Urban Hellgren

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.

Mefloquine tolerability during chemoprophylaxis: focus on adverse event assessments, stereochemistry and compliance

This longitudinal study of travellers to Africa taking mefloquine (MQ) chemoprophylaxis aimed to quantify and assess non‐serious adverse events (AE) occurring during short‐term prophylaxis and relate these to concentrations of racemic MQ, its enantiomers and metabolite. A total of 420 volunteers (52% F) participated. AEs with some impact on activities were reported by 11.2% of participants including 7.9% of neurological/psychiatric symptoms. Women were more likely to report AEs (P=0.02). The standardized questionnaires used showed more pathological indicators in travellers who reported subjective AE with significantly more dizziness, distress, sleep disturbances and a high total mood disturbance (TMD) in the AE group. There was, however, no significant performance deficit in computerized psychomotor tests in those experiencing AE. Furthermore, no significant differences were observed in enantiomer ratios, metabolite concentrations, or racemic MQ levels in participants with or without AEs suggesting that these factors are not the main predictors of mefloquine intolerability.

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.

High-performance liquid chromatographic assay for the simultaneous monitoring of mefloquine and its acid metabolite in biological samples using protein precipitation and ion-pair extraction

A high-performance liquid chromatographic (HPLC) method is presented for the simultaneous determination of mefloquine and its acid metabolite in plasma and whole blood. Plasma and whole blood are deproteinized with a combination of zinc and acetonitrile before extraction. Mefloquine and its acid metabolite are extracted simultaneously at pH 4 by methyl tert.-butyl ether, where mefloquine is extracted as an ion pair with heptanesulphonate. After evaporation of the organic phase, the residue is dissolved in mobile phase and injected on to the chromatographic column. A reversed-phase column (Spherisorb ODS-1) is used with acetonitrile-phosphate buffer (0.1 mol/l, pH 2.5) (42:58) containing 40 mmol/l perchlorate as the mobile phase. N,N-Dioctylamine was added to the mobile phase to give a concentration of 0.1% and the pH was adjusted to 2.3-2.7 with concentrated phosphoric acid. The method permits the determination of 0.10 mumol/l (30 ng/ml) mefloquine and its acid metabolite in plasma. The coefficient of variation was 5-6% at the therapeutic level (mefloquine 1-4 mumol/l, its carboxylic metabolite 2-6 mumol/l) in 0.5-ml samples. An alternative method is also described with a similar clean-up procedure that uses protein precipitation with zinc-acetonitrile as a sample pretreatment for therapeutic monitoring of mefloquine and metabolite in plasma and whole blood. Using this method, 0.25 mumol/l mefloquine and its metabolite can be determined. The results from the two methods correlate well.

The low and declining risk of malaria in travellers to Latin America: is there still an indication for chemoprophylaxis?

A comparison was made between local malaria transmission and malaria imported by travellers to identify the utility of national and regional annual parasite index (API) in predicting malaria risk and its value in generating recommendations on malaria prophylaxis for travellers.Regional malaria transmission data was correlated with malaria acquired in Latin America and imported into the USA and nine European countries. Between 2000 and 2004, most countries reported declining malaria transmission. Highest APIs in 2003/4 were in Surinam (287.4) Guyana (209.2) and French Guiana (147.4). The major source of travel associated malaria was Honduras, French Guiana, Guatemala, Mexico and Ecuador. During 2004 there were 6.3 million visits from the ten study countries and in 2005, 209 cases of malaria of which 22 (11%) were Plasmodium falciparum. The risk of adverse events are high and the benefit of avoided benign vivax malaria is very low under current policy, which may be causing more harm than benefit.

The roles of cytochrome P450 3A4 and lA2 in the 3-hydroxylation of quinine in vivo

To investigate the roles of CYP3A4 and CYP1A2 in the 3‐hydroxylation of quinine in vivo.

The Value of C-reactive Protein as a Marker of Bacterial Infection in Patients with Septicaemia/Endocarditis and Influenza

In order to evaluate the capacity of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cell count (WBC) and polymorphonuclear neutrophils (PMNs) to differentiate between bacterial and viral infection we studied 176 patients with septicaemia/endocarditis (SE), 59 patients with uncomplicated influenza (UI) and 22 patients with complicated influenza (CI) retrospectively. All 4 parameters were significantly more elevated in SE and CI than in UI. Among patients with SE 10 176 had a CRP value less than 50 mg/l and in patients with UI 5/56 had a CRP value greater than 100 mg/l. Patients with SE caused by pneumococci had the highest CRP levels and patients with alfa-haemolytic streptococci the lowest. The sensitivity and specificity favours the use of CRP as an indicator of bacterial superinfection in influenza.

The incidence of malaria in travellers to South-East Asia: is local malaria transmission a useful risk indicator?

BackgroundThe presence of ongoing local malaria transmission, identified though local surveillance and reported to regional WHO offices, by S-E Asian countries, forms the basis of national and international chemoprophylaxis recommendations in western countries. The study was designed to examine whether the strategy of using malaria transmission in a local population was an accurate estimate of the malaria threat faced by travellers and a correlate of malaria in returning travellers.MethodsMalaria endemicity was described from distribution and intensity in the local populations of ten S-E Asian destination countries over the period 2003-2008 from regionally reported cases to WHO offices. Travel acquired malaria was collated from malaria surveillance reports from the USA and 12 European countries over the same period. The numbers of travellers visiting the destination countries was based on immigration and tourism statistics collected on entry of tourists to the destination countries.ResultsIn the destination countries, mean malaria rates in endemic countries ranged between 0.01 in Korea to 4:1000 population per year in Lao PDR, with higher regional rates in a number of countries. Malaria cases imported into the 13 countries declined by 47% from 140 cases in 2003 to 66 in 2008. A total of 608 cases (27.3% Plasmodium falciparum (Pf)) were reported over the six years, the largest number acquired in Indonesia, Thailand and Korea. Four countries had an incidence > 1 case per 100,000 traveller visits; Burma (Myanmar), Indonesia, Cambodia and Laos (range 1 to 11.8-case per 100,000 visits). The remaining six countries rates were < 1 case per 100,000 visits. The number of visitors arriving from source countries increased by 60% from 8.5 Million to 13.6 million over the 6 years.ConclusionThe intensity of malaria transmission particularly sub-national activity did not correlate with the risk of travellers acquiring malaria in the large numbers of arriving visitors. It is proposed to use a threshold incidence of > 1 case per 100,000 visits to consider targeted malaria prophylaxis recommendations to minimize use of chemoprophylaxis for low risk exposure during visits to S-E Asia. Policy needs to be adjusted regularly to reflect the changing risk.

Reversed-phase high-performance liquid chromatography determination of quinine in plasma, whole blood, urine, and samples dried on filter paper

The analysis of quinine in whole blood, plasma, urine, and samples dried on filter paper is described. Extraction was made with toluene followed by back-extraction into phosphate buffer. A reversed-phase liquid chromatography system with fluorescence detection was used. The within-day coefficient of variation of the method was 4–10% at the lower limit of determination (2 nM in plasma and 50 nM in whole blood, dried samples, and urine) and 2–4% at 10μM. The quinine concentration was found to be lower in whole blood than in plasma (mean ratio, plasma-whole blood, 1.17). The concentration in capillary blood was lower than that in venous blood (mean ratio, capillary blood-venous blood, 0.93).