Imported malaria in Spain (2009-2016): results from the +REDIVI Collaborative Network.

BACKGROUND: Imported malaria is a frequent diagnosis in travellers and migrants. The objective of this study was to describe the epidemiological and clinical characteristics of patients diagnosed with imported malaria within a Spanish collaborative network registering imported diseases (+REDIVI). In addition, the possible association between malaria and type of case, gender, age or area of exposure was explored. METHODS: Cases of imported malaria were identified among all cases registered in the +REDIVI database during the period October 2009-October 2016. Demographic, epidemiological and clinical characteristics were analysed. RESULTS: In total, 11,816 cases of imported infectious diseases were registered in +REDIVI's database between October 2009 and October 2016. Immigrants seen for the first time after migration accounted for 60.2% of cases, 21.0% of patients were travellers, and 18.8% were travellers/immigrants visiting friends and relatives (VFRs). There were 850 cases of malaria (850/11,816, 7.2%). Malaria was significantly more frequent in men than in women (56.8% vs 43.2%) and in VFR-immigrants (52.6%) as compared to travellers (21.3%), immigrants (20.7%) and VFR-travellers (5.4%) (p < 0.001). Although this data was not available for most patients with malaria, only a minority (29/217, 13.4%) mentioned correct anti-malarial prophylaxis. Sub-Saharan Africa was found to be the most common region of acquisition of malaria. Most common reason for consultation after travel was a febrile syndrome although an important proportion of immigrants were asymptomatic and presented only for health screening (27.3%). Around 5% of travellers presented with severe malaria. The most prevalent species of Plasmodium diagnosed was Plasmodium falciparum (81.5%). Malaria due to Plasmodium ovale/Plasmodium vivax was frequent among travellers (17%) and nearly 5% of all malaria cases in immigrants were caused by Plasmodium malariae. CONCLUSIONS: Malaria was among the five most frequent diagnoses registered in +REDIVI's database. Some significant differences were found in the distribution of malaria according to gender, type of case, species. Among all malaria cases, the most frequent diagnosis was P. falciparum infection in VFR-immigrant men.

Safety Profile of Benznidazole in the Treatment of Chronic Chagas Disease: Experience of a Referral Centre and Systematic Literature Review with Meta-Analysis.

INTRODUCTION: Benznidazole is the preferred drug for treatment of Chagas disease. However, it is toxic and of limited value in chronic infection. OBJECTIVE: We aimed to estimate the rates of and factors related to adverse reactions (ARs) to benznidazole and treatment discontinuations (TDs). METHODS: A meta-analysis was performed using an electronic search of the published literature with no language restrictions until June 2017. Prospective studies were included of chronically infected patients in which at least one treatment arm included benznidazole. Data were added from a prospective cohort of patients with Chagas disease at our centre (January 2007-June 2017). Weighted rates of ARs and TDs were estimated, and potentially related factors were analysed. RESULTS: Some 413 studies were found, from which we chose 42 (nine clinical trials and 33 observational studies, including ours), comprising data for 7822 patients. The weighted rate of ARs to benznidazole was 44.1% (95% confidence interval [CI] 37.2-51.2). ARs were more frequent in adults than in children (51.6 vs. 24.5%), with the most common being skin reactions (34%), gastrointestinal complaints (12.6%) and neurological symptoms (11.5%). Grade 4 ARs were recorded in 3% of cases. The weighted rate of TDs was 11.4% (95% CI 8.5-14.5); TDs were more frequent in adults than in children (14.2 vs. 3.8%). In our cohort, only female sex was related to an increased rate of ARs but not to TDs. CONCLUSION: Benznidazole had a poor tolerability profile, with a high incidence of TDs, especially in adult patients and women. Optimised dosing schedules and/or new drugs are urgently needed.

Delayed haemolysis secondary to treatment of severe malaria with intravenous artesunate: Report on the experience of a referral centre for tropical infections in Spain.

BACKGROUND: Post-artesunate delayed haemolysis is described as hemolytic anemia presenting days after malaria treatment in hyperparasitemic patients. Physiopathological mechanisms and clinical manifestations have not been thoroughly characterised. METHODS: We conducted a retrospective study of hospitalised malaria patients who received artemisinin derivatives from January 1, 2010 to December 31, 2015. RESULTS: 21 patients were included in the study: 11 travellers, 8 travellers visiting friends and relatives and 2 immigrants. Median age was 35.5 years (IQR: 25.7-44.8) and 11 were men. Eight patients received oral and 13 received intravenous (IV) artemisinin-based drugs. Follow-up after the malaria episode was available for 15 patients (12 with IV treatment). Four patients presented with delayed haemolysis 9-14 days after artesunate treatment; all had been admitted with severe malaria, were treated IV and had hyperparasitaemia (17%-33%). Other than hyperparasitaemia, no other factors were associated with artesunate haemolysis. Patients' outcomes were favourable and the only additional therapeutic measure needed was a blood transfusion. CONCLUSIONS: Delayed haemolysis is a frequent complication in hyperparasitemic malaria treated with IV artesunate. Follow-up is mandatory for at least 2 weeks after treatment initiation. This condition is potentially severe but does not appear to be life threatening.

6-year review of +Redivi: a prospective registry of imported infectious diseases in Spain.

Background: Understanding and detecting imported diseases is a priority in the prevention and management of prevalent and emergent infectious diseases acquired abroad. The +Redivi network measures the burden of imported infections in Spain and is essential for closing the gap in travel medicine. Methods: Demographic characteristics, travel information, syndromes and confirmed travel-related diagnoses were registered in a standardised online database. Results: A total of 10 767 cases of imported infectious diseases were registered between October 2009 and December 2015. Of these, 60.8% of cases were immigrants seen for the first time after arrival, 20.6% were travellers, and 18.4% were individuals visiting friends and relatives (VFR [immigrants and travellers]). The median time between arrival and medical consultation was 5.5 years for immigrants, 2.0 weeks for travellers, 3.1 weeks for VFR-travellers and 11.4 for VFR-immigrants. The most prevalent diagnoses were Chagas disease in immigrants and nonspecific acute diarrhoea in travellers. Malaria by P. falciparum was one of the most prevalent diagnoses among VFR. More than half the travellers saw a physician before travelling, although one-third of those for whom antimalarial medication was indicated did not take their medication correctly. As for VFR, only 10.4% of VFR-immigrants and 32.5% of VFR-travellers sought pre-travel advice. Only 23 and 21%, respectively, of those for whom antimalarial prophylaxis was indicated took the medication properly. Conclusions: +Redivi provides a clear picture of the prevalence of imported infectious diseases among travellers and immigrants in Spain. The data collected could be used to improve everyday health care provided to travellers and immigrants after travel, to guide pre-travel consultations and to monitor the potential occurrence of tropical or exotic infectious diseases.