Clinical presentation and diagnosis of imported strongyloidiasis at a tertiary hospital, Stockholm, Sweden.

BACKGROUND: Since Strongyloides can persist in its host for decades, and cause life threatening infections data on prevalence, the burden and risk factors for infection is crucial in migrant populations. METHODS: In this observational retrospective cohort study, we describe the epidemiological, clinical, and microbiological characteristics of imported strongyloidiasis diagnosed at the Karolinska University Hospital, Stockholm, Sweden, during 2010-2021. RESULTS: We identified 98 individuals with strongyloidiasis, 89 (90.8%) born in endemic and 9 (9.2%) in non-endemic countries. Sub-Saharan Africa was the most common origin among the group born in endemic countries (62, 69.7%), (p < 0.005). There were 22 individuals with an underlying immunosuppressive condition. Gastrointestinal symptoms (53/98, 54.1%) were the symptoms most frequently described, and were more frequent in adults (57.0%) vs children (0%) (p = 0.013). Eosinophilia was detected in 74 (75.5%), being more frequent in the endemic-borne group (79.8% vs 33.3%, p = 0.002). Eight persons developed complications of strongyloidiasis because of either hyperinfection or disseminated disease. No people living with HIV with CD4 <500/mm3 (n = 6) developed severe strongyloidiasis. CONCLUSION: A limited number of strongyloidiasis cases was identified, with few complicated cases in immunosuppressed patients. Further studies focusing on identifying and exploring the risk of complicated strongyloidiasis in immunosuppressed patients are needed.

Malaria parasite prevalence in Sub-Saharan African migrants screened in Sweden: a cross-sectional study.

Background: Asymptomatic infections with malaria parasites are common in populations in endemic areas. These infections may persist in migrants after arrival in a non-endemic area. Screening to find and clear these infections is generally not implemented in non-endemic countries, despite a potential negative health impact. We performed a study to evaluate the Plasmodium parasite prevalence in migrants living in Sweden. Methods: Adults and children born in Sub-Saharan Africa (SSA) were invited in the study between April 2019 and June 2022 at 10 different sites, mainly as part of the national Migrant Health Assessment Program in Stockholm and Västerås, Sweden. Rapid diagnostic tests (RDT) and real-time PCR were used to detect malaria parasites. Prevalence and test sensitivity were calculated with 95% confidence intervals (CI). Univariate and multivariable logistic regression were used to evaluate associations with PCR positivity. Findings: In total, 789 individuals were screened for Plasmodium spp. of which 71 (9.0%) were positive by PCR and 18 (2.3%) also by RDT. When performed during the national screening program, 10.4% was PCR positive. A high prevalence was detected in migrants with Uganda as the country of last residence, 53/187 (28.3%), and in this group the prevalence was highest in children, 29/81 (35.8%). Among the PCR positive, 47/71 (66.2%) belonged to families with at least one other member testing positive (odds ratio [OR] 43.4 (95% CI 19.0-98.9), and the time lived in Sweden ranged between 6 and 386 days. Interpretation: A high malaria parasite prevalence was found in migrants from SSA, particularly in children offered screening in Stockholm, Sweden during the study period. Awareness of asymptomatic malaria infection is needed and screening for malaria in migrants arriving from high endemic countries should be considered. Funding: The Swedish Research Council, Stockholm County Council and Centre for Clinical Research, Västmanland, Sweden.

Relapse of Plasmodium vivax and Plasmodium ovale Malaria With and Without Primaquine Treatment in a Nonendemic Area.

BACKGROUND: The effect of primaquine in preventing Plasmodium vivax relapses from dormant stages is well established. For Plasmodium ovale, the relapse characteristics and the use of primaquine is not as well studied. We set to evaluate the relapsing properties of these 2 species, in relation to primaquine use among imported malaria cases in a nonendemic setting. METHODS: We performed a nationwide retrospective study of malaria diagnosed in Sweden 1995-2019, by reviewing medical records of 3254 cases. All episodes of P. vivax (n = 972) and P. ovale (n = 251) were selected for analysis. RESULTS: First time relapses were reported in 80/857 (9.3%) P. vivax and 9/220 (4.1%) P. ovale episodes, respectively (P < .01). Without primaquine, the risk for relapse was higher in P. vivax, 20/60 (33.3%), compared to 3/30 (10.0%) in P. ovale (hazard ratio [HR] 3.5, 95% confidence interval [CI] 1.0-12.0). In P. vivax, patients prescribed primaquine had a reduced risk of relapse compared to episodes without relapse preventing treatment, 7.1% vs 33.3% (HR 0.2, 95% CI .1-.3). In P. ovale, the effect of primaquine on the risk of relapse did not reach statistical significance, with relapses seen in 2.8% of the episodes compared to 10.0% in patients not receiving relapse preventing treatment (HR 0.3, 95% CI .1-1.1). CONCLUSIONS: The risk of relapse was considerably lower in P. ovale than in P. vivax infections indicating different relapsing features between the two species. Primaquine was effective in preventing P. vivax relapse. In P. ovale, relapse episodes were few, and the supportive evidence for primaquine remains limited.

Enhanced virulence of Plasmodium falciparum in blood of diabetic patients.

Rising prevalence of diabetes in sub-Saharan Africa, coupled with continued malaria transmission, has resulted more patients dealing with both communicable and non-communicable diseases. We previously reported that travelers with type 2 diabetes mellitus (T2DM) infected with Plasmodium falciparum were three times more likely to develop severe malaria than non-diabetics. Here we explore the biological basis for this by testing blood from uninfected subjects with type 1 and type 2 diabetes, ex vivo, for their effects on parasite growth and rosetting (binding of infected erythrocytes to uninfected erythrocytes). Rosetting was associated with type 2 diabetes, blood glucose and erythrocyte sedimentation rate (ESR), while parasite growth was positively associated with blood glucose, glycated hemoglobin (HbA1c), body mass index (BMI), fibrinogen and triglycerides. This study establishes a link between diabetes and malaria virulence assays, potentially explaining the protective effect of good glycemic control against severe malaria in subjects with diabetes.

Malaria and risk of lymphoid neoplasms and other cancer: a nationwide population-based cohort study.

BACKGROUND: Malaria is associated with Burkitt lymphoma among children in Sub-Saharan Africa. No longitudinal studies have assessed the long-term risk of other lymphoma or cancer overall. Here, we investigated the risk of lymphoid neoplasms and other cancer after malaria. METHODS: We included 4125 patients diagnosed with malaria in Sweden in 1987-2015, identified either through the National Surveillance Database at the Public Health Agency of Sweden, the National Inpatient and Outpatient Register, or by reports from microbiology departments. A comparator cohort (N = 66,997) matched on sex, age and birth region was retrieved from the general population and an additional cohort with all individuals born in Sub-Saharan Africa registered in the Total Population Register in 1987-2015 (N = 171,756). Incident lymphomas and other cancers were identified through linkage with the Swedish Cancer Register. Hazard ratios (HRs) were assessed using Cox regression with attained age as the timescale. RESULTS: A total of 20 lymphoid neoplasms and 202 non-haematological cancers were identified among malaria patients during a mean follow-up of 13.3 and 13.7 years, respectively. The overall risk of lymphoid neoplasms was not significantly increased (hazard ratio [HR] 1.24, 95% confidence interval [CI] 0.79-1.94), neither did we find any association with all-site non-haematological cancer (HR 0.89, 95% CI 0.77-1.02). However, in the Sub-Saharan Africa cohort, we observed an increased risk of lymphoid neoplasms after malaria diagnosis (HR 2.39, 95% CI 1.06-5.40), but no difference in the risk of other cancer (HR 1.01, 95% CI 0.70-1.45). The association could not be explained by co-infection with HIV or chronic hepatitis B or C, since the risk estimate was largely unchanged after excluding patients with these comorbidities (HR 2.63, 95% CI 1.08-6.42). The risk became more pronounced when restricting analyses to only including non-Hodgkin and Hodgkin lymphomas (HR 3.49, 95% CI 1.42-8.56). CONCLUSION: Individuals born in malaria-endemic areas and diagnosed with malaria in Sweden had an increased risk of lymphoid neoplasms, especially B cell lymphoma. There was no association with cancer overall nor did single malaria episodes confer an increased risk in travellers.

[Management of malaria in Sweden]. / Handläggning av malaria ­ ur ett svenskt perspektiv.

Malaria is a potentially severe infection and time to treatment can be decisive for the outcome. Febrile patients returning from travel in endemic areas should therefore be promptly investigated for malaria. This review focuses on the acute management of malaria in Sweden. The disease is diagnosed in travellers, migrants and temporary visitors from malaria-endemic countries. Malaria is a relatively rare infection in Sweden, with approximately 150 imported cases per year in a population of 10 million. Health care delay is a risk of more severe disease. Children, pregnant women, elderly, and individuals from endemic areas who lived in Sweden for a long time as well as those with comorbidities are at increased risk of severe malaria. Microscopy is used for diagnosis and determination parasite density; rapid diagnostic tests are supportive diagnostic tools. First-line treatment for severe malaria is intravenous artesunate and for uncomplicated P. falciparum malaria artemether-lumefantrine (AL) or chloroquine in cases with non-P. falciparum infections from areas without known resistance. Treatment failures have been observed in non-immune travelers treated with AL, and patients should be recommended to seek care in the event of new fever. Being a relative rare disease in Sweden, management of malaria is performed at specialized centers with infectious disease specialists.

Severity of Plasmodium falciparum and Non-falciparum Malaria in Travelers and Migrants: A Nationwide Observational Study Over 2 Decades in Sweden.

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.

Obesity and Diabetes as Risk Factors for Severe Plasmodium falciparum Malaria: Results From a Swedish Nationwide Study.

BACKGROUND: Noncommunicable diseases and obesity are increasing in prevalence globally, also in populations at risk of malaria. We sought to investigate if comorbidity, in terms of chronic diseases and obesity, is associated with severe Plasmodium falciparum malaria. METHODS: We performed a retrospective observational study in adults (≥18 years of age) diagnosed with malaria in Sweden between January 1995 and May 2015. We identified cases through the surveillance database at the Public Health Agency of Sweden and reviewed clinical data from 18 hospitals. Multivariable logistic regression was used to assess associations between comorbidities and severe malaria. RESULTS: Among 937 adults (median age, 37 years; 66.5% were male), patients with severe malaria had higher prevalence of chronic diseases (28/92 [30.4%]) compared with nonsevere cases (151/845 [17.9%]) (P = .004). Charlson comorbidity score ≥1 was associated with severe malaria (adjusted odds ratio [aOR], 2.63 [95% confidence interval {CI}, 1.45-4.77), as was diabetes among individual diagnoses (aOR, 2.98 [95% CI, 1.25-7.09]). Median body mass index was higher among severe (29.3 kg/m2) than nonsevere cases (24.7 kg/m2) (P < .001). Obesity was strongly associated with severe malaria, both independently (aOR, 5.58 [95% CI, 2.03-15.36]) and in combination with an additional metabolic risk factor (hypertension, dyslipidemia, or diabetes) (aOR, 6.54 [95% CI, 1.87-22.88]). The associations were observed among nonimmune travelers as well as immigrants from endemic areas. CONCLUSIONS: Comorbidities, specifically obesity and diabetes, are previously unidentified risk factors for severe malaria in adults diagnosed with P. falciparum. Noncommunicable diseases should be considered in the acute management and prevention of malaria.

High Rate of Treatment Failures in Nonimmune Travelers Treated With Artemether-Lumefantrine for Uncomplicated Plasmodium falciparum Malaria in Sweden: Retrospective Comparative Analysis of Effectiveness and Case Series.

BACKGROUND: Artemisinin-based combination therapy (ACT) is the first-line treatment of Plasmodium falciparum malaria. Since the introduction of artemether-lumefantrine (AL) for treatment of uncomplicated malaria in Sweden, treatment failures have been reported in adults. METHODS: A retrospective comparative analysis of treatment regimen for P. falciparum malaria in adults in Stockholm during 2000-2015 was performed to evaluate the effectiveness of AL. Parasite genotyping and drug concentrations were investigated in the AL treatment failures. RESULTS: Among the total 397 P. falciparum episodes, 310 were treated with oral regimen only (95 AL, 162 mefloquine, 36 atovaquone-proguanil [AP], and 17 others), and 87 were administered initial intravenous therapy (38 artesunate and 49 quinine) followed by oral treatments. Five late treatment failures were detected after AL and one slow response to AP. The effectiveness of AL alone was 94.7% (95% confidence interval [CI], 88.1%-98.3%), compared with 99.5% for other oral regimens (P = .003). All AL failures occurred in European men and the effectiveness in this group was only 73.7% (95% CI, 48.8%-90.0%). Genotyping confirmed recrudescence of the initial parasite populations and drug resistance markers revealed no clinically significant resistance patterns. Lumefantrine concentrations suggested subtherapeutic concentrations in at least 2 cases. CONCLUSIONS: Our findings indicate a high rate of symptomatic late treatment failures after 6-dose AL regime in nonimmune adults, especially in men. Our report warrants the need to establish optimal dosing of AL in adults and to alert clinicians about the importance of informing patients regarding the risk of parasites reappearing weeks after AL treatment.

Which Medication Is the Patient Taking at Admission to the Emergency Ward? Still Unclear Despite the Swedish Prescribed Drug Register.

INTRODUCTION: Correct information on patients' medication is crucial for diagnosis and treatment in the Emergency Department. The aim of this study was to investigate the concordance between the admission chart and two other records of the patient's medication. METHODS: This cohort study includes data on 168 patients over 18 years admitted to the Emergency Ward between September 1 and 30, 2008. The record kept by the general practitioner and the patient record of dispensed drugs in the Swedish Prescribed Drug Register were compared to the admission chart record. RESULTS: Drug record discrepancies of potential clinical significance between the admission chart record and the Swedish Prescribed Drug Register or general practitioner record were present in 79 and 82 percent, respectively. For 63 percent of the studied patients the admission chart record did not include all drugs registered in the Swedish Prescribed Drug Register. For 62 percent the admission chart record did not include all drugs registered in the general practitioner record. In addition, for 32 percent of the patients the admission chart record included drugs not registered in the Swedish Prescribed Drug Register and for 52 percent the admission chart record included drugs not found in the general practitioner record. The most discordant drug classes were cardiovascular and CNS-active drugs. Clinically significant drug record discrepancies were more frequent in older patients with multiple medication and caregivers. CONCLUSION: The apparent absence of an accurate record of the patient's drugs at admission to the Emergency Ward constitutes a potential patient safety hazard. The available sources in Sweden, containing information on the drugs a particular patient is taking, do not seem to be up to date. These results highlight the importance of an accurate list of currently used drugs that follows the patient and can be accessed upon acute admission to the hospital.

Stability of minute virus of mice against temperature and sodium hydroxide.

Treatment with steam and/or dilute NaOH are commonly used techniques to disinfect manufacturing vessels and tools in the pharmaceutical industry. The aim of this procedure is sanitisation and inactivation of microbiological and viral contaminants. Here we describe the inactivation of the mouse parvovirus Minute Virus of Mice (MVM) under these conditions. Parvoviruses are known to be resistant to physico-chemical treatment and one representative of this family, the human parvovirus B19, is a potential contaminant of blood plasma. We show inactivation kinetics for MVM treated with wet-heat (70, 80, 90 degrees C) and with 0.01-1 M NaOH solutions (pH >/=11.9). Robust inactivation was only achieved at 90 degrees C for at least 10 min and in NaOH solutions of pH >/=12.8 (0.1 M NaOH). It was observed, that aggregation of viruses might protect viral particles from inactivation by NaOH. Therefore, appropriate sample preparation of spiking material is important for accurate simulation of the naturally occurring situation. The observed stability at pH 11.8 exceeds the previously reported upper limit of pH 9. Inactivation was due to disintegration of the viral capsid as assessed by accessibility of viral DNA for endonucleases.