European cluster of imported falciparum malaria from Gambia.

A cluster of 56 patients returning from Gambia with falciparum malaria has been noted in several countries of the European Union since September this year. TropNetEurop, the European Network on Imported Infectious Disease Surveillance, collected and reported the cases. Lack of awareness and, consequently, of prophylactic measures against malaria were apparent in the majority of patients.

Drug addiction in hepatitis C patients leads to a lower quality of life.

The subjective health status of hepatitis C patients has been relatively poorly studied. By using the Short Form 36 (SF-36), health-related quality of life (HRQOL) was assessed in a group of 42 hepatitis C patients. In all nine scales examined, the scores were generally low, and present drug use and being single were associated with especially large reductions in HRQOL. Compared with the Norwegian norms, scores were lower across all nine scales and significantly lower in eight. The study showed that the hepatitis C patients had definite reductions in HRQOL, but the impairment could not be fully explained by their hepatitis. Different non-viral factors such as drug use and marital status significantly influenced the results. This underlines the importance of taking other factors into account when studying the health status of hepatitis C patients.

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.

Sequential changes in hematologic and biochemical parameters in African tick bite fever.

OBJECTIVE: To evaluate the sequential changes and to estimate the frequencies of abnormalities in some commonly measured biological variables in patients with African tick bite fever (ATBF), an emerging spotted fever group (SFG) rickettsiosis in international travelers to rural sub-Saharan Africa. METHODS: A study was done of hemoglobin, total leukocyte count, absolute lymphocyte count, blood platelet count and serum levels of C-reactive protein (S-CRP), alanine aminotransferase (S-ALAT), aspartate aminotransferase, lactic dehydrogenase, gamma-glutamyl transferase, alkaline phosphatase, bilirubin, sodium and creatinine during the first two weeks of illness and prior to the institution of antirickettsial therapy in 108 patients with travel-associated ATBF. RESULTS: There were significant falls in mean total leukocyte count, mean absolute lymphocyte count, and mean platelet count, and significant increases in mean S-CRP and S-ALAT. During the first ten days of illness, elevated S-CRP, lymphopenia and elevated S-ALAT were detected in 91.7%, 73.3% and 40.7% of patients, respectively. Most abnormalities were mild. For 55 patients who underwent both S-CRP and absolute lymphocyte count determination, at least one parameter was abnormal in 52 (94.5%) patients. CONCLUSIONS: The sequential changes in many biological parameters during the acute phase of ATBF mimic those reported in other SFG rickettsioses. Mild abnormalities are frequent, with increased S-CRP and lymphopenia being the two most consistent findings.

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.

Raised serum ferritin predicts non-response to interferon and ribavirin treatment in patients with chronic hepatitis C infection.

BACKGROUND/AIM: Previous studies have indicated that response to interferon therapy is inversely proportional to the amount of body iron stores. We have studied the relationship between serum ferritin, transferrin saturation, liver iron, presence of HFE-C282Y gene mutation and response to treatment in patients with chronic hepatitis C infection. METHODS: Two hundred and fifty-six naive, HCV-RNA positive patients (60% males, median age 38 years, range 21-70) were treated with interferon and ribavirin for 6 months. Iron indices and the presence of the C282Y mutation were measured. In 242 (94%) patients iron deposition were determined by Perls staining method. Patients with negative HCV-RNA at 6 months after the end of treatment were defined as sustained viral responders. RESULTS: Non-responders (n = 127) had significantly higher median s-ferritin values compared with sustained viral responders (130 microg/L vs. 75 microg/L P < 0.001). There was no difference in transferrin saturation among the two response groups. Only 23% (4/7) of patients with Perls grade 1 in liver biopsies responded to treatment vs. 54% (122/225) patients without iron deposition (P = 0.02), however, 10/13-non-responders had HCV genotype one. Two patients (0.8%) were homozygous for the C282Y mutation, 36 patients were heterozygous (14%). Among mutation carriers 26/38 achieved sustained response compared with 102/216 non-carriers (68% vs. 48%, P = 0.02). In a multivariate analysis s-ferritin (P = 0.030) and C282Y carrier status (P = 0.012) remained independent predict of sustained response. CONCLUSIONS: Raised s-ferritin values predicate non-response to interferon-ribavirin therapy in hepatitis C patients. Response rate in C282Y mutation carriers seems greater than in non-carriers.

Thyroid dysfunction during treatment of chronic hepatitis C with interferon alpha: no association with either interferon dosage or efficacy of therapy.

OBJECTIVES: Treatment of chronic hepatitis C with interferon-alpha (IFN-alpha) may induce thyroid disorders. We evaluated whether this risk is related to the dosage of IFN-alpha or the virological treatment response. Other possible risk factors as well as the evolution of the thyroid abnormalities were also studied. METHODS: In this prospective trial (n=254), thyroid-stimulating hormone (TSH), free thyroxin (fT4) and thyroid peroxidase autoantibodies were measured before, during and after treatment for hepatitis C virus (HCV). The patients were randomized to either induction therapy [IFN-alpha 6 million units (MIU) daily for 4 weeks and 3 MIU 3/7 days for 22 weeks] or conventional therapy [IFN-alpha 3 MIU 3/7 days for 26 weeks]. In addition, all patients received ribavirin (1000 or 1200 mg) daily. Sustained virological response was defined as loss of detectable HCV RNA at 6 months follow-up. Thyroid dysfunction was defined as TSH level below or above the normal range (0.2-4.5 MIU L-1). RESULTS: Biochemical thyroid dysfunction developed in 30 (11.8%) of 254 patients. Hypothyroidism (TSH > 4.5 MIU L-1) was seen in 20 and hyperthyroidism (TSH < 0.2 MIU L-1) in 10 patients. Nine of the 30 patients developed symptomatic thyroid disease and HCV treatment was discontinued because of thyroid dysfunction in three of these patients. Thyroid dysfunction occurred in 15 (11.7%) of 128 patients who received high-dose IFN-alpha induction therapy as compared with 15 (11.9%) of 126 patients who received conventional IFN-alpha therapy (P=0.96). Amongst 231 patients who completed all 6 months of HCV treatment, a sustained virological response was obtained in 19 (66%) of 29 with thyroid dysfunction and 109 (54%) of 202 without (P=0.24). By multivariate analysis female gender and Asian origin were independent predictors of developing biochemical thyroid dysfunction (P < 0.01). CONCLUSION: Thyroid dysfunction occurred in 11.8% of patients treated for chronic hepatitis C with IFN-alpha and ribavirin. Neither the IFN-alpha dosage nor the virological response to treatment were related to the incidence of thyroid dysfunction.

Early psychomotor slowing predicts the development of HIV dementia and autopsy-verified HIV encephalitis.

OBJECTIVES- To ask if slowed motor speed predicts later human immunodeficiency virus (HIV) dementia and HIV encephalitis. METHODS- In 100 deceased acquired immunodeficiency syndrome (AIDS) patients prior results from repeated testing of the movement reaction time test were correlated with later clinical signs of HIV dementia and with neuropathological signs of HIV encephalitis. Autopsy was performed in 72 patients. RESULTS- Movement reaction time 1-2 years prior to death, or at the time of clinical AIDS diagnosis predicted both development of HIV dementia (P<0.05) and HIV encephalitis at autopsy (P<0.01). CONCLUSION- Testing for early psychomotor slowing may be used to identify patients at risk of HIV dementia and HIV encephalitis.

Effect of interferon-alpha induction therapy on genotype 2b/3a and low viral load hepatitis C virus infection. A randomized multicentre study.

BACKGROUND: Interferon monotherapy for chronic hepatitis C virus (HCV) infection leads to sustained viral eradication in a minority of patients. However, in selected groups of patients, sustained virological response is observed in as many as 50% of patients. High initial interferon dose (induction therapy) has been reported to increase the initial response rate. We have studied the effect of interferon induction therapy in patients infected with HCV genotype 2b/3a, low viral load and no cirrhosis. METHODS: A total of 71 treatment-naive HCV RNA-positive patients with biopsy-confirmed chronic hepatitis, with genotype 2b or 3a, viral load < or = 3 million copies per ml and no cirrhosis were randomized to receive either standard interferon therapy (3 MIU interferon-alpha-2a thrice weekly) for 26 weeks or 6 MIU interferon-alpha-2a daily for 4 weeks (induction group) followed by the standard dose (3 MIU thrice weekly) for 22 weeks. Those with persistent HCV RNA at 4 weeks stopped treatment. Patients were monitored for HCV RNA during and following treatment, and data were interpreted according to intention-to-treat analysis. RESULTS: Viral clearance occurred more rapidly (after 4 weeks) in the induction group (33/36 = 92%) compared to the standard interferon group (21/35 = 60%) (P = 0.01). Among the initial responders, 23/33 (induction group) compared to 16/21 (standard group) were persistently HCV RNA-negative at the end of treatment. At 52 weeks (6 months' follow-up), 22/36 (61%) (induction group) compared to 10/35 (29%) (standard group) were HCV RNA-negative. Among initial responders, 22/33 (induction group) and 10/21 (standard group) achieved a sustained virological response. Among end-of-treatment responders, 22/24 (induction group) and 10/16 (standard group) were HCV RNA-negative at 6 months' follow-up (P = 0.013). CONCLUSIONS: In patients infected with HCV genotype 2b/3a, low viral load and without cirrhosis, IFN induction therapy increases the initial viral clearance and reduces the risk of relapse in end-of-treatment responders. A sustained virological response was achieved in 61% of the patients receiving IFN induction therapy.

Effect of combined interferon-alpha induction therapy and ribavirin on chronic hepatitis C virus infection: a randomized multicentre study.

BACKGROUND: The efficacy of interferon-alpha (IFN) induction in combination with ribavirin for chronic hepatitis C virus (HCV) infection is not known. METHODS: A total of 256 treatment-naive HCV RNA-positive patients with biopsy-confirmed chronic hepatitis were enrolled in a randomized multicentre study. The patients received either standard combination therapy with 3 MIU interferon-alpha2b thrice weekly for 26 weeks or 6 MIU interferon-alpha2b daily for 4 weeks and 3 MIU 3/7 days for 22 weeks. All patients received ribavirin 1000 mg or 1200 mg (weight dependent) daily during the 26-week treatment period. Patients were monitored for HCV RNA during and following treatment. RESULTS: The sustained virological response rates (26 weeks after end of treatment) were 54% and 47% for patients receiving IFN induction/ribavirin and standard IFN/ribavirin, respectively (P = 0.35). Among patients infected with genotype 1a/1b, the sustained response rates were 32% and 35%. In patients infected with genotype 2b/3a IFN induction/ribavirin led to a sustained response rate of 80% as compared to 65% in the standard combination therapy group (P = 0.073). Steatosis was more frequently seen in liver biopsies from patients infected with genotype 3a as compared to genotypes la/lb. Among genotype 1a/1b infected patients. steatosis was a highly significant predictor of failure to achieve sustained virological response. Logistic regression analysis (multivariate analysis) showed that independent predictors of sustained virological response were low age, female gender, genotype 2b/3a and HCV RNA negativity at 2 weeks. CONCLUSIONS: IFN induction in combination with ribavirin does not increase the sustained virological response rate among patients infected with HCV. Absence of steatosis is an independent predictor of sustained virological response in patients infected with genotypes 1a/1b.

Treatment of chronic hepatitis C in injecting drug users: 5 years' follow-up.

AIM OF THE STUDY: To assess the long-term hepatitis C (HCV) treatment outcome in former injecting drug users (IDUs). MATERIALS AND METHODS: A long-term follow-up of 27 former IDUs who had been successfully treated for chronic hepatitis C was performed. These patients represented all IDUs who had obtained a sustained virological response in a Norwegian HCV treatment trial. The patients had been treated with interferon-alpha alone or in combination with ribavirin. At 5 years' follow-up the 27 IDUs were retested for HCV RNA and risk behaviour for HCV transmission after treatment was assessed. In the control group all 18 non-IDUs who had obtained a sustained virological response in the same treatment trial were included. RESULTS: At follow-up 13-82 months (median 64) after the end of treatment only one case of probable reinfection was seen among the 27 IUDs. No reoccurrence of HCV was observed in the control group. The IDU who was HCV RNA positive at follow-up had continued injecting drugs and reported frequent needle sharing. At follow-up HCV of genotype 1a was detected in contrast to genotype 1b before treatment indicating that this patient was reinfected with HCV. A return to injecting drug use occurred in 9 (33%) of 27 IDUs. CONCLUSION: The long-term outcome of HCV treatment in former IDUs was excellent. Despite frequent reinitiation of drug injection all but 1 remained HCV RNA negative.

Hepatitis B virus infection in drug addicts: no acute fatalities, no chronicity and could have benefits.

In a group of 159 drug addicts with acute hepatitis B in the 1970s there were no fatalities. During an observation period of about 25 years, 51 of the 159 died of various causes, but no deaths could be attributed to the hepatitis B infection. From 1998 to 2001, a follow-up examination of 53 of the 108 patients still alive, none of the 53 had a chronic hepatitis B virus infection. Fifteen out of thirty-five patients who had completely stopped using narcotics claimed that hospitalisation for acute hepatitis B had been an important factor in their decision to quit drugs.

Death rates and causes of death in cohorts of serum hepatitis patients followed up for more than 20 years.

A cohort of 214 drug addicts with serum hepatitis and a cohort of 193 hepatitis patients without drug addiction were examined in respect of death rates, causes of death and a number of risk factors for reduced survival. The death rate was significantly higher among the drug addicts than among non-addicts. The annual mortality rate was 1.5% in the drug addict group and 0.7% in the non-addict group. The highest relative risk of death was 860 for female drug addicts in age group 15-24 compared to females of the same age in the general population. The most prevalent cause of death in the drug addict group was drug overdose (53%), whereas in the other group 66% died from various somatic diseases. Hepatitis or complications of viral hepatitis played no role as cause of death among the drug addicts, and infections as a whole were also responsible for very few deaths. For male drug addicts, imprisonment before admission and leaving hospital without the doctors' permission were risk factors for early death.

Association between apolipoprotein E genotypes and cancer risk in patients with acquired immunodeficiency syndrome.

The apolipoprotein E (apoE) genotype was determined in 197 deceased acquired immunodeficiency syndrome (AIDS) patients treated at Ullevaal Hospital in Oslo, Norway. A full autopsy had been performed on all. Cancer had developed in 71 individuals, mainly lymphomas (46) and Kaposi's sarcomas (18). The apoE genotype distribution was consistent with Hardy-Weinberg equilibrium, and allele frequencies were in the typical Scandinavian range (6.9% apoE2; 75.6% apoE3; and 17.5% apoE4). Cancer cases had a significantly higher frequency of apoE4 alleles than noncancer cases (24.6% and 13.5%, respectively) and a lower frequency of apoE2 alleles (3.5% versus 8.7%). Background factors, such as survival from AIDS diagnosis, could not explain these differences. Our study thus indicates that apoE genotype affects the development of cancers among AIDS patients.

[Malaria in Norway--diagnosis, treatment and prevention]. / Malaria i Norge--diagnostikk, behandling og profylakse.

The paper describes and discusses procedures and problems related to diagnostics, therapy and prophylaxis of malaria in Norway. A high degree of suspicion in physicians evaluating febrile travellers is of the utmost importance. The clinical symptoms and findings are initially rather unspecific, with fever and fever related symptoms. A definite diagnosis is made by the demonstration of malaria parasites in thin and thick blood smears, which is best performed by an infectious disease physician. Before treatment is started, it is important to determine whether the patient is infected with Plasmodium falciparum or with one of the more benign malaria species. If this is difficult microscopically, a test that detects P. falciparum antigen in blood may be useful in some cases. The therapy of benign malaria is still chloroquine plus primaquine; most patients with malaria falciparum can be routinely treated with mefloquine. Cases of complicated falciparum malaria, usually due to delayed diagnosis and start of treatment, require extensive and sophisticated treatment, usually including parenteral treatment with quinine. Prophylaxis consists of prevention of mosquito bites and chemoprophylaxis; the importance of avoiding bites should never be underestimated. A more widespread use of mefloquine among travellers to Africa is the most important change in chemoprophylaxis in recent years. Finally the article discusses possible improvements in diagnostic procedure, therapy and chemoprophylaxis.

[WHO's malaria program Roll Back Malaria]. / WHOs malariaprogram Roll Back Malaria.

Malaria is one of the main health problems in the world with 300-500 millions cases yearly and about one million deaths, mainly children in Sub-Saharan Africa. In the 1990s the malaria problem in Africa has increased, although we have methods to control the disease. In 1998 the new secretary general of WHO, Gro Harlem Brundtland, established the Roll Back Malaria programme, with the aim to markedly reduce malaria morbidity and mortality. Governments in malaria-affected countries have to take the lead in Roll Back Malaria. Their health systems must be improved and malaria control integrated into the general health system, and the methods available for prevention and treatment have to be intensified and improved. At the same time, Roll Back Malaria will encourage and promote malaria research which hopefully will result in new medicines, vaccines and other tools which will improve the chances of reducing malaria-related deaths and suffering. Roll Back Malaria is a cabinet project within the WHO, and the organisation has a key role as manager, co-ordinator and monitor of the project. However, it depends for resources on international support and commitment from other UN bodies, the World Bank, governments in the western world, pharmaceutical industry, philanthropists and other sources. At present an optimistic view prevails, and the preliminary aim, to halve the malaria mortality by the year 2010, seems realistic even with the control methods of today. However, if research efforts result in new and better tools to combat the disease, the task will definitely be easier.

[Falciparum malaria in Oslo and Akerhus]. / Falciparummalaria i Oslo og Akershus.

BACKGROUND: Imported falciparum malaria in an increasingly frequent health problem in many areas in which it is not endemic. Complications are commonly seen, and reported case-fatality rates may exceed 3%. MATERIAL AND METHODS: The study is a medical chart-based retrospective study of all cases of falciparum malaria diagnosed in Oslo and Akershus counties, south-eastern Norway, 1988-1997. RESULTS: We identified 232 diagnosed cases; of these, records were available for 222 cases (95%). The incidence rate almost quadrupled during the study period. The two largest groups were immigrants visiting their country of origin (35%) and Norwegian tourists (29%). 95% of the cases were infected in Sub-Saharan Africa. There were no fatal cases, and only eight cases (3.6%) developed complicated falciparum malaria. In a statistical analysis, the following factors were found to be significantly associated with complicated disease: higher age, noncompliance to recommended chemoprophylaxis in assumed non-immune subjects, prolonged doctor's delay and prolonged diagnostic delay. INTERPRETATION: The study suggests that complications in imported falciparum malaria may largely be prevented by a high rate of chemoprophylaxis compliance in non-immune travellers and a high awareness of this possibility among physicians evaluating febrile travellers from endemic areas.