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.

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.

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 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.

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.

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.

[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.

[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.

[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.

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.

Serum selenium and zinc concentrations in morbid obesity. Comparison of controls and patients with jejunoileal bypass.

The concentrations of serum selenium and zinc (both in micromoles per litre) were determined in 18 patients 5-12 years after jejunoileal bypass and in 13 controls with untreated morbid obesity. Selenium concentrations were significantly lower in the operated patients than among controls, whereas there was no significant difference with regard to zinc. Ninety-five per cent confidence limits for the median difference between pre- and post-operative concentrations were 0.03-0.41 with regard to selenium and -0.3 to 2.7 with regard to zinc. Even though little is known about the clinical consequences of chronic selenium deficiency, substitution might prove beneficial.

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.

The effect of the benzodiazepine antagonist flumazenil on the sequels of diazepam given before upper gastrointestinal endoscopy. A double-blind randomized trial.

The prolonged sedation of benzodiazepines may be inconvenient for the patient. Reversal of sedation, therefore, would be desirable. Accordingly, we assessed the efficacy of the benzodiazepine antagonist flumazenil in a placebo-controlled randomized trial including 40 adults undergoing upper gastrointestinal endoscopy under diazepam (Diazemuls) sedation. We found no significant differences between groups with regard to either performance (two tests) or duration (within 240 min) of sedation. There were no noticeable side effects.

Ethanol in pancreatic juice after oral and intravenous administration.

Six patients with a drain in the main pancreatic duct were studied. Ethanol was given orally with individually adjusted doses aiming at a blood value of 0.8/1000 (17.6 mmol/l). Concentrations of ethanol in venous blood and pancreatic juice were recorded for three hours. Similar studies were made when ethanol was administered as an intravenous priming dose followed by a maintenance infusion. After orally administered ethanol, pancreatic juice values were higher than those in blood for a short period of time. The relations between median concentrations and time were incongruous curves consistent with a significant treatment by time interaction. Intravenous administration resulted in a similar pattern, but the interaction was not statistically significant. These findings indicate that the human pancreas may secrete ethanol.

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.