Background The aim was to assess factors affecting disease severity in imported P. falciparum and non-falciparum malaria. Methods We reviewed medical records from 2793/3260 (85.7%) of all episodes notified in Sweden between 1995 and 2015 and performed multivariable logistic regression. Results Severe malaria according to WHO 2015 criteria was found in P. falciparum (9.4%), P. vivax (7.7%), P. ovale (5.3%), P. malariae (3.3%), and mixed P. falciparum episodes (21.1%). Factors associated with severe P. falciparum malaria were age <5 years and >40 years, origin in nonendemic country, pregnancy, HIV, region of diagnosis, and health care delay. Moreover, oral treatment of P. falciparum episodes with parasitemia ≥2% without severe signs at presentation was associated with progress to severe malaria with selected criteria. In non-falciparum, age >60 years, health care delay and endemic origin were identified as risk factors for severe disease. Among patients originating in endemic countries, a higher risk for severe malaria, both P. falciparum and non-falciparum, was observed among newly arrived migrants. Conclusions Severe malaria was observed in P. falciparum and non-falciparum episodes. Current WHO criteria for severe malaria may need optimization to better guide the management of malaria of different species in travelers and migrants in nonendemic areas.

SummaryIn this nationwide observational study of 937 adults diagnosed with Plasmodium falciparum malaria in Sweden, Charlson comorbidity score ≥1 as well as diabetes and obesity were significantly associated with severe malaria in both nonimmune travelers and immigrants from endemic countries.

e Malaria predisposes children in areas where malaria is endemic to concurrent bacteremia, often with severe outcomes. The importance of bacterial coinfections in patients diagnosed with malaria in nonendemic settings has, however, not been reported. A retrospective analysis of microbiology data was performed in 755 travelers diagnosed with malaria in Sweden. Bacterial cultures from blood and other locations were correlated to clinical outcome and antibiotic treatment. Blood cultures were drawn from 417 (55%) patients (88% of whom were >15 years old), and bacterial isolates of clinical relevance (Salmonella enterica serovar Enteritidis and Escherichia coli) were detected in 2 patients (0.3%). Cultures from other locations (mainly urine, nasopharyngeal, and fecal samples) were obtained from 44% of the patients with 4.9% positivity. Of the 38 patients given antibiotics, 47% had neither severe malaria nor positive cultures and/or radiology signs indicative of treatment. C-reactive protein levels were associated with bacterial infections but had only a fair predictive value. Bacterial coinfections are uncommon among travelers with malaria. These data suggest a weaker association between malaria and bacteremia than previously described in endemic settings and might indicate different patient populations with different pathophysiological mechanisms and microbial environments. The study supports a restrictive antibiotic policy in returning travelers with malaria.

In malaria-endemic areas, adults very rarely succumb to severe malaria, suggesting that immunity to severe disease is life-long under conditions of repeated exposure. To what extent this protection persists in the absence of exposure remains to be established. The aim of this study was to assess whether duration of residency in a malaria-free country affects the risk for severe malaria in immigrants originating from sub-Saharan Africa. We conducted a retrospective chart review of 948 cases of malaria diagnosed in Stockholm, Sweden in 1995-2013. Among 501 adult patients with Plasmodium falciparum (315 of endemic origin and 186 of non-endemic origin, mainly Sweden), 41 (8.2%) had severe malaria according to WHO criteria (including 5% with parasitaemia), 22 (4.4%) had factors prognostic of poor outcome, and 35 (7.0%) were admitted to intensive care. Overall, patient origin did not affect the odds of severe malaria, according to any of these definitions. However, when the immigrants were stratified with regard to their duration of residency in Sweden, the risk of factors prognostic for poor outcome was associated with duration of prior residency in a malaria-free country among patients of endemic origin (p 0.02), and immigrants who had lived for ≥ 15 years in Sweden had a similar risk as non-immune travellers. The results of this explorative study suggest that, although immunity to severe malaria is maintained for several years in African adults, this protection might be lost with time without repeated re-exposure. A larger study, preferably including multiple centres, will be needed to confirm our findings.