[Severe "malignant" influenza in the light of past history]. / La grippe maligne vue à la lumière du passé.

The first influenza pandemic of the xxist century is due to a novel A (H1N1) strain. The infection, which affects younger patients than seasonal influenza, presents most often under a benign form. But it can rarely and rapidly evolve to pulmonary parenchymal involvement, independently of any bacterial superinfection or co-infection. It becomes a true viral pneumonia, which can evolve to acute respiratory distress syndrome (ARDS). This phenomenon was well described for the three xxth century pandemics, especially for the 1968-1969 one. These cases of "malignant flu" benefitted from the great breakthroughs in medical intensive care made in the previous 15 years. The specificity of these pandemic strains to infect lower respiratory tract is of immunological origin: only patients with little or no immunity to the virus can develop viral pneumonia and ARDS. This is why trivalent vaccination against seasonal flu appears to be somewhat protective against severe presentations of the disease. During winter 2009-2010, an inflow of flu-related ARDS cases is expected in French ICUs. Aggressive oxygenation techniques, high dose and prolonged antiviral treatment, and steroid adjunctive therapy, could be used, adding to the experience acquired during previous pandemics.

[Blackwater fever]. / Fièvre bilieuse hémoglobinurique.

DEFINITION: Blackwater fever is a clinical entity characterized by acute intravascular hemolysis classically occuring after the re-introduction of quinine in long-term residents in Plasmodium falciparum endemic areas and repeatedly using the product. CLINICAL PROFILE: The symptomatology appears brutally with emission of porto-colored urine, icterus, pallor, nausea, fever and acute renal failure. The hemolytic-like anemia is immediately severe. Parasitemia is mild or absent. The mechanism of renal failure is tubular necrosis. QUININE AND SIMILAR MOLECULES: Well known at the start of the 20th century, blackwater fever has become exceptional since 1950, when quinine was replaced by chloroquine. The disease reappeared in 1990, following the re-utilization of quinine because of resistance to chloroquine. Thereafter, several cases have been described with halofantrine and mefloquine, two new molecules similar to quinine (amino-alcohol family). The physiopathogenesis of the disease is not well known, however it would appear that the concomitance of a double sensitivization of the red blood cells to the P. falciparum red blood cells and to the amino-alcohols is necessary to provoke the hemolysis. EVOLUTION: The severity of the clinical picture often requires initial management in intensive care unit. Nowadays, however, prognosis is good and the disease usually regresses without after effects.

The influence of human immunodeficiency virus coinfection on chronic hepatitis C in injection drug users: a long-term retrospective cohort study.

In this study we analyzed the influence of human immunodeficiency virus (HIV) infection on the course of chronic hepatitis C through multivariate analysis including age, alcohol consumption, immune status, and hepatitis C virus (HCV)-related virologic factors. Eighty HIV-positive and 80 HIV-negative injection drug users included between 1980 and 1995 were matched according to age, gender, and duration of HCV infection and followed-up during 52 months. The progression to cirrhosis was the primary outcome measure. The impact of HIV on HCV-RNA load, histologic activity index, response to interferon therapy, and liver-related death was also considered. In HIV-positive patients, chronic hepatitis C was characterized by higher serum HCV-RNA levels (P =.012), higher total Knodell score (P =.011), and poorer sustained response to interferon therapy (P =.009). High serum HCV-RNA level was associated with low CD4-lymphocyte count (P =.001). Necroinflamatory score was higher in HIV-positive patients (P =.023) independently of the CD4-lymphocyte count, whereas increased fibrosis was related to decreased CD4-lymphocyte count (P =.011). The progression to cirrhosis was accelerated in HIV-positive patients with low CD4 cell count (RR = 4.06, P =.024) and in interferon-untreated patients (RR = 4.76, P =.001), independently of age at HCV infection (P =.001). Cirrhosis caused death in 5 HIV-positive patients. The risk of death related to cirrhosis was increased in heavy drinkers (RR = 10.8, P =.001) and in HIV-positive patients with CD4 cell count less than 200/mm(3) (RR = 11.9, P =.007). In this retrospective cohort study, HIV coinfection worsened the outcome of chronic hepatitis C, increasing both serum HCV-RNA level and liver damage and decreasing sustained response to interferon therapy. Age and alcohol were cofactors associated with cirrhosis and mortality. Interferon therapy had a protective effect against HCV-related cirrhosis no matter what the patient's HIV status was.

Resurgence of blackwater fever in long-term European expatriates in Africa: report of 21 cases and review.

Blackwater fever (BWF) is a severe clinical syndrome, characterized by intravascular hemolysis, hemoglobinuria, and acute renal failure that is classically seen in European expatriates chronically exposed to Plasmodium falciparum and irregularly taking quinine. BWF virtually disappeared after 1950, when chloroquine superseded quinine. We report 21 cases of BWF seen in France from 1990 through 1999 in European expatriates who lived in sub-Saharan Africa. All patients had macroscopic hemoglobinuria, jaundice, and anemia. Acute renal failure occurred in 15 patients (71%), 7 of whom required dialysis. The presumed triggers of BWF were halofantrine (38%), quinine (24%), mefloquine (24%), and halofantrine or quinine (14%). Glucose-6-phosphate dehydrogenase (G6PD) activity was normal in the 14 patients who underwent this test. Low-level P. falciparum parasitemia was found in 8 patients. All 21 patients survived. Our data and 13 cases reported in the literature suggest a resurgence of classic BWF among Europeans living in Africa and a need to discuss attendant therapeutic implications.

Fatal invasive aspergillosis complicating severe Plasmodium falciparum malaria.

We report the first 2 cases of fatal invasive aspergillosis complicating severe malaria. In 2 nonimmune European adults without underlying disease, death was directly ascribable to invasive aspergillosis. We believe that transient malaria-induced immunosuppression allowed massive growth and overwhelming dissemination of preexisting Aspergillus colonization.

Report of a fatal case of dengue infection with hepatitis: demonstration of dengue antigens in hepatocytes and liver apoptosis.

A fatal case of dengue (DEN) infection associated with a spleen rupture and with hepatitis is reported here. Microscopic studies showed numerous areas of spleen rupture with hematomas and revealed necrotic foci in liver samples obtained at autopsy. Although hepatitis was reported in several cases of DEN fever, the mechanism of liver injury remains poorly understood. In this case, immunohistochemistry showed that DEN viral antigens were mostly detected in hepatocytes surrounding the necrotic foci. By in situ detection of DNA fragmentation, apoptotic hepatocytes were found to be colocated with DEN virus-infected hepatocytes. These findings suggest that hepatocytes are the major sites of DEN virus replication in the liver and that DEN virus induces apoptosis of hepatocytes in vivo.

[Emergence of dengue hemorrhagic fever in French Antilles. 3 initial fatal cases in Guadeloupe]. / Emergence de la dengue hémorragique aux antilles françaises. Trois premiers décès en Guadeloupe.

BACKGROUND: Two outbreaks of dengue hemorrhagic fever occurred in Guadeloupe (French West Indies) in successive epidemics in 1994 and 1995. The first outbreak was caused by DEN-2 virus and the second by DEN-1. CASE REPORTS: Seven life-threatening infections (WHO grade 3/4) were identified. Three previously healthy adults (including two brothers) died. Autopsy reports (2 patients) disclosed hemorrhagic serous effusions, disseminated intravascular coagulation, and in one case a spontaneous spleen rupture. DISCUSSION: Dengue fever is an emerging disease. Its severe hemorrhagic form tends to an uprising incidence and can no longer be considered a disease limited to children in Far-Eastern Asia. Fatalities may occur very suddenly and unexpectedly, even in optimal health care settings, in healthy adults living or travelling in endemic areas, notably the Caribbean.

Predictors of short- and long-term survival in HIV-infected patients admitted to the ICU.

STUDY OBJECTIVES: To evaluate the prognosis of HIV-infected patients admitted to ICUs and to identify factors predictive of short- and long-term survival. DESIGN: A prospective study from January 1, 1990, to December 31, 1992, including all consecutive HIV-infected patients admitted to our ICU for the first time. ICU survivors were followed up until January 1, 1994. SETTING: An 18-bed infectious diseases ICU in a 1,300-bed university hospital in Paris. PATIENTS: Four hundred twenty-one HIV-related admissions were recorded during the study period (33.5% of 1,258 admissions to ICU); 354 HIV-infected patients were first ICU admissions and were analyzed. MEASUREMENTS AND RESULTS: Predictive factors on univariate and multivariate analyses (logistic regression and Cox model) for short- and long-term mortality were performed. Respiratory failure was the main cause of admission (49.2%), followed by neurologic disorders (26.8%), sepsis (10.2%), heart failure (4.5%), and miscellaneous disorders (9.3%). For these groups, in-ICU and in-hospital mortality rates were as follows: 16.7% and 33.9%; 23.2% and 41.1%; 38.9% and 58.3%; 25% and 68.8%; and 12.1% and 24.2%, respectively. In-ICU and in-hospital mortality rates were significantly different across the groups (p=0.026 and 0.002, respectively). Multivariate analysis showed that the in-hospital outcome was significantly associated with functional status (p=0.05), time since AIDS diagnosis (p=0.04), HIV disease stage (0.016), simplified acute physiology score (SAPS I) (p=0.06), need for mechanical ventilation (p<0.000001), and its duration (p=0.0001). In the 281 patients who were discharged alive from the ICU, cumulative survival rates were 51%+/-38% at 6 months, 28%+/-38% at 12 months, and 18%+/-30% at 24 months. Median and crude mean+/-SD survival times were 199 days and 316+/-343 days. Multivariate analysis showed that the long-term outcome was significantly associated with functional status (p=0.000001), weight loss (p=0.00001), the CD4 count (p=0.00001), the HIV disease stage (p=0.01), the duration of AIDS (p=0.001), the admission cause group (p=0.03), and the SAPS I at admission (p=0.00001). CONCLUSIONS: The short-term (in-ICU and in-hospital) outcome of HIV-infected patients was mainly related to the severity of the acute illness (SAPS I, cause of admission, need for and duration of mechanical ventilation), and to the preadmission health status, based on functional status and weight loss. Some of these parameters, in particular the SAPS I and preadmission health status, also influenced the long-term outcome. Whereas HIV-related variables had little impact on the in-ICU outcome, they were closely related with the in-hospital outcome and even more strikingly with the long-term outcome. Thus, the life expectancy of HIV-infected patients, which depends primarily on the natural history of the HIV infection, is the most powerful determinant of the long-term prognosis. Our results confirm that ICU support for HIV-infected patients should not be considered futile.

Ruptured mycotic pulmonary artery aneurysm: an unusual complication of right-sided endocarditis.

Mycotic pulmonary aneurysm is an infrequently diagnosed complication of endocarditis. We report here a case of mycotic pulmonary aneurysm and a review of 25 cases from the literature. The mortality rate is greater than 50%. Prompt diagnosis is necessary because early intrasaccular embolization and/or surgical repair is essential to avoid death from rupture of the aneurysm.

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.

Pitfalls in the diagnosis of airport malaria. Seven cases observed in the Paris area in 1994.

Clinical and biological pitfalls that lead to incorrect or delayed diagnoses of airport malaria are described based on 7 cases reported from the Paris region in the summer of 1994. We also report the outcome and the epidemiological features of these patients.

[Optimum quinine therapy in falciparum malaria attacks contracted in Africa]. / Du bon usage thérapeutique de la quinine dans l'accès palustre à P. falciparum contracté en Afrique.

A review about the use of quinine for uncomplicated falciparum malaria contracted in Africa is proposed. The dose of 8 mg/kg of quinine base 3 times a day seems to be admitted by all. On the other way, the duration of treatment fluctuates from 2 to 10 days without evidence of difference in efficacy between 3, 5 and 7 days. The pharmacodynamic and pharmacokinetic properties of quinine are reviewed and suggest that 3, 5 and 7 days are efficient at least on, respectively, 1, 2 and 3 parasite cycles and suggest that a five day treatment may be curative for all kind of patients infested with a quinine-sensitive strain of P. falciparum in Africa.

Assessment of right ventricle function and pulmonary artery circulation by cine-MRI in patients with AIDS.

OBJECTIVE: To evaluate right ventricle (RV) anatomy and performance and its relationships with pulmonary circulation in AIDS patients. DESIGN: We conducted a prospective blinded study by using cine-MRI, a well-accepted method to assess RV and pulmonary circulation. SETTING: A university hospital. PARTICIPANTS: Ten healthy volunteers and 13 asymptomatic AIDS patients. MEASUREMENTS: RV end-diastolic and end-systolic volumes, RV ejection fraction (RVEF), pulmonary artery (PA) diameter, main pulmonary artery distensibility (MPAD), RV free wall diastolic thickness (RVWT), and RV mass were measured. The RVWT/left ventricular wall thickness index was calculated. RESULTS: AIDS patients had significantly increased RV end-diastolic and end-systolic volumes and decreased RVEF (50 +/- 10 vs 59 +/- 6; p < 0.03). Four AIDS patients had RV wall motion abnormalities; 5 (38%) had an RVEF under 45%. RVWT, the RVWT/left ventricular wall thickness index, and PA diameter were significantly increased in AIDS patients. RV mass was increased in 54% of AIDS patients. MPAD was significantly lower in AIDS patients (18.8 +/- 15 vs 26 +/- 4; p < 0.01). A significant relationship was found between RV mass and MPAD (r = 0.76; p = 0.02). CONCLUSIONS: RV function is frequently impaired in AIDS patients. Anatomic and functional abnormalities found in RV and PA parameters suggest a systolic overload on RV. Pulmonary circulation abnormalities may influence RV structure and function in AIDS patients.

Possible prognostic significance of a brief rise in parasitaemia following quinine treatment of severe Plasmodium falciparum malaria.

An increase in parasitaemia is not uncommon after initiation of treatment for Plasmodium falciparum malaria, but its exact significance is unknown. The time-course of parasitaemia was assessed retrospectively in 33 patients with severe imported malaria. In 19 patients (group 1) mean parasitaemia (+/- SEM) fell promptly after starting quinine treatment, from 24.9 +/- 4.1% on day 0 to 9.7 +/- 2.3% on day 1 and 1.8 +/- 0.7% on day 2. In 14 other patients (group 2), parasitaemia did not change significantly or increased, with mean parasitaemia (+/- SEM) of 9.5 +/- 2.1% on day 0, 17.2 +/- 2.6% on day 1, and 3.7 +/- 1.8% on day 2. Simplified acute physiology scores on admission (mean +/- SEM) were 17.4 +/- 1.4 in group 1 and 11.7 +/- 1.0 in group 2 (P = 0.006). The mean number of complications of malaria per patient (+/- SEM) was 2.9 +/- 0.5 in group 1 and 1.6 +/- 0.3 in group 2 (P = 0.046). Two group 1 patients died. Initially, more than 95% of peripheral blood parasites were tiny and small rings in both groups, and this distribution was unchanged on day 1, suggesting that the parasitaemia increase in group 2 was not due to release of sequestered mature parasites. In severe falciparum malaria, a rise in parasitaemia after treatment initiation may be of favourable prognostic significance and should not lead to aggressive therapeutic approaches such as exchange transfusion.

[Prognostic factors of prosthetic valve endocarditis. Apropos of 122 cases]. / Facteurs pronostiques des endocardites sur prothèse valvulaire. A propos de 122 observations.

The prognostic factors of 122 patients suffering from prosthetic valve endocarditis between 1978 and 1992 were studied by univariate and multivariate analysis. The principal causative organisms were Staphylococcus aureus (33%), streptococci (20%), coagular-negative staphylococci (12%), enterococci (10%) and gram-negative bacilli (9%). The 4 month survival rate was 66% (42 deaths). The main predictive factor for death was infection with S. aureus (75% vs 15% with other organisms). In S. aureus infection, multivariate analysis identified the following predictive factors for death: a prothrombin ratio less than 30% (RR = 8.3), mediastinitis (RR = 4.9), cardiac failure (RR = 4.4) and septic shock (RR = 2.6). In cases of infection with other organisms, the following factors were predictive of death: a prothrombin ratio of less than 30% (RR = 32.26), renal failure (RR = 7.31) and cardiac failure (RR = 6.07). In patients with S. aureus infection, survival was better after than without surgery: 9/20 (45%) versus 0/20 (p < 0.001). In infection with other organisms, there was no difference in a survival after surgical (89%) or medical therapy (81%). Chronic endocarditis relapses over 1 to 5 years was observed in 9 cases. All patients were reoperated a total number of 18 times with 5 deaths. Very prolonged antibiotic therapy is recommended in these patients. The authors conclude that endocarditis not due to S. aureus and without complications may be treated medically. Rapid reoperation is necessary in all other cases.

Prosthetic valve endocarditis in the ICU. Prognostic factors of overall survival in a series of 122 cases and consequences for treatment decision.

We carried out univariate and multivariate analysis of outcome among 122 patients with prosthetic valve endocarditis (PVE) admitted to our ICU between 1978 and 1992. The predominant pathogens were Staphylococcus aureus (33%), streptococci (20%), coagulase-negative staphylococci (12%), enterococci (10%), and Gram-negative bacilli (9%). At 4 months, overall survival was 66% (42 deaths). Staphylococcus aureus was the main predictor of death (75% vs 15% with other pathogens). In S aureus PVE, multivariate analysis identified the following predictors of death: prothrombin time < 30% (relative risk [RR]: 8.3), concomitant mediastinitis (RR: 4.9), heart failure (RR: 4.4), and septic shock (RR: 2.6). In PVE due to other pathogens, prothrombin time < 30% (RR: 32.26), renal failure (RR: 7.31), and heart failure (RR: 6.07) were associated with death. In S aureus PVE, survival was higher in patients who received medical-surgical therapy than in those who received medical therapy alone (9/20 [45%] vs 0/20) (p < 0.01). In PVE due to other pathogens, there was no difference in survival between patients who underwent prosthesis replacement (89%) and those who received only medical treatment (81%). Among the 65 patients who underwent heart surgery, the mortality rate and incidence of postoperative paravalvular leakage did not correlate with positive prosthesis cultures. We conclude that non-S aureus and uncomplicated PVE may be managed without valve replacement but that prompt surgical intervention should be required in all other situations.

Acute lung injury complicating imported Plasmodium falciparum malaria.

STUDY OBJECTIVE: To characterize adult patients with acute lung injury complicating severe imported Plasmodium falciparum malaria. DESIGN AND SETTING: Retrospective study of patients with severe P falciparum malaria admitted to the medical ICU of a university hospital infectious diseases department. PATIENTS: Forty adults with complicated malaria, with (group 1, 12 patients) or without (group 2, 28 patients) acute lung injury. RESULTS: Patients with acute lung injury had a higher simplified acute physiology score on admission (24.2 +/- 3.2 vs 13.7 +/- 0.7 in group 2, p < 0.0001) and a longer time interval to adequate antimalarial therapy (8.8 +/- 2.5 vs 4.9 +/- 0.6 days in group 2, p = 0.046). Of the nine group 1 patients given mechanical ventilation, eight had a PaO2/FIO2 < or = 200 mm Hg. Two patients with moderate hypoxemia received oxygen through a nasal tube and one received continuous positive airway pressure via a face mask. Acute renal failure, unrousable coma, metabolic acidosis, and shock were significantly more common among group 1 patients. The number of complications of malaria was significantly higher in patients with acute lung injury (4.7 +/- 0.5 vs 1.6 +/- 0.1 in group 2, p < 0.0001). Five patients, including four with acute lung injury, had evidence of bacterial infection (pneumonia or primary bacteremia) at ICU admission. Four patients with acute lung injury died (33%) vs one patient without acute lung injury (4%, p = 0.022). CONCLUSIONS: Acute lung injury is more likely to occur in patients with extremely severe, multisystemic P falciparum malaria. In patients with acute lung injury and septic shock, bacterial coinfection should be suspected and treated empirically since it contributes substantially to early mortality.