Human cerebral malaria: 2019 mini review.

During severe malaria, both in endemic and non-endemic areas, cerebral malaria is strongly associated with mortality and morbidity. The main mechanisms of cerebral malaria combine sequestration of parasitized red blood cells in brain capillaries, production of cytokines, immune cell/platelet accumulation, and release of microparticules, finally resulting in endothelial lesions of the blood brain barrier, which contribute to various brain injuries (oedema, ischemia, haemorrhages). The neurological clinical findings range from simple delirium to profound coma. Fundoscopy, reflect of the brain microcirculation, is now currently realized in endemic areas, and should be recommended during imported cerebral malaria. Likewise, cerebral imaging should be systematically realized in patients with cerebral malaria. Intravenous artesunate is now firmly established as the treatment of choice for severe malaria worldwide in adults, children and during pregnancy. General care and supportive treatment are crucially important and supportive treatment of cerebral malaria should be better standardized. Finally, experimental and clinical research has a key role in cerebral malaria, so as to identify possible therapeutic targets in order to develop innovative therapies.

Diagnostic accuracy of urinary dipstick to exclude catheter-associated urinary tract infection in ICU patients: a reappraisal.

OBJECTIVES: We wanted to assess the diagnostic accuracy of urinary dipstick testing in excluding catheter-associated urinary tract infection (CAUTI) in intensive care unit (ICU) patients with fever or hypothermia. METHODS: This was a prospective observational cohort study in a medical-surgical ICU. Patients with new-onset fever >38.3 °C or hypothermia <36 °C at least 48 h after urinary catheter insertion were included over a 2-year period. At each episode, a urinary dipstick test and a urine culture were performed as the criterion standard. Extensive microbiological investigations for extra-urinary infections were performed also. The performances of various urinary dipstick result combinations in ruling out CAUTI were compared based on the likelihood ratios (LR+ and LR-). RESULTS: Symptomatic CAUTI was diagnosed in 31 (24.4 %) of the 127 included patients (195 episodes of fever or hypothermia). LR+ was best for combined leukocyte esterase-positive and nitrite-positive dipstick results (overall population: 14.91; 95 % confidence interval [95 % CI], 5.53-40.19; patients without urinary symptoms: 15.63; 95 % CI, 5.76-42.39). LR- was best for either leukocyte esterase-positive or nitrite-positive dipstick results (overall population: 0.41; 95 % CI, 0.57-0.65; patients without urinary symptoms, 0.36; 95 % CI, 0.21-0.60). CONCLUSIONS: Urinary dipstick testing at the bedside does not help to rule out symptomatic CAUTI in medical or surgical ICU patients with fever or hypothermia.

Favorable outcome after life-threatening meningococcal disease complicating influenza A(H1N1) infection.

PURPOSE: Neurological complications of influenza A(H1N1) have been reported in several patients since the onset of the pandemic in 2009. However, meningococcal disease complicating influenza A(H1N1) has not been reported. PATIENTS: Two patients were admitted to an intensive care unit (ICU) for altered mental status, fever, and rapidly spreading petechial purpura. They were diagnosed with meningococcal meningitis and/or meningococcemia and influenza A(H1N1) co-infection. CONCLUSIONS: Meningococcal disease presenting as meningitis and/or meningococcemia is among the potential complications of influenza A(H1N1) infection. Physicians should be aware of this co-infection, as it must be detected and treated promptly with antibiotics in addition to supportive care.

Management of severe imported malaria in adults.

Severe malaria accounts for approximately 10% of all cases of imported malaria in France; cases are mainly due to Plasmodium falciparum, while other Plasmodium species are possible but uncommon (P. vivax, P. knowlesi, P. malariae, and P. ovale). On the basis of WHO criteria for endemic areas, the French criteria defining severe imported malaria in adults have been progressively adapted to the European healthcare level. Management of severe imported malaria is a diagnostic and treatment emergency and must be initially conducted in the intensive care unit. Anti-infective treatment is now based on intravenous artesunate, which must be available in every hospital of the country likely to receive severe imported malaria patients. Intravenous quinine is thus used as a second-line treatment and is restricted to limited indications. Critical care management of organ failure is essential, particularly in patients presenting with very severe malaria. To date, no adjunctive therapy (including exchange transfusion) has demonstrated clear beneficial effects.

Use of artesunate in non-malarial indications.

INTRODUCTION: Artesunate and other artemisinin derivatives are used in various infectious and non-infectious diseases. We aimed to analyze available data on artesunate and artemisinin derivatives activity in humans and their potential clinical benefits in non-malarial indications. MATERIAL AND METHODS: Literature review performed on PubMed and the Cochrane Library databases using the PRISMA method. We analyzed studies published in English from January 2008 to August 2017 using the same indicators of drug efficacy. RESULTS: We included 19 studies performed in humans (1 meta-analysis, 1 literature review, 4 randomized controlled trials, 3 prospective controlled trials, 3 prospective uncontrolled trials, 2 exploratory phase 1 or 2 trials, 1 case series, and 4 case reports). Artesunate and artemisinin derivatives demonstrated efficacy in the treatment of schistosomiasis in combination with praziquantel (P=0.003). Artesunate monotherapy was less effective than praziquantel alone (P<0.001) probably because its activity only affects the early stages of Schistosoma parasites. Artesunate monotherapy could be interesting as a chemoprophylactic drug against schistosomiasis (P<0.001). Findings seem promising but are still controversial in the treatment of multidrug-resistant CMV infections. Studies do not conclude on artesunate and artemisinin derivatives efficacy in the treatment of cervix, breast, colorectal, and lung cancers. CONCLUSION: Artesunate and artemisinin derivatives in combination with praziquantel were effective against schistosomiasis, and could be used as a chemoprophylactic drug alone. They could be interesting as anti-CMV and anti-tumor treatment. Additional trials in humans are required to assess the efficacy of artesunate and artemisinin derivatives in diseases other than malaria.

Severe atypical pneumonia in critically ill patients: a retrospective multicenter study.

BACKGROUND: Chlamydophila pneumoniae (CP) and Mycoplasma pneumoniae (MP) patients could require intensive care unit (ICU) admission for acute respiratory failure. METHODS: Adults admitted between 2000 and 2015 to 20 French ICUs with proven atypical pneumonia were retrospectively described. Patients with MP were compared to Streptococcus pneumoniae (SP) pneumonia patients admitted to ICUs. RESULTS: A total of 104 patients were included, 71 men and 33 women, with a median age of 56 [44-67] years. MP was the causative agent for 76 (73%) patients and CP for 28 (27%) patients. Co-infection was documented for 18 patients (viruses for 8 [47%] patients). Median number of involved quadrants on chest X-ray was 2 [1-4], with alveolar opacities (n = 61, 75%), interstitial opacities (n = 32, 40%). Extra-pulmonary manifestations were present in 34 (33%) patients. Mechanical ventilation was required for 75 (72%) patients and vasopressors for 41 (39%) patients. ICU length of stay was 16.5 [9.5-30.5] days, and 11 (11%) patients died in the ICU. Compared with SP patients, MP patients had more extensive interstitial pneumonia, fewer pleural effusion, and a lower mortality rate [6 (8%) vs. 17 (22%), p = 0.013]. According MCA analysis, some characteristics at admission could discriminate MP and SP. MP was more often associated with hemolytic anemia, abdominal manifestations, and extensive chest radiograph abnormalities. SP-P was associated with shock, confusion, focal crackles, and focal consolidation. CONCLUSION: In this descriptive study of atypical bacterial pneumonia requiring ICU admission, mortality was 11%. The comparison with SP pneumonia identified clinical, laboratory, and radiographic features that may suggest MP or CP pneumonia.

Management of adult infectious encephalitis in metropolitan France.

Infectious encephalitis is a severe disease leading to a high mortality and morbidity. The most frequent causes include Herpes simplex virus, Varicella Zoster virus, Listeria monocytogenes, and Mycobacterium tuberculosis. Urgent treatment is required (anti-infective therapy and nonspecific supportive care). The aim of this study was to define treatment strategy, empirical and after microbiological documentation at 48hours, through a systematic literature review.

Noninvasive ventilation during acute respiratory distress syndrome in patients with cancer: Trends in use and outcome.

PURPOSE: The objectives of our study were to describe the outcome of patients with malignancies treated for acute respiratory distress syndrome (ARDS) with noninvasive ventilation (NIV) and to evaluate factors associated with NIV failure. METHODS: Post hoc analysis of a multicenter database within 20 years was performed. All patients with malignancies and Berlin ARDS definition were included. Noninvasive ventilation use was defined as NIV lasting more than 1 hour, whereas failure was defined as a subsequent requirement of invasive ventilation. Conditional backward logistic regression analyses were conducted. RESULTS: A total of 1004 met the Berlin definition of ARDS. Noninvasive ventilation was used in 387 patients (38.6%) and NIV failure occurred in 71%, with an in-hospital mortality of 62.7%. Severity of ARDS defined by the partial pressure arterial oxygen and fraction of inspired oxygen ratio (odds ratio [OR], 2.20; 95% confidence interval [CI], 1.15-4.19), pulmonary infection (OR, 1.81; 95% CI, 1.08-3.03), and modified Sequential Organ Failure Assessment (SOFA) score (OR, 1.13; 95% CI, 1.06-1.21) were associated with NIV failure. Factors associated with hospital mortality were NIV failure (OR, 2.52; 95% CI, 1.56-4.07), severe ARDS as compared with mild ARDS (OR, 1.89; 95% CI, 1.05-1.19), and modified SOFA score (OR, 1.12; 95% CI, 1.05-1.19). CONCLUSION: Noninvasive ventilation failure in ARDS patients with malignancies is frequent and related to ARDS severity, SOFA score, and pulmonary infection-related ARDS. Noninvasive ventilation failure is associated with in-hospital mortality.

[Cryptococcal meningo-encephalitis in an apparently immunocompetent patient]. / Cryptococcose neuroméningée chez un sujet en apparence immunocompétent.

INTRODUCTION: Cryptococcal meningo-encephalitis is a rare disease occurring more frequently in immunocompromised hosts. CASE REPORT: We report the case of an apparently immunocompetent patient who developed a recurrent neurological deficit with lymphocytic meningitis. The time from the first symptoms to diagnosis was 8 months. We noted mild CD4+ lymphocytopenia (500 cells/mm3) without HIV infection. CD4+ lymphocytes were not reactive for a panel of antigens. CONCLUSION: This case illustrates the usefulness of cerebrospinal fluid Cryptococcus Neoformans antigen test in patients with an unexplained neurological syndrome with a lymphocytic meningitis together with quantification of circulating lymphocytes clusters and analyse of their function in opportunistic infections.

[Antibiotic therapy for community acquired Streptococcus pneumoniae pneumonia: clinical relevance of antibiotic resistance]. / Antibiothérapie des pneumonies aiguës communautaires à Streptococcus pneumoniae: impact clinique de la résistance bactérienne.

The emergence of Streptococcus pneumoniae strains with reduced susceptibility to beta-lactams and with multiple drug resistance has not led to major changes in recommendations for antibiotic therapy in patients with acute community-acquired pneumococcal pneumonia. Numerous factors explain the limited clinical impact of this major microbiological change. The frequency of intermediate strains is high but the frequency of resistant strains to beta-lactams is very low. There is a complex relation between the acquisition of resistance to beta-lactams and the decreased virulence of S. pneumoniae strains. The only finding in studies of humanized experimental animal models of lethal bacteremic pneumonia caused by resistance and tolerant strains was a slowing in the kinetics of beta-lactams bactericidal activity, especially for amoxicillin. Taken together, this preclinical data shows that microbiological resistance of pneumococci to beta-lactams has very little influence on a possible failure of recommanded treatment regimens for pneumococcal pneumonia. The high rate of multiple drug resistance, particularly among beta-lactam resistant strains, rules out the probabilistic use of macrolides. Conversely, fluoroquinolone (FQ) resistance remains low, inferior to 3%, and the same is true for ketolides (<1%). Only a global strategy of patient management in the use of these new drugs could ensure their long-term activity. The high mortality rate of hospitalized S. pneumoniae pneumonia will only be improved with a better understanding of the complex host-bacteria interactions.

What is the outcome of cancer patients admitted to the ICU after cardiac arrest? Results from a multicenter study.

AIM: Low survival rate was previously described after cardiac arrest in cancer patients and may challenge the appropriateness of intensive care unit (ICU) admission after return of spontaneous circulation (ROSC). Objectives of this study were to report outcome and characteristics of cancer patients admitted to the ICU after cardiac arrest. METHODS: A retrospective chart review in seven medical ICUs in France, in 2002-2012. We studied consecutive patients with malignancies admitted after out-of-hospital cardiac arrest (OHCA) or in-hospital cardiac arrest (IHCA). RESULTS: Of 133 included patients of whom 61% had solid tumors, 48 (36%) experienced OHCA and 85 (64%) IHCA. Cardiac arrest was related to the malignancy or its treatment in 47% of patients. Therapeutic hypothermia was used in 51 (41%) patients. The ICU mortality rate was 98/133 (74%). Main causes of ICU death were refractory shock or multiple organ failure (n = 64, 48%) and neurological injury (n = 27, 20%); 42 (32%) patients died in ICU after treatment-limitation decisions. Twenty-four (18%) patients were discharged alive from the hospital. Overall 6-month survival rate was 14% (18/133, 95% confidence interval, 8-21%). Survival rates at ICU discharge and after 6 months did not differ significantly across type of malignancy or between the OHCA and IHCA groups, and neither were they significantly different from those in matched controls who had cardiac arrest but no malignancy. CONCLUSIONS: Even if low, the 6-month survival rate of 14% observed in cancer patients admitted to the ICU after cardiac arrest and ROSC may support the admission of these patients to the ICU and may warrant an initial full-code ICU management.

Prognosis of neutropenic patients admitted to the intensive care unit.

PURPOSE: The prognosis of critically ill cancer patients has improved recently. Controversies remain as regard to the specific prognosis impact of neutropenia in critically ill cancer patients. The primary objective of this study was to assess hospital outcome of critically ill neutropenic cancer patients admitted into the ICU. The secondary objective was to assess risk factors for unfavorable outcome in this population of patients and specific impact of neutropenia. METHODS: We performed a post hoc analysis of a prospectively collected database. The study was carried out in 17 university or university-affiliated centers in France and Belgium. Neutropenia was defined as a neutrophil count lower than 500/mm(3). RESULTS: Among the 1,011 patients admitted into the ICU during the study period 289 were neutropenic at the time of admission. Overall, 131 patients died during their hospital stay (hospital mortality 45.3 %). Four variables were associated with a poor outcome, namely allogeneic transplantation (OR 3.83; 95 % CI 1.75-8.35), need for mechanical ventilation (MV) (OR 6.57; 95 % CI 3.51-12.32), microbiological documentation (OR 2.33; CI 1.27-4.26), and need for renal replacement therapy (OR 2.77; 95 % CI 1.34-5.74). Two variables were associated with hospital survival, namely age younger than 70 (OR 0.22; 95 % CI 0.1-0.52) and neutropenic enterocolitis (OR 0.37; 95 % CI 0.15-0.9). A case-control analysis was also performed with patients of the initial database; after adjustment, neutropenia was not associated with hospital mortality (OR 1.27; 95 % CI 0.86-1.89). CONCLUSION: Hospital survival was closely associated with younger age and neutropenic enterocolitis. Conversely, need for conventional MV, for renal replacement therapy, and allogeneic hematopoietic stem cell transplantation (HSCT) were associated with poor outcome.

Microbiological evaluation of central venous catheter administration hubs.

We compared, in three intensive care units, colonization of hubs with hub protection boxes or hubs with needleless closed connectors; 137 central venous catheters and 451 hubs were randomized in two groups with similar characteristics. Catheter and hub colonization were not different between the two groups. Among 30 colonized catheters, the same isolate was found in only two hubs; hub contamination rarely is responsible for catheter colonization in short-term catheters. Further studies are required to evaluate the benefit of protected hubs compared with unprotected hubs.

Shock complicating severe falciparum malaria in European adults.

OBJECTIVE: To study adult patients with severe falciparum malaria who developed shock. DESIGN: Retrospective study from 1987 to 1993. SETTING: Medical intensive care unit in a university hospital. PATIENTS: 14 patients admitted with severe falciparum malaria who developed shock. All received intravenous quinine. MEASUREMENTS AND RESULTS: The mean Simplified Acute Physiology Score II was 59.5 +/- 7.1; 2.6 +/- 0.4 criteria defining severe disease were present on admission in 12 patients; and initial parasitemia was 21 +/- 6%. Twelve patients received inotropic drugs. Pulmonary artery catheterization showed the following results in 7 patients: mean arterial pressure 57 +/- 4 mmHg; pulmonary artery occlusion pressure 11 +/- 1 mmHg; cardiac index 5.5 +/- 0.91.min-1.m-2, and systemic vascular resistance index 783 +/- 122 dyne.s.cm-5.m-2. Seven patients had evidence of bacterial infection at the time of shock. Of the 7 deaths (50%), 5 were due to shock, with documented bacterial infection in all patients and persistent parasitemia in 4. CONCLUSIONS: Shock complicating severe falciparum malaria in adults is associated with peripheral vasodilation and carries a poor prognosis. In falciparum malaria with shock, bacterial coinfection should be suspected immediately and treated empirically with broad-spectrum antibiotics. Nevertheless, Plasmodium falciparum may contribute directly or indirectly to the onset of shock.

Usefulness of a strategy based on bronchoscopy with direct examination of bronchoalveolar lavage fluid in the initial antibiotic therapy of suspected ventilator-associated pneumonia.

OBJECTIVES: To evaluate (a) the routine accuracy of bronchoalveolar lavage by direct examination (BAL-D) in diagnosing ventilator-associated pneumonia (VAP), and (b) the impact of a diagnostic strategy including clinical judgment, bronchoscopy, and BAL-D on the initial diagnosis and appropriateness of treatment when VAP is suspected. DESIGN AND SETTING: Prospective cohort study in two academic ICUs in Paris, France. PATIENTS AND PARTICIPANTS: Mechanically ventilated patients with suspected VAP underwent bronchoscopy with BAL and protected specimen brush (PSB). BAL-D results were available within 2 h, BAL on culture and PSB results after 24 h, and antibiotic susceptibility after 48 h. At each step in the strategy the senior and the resident in charge of the patient were asked their diagnosis and their therapeutic plan on the basis of presently available data. Definite diagnosis of suspected VAP was based on histology, appearance of cavitation, positive pleural fluid culture, results of PSB and BAL culture, and follow-up. MEASUREMENT AND RESULTS: A total of 110 episodes of suspected VAP were studied; 94 definite diagnoses were made (47 VAP, 47 no VAP). Using a threshold 1% of infected cells, BAL-D discriminated well between patients with and those without VAP (sensitivity 93.6%, specificity 91.5%, area under the receiver-operating characteristic curve 0.953). The senior clinical judgment was correct in 71% cases. It was correct in 78% and 94% of cases after airway visualization and BAL-D findings, respectively. After BAL-D the positive and negative predictive values in diagnosing VAP were 90% and 98%, respectively. However, the therapeutic plan was correct in only 65% using clinical judgment (15 untreated patients, 3 ineffective treatment, 15 useless treatment), 66% using airway visualization (14 untreated VAP, 4 ineffective treatment, 14 useless treatment), and 88% using BAL-D results (1 untreated patients, 6 ineffective, 4 useless), according to definite diagnosis and final antibiotic susceptibility testings. CONCLUSIONS: A strategy based on bronchoscopy and BAL-D generally leads to a rapid and appropriate treatment of nosocomial pneumonia in ventilated patients.

Successful treatment of brain aspergillosis with voriconazole.

Until recently, brain aspergillosis was almost always fatal, with a response rate to amphotericin B of < 10%. This study describes a retrospective analysis of eight consecutive cases of brain aspergillosis. All patients were immunosuppressed and five required mechanical ventilation. Antifungal treatment included amphotericin B (n = 7), itraconazole (n = 3), voriconazole (n = 2) and flucytosine (n = 1). Three (38%) patients survived following prolonged azole therapy after initial amphotericin B treatment, combined with a reduction in their immunosuppressive treatment. The prognosis of brain aspergillosis might be improved if immunosuppression could be reduced and prolonged oral azole therapy used.

[Methemalbuminnemia after massive hemolysis during blackwater fever]. / Methémmalbuminémie après hémolyse massive au cours d'une fièvre bilieuse hémoglobinurique.

We report a case of blackwater fever with brown plasma due to the presence of methemalbumin. The discovery of plasma with this color is a rare event at the laboratory. This compound appears during intravascular hemolysis or hemorrhagic pancreatitis when the ability of haptoglobin and hemopexin to bind free hemoglobin has been exceeded. In these cases some of heme is oxidized to hematin and taken up by serum albumin to form an albumin-hematin complex called methemalbumin. The major clinical problem is to evoke the diagnosis of methemalbuminemia and not confuse with methemoglobinemia. In our case, methemalbumin was detected and quantified using a scanning spectrophotometer. Its diagnostic and clinicals consequences are discussed.