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Epidemiology and clinical features of vivax malaria imported to Europe: Sentinel surveillance data from TropNetEurop
1Institute of Tropical Medicine, Humboldt University, Berlin, Germany
2Secció Medicina Tropical, Hospital Clinic Barcelona – IDIBAPS., Barcelona, Spain
3Department of Medicine (Infectious Diseases), Charité, Humboldt University, Berlin, Germany
4Department of Infectious Diseases and Tropical Medicine, University of Munich, Germany
5Department of Infectious Diseases, University Hospital Hradec Králové, Czech Republic
6Department of Infectious Diseases, Rigshospitalet, University of Copenhagen; Denmark
7Hospital for Tropical Diseases, London, UK
8Clinical Services, Prins Leopold Instituut voor Tropische Geneeskunde, Antwerp; Belgium
9Department of Medicine, Unit of Infectious Diseases, Karolinska Institute, Stockholm, Sweden
10Infection and Tropical Medicine, Bradford Royal Infirmary, Bradford, UK
11Clinica di Malattie Infettive e Tropicali, Universitá di Brescia, Italy
12Infectious Diseases–Microbiology Department, Tropical Medicine & Clinical Parasitology Unit, Hospital Ramon y Cajal, Madrid, Spain
13Centro per le Malattie Tropicali, Ospedale S. Cuore, Negrar Verona, Italy
14Division of Infectious Diseases, Huddinge University Hospital, Karolinska Institute, Stockholm, Sweden
15Sección de Medicina Tropical-Servicio de Enfermedades Infecciosas, Hospital Carlos III- Instituto de Salud Carlos III, Madrid, Spain
16Department of Infection & Tropical Medicine, Newcastle General Hospital, Newcastle- upon-Tyne, UK
17Department of Infectious Diseases, Ullevaal University Hospital, Oslo, Norway
18Missionsärztliche Klinik, Würzburg, Germany
194. Medizinische Abteilung mit Infektions- und Tropenmedizin, Kaiser-Franz-Josef-Spital der Stadt Wien, Vienna, Austria
20Swiss Tropical Institute, Basel, Switzerland
21Abteilung fur spezifische Prophylaxe und Tropenmedizin am Institut für Pathophysiologie, University of Vienna, Austria
22Institut für Tropenhygiene und öffentliches Gesundheitswesen, Universität Heidelberg, Germany
23Institut für Tropenmedizin, Universitätsklinikum Tübingen, Germany
24Department of Infectious Diseases, Hvidovre Hospital, Hvidovre, Denmark
25Department of Tropical Medicine and Epidemiology, Medical University of Gdansk, Interfacultary Institute of Maritime and Tropical Medicine in Gdynia, Poland
26Hôpital St André-CHU, Bordeaux, France
27Sektion Infektiologie und Klinische Immunologie, Universität Ulm, Germany
28Tropical Medical Bureau, Dublin, Ireland
29Department of Medicine, Division of Infectious Diseases, Helsinki University Central Hospital, Helsinki, Finland
302. Klinik für Innere Medizin, Städtische Kliniken "St. Georg", Leipzig, Germany
31Department of Infectious and Tropical Diseases, Hopital Nord CHU, Marseille, France
32Department and Clinic of Tropical and Parasitic Diseases, Karol Marcinkowski University of Medical Sciences, Poznan, Poland
33Unitat de Malalties Tropicals, Importades i Vacunacions Internationales, Institut Català de la Salut, Barcelona, Spain
34Centre for Tropical Medicine and Imported Infectious Diseases, Haukeland University Hospital, Bergen, Norway
35Consultation de médecine tropicale, Hôpital Avicenne, Bobigny, France
36Consulta de Medicina do Viajante, Departamento de Doenças Infecciosas, Hospital Universitário, Coimbra, Portugal
37Instituto de Higiena e Medicina Tropical, Universidade Nova de Lisboa, Lisbon, Portugal
38The German Navy Institute for Maritime Medicine, Center for Applied Tropical Medicine and Infectious Diseases Epidemiology, Kronshagen, Germany
Received December 8, 2003; Accepted March 8, 2004.
Between January 1999 and September 2003, a total of 4,801 patients with travel-related malaria were reported within the TropNetEurop network. P. vivax was involved in 618 (12.9%) cases, either as sole pathogen (n = 585) or in mixed-infections with other species (n = 33), thus accounting for the second highest number of cases after P. falciparum. The reported proportion of P. vivax was rather steady with 10.9% in 1999, 12.6% in 2000, 15.1% in 2001, 12.3% in 2002 and 12.9% in 2003. All 16 TropNetEurop countries reported P. vivax malaria. However, as shown in table , the number of cases varied strongly between countries. Germany (24.3%), Spain (15.5%) and the UK (12.0%) reported most cases, whereas reports from Switzerland (1.8%), Poland (1.6%), Finland (1.0%), Ireland (1.0%) and Portugal (0.3%) were scarce. According to diagnostic information 557 (90.1%) of the 618 infections were confirmed, two (0.3%) were probable and eight (1.3%) were suspected cases. The remaining 51 (8.3%) could not be classified, due to missing information on the underlying diagnostic procedure. Those and the suspected cases were excluded from analyses with clinical endpoints in the latter.
Frequency of P. vivax malaria by year and reporting country
Table describes characteristics of the 618 patients. About 2/3 were male. The median age was 32 years (inter-quartile range 26–43). About 50% reported reception of pre-travel advice, 42.2% stated use of anti-malarial chemoprophylaxis. Among those with prophylaxis, 62.1% stated compliance with the recommended regimen.
Characteristics of patients with P. vivax malaria
The majority of patients who imported vivax malaria into Europe were Europeans living and working in Europe (66.0%). Immigrants and refugees, summarising both those of overseas origin who may have lived in the reporting country for many years and very recent immigrants, made up the second largest group (19.7%), followed by European expatriates (8.5%) and foreign visitors (5.8%). Analysing patient classifications by reporting country revealed that immigrants and refugees accounted for distinctly more than the overall 20% proportion in Norway (61.5%), Italy (45.9%), France (40.0%), Spain (31.3%) and Denmark (25.0%).
Reasons for travel differed for Europeans and immigrants. While Europeans living in Europe mainly travelled for tourism (71.4%), followed by business (7.8%), missionary work (7.0%), research (6.3%), visits to relatives or friends (6.0%), military missions (0.8%) or other reasons (0.8%). The main reasons for travel in the immigrant group were immigration to Europe (47.0%) or visits to relatives or friends in the former home country (44.4%).
Figure marks 16 geographical regions from which P. vivax malaria was imported from during the 56 month surveillance period. The main regions of infection were the Indian subcontinent (17.0%), Indonesia (12.1%), South America (11.4%) and Western Africa (11.4%), as a group accounting for 52% of the cases. However, while the Indian subcontinent was the main region of infection each year, the others switched places in the annual ranking order. Further regions of importance were Eastern Africa (10.0%), Southeast Asia (8.6%), and Oceania (8.5%), contributing another 27% of the cases. Main countries of infection were Indonesia (12.1%), India (8.7%), Papua New Guinea (8.0%), Pakistan (7.8%) and Ecuador (5.7%).
Geographical origin of P. vivax malaria imported to Europe between January 1999 and September 2003 (n = 618)
Exclusion of patients with concomitant plasmodial or other infections and cases with suspected or unknown diagnostic status left 526 patients for the analysis of clinical endpoints. Symptom information was given for 487 of those. The most frequent complaints were fever, headache, fatigue and musculo-skeletal symptoms, affecting 95.5%, 51.3%, 32.6% and 29.6% of the patients, respectively. However, a variety of other symptoms was noted, too. Further information on the course of the disease is summarised in table . The median time from end of journey to symptom onset was 60 days (inter-quartile range 8–149). However, with 86 versus 31 days the median onset of symptoms was significantly delayed in patients with chemoprophylaxis (p<0.0001 Wilcoxon rank test). More than half of the patients (60.1%) were hospitalised, although in-patient treatment was distinctly less common in Ireland (0%), Switzerland (9.1%), Belgium (15.6%) and Spain (26.1%). The median length of hospitalization was four days (inter-quartile range 2–5). Information whether complications occurred during the course of the disease, was given for 270 of the 526 patients. Complications were reported in 30 of them, 22 mentioning recrudescence or relapse, one G6PD-deficiency and seven indicating severe disease. Specific complications in the latter group were serious spleno- or hepatomegaly (3 patients), spleen-rupture (1 patient), pancytopenia (1 patient), macrohaematuria (1 patient) and psychosis (1 patient). All 618 patients survived.
Course of disease in 526 patients with confirmed or probable P. vivax mono-infection
Treatment information was given for 518 confirmed and probable mono-infections. Table presents frequencies of drugs used in the treatment of P. vivax malaria. Although primaquine and chloroquine was the most frequently used drug combination, 84 (16.2%) patients, including 61 males older than four, were not treated with primaquine. Least frequent use of primaquine was reported from France (0.0%), Ireland (20%), Poland (40.0%) and Finland (50.0%).
Drugs used in the treatment of 518 patients with P. vivax malaria