Severe malaria in Europe: an 8-year multi-centre observational study.

BACKGROUND: Malaria remains one of the most serious infections for travellers to tropical countries. Due to the lack of harmonized guidelines a large variety of treatment regimens is used in Europe to treat severe malaria. METHODS: The European Network for Tropical Medicine and Travel Health (TropNet) conducted an 8-year, multicentre, observational study to analyse epidemiology, treatment practices and outcomes of severe malaria in its member sites across Europe. Physicians at participating TropNet centres were asked to report pseudonymized retrospective data from all patients treated at their centre for microscopically confirmed severe Plasmodium falciparum malaria according to the 2006 WHO criteria. RESULTS: From 2006 to 2014 a total of 185 patients with severe malaria treated in 12 European countries were included. Three patients died, resulting in a 28-day survival rate of 98.4%. The majority of infections were acquired in West Africa (109/185, 59%). The proportion of patients treated with intravenous artesunate increased from 27% in 2006 to 60% in 2013. Altogether, 56 different combinations of intravenous and oral drugs were used across 28 study centres. The risk of acute renal failure (36 vs 17% p = 0.04) or cerebral malaria (54 vs 20%, p = 0.001) was significantly higher in patients ≥60 years than in younger patients. Respiratory distress with the need for mechanical ventilation was significantly associated with the risk of death in the study population (13 vs 0%, p = 0.001). Post-artemisinin delayed haemolysis was reported in 19/70 (27%) patients treated with intravenous artesunate. CONCLUSION: The majority of patients with severe malaria in this study were tourists or migrants acquiring the infection in West Africa. Intravenous artesunate is increasingly used for treatment of severe malaria in many European treatment centres and can be given safely to European patients with severe malaria. Patients treated with intravenous artesunate should be followed up to detect and manage late haemolytic events.

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.

Quantitative B-lymphocyte deficiency and increased TCRγδ T-lymphocytes in acute infectious spondylodiscitis.

Acute infectious spondylodiscitis (AIS) is a serious infection of the spine with rising incidence and a mortality of 3-6%. The role of the immune system in AIS is largely unknown. We performed extensive B and T-lymphocyte phenotyping in patients with AIS at diagnosis and after treatment cessation. In this prospective multicentre study, flow cytometric analysis of T and B-lymphocyte subsets was performed in 35 patients at diagnosis and 3 months after treatment cessation. We additionally analysed levels of immunoglobulins and IgG subclasses, serum level and genetic variants of mannose-binding lectin, and somatic hypermutation. A total of 22 (61%) patients had B-lymphocytes below reference limit at baseline, persisting in 7 (30%) patients at follow-up. We found a lower proportion of CD19 + CD27 + IgD+ marginal zone B-lymphocytes and a higher proportion of γδ+ T-lymphocyte receptors compared with controls at both time points. Immunoglobulin levels were elevated at baseline compared to follow-up, and not associated with absolute B-lymphocyte count. In conclusion, a large proportion of AIS patients presented with profound B-lymphocyte deficiency, only partly reversible at follow-up. Identification of immune dysfunction related to AIS may allow for future targeted therapeutic interventions to restore host immunity.

Schistosomiasis in European Travelers and Migrants: Analysis of 14 Years TropNet Surveillance Data.

Schistosomiasis remains one of the most prevalent parasitic diseases worldwide and the infection is frequently found in travelers and migrants. The European Network for Tropical Medicine and Travel Health conducted a sentinel surveillance study on imported schistosomiasis between 1997 and 2010. This report summarizes epidemiological and clinical data from 1,465 cases of imported schistosomiasis. Direct pathogen detection and serology were the main diagnostic tools applied. Of these, 486 (33%) cases were identified among European travelers, 231 (16%) among long-term expatriates, and 748 (51%) among non-European immigrants. Overall, only 18.6% of travelers had received pretravel advice; 95% of infections were acquired in the African region. On species level, Schistosoma mansoni was identified in 570 (39%) and Schistosoma haematobium in 318 (22%) cases; 57.5% of patients were symptomatic. Acute symptoms were reported in 27% of patients leading to earlier presentation within 3 months. Praziquantel was used in all patients to treat schistosomiasis. Many infections were detected in asymptomatic patients. In 47.4% of asymptomatic patients infection was detected by microscopy and in 39% by serology or antigen testing. Schistosomiasis remains a frequent infection in travelers and migrants to Europe. Travelers should be made aware of the risk of schistosomiasis infection when traveling to sub-Saharan Africa. Posttravel consultations particularly for returning expatriates are useful given the high potential for detecting asymptomatic infections.

Laboratory indicators of the diagnosis and course of imported malaria.

When travellers return from malaria-endemic areas and present to hospital with fever, microscopy of blood smears remains the leading method to verify a suspected diagnosis of malaria. Additional laboratory abnormalities may, however, also be indicative of acute malaria infection. We monitored prospectively a group of patients with imported Plasmodium falciparum (n=28) or P. vivax/P. ovale (n=12) infection, respectively, and assessed haemoglobin, leucocytes, thrombocytes, C-reactive protein, coagulation factor II-VII-X, lactate dehydrogenase and bilirubin during 7 d of admission and weekly until d 28. For comparison, admission values of a group of febrile patients with suspected malaria, but with negative blood slides, were also assessed (n=66). The thrombocyte, leucocyte counts and coagulation factor II-VII-X were significantly lower in the malaria group compared to the non-malaria group, whereas the C-reactive protein, lactate dehydrogenase and bilirubin were significantly higher in the malaria group. The differences were particularly strong with falciparum malaria. By contrast, haemoglobin levels were not affected. In conclusion, our study emphasizes the role of a few commonly analysed laboratory parameters, in particular thrombocyte counts, in guiding the clinician managing a returning traveller with fever.

[Addison's disease and infection]. / Addisons sygdom og infektion.

Addison's disease, or primary adrenocortical insufficiency, is a diagnosis that may often be overlooked. A case is presented of a 28-year-old male who, within a six-month period, was admitted on three occasions with symptoms mimicking sepsis, for which no microbiological etiology could be established. Each time he recovered, however, on antibiotic treatment. Not until the third admission was Addison's disease suspected.

New aspects on the natural history of chronic hepatitis B infection: implication for therapy.

The incidence and sequelae of chronic hepatitis B (HBV) infection appear to have been overestimated previously, especially in areas outside Asia where neonatal infection predominates. A high rate of spontaneous HBeAg seroconversion is found in children as well as adults, and 40 to 50 y of replicative infection seems to be the most important risk factor for cirrhosis and hepatocellular carcinoma necessitating a cautious attitude towards antiviral treatment. Of concern, however, HBeAg seroconversion, which usually predicts a good outcome, is not always an irreversible event. Low grade replication of HBV may continue in anti-HBe positive individuals and shift in HBe status does occur in up to 10% of viral carriers with evidence of an increased risk of complications. Viral replication (HBV DNA positivity) is also found in HBeAg negative mutant infection and is an important parameter to note. To date, the data do not suggest any different prognosis for patients with this kind of infection. Also the various viral genotypes might have different prognoses partly due to the association with precore mutations, but the present knowledge does not allow different therapeutic management as in the case of hepatitis C. Treatment is available with a number of safe antiviral agents. However, all of them are mainly suppressive with low cure rates after 1 y. Initiation of therapy should therefore mainly be considered in symptomatic chronic infection and in cases with high risk of complications i.e. patients with ongoing viral replication and age above 40 y or bridging necroses verified by liver biopsy.