Matthias L. Schmid

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.

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.

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

BackgroundPlasmodium 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.ObjectivesTo present epidemiological and clinical data on imported P. vivax malaria collected at European level.Material and methodsData 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.ResultsWithin 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.ConclusionsTropNetEurop data can contribute to the harmonization of European treatment policies.

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.

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.

Low prevalence of transmitted antiretroviral drug resistance in a large UK HIV-1 cohort

OBJECTIVES To describe current practice in testing for transmitted antiretroviral drug resistance (TDR) and the prevalence of TDR in a large UK HIV-1 cohort. METHODS The study includes a retrospective analysis of newly diagnosed HIV-1-infected patients presenting to eight HIV clinics in the north of England between March 2005 and March 2007. Resistance mutations were defined by IAS-USA. Predicted phenotypes were calculated by the Stanford University database. RESULTS Five hundred and fifty-eight patients were studied, of whom 394 (70.6%) had heterosexually acquired HIV and 377 (67.6%) were infected outside the UK. TDR testing was performed in 406 patients (72.8%). Thirteen of 392 viral resistance profiles (3.3%) showed genotypic TDR. There was no significant association between TDR and any demographic or risk factor or baseline CD4 count. In particular, rates of TDR were similar in white British (6/147, 4.1%) and black African (7/224, 3.1%) patients. The numbers of patients with TDR to individual drug classes were: nucleoside reverse transcriptase inhibitors, 2 (0.5%); non-nucleoside reverse transcriptase inhibitors, 7 (1.8%); and protease inhibitors, 4 (1.0%). No patients had multi-class resistance detected. Eleven patients (2.8%) were predicted to have significant phenotypic resistance to at least one drug. CONCLUSIONS In a large unselected UK cohort, with high coverage of TDR testing, the prevalence of TDR was low and is in accordance with recent data, showing a decrease in the prevalence of TDR in the UK. Differences in population mix did not appear to explain this low rate.

The significance of very low-level viraemia detected by sensitive viral load assays in HIV infected patients on HAART

OBJECTIVES Viral load (VL) measurement is critical for monitoring the effectiveness of highly active antiretroviral therapy (HAART). HAART aims to maintain plasma HIV RNA at undetectable levels. A VL <50 copies/ml was previously considered undetectable. After introducing more sensitive assays many patients with VL <50 copies/ml were found to have very low-level viraemia (VLLV), defined as a detectable VL <40 copies/ml. This study aimed to determine the significance of VLLV. METHODS This retrospective case-control study included 69 individuals on HAART with VLLV. Immunological and virological outcomes over 36 months were compared to those of 70 well-matched controls with persistently undetectable VL. RESULTS We detected no significant association between VLLV and the development of virological failure or inferior immunological outcomes. However, individuals with VLLV were significantly less likely to achieve subsequent sustained virological suppression (VL <50 copies/ml, p<0.001), including completely undetectable suppression (undetectable VL <40 copies/ml, p=0.002). CONCLUSIONS The significance of VLLV has been uncertain. Our results clearly suggest that VLLV is predictive of future suboptimal virological control, particularly a reduced likelihood of achieving virological suppression. Further work should confirm our findings and evaluate strategies for managing VLLV in HAART-treated patients.

Therapy of uncomplicated falciparum malaria in Europe: MALTHER – a prospective observational multicentre study

BackgroundMalaria continues to be amongst the most frequent infectious diseases imported to Europe. Whilst European treatment guidelines are based on data from studies carried out in endemic areas, there is a paucity of original prospective treatment data. The objective was to summarize data on treatments to harmonize and optimize treatment for uncomplicated malaria in Europe.MethodsA prospective observational multicentre study was conducted, assessing tolerance and efficacy of treatment regimens for imported uncomplicated falciparum malaria in adults amongst European centres of tropical and travel medicine.ResultsBetween December 2003 and 2009, 504 patients were included in 16 centres from five European countries. Eighteen treatment regimens were reported, the top three being atovaquone-proguanil, mefloquine, and artemether-lumefantrine. Treatments significantly differed with respect to the occurrence of treatment changes (p = 0.005) and adverse events (p = 0.001), parasite and fever clearance times (p < 0.001), and hospitalization rates (p = 0.0066) and durations (p = 0.001). Four recrudescences and two progressions to severe disease were observed. Compared to other regimens, quinine alone was associated with more frequent switches to second line treatment, more adverse events and longer inpatient stays. Parasite and fever clearance times were shortest with artemether-mefloquine combination treatment. Vomiting was the most frequent cause of treatment change, occurring in 5.5% of all patients but 9% of the atovaquone-proguanil group.ConclusionsThis study highlights the heterogeneity of standards of care within Europe. A consensus discussion at European level is desirable to foster a standardized management of imported falciparum malaria.

Intravenous Artesunate Reduces Parasite Clearance Time, Duration of Intensive Care, and Hospital Treatment in Patients With Severe Malaria in Europe: The TropNet Severe Malaria Study

Intravenous artesunate improves survival in severe malaria, but clinical trial data from nonendemic countries are scarce. The TropNet severe malaria database was analyzed to compare outcomes of artesunate vs quinine treatment. Artesunate reduced parasite clearance time and duration of intensive care unit and hospital treatment in European patients with imported severe malaria.

Pancreatic exocrine insufficiency in HIV‐positive patients

We describe the management of a cohort of eight HIV‐positive patients on antiretroviral medication with evidence of pancreatic insufficiency consisting of chronic diarrhoea and a low faecal elastase measurement.