Laurent Thomas

Prospective observational study of low thresholds for platelet transfusion in adult dengue patients

BACKGROUND: The practice of platelet (PLT) transfusions has been adopted into the standard clinical practice in many dengue‐endemic countries. Because many patients were found to have received unnecessary PLT transfusions, the development of guidelines for the management of dengue patients with thrombocytopenia has become a necessity.

Predictors of severe manifestations in a cohort of adult dengue patients

BACKGROUND Key symptoms observed during the febrile phase of dengue may identify patients who are likely to progress to severe disease. OBJECTIVES To test this hypothesis, we examined the relationships between symptoms reported by patients at presentation and the development of severe outcomes. STUDY DESIGN Retrospective analysis of data recorded prospectively in 560 adult dengue patients admitted to an emergency department. A logistic regression analysis was used to quantify the association between symptoms reported at presentation and outcome. RESULTS Plasma leakage was observed in 95 patients (17%), severe thrombocytopenia (platelet counts <20 x 10(9)/L) in 93 patients (16.6%) and acute hepatitis in 42 patients (7.5%). Severe thrombocytopenia developed in 57% of patients with plasma leakage and 40.5% of patients with hepatitis. Patients who developed a plasma leakage syndrome were older, mainly male, and reported more often an abdominal pain and a cough. Diarrhea and taking paracetamol >60 mg/kg/day before admission were associated with the development of acute hepatitis. Seven patients died. The mortality rate was 6/95 (6.3%) in patients who developed plasma leakage, 3/42 (7.1%) in patients who developed hepatitis, 5/93 (5.4%) in patients with severe thrombocytopenia, and 3/12 (25%) in the patients who demonstrated together all these severe manifestations. CONCLUSION Plasma leakage, severe thrombocytopenia and acute hepatitis identified subgroups of adult dengue patients with increased mortality rates. Key symptoms reported by the patients at presentation such as abdominal pain, cough or diarrhea were significantly associated with the development of severe manifestations and should be considered as warning signs.

Relationship between Nonstructural Protein 1 Detection and Plasma Virus Load in Dengue Patients

We report data from a prospective observational study performed in Martinique during a co-epidemic of dengue virus serotype 2 (DENV-2) and serotype 4 (DENV-4). Among 70 serum samples from patients with DENV-2 (n = 21) or DENV-4 (n = 49) infections, 47 (67.1%) were positive for dengue nonstructural protein 1 (NS1). Antigenemia correlated with plasma virus load and was independent of immune status and the time of sampling. Increased viremia 4-6 days after onset of illness was associated with NS1 positivity, secondary infection, and severe disease. Testing for NS1 could help identify the potentially most severely ill patients during the critical phase of dengue.

Prospective evaluation of nonstructural 1 enzyme-linked immunosorbent assay and rapid immunochromatographic tests to detect dengue virus in patients with acute febrile illness

We prospectively evaluated the Bio-Rad nonstructural 1 (NS1) enzyme-linked immunosorbent assay (ELISA) and lateral flow immunochromatographic assay (LFIA) in comparison to an in-place reverse transcription-polymerase chain reaction for dengue diagnosis. Among 537 consecutive samples from patients with acute febrile disease, 264 (49.2%) tested positive in reverse transcription-polymerase chain reaction (RT-PCR), 156 (29.1%) in NS1-antigen (Ag) ELISA, and 125 (23.3%) in NS1-Ag LFIA. Compared to the RT-PCR status, the specificity was 100% for the NS1-Ag ELISA and LFIA, but their respective sensitivities were 61.2% [95% confidence interval (CI), 55.2-67.2] and 49.4% (95% CI, 43.2-55.6), with nadirs of 37.9% and 24.1% on day 6 of illness. The NS1-Ag ELISA and LFIA were positive, respectively, for 48.0% and 40.7% of the secondary infections versus 85.0% and 66.7% of the primary infections. For patients <5 years old, NS1-Ag ELISA and LFIA reached respective sensitivities of 100% and 90.5%. Reports of results of dengue NS1-Ag assays should specify that negativity does not preclude DENV infection, and require further investigations in the case of severe disease.

Clinical presentation of dengue among patients admitted to the adult emergency department of a tertiary care hospital in Martinique: implications for triage, management, and reporting.

STUDY OBJECTIVE During dengue epidemics, emergency physicians face large numbers of patients with acute febrile illness. Triage algorithms and appropriate reporting systems are useful to manage patients and prioritize resources. We identify possible adaptations to these systems to improve the management of patients during epidemics. METHODS In a prospective observational study in the adult emergency department (ED) of a tertiary care hospital, we enrolled all patients with febrile illness and a confirmed diagnosis of dengue (ribonucleic acid identification). We then retrospectively classified cases according to the initial clinical presentation at the ED. RESULTS We enrolled 715 patients (332 male patients), aged 14 to 91 years (median 35 years). Severe illness was documented in 332 cases (46.4%) and was mostly caused by serotype 2, or a secondary infection of any serotype. Severe forms included dengue hemorrhagic fever or dengue shock syndrome (104/332; 31.3%), severe bleeding (9/332; 2.7%), and acute organ failure (56/332; 16.9%). The other patients with severe illness (171/332; 51.5%) presented with symptoms of presyncope, intense weakness, prolonged gastrointestinal symptoms, and hypotension. This presentation was common during epidemics and appeared to be associated with dehydration and electrolyte loss that improved markedly within 24 hours with saline solution infusion. This group did not have evidence of plasma leakage, although similar features were observed in patients with dengue hemorrhagic fever/dengue shock syndrome. CONCLUSION Dengue has a wide range of clinical presentations in the ED. Many patients who appear seriously ill on presentation will respond to intravenous fluids.

Bothrops lanceolatus Bites: Guidelines for Severity Assessment and Emergent Management

Approximately 20-30 declared snakebite cases occurin Martinique each year. Bothrops lanceolatus, a member of the Crotalidae family, is considered to be the only involved snake. B. lanceolatus, commonly named “Fer-de-Lance”, is endemic and only found on this Caribbean island. Envenomation local features include the presence of fang marks, swelling, pain, bleeding from punctures, and ecchymosis. Severe envenomation is associated with multiple systemic thromboses appearing within 48 h of the bite and resulting in cerebral, myocardial or pulmonary infarctions. Diagnosis requires first of all identification of the snake. Coagulation tests are helpful to identify thrombocytopenia or disseminated intravascular coagulation. A clinical score based on 4 grades is helpful to assess envonimation severity. A specific monovalent equine anti-venom (Bothrofav®, Sanofi-Pasteur, France) to neutralize B. lanceolatus venom is available. Its early administration within 6h from the biting in case of progressive local injures, general signs or coagulation disturbances is effective to prevent severe thrombosis and coagulopathy. Its tolerance is considered to be good. Despite an increasing incidence of bites, no deaths have been recently attributed to B. lanceolatus in Martinique, probably due to the currently recommended strategy of early antivenom administration when required.

Prospective and descriptive study of adult dengue cases in an emergency department, in Martinique.

OBJECTIVE Knowing about the clinical aspects of dengue in endemic zones is essential to implementation of appropriate case management protocols and public health interventions. PATIENTS AND METHODS The authors made a 4-year prospective, observational study of dengue-infected patients admitted to the emergency department of the Fort-de-France University Hospital. RESULTS Two hundred and sixty-three male and 297 female patients were included. The median age was 37 years (range: 14-91). The diagnosis was based on a positive RT-PCR (463 patients) or on the presence of specific IgM (97 patients). Two hundred and seventy-seven patients (49.5%) presented with dengue fever without complications. According to WHO criteria, 95 patients (17%) developed plasma leakage, including 39 patients (7%) diagnosed with DHF, and 10 (1.8%) diagnosed with DSS. Among the other patients without plasma leakage, 84 (15%) had isolated thrombocytopenia, 14 (2.5%) had internal bleeding, and 90 (16%) had unusual manifestations. Seven patients died (1.3%): fulminant hepatitis (two), myocarditis (one), encephalitis (one), acute respiratory failure (one), gangrenous cholecystitis (one), and post-traumatic intracranial hemorrhage (one). The other patients recovered. Seven patients were pregnant (1.3%) from 6 to 27 weeks of amenorrhea and carried their pregnancy to term without complications. CONCLUSION With this experience, we were able to develop appropriate case management protocols for patients during dengue epidemics.

Clinical Presentation of Dengue by Serotype and Year of Epidemic in Martinique

During the last decade Martinique experienced four dengue epidemics, each characterized by the predominance of 1 or 2 serotypes. In this retrospective database analysis, we investigated the relationship between dengue serotype and disease severity. Data on dengue were collected from 715 patients (male/female ratio 0.87), 14 to 91 years of age (median 35 years) examined in the adult emergency department between 2005 and 2010. In this series, DENV-4 infections more frequently had a milder clinical presentation. The DENV-2 infections were most often secondary infections admitted at the critical phase of dengue illness with signs of plasma leakage. The DENV-1 infections were disabling, particularly in females, and most often led to disease of intermediate severity, without overt plasma leakage. These data were consistent with there being differences in virulence between serotypes, regardless of the hosts immune status. However, secondary DENV-2 infections showed an increased risk of plasma leakage.

Dengue Shock Syndrome or Dehydration? The Importance of Considering Clinical Severity When Classifying Patients With Dengue

TO THE EDITOR—In a recent issue of Clinical Infectious Diseases, Lam et al reported the outcome of 1719 children admitted over a 10-year period and diagnosed with dengue shock syndrome (DSS) [1]. Patients were described as having had a severe clinical presentation resulting from plasma leakage and pulse pressure ≤20 mm Hg. The definition of DSS used was the 1997 World Health Organization (WHO) definition regarding pulse pressure and hematocrit determinations. However, other diagnostic procedures, such as laboratory tests for liver and renal function, coagulation, and acidbase determination, and the detection of serous effusion by imagery, were not completed in many patients. Finally, as stated by the authors, the main inclusion criterion was evidence of impaired perfusion “thought by the treating clinician to be due to vascular leakage and to require volume resuscitation.” In this series, most patients recovered within a few hours with a single infusion of saline and only 8 patients died, resulting in the lowest case-fatality rate in hospitalized dengue patients ever reported in Southeast Asia [2, 3]. Although the rapidity and quality of treatment are key factors in determining the chances of recovery, one can question the representativeness of this group of patients reported as having DSS. It is reasonable to suspect that many of these patients were not actually in shock, and that many patients with a straightforward dehydration associated with the febrile phase of the disease were included in a group of patients diagnosed with a severe plasma leakage. The issue is important when it comes to the inclusion of patients in clinical trials [4]. Describing the clinical forms of dengue is difficult because of the diversity and overlapping nature of the clinical manifestations. The frequency of any given category of patients in a cohort may be confounded by selection bias, and by the misuse of medical terms such as “hemorrhage” in patients who do not have clinically significant bleeding, or “shock” in patients with transient hypotension. Based on our clinical experience of severe dengue in adults [5] and field epidemic experiences in Martinique and in Cape Verde, the 2009 WHO guideline that includes warning signs may be of value for the triage of patients by field clinicians. However, many patients with warning signs do not develop severe disease. Specifically, hypotensive patients who improve dramatically within a few hours with an infusion of saline represent a significant category of intermediate severity that do not deserve to be classified in the same group as that of patients in shock [6]. To meet the requirements of representativeness, consistency, and comparability, the description of the severe forms of dengue should include an assessment using an