurements were performed until recovery or death. Individual autoregulation curves were analyzed by a computer program. Autoregulation was classified as impaired if Vmean increased by >10% per 30 mm Hg increase in MAP and if no lower limit of autoregulation was identified by the computer program; otherwise, autoregulation was classified as preserved. MAIN RESULTS: Initially, Vmean increased from a median value of 46 cm/sec (range, 30-87 cm/sec) to 63 cm/sec (33-105 cm/sec) (p < .0001), and arterial to jugular oxygen saturation difference decreased from 0.28 (0.16-0.51) to 0.21 (0.08-0.39) (p < .001) when MAP was raised from 69 mm Hg (55-102 mm Hg) to 110 mm Hg (93-129 mm Hg). CBF autoregulation was restored in eight of ten patients undergoing serial examination after 7 (range, 2-10) days. Six of these patients had an uncomplicated course, one had a protracted recovery, and one died. Autoregulation was not restored in two patients; one died and one had a protracted recovery. CONCLUSION: In patients in the early phase of acute bacterial meningitis, CBF autoregulation is impaired. With recovery from meningitis, the cerebral vasculature regains the ability to maintain cerebral perfusion at a constant level despite variations in MAP.

[Randomized trial and meta-analysis of somatostatin versus placebo in bleeding esophageal varices]. / Randomiseret undersøgelse og metaanalyse af somatostatin over for placebo ved blødende esophagusvaricer.

We studied whether somatostatin or its derivative, octreotide, is more effective than placebo in the treatment of bleeding oesophageal varices in a randomised, double-blind trial and a meta-analysis with blinded data analysis and manuscript writing. Patients suspected of bleeding from oesophageal varices and of having cirrhosis of the liver were eligible. Eighty-six patients were randomised; 16 died in each group within six weeks (95% confidence interval (CI) for difference in mortality -19% to 22%). There were no differences between somatostatin and placebo in median number of blood transfusions (8 vs 5, p = 0.07, CI 0 to 4 transfusions) or in numbers of patients who needed balloon tamponade (16 vs 13, p = 0.54, CI -11% to 28%). In a meta-analysis of three trials, involving 290 patients, somatostatin had no effect on survival compared with placebo (p = 0.59, odds ratio 1.16, CI 0.67 to 2.01). For blood transfusions and use of balloon tamponade there was heterogeneity between the trials with no convincing evidence in favour of somatostatin.

Somatostatin v placebo in bleeding oesophageal varices: randomised trial and meta-analysis.

OBJECTIVE: To study whether somatostatin or its derivative octreotide is more effective than placebo for treating bleeding oesophageal varices. METHODS: Randomised, double blind trial and meta-analysis with blinded analysis of data and writing of manuscripts. SETTING: Departments of medical and surgical gastroenterology in Copenhagen. SUBJECTS: Patients suspected of bleeding from oesophageal varices and of having cirrhosis of the liver. MAIN OUTCOME MEASURES: Survival, number of blood transfusions, and use of Sengstaken-Blakemore tube. RESULTS: 86 patients were randomised; in each group 16 died within six weeks (95% confidence interval for difference in mortality--19% to 22%). There were no differences between those treated with somatostatin or placebo in median number of blood transfusions (8 v 5, P = 0.07, 0 to 4 transfusions) or in numbers of patients who needed balloon tamponade (16 v 13, P = 0.54, -11% to 28%). In a meta-analysis of three trials involving 290 patients somatostatin had no effect on survival compared with placebo (P = 0.59, odds ratio 1.16; 0.67 to 2.01). For blood transfusions and use of balloon tamponade there was heterogeneity between the trials with no convincing evidence in favour of somatostatin. No placebo controlled trials have been performed with octreotide. CONCLUSION: Within the limited power of this study and meta-analysis we were unable to show a clinical benefit of somatostatin in the emergency treatment of bleeding oesophageal varices.

[Collagenous colitis]. / Kollagen colitis.

Collagenous colitis was first described in 1976 by Lindström as an unusual cause of persistent, watery diarrhea. He noted a large subepithelial band of collagen deposited in the rectum and the colon. Collagenous colitis occurs predominantly in females and is more frequent in the elderly. Radiographic examination of the colon is unremarkable, and the patients show no signs of malabsorption. The diagnosis requires biopsy specimens from the colon, as the disease is focal and less frequently affects the rectum. Biopsies taken only from the rectum cannot exclude the diagnosis. For the time being there is no consensus as to the treatment of the disease. We describe two patients with collagenous colitis successfully treated with prednisolone. The diagnostic importance of total colonoscopy with multiple biopsies in a normal-appearing colon in patients with unexplained chronic watery diarrhea is stressed.

A double-blinded multicenter trial of somatostatin in the treatment of acute pancreatitis.

To evaluate the effect of somatostatin in the treatment of acute pancreatitis, 63 patients were randomly allocated to continuous intravenous infusion for three days of 250 micrograms of somatostatin (Dura Scan, Odense, Denmark) per hour (n = 33), or placebo (n = 30). Patients with a first attack of pancreatitis, serum amylase level of more than 450 units per liter and symptoms for less than 24 hours were eligible for participation in the study. Apart from a slightly significant faster decrease in serum amylase concentrations, we were unable to demonstrate any significant benefit from somatostatin with regard to paraclinical values and clinical course.

Development of stress ulcers assessed by gastric electrical potential difference, pH of gastric juice, and endoscopy in patients in the intensive care unit.

OBJECTIVE: To assess measurement of gastric electrical potential difference, pH of gastric mucosa, and endoscopic findings in patients in intensive care units who are at risk of developing stress ulcers. DESIGN: Open comparison with age- and sex-matched control subjects. SETTING: Herlev Hospital, Denmark. SUBJECTS: Sixteen consecutive patients with no history of gastrointestinal haemorrhage, coagulopathy, or ulcer disease who had been admitted to the intensive care unit, and 16 age- and sex-matched outpatients with normal endoscopic findings. INTERVENTIONS: Upper gastrointestinal endoscopy, during which any lesions that were found were scored according to severity, the gastric potential difference, and the pH of gastric juice were measured. OUTCOME MEASURES: Correlation between the incidence of stress ulceration found at endoscopy, gastric potential difference, and gastric pH. RESULTS: Gastric potential difference was significantly reduced and gastric pH significantly increased in the patients in the intensive care unit (p less than 0.05 in both cases), all of whom had stress ulcers in more than one gastric segment. Nine of the patients had gastric pH readings of greater than 4. CONCLUSION: Gastric electrical potential difference may be useful measurement for the assessment of stress ulceration in patients in intensive care units.

The effect of the cholecystokinin receptor antagonist MK-329 on meal-stimulated pancreaticobiliary output in humans.

To determine the physiological role of circulating cholecystokinin (CCK), the effect of the CCK receptor antagonist MK-329 on upper digestive processes was investigated in six normal volunteers after a mixed meal. In a double-blind, two-period, randomized crossover design, the subjects received either 10 mg MK-329 or placebo orally 3 hours 15 minutes before the meal, which contained 51CrCl3 as food marker. A five-lumen tube with the tip in the distal duodenum allowed continuous marker infusion (57Co-B12) and duodenal aspiration as well as recordings of antral and duodenal motility patterns via three pressure sensors. Postprandially, MK-329 caused a significant reduction of 30%-60% (P less than 0.05) in pancreatic trypsin output during the initial three 15-minute periods; thereafter, the output was virtually the same than after placebo. Thus, the integrated enzyme response was only reduced by 15% (NS) during the 3-hour period beginning 15 minutes after the meal. In contrast, gallbladder contraction, determined by total bile acid excretion, was inhibited by 77% (P less than 0.05), indicating a crucial role of CCK in regulating gallbladder motility. Except for the initial 30 minutes postprandially, MK-329 also induced a significant reduction in duodenal pH with mean values ranging from 3.5 +/- 0.2 to 4.1 +/- 0.3 compared with 4.5 +/- 0.3 to 5.0 +/- 0.4 after placebo (P less than 0.05), probably because of lowered secretion of pancreatic bicarbonate. Gastric emptying rate was significantly accelerated by MK-329 during the initial 75 minutes after the meal, but the time for 50% emptying did not differ from placebo [127.5 +/- 7.7 vs. 140.0 +/- 9.0 minutes (NS)]. No changes were observed in the motility pattern of the proximal duodenum after feeding. Whereas MK-329 only caused a slight increase of the basal plasma CCK concentrations, the postprandial levels were markedly enhanced. Peak concentrations were 10.0 +/- 1.3 vs. 4.0 +/- 0.5 pmol/L after placebo (P less than 0.001), and the integrated response exceeded the control value by 175% (P less than 0.01). The results suggest that circulating CCK is not an essential mediator of the postprandial pancreatic enzyme secretion in humans, whereas it plays a critical role in gallbladder emptying.

Surgical treatment of morbid obesity. A survey of overall outcome 1968-1989.

This survey evaluates benefits and costs from a policy of employing surgical treatment in selected cases of morbid obesity. Between 1968 and 1978, we used end-to-side jejunoileal bypass. Despite many satisfied patients, complications were frequent and severe. For the next decade, we employed various types of gastric surgery. We eventually assessed a gastric balloon, but without success. Median duration of follow-up was 132 months in 145 patients with jejunoileostomy, 103 months in seven gastric bypass patients, and 36 months in 108 gastroplasty patients. Three patients were lost to follow-up. There have been four deaths after intestinal shunt and one after gastroplasty. The median re-admission rate was 1.6 per patient, while the median number of re-operations was 2.0 after intestinal shunt and 0.8 after gastric interventions. The median weight loss in our 260 patients was 32.1% of the preoperative weight. Outcome was good in 38.8%, acceptable in 40.4% and poor in 11.5% while there were 9.2% failures. Truly satisfactory outcomes, however, were rare, owing possibly to a negative relationship between weight loss and complications. Only 8.8% have obtained a stable normal weight without any side-effects.