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.

No evidence of Chlamydia pneumoniae in the synovia of patients with osteoarthritis.

OBJECTIVE: Osteoarthritis (OA) is a common cause of disability affecting millions of people of all ages worldwide. The pathogenesis involves an inflammatory component, but the cause of the inflammation remains incompletely understood. The intracellular bacteria Chlamydia trachomatis and C. pneumoniae have been demonstrated in patients with reactive arthritis. Both of these microorganisms can cause chronic and persistent infections, with C. trachomatis being the most common cause of reactive arthritis. This study was performed to investigate the presence of C. pneumoniae in a large number of patients with primary OA. METHODS: The study included 75 patients who underwent total knee arthroplasty. During surgery, a synovial biopsy was performed and synovial fluid drawn. Real-time polymerase chain reaction (PCR) of C. pneumoniae was run on all patients, and real-time PCR of bacterial 16S rDNA was conducted on 30 of the 75 patients to screen for the presence of other bacteria. RESULTS: Real-time PCR showed no evidence of the presence of C. pneumoniae in the patients' specimens, nor were other bacteria detected. CONCLUSIONS: Although an inflammatory component is part of the pathogenesis of OA, we found no evidence indicating that C. pneumoniae is a stimulator of that inflammation.

Febrile Plasmodium falciparum malaria 4 years after exposure in a man with sickle cell disease.

We report a case of symptomatic Plasmodium falciparum malaria that manifested 4 years after a visit to an area of endemicity in an 18-year-old male patient with sickle cell disease. The exceptionally long incubation time raises the questions of how and where P. falciparum parasites can reside for several years before suddenly causing disease.

Medication Reviews Bridging Healthcare (MedBridge): Study protocol for a pragmatic cluster-randomised crossover trial.

BACKGROUND: Mismanaged prescribing and use of medication among elderly puts major pressure on current healthcare systems. Performing a medication review, a structured critical examination of a patient's medications, during hospital stay with active follow-up into primary care could optimise treatment benefit and minimise harm. However, a lack of high quality evidence inhibits widespread implementation. This manuscript describes the rationale and design of a pragmatic cluster-randomised, crossover trial to fulfil this need for evidence. AIM: To study the effects of hospital-initiated comprehensive medication reviews, including active follow-up, on elderly patients' healthcare utilisation compared to 1) usual care and 2) solely hospital based reviews. DESIGN: Multicentre, three-treatment, replicated, cluster-randomised, crossover trial. SETTING: 8 wards with a multidisciplinary team within 4 hospitals in 3 Swedish counties. PARTICIPANTS: Patients aged 65years or older, admitted to one of the study wards. EXCLUSION CRITERIA: Palliative stage; residing in other than the hospital's county; medication review within the last 30days; one-day admission. INTERVENTIONS: 1, comprehensive medication review during hospital stay; 2, same as 1 with the addition of active follow-up into primary care; 3, usual care. PRIMARY OUTCOME MEASURE: Incidence of unplanned hospital visits during a 12-month follow-up period. DATA COLLECTION AND ANALYSES: Extraction and collection from the counties' medical record system into a GCP compliant electronic data capture system. Intention-to-treat-analyses using hierarchical models. RELEVANCE: This study has a high potential to show a reduction in elderly patients' morbidity, contributing to more sustainable healthcare in the long run.

Atypical clinical presentation of laboratory-acquired meningococcal disease.

We report a case of laboratory-acquired meningococcal disease in a 31-y-old female research assistant. The clinical presentation of the case was atypical with polyserositis affecting knees, pleura and pericardium, without septicaemia or meningitis. The diagnosis was made by positive PCR for Neisseria meningitidis (genogroup C, genosubtype P1.7, 16, 35 and without mutations of the penA gene) in the patient's right knee. Serology confirmed the diagnosis after recovery. This case had an atypical clinical picture, exemplifies the use of non-culture methods for diagnosis and characterization, and reminds us about the importance of safe routines for the laboratory work.

Gas within the liver and polymicrobial bacteraemia due to colovenous fistula: two cases in one month.

Two cases presented at our hospital within 1 month with polymicrobial bacteraemia and gas within the liver shown on CT scan. Both transpired to have colovenous fistula due to diverticulitis. Because of our awareness of the first case, the colovenous fistula of the second case was identified rapidly. As surgical treatment is probably essential for this condition, the possibility of colovenous fistula should be borne in mind in patients with gas within the liver, especially if they have bacteraemia.

Local gentamicin reduces sternal wound infections after cardiac surgery: a randomized controlled trial.

BACKGROUND: Sternal wound infections remain a major cause of morbidity after cardiac surgery. Vancomycin is often the only effective antibiotic available for their treatment but its use for routine prophylaxis is inadvisable for ecological reasons. Local application of gentamicin produces high antibiotic concentrations in the wound. We aimed to determine whether this treatment could have an additive effect on the incidence of sternal wound infections when combined with routine prophylaxis. METHODS: Two thousand cardiac surgery patients were randomized to routine prophylaxis with intravenous isoxazolyl-penicillin alone (control group) or to this prophylaxis combined with application of collagen-gentamicin (260 mg gentamicin) sponges within the sternotomy before wound closure. Endpoint was any sternal wound infection within 2 months postoperatively. Evaluations were double-blind and made on an intention-to-treat basis. RESULTS: Evaluation was possible in 967 and 983 patients in the control and treatment groups, respectively. The incidence of sternal wound infection was 4.3% in the treatment group and 9.0% in the control group (relative risk 0.47; 95% confidence interval 0.33-0.68; p < 0.001). Early reoperation for bleeding was more common in the treatment group (4.0% vs 2.3%, p = 0.03). No difference in postoperative renal function was noted. CONCLUSIONS: Local collagen-gentamicin reduced the risk for postoperative sternal wound infections. Further studies are warranted to confirm these results, particularly with regard to deep infections.

Assessment of systemic inflammation markers to differentiate a stable from a deteriorating clinical course in patients with febrile neutropenia.

In this study, we evaluated the predictive values of procalcitonin (PCT), C-reactive protein (CRP), interleukin-6 (IL-6) and serum amyloid A (SAA) for determining the clinical course in febrile neutropenic patients. Daily plasma analyses during the fever course were performed in 101 episodes with fever and chemotherapy-induced neutropenia (neutrophil count <0.5 x 10(9)/L). Procalcitonin (PCT) and IL-6 values were significantly higher in febrile episodes in patients who developed complications. Procalcitonin with a cut-off value of < or =0.4 ng/mL or IL-6 < or =50 pg/mL 3 d after fever onset indicated daily high negative predictive values (NPVs) (91-100%) for episodes with complications. No marker could predict deterioration; however, daily low plasma concentrations of PCT or IL-6 during the first 8 d of fever were found to be a good predictor of no subsequent complications in neutropenic patients and therefore to be a helpful tool for limiting anti-microbial therapy.

Granulocyte colony-stimulating factor (G-CSF) and interleukin (IL)-8 in sera from patients with Staphylococcus aureus septicemia.

OBJECTIVE: To determine the concentrations of granulocyte colony-stimulating factor (G-CSF) and interleukin (IL)-8 in sera from patients with Staphylococcus aureus septicemia and to correlate the results to peripheral neutrophil counts and the clinical outcome. METHODS: Serum samples from 64 consecutive patients with S. aureus septicemia were sequentially collected in a prospective study. RESULTS: The mean plus minus standard deviation (SD) serum G-CSF value on admission was 348 plus minus 830 with a range of 8 to 5400 pg/mL. G-CSF concentrations were elevated (> 76 pg/mL) in 38/64 patients (59%) as were serum IL-8 concentrations (> 67 pg/mL) in 23/64 patients (36%) on admission. The mean plus minus SD IL-8 value was 266 plus minus 422 pg/mL with a range of 2 to 1366 pg/mL. A correlation was found between serum IL-8 and white blood cell count on admission (p=0.008). CONCLUSIONS: Patients with uncomplicated septicemia frequently have elevated G-CSF values (84%) in comparison to patients with complicated septicemia (49%; p=0.02), indicating a possible protective effect of G-CSF in septic complications.

Plasma exchange as rescue therapy in multiple organ failure including acute renal failure.

OBJECTIVE: To describe the outcome of using a rescue therapy including plasma exchange given to patients with a progressive acute disseminated intravascular coagulation and multiple organ dysfunction syndrome. STUDY DESIGN: Retrospective study. SETTING: University and county hospital. PATIENTS: Included were 76 consecutive patients (41 men and 35 women) treated with plasma exchange as rescue therapy besides optimal conventional therapy during a progressive course of disseminated intravascular coagulation and multiple organ dysfunction syndrome, including acute renal failure. Of the 76 patients, 66% needed dialysis. The distribution was hemodialysis in 76%, continuous arteriovenous hemofiltration in 36%, continuous venovenous hemodialysis in 12%, and peritoneal dialysis in 24%. The median organ-failure score was 5 (range, 1-6). Seventy-two percent required mechanical ventilation; septic shock was present in 88%. The median septic shock score was 4 (range, 2-4). Nine patients had another reason than sepsis for the multiple organ dysfunction syndrome. INTERVENTION: Plasma exchange (centrifugation technique) was performed until disseminated intravascular coagulation was reversed (median, two times; range, 1-14). Besides antibiotics and fluid administration, most patients received heparin or low molecular weight heparin (77%), steroids (87%), and inotropes (88%). More than one vasoactive drug was used in 57% of the patients. MEASUREMENTS AND MAIN RESULTS: Eighty-two percent of the patients survived and could leave the hospital. The previously observed survival rates by others for this category of patients would be <20%, and thus, the outcome in this study is significantly better. CONCLUSION: Plasma exchange using plasma as replacement may, in addition to conventional intensive care, help to reverse severe progressive disseminated intravascular coagulation and multiple organ dysfunction syndrome and improve survival.

Production of tumor necrosis factor-alpha and interleukin-6 in whole blood stimulated by live Gram-negative and Gram-positive bacteria.

OBJECTIVE: To investigate the production of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) induced by live Gram-negative and Gram-positive bacteria in whole blood in vitro. METHODS: In all, 49 different isolates were studied. Each of the 49 different isolates was incubated for 4 h with whole blood at a ratio of one monocyte per 1--5 bacteria. Plasma was then separated and frozen, and the concentrations of TNF-alpha and IL-6 were measured by enzyme immunoassays. RESULTS: There was a positive correlation between TNF-alpha and IL-6 values, r=0.9. Gram-negative bacteria induced higher levels of both TNF-alpha and IL-6 than Gram-positive bacteria. Group G streptococci (GGS) induced higher levels of TNF-alpha than Streptococcus pneumoniae, Staphylococcus aureus, Staphylococcus epidermidis and group A streptococci (GAS). Klebsiella pneumoniae induced higher levels of TNF-alpha than Haemophilus influenzae, Escherichia coli and Neisseria meningitidis. GGS induced higher levels of IL-6 than Staphylococcus epidermidis, Staphylococcus aureus and GAS. When the relative amounts of cytokine induced by the strains were compared to serum concentrations measured on admission in patients with bacteremia caused by the same bacterial isolates there was no significant correlation. CONCLUSION: Species- and strain-related differences in cytokine-inducing properties were found which may have significance in clinical infections.

Use of inflammatory markers for early detection of bacteraemia in patients with febrile neutropenia.

The aim of the study was to evaluate the ability of procalcitonin, C-reactive protein, serum amyloid A, interleukin-6 and interleukin-8 to predict bacteraemia during the 2 first d of fever in neutropenic patients. A total of 94 febrile neutropenic episodes in 60 patients were studied. Plasma samples were analysed at 10-h intervals from the onset of fever. Clinical events were categorized into 4 groups: 1) bacteraemia caused by other agents than coagulase-negative staphylococci (non-CNS bacteraemia) (n = 21), 2) coagulase-negative staphylococci bacteraemia (n = 15), 3) microbiologically or clinically documented infection without bacteraemia (n = 26) and 4) fever of unknown origin (n = 32). In non-CNS bacteraemia all markers, except for serum amyloid A, showed significantly higher levels compared to patients with fever of unknown origin (p < 0.05). For non-CNS bacteraemia the highest negative predictive value was found for procalcitonin (94%), followed by interleukin-6 (89%), C-reactive protein (88%) and interleukin-8 (87%). Procalcitonin, with a cut-off level of 1.4 ng/ml during 10-20 h after fever onset, showed the highest positive predictive value (67%) for a non-CNS bacteraemia. In conclusion, the value of the analysed markers to predict a non-CNS bacteraemia in neutropenic patients was limited due to low sensitivity and positive predictive value. However, procalcitonin, interleukin-6, C-reactive protein, and interleukin-8 could give useful information for the clinician in excluding a non-CNS bacteraemia.

Cytokine response to staphylococcal exotoxins in Staphylococcus aureus septicemia.

OBJECTIVE: To investigate if exposure to exotoxins results in augmented serum cytokine response of patients with Staphylococcus aureus septicemia. METHODS: Serum samples and strains from 63 patients with S. aureus septicemia were collected in a prospective study. Toxin production by strains in vitro was determined by enzyme immunoassay (EIA) or reversed passive latex agglutination (RPLA). Antibodies against the toxins and cytokine levels in serum on admission were analyzed with EIA. RESULTS: Patients infected with strains producing staphylococcal enterotoxins (SEs) A, B, C and D and/or toxic shock syndrome toxin-1 (TSST-1) in vitro (n=37) showed higher serum TNF-alpha levels than those infected with non-toxigenic strains (p=0.04). A significant titer rise against the corresponding SE and/or TSST-1 produced by the isolate (14/35), indirectly reflecting exposure to the antigen, was associated with higher TNF-alpha concentrations on admission than in those without titer rise (p=0.03). Patients with low antibody titers against SE and/or TSST-1 on admission (19/37) were found to have higher serum TNF-alpha concentrations on admission than those with elevated antibody titers on admission (p=0.03). CONCLUSION: Patients infected with toxigenic S. aureus strains produce significantly higher levels of serum TNF-alpha on admission compared to patients infected with non-toxigenic strains.