Martinique experienced a dengue outbreak with co-circulation of DENV-2 and DENV-4. In an emergency department-based study, we analyzed whether the clinical presentation and outcome of adult patients were related to serotype, immune status, or plasma viral load. Of the 146 adult patients who had confirmed dengue infection, 91 (62.3%) were classified as having classic dengue fever, 11 (7.5%) fulfilled World Health Organization criteria for dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS), 21 other patients (14.4%) presented with at least one typical feature of DHF/DSS [i.e., internal hemorrhage, plasma leakage, marked thrombocytopenia (platelet count < or = 50,000 platelets/mm(3)) and/or shock], and 23 further patients (15.8%) had unusual manifestations. Four patients died. Severe illness was more frequent in patients with secondary dengue infection (odds ratio, 7.18; 95% confidence interval, 3.1-16.7; P < 0.001). Multivariate regression analysis showed that gastrointestinal symptoms and other unusual manifestations were independently associated with DENV-2 infection, whereas cough and DHF/DSS features were independently associated with secondary immune response. A high plasma viral load was associated with DENV-2 infection, increased serum liver enzymes, and with DHF/DSS features in patients presenting after the third day of illness. The most severe cases of dengue resulted from the combined effects of DENV-2 and secondary infection.
RNMO is a very rapidly disabling disease affecting primarily young women. This study has identified clinical features that predict a poor outcome. These findings suggest that early and aggressive immunotherapy might be warranted in RNMO.
Onset of adult T-cell leukemia (ATL) usually follows a long period of viral latency. Strongyloides stercoralis infection has been considered a cofactor of leukemogenesis. Hypereosinophilia (HE) is also observed and could be associated with either the presence of parasites or the leukemic process. In non-Hodgkin's lymphoma, eosinophilia may or may not affect prognosis. To determine whether infection with S stercoralis and therefore eosinophilia has a significant effect on the development of ATL, we studied two variables in 38 patients: age at onset and median survival rate. Infected (Ss+) patients (n = 19) were younger (P = .0002) and survived longer (P = .0006) than uninfected (Ss-) patients (n = 19) (median age, 39 vs 70 years; median survival, 167 vs 30 days). Mean survival of patients with hypereosinophilia (HE+) was not significantly different from that of patients without hypereosinophilia (HE-) (P = .57). However, overall survival was longer for Ss + HE + patients than for Ss-HE-patients (P = .01; 180 vs 30 days) or Ss-HE + patients (P = .03; 180 vs 45 days). Among patients with mean survival more than 180 days, Ss + HE + patients survived longer (P = .028). Our data confirm that cofactors related to the environment, such as S stercoralis and hypereosinophilia associated with S stercoralis or human T-cell leukemia virus, type 1 (HTLV-1) might be important in HTLV-1-associated leukemogenesis and suggest that hypereosinophilia affects the prognosis of HTLV-1-associated leukemia.
NMO IgG positive antibodies in NMO patients had a lower rate in the Caribbean area - where the population has a predominant African ancestry - than in Caucasian Europeans, suggesting the influence of a possible ethnic factor in the pathogenesis of the disease, but they confer a worse course with more attacks, more disability and MRI lesions.
In Martinique, a man bitten two days earlier by a pit viper (Bothrops lanceolatus) was hospitalized with impaired consciousness and tetraplegia. Investigations confirmed cerebral and myocardial infarctions. Resolving thrombocytopenia was associated with virtually normal blood prothrombin time/activated partial thromboplastin time but increasing hyperfibrinogenemia. Despite specific antivenom treatment, he developed fatal left ventricular failure six days after the bite. At autopsy, multiple cerebral, myocardial and mesenteric infarctions were found. Rupture of mitral chordae tendinae was the likely cause of death. Histopathologic examination showed multi-focal thrombotic microangiopathy with intimal-medial dissection by thrombi extending from foci of endothelial damage in small cerebral, myocardial, pulmonary, mesenteric, and interlobular renal arteries and arterioles. These findings were the causes of infarctions. There was intense angiogenesis in organizing cerebral infarcts. Immunohistochemical analysis showed platelet aggregates and endothelial cells within microthrombi. Viperidae venoms contain vascular endothelial toxins, notably metalloproteinase hemorrhagins, but von Willebrand factor activators or vascular endothelial growth factor-type factors are more likely to have been implicated in this case.
Dengue nonstructural 1 protein (NS1) is secreted by cells infected with dengue virus (DENV).1 This glycoprotein is highly conserved for all DENV serotypes and is strongly immunogenic. The NS1 antigen and NS1-specific antibodies may play a central role in the pathogenesis of dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS).2 It has been suggested that high plasma levels of NS1 could help identify patients at risk for plasma leakage.3-5 Commercial enzyme-linked immunosorbent assays (ELISAs) for detection of DENV NS1 in human serum samples have been proposed for dengue diagnosis, 6, 7 but the value of NS1 detection in predicting clinical severity remains to be evaluated.In a previous study conducted during a co-epidemic of DENV serotype 2 (DENV-2) and serotype 4 (DENV-4), blood samples were obtained form patients with acute dengue infection and stored in a serum bank.8 These serum samples provided an opportunity to screen serum samples from dengue patients for NS1 and to explore the relationships between NS1 antigenemia, plasma virus loads, dengue serotypes, immune status, and outcomes of illnesses.The data reported were derived from a prospective observational study.8 All patients who came to an emergency department in Martinique with a history of acute febrile illness were invited to participate in the study after providing written informed consent. Clinical data were recorded at the bedside in a computerized medical record system by means of a standardized questionnaire. The final severity of illness was diagnosed on the basis of data recorded at the first visit and during follow-up. The distinction between uncomplicated dengue fever, DHF/DSS, and other severe clinical forms of dengue illnesses was adapted from the 1997 World Health Organization classification system. 8,9 Blood was obtained by venous puncture at admission time, and serum aliquots were stored at -70°C for virologic studies. Laboratory methods for the diagnosis of dengue infections and plasma virus load measurements have been described. 8 Briefly, a hemi-nested reverse transcription-polymerase chain reaction (RT-PCR) was carried out with DENV generic and serotype specific primers, as described by Lanciotti and others.10 Quantitative real-time PCR was performed using generic primers, the iQ SYBR Green Supermix Kit, and the iCycler iQ Real Time PCR Detection System (Bio-Rad, Marne la Coquette, France). Plasma virus load was derived from standard curves obtained by serial dilution of titrated DENV-2 and DENV-4 supernatants and were expressed as plaque-forming unit (PFU) equivalents per milliliter. In addition, an ELISA for detection of NS1 was performed using PLATELIA™ Dengue NS1Ag Kits (Bio-Rad, Marne la Coquette, France) according to the manufacturer's recommendations. Dengue-specific antibodies were detected using IgM capture, IgG capture, and IgG indirect ELISA kits (Panbio, Brisbane, Queensland, Australia). A positive IgG capture test result for a serum sample obtained within six days of the onset of fever indicated a secondary inf...
The correlation between clinical grading of patients bitten by Bothrops lanceolatus and the subsequent development of their envenoming was examined. Severity of envenoming was graded using a 1-4 scale (minor to major). Patients were classified into 2 groups according to the time elapsed between bite and treatment with a specific purified equine F(ab')2 antivenom. The late/no treatment group (n = 33) was characterized by a systemic thrombotic complication rate of 14/33 (42.4%) leading to 4 deaths, which increased with the maximum severity assessed on the first day following the bite (P = 0.003). However, infarctions could develop in patients who presented initially with signs of moderate envenoming, normal blood clotting and low serum levels of venom antigens. No such complication of fatality occurred in the early (0.5-6 h) treatment group (n = 70). Multiple regression analysis showed that duration of stay in hospital in this group increased with the length of the snake (P = 0.017), venom antigenaemia (P = 0.016), initial grading (P < 0.001), and with the need for surgical debridement (n = 10/70, P < 0.001). Outcome was correlated with initial severity of envenoming. However, the only factor with a positive prognostic significance for the individual envenomed patient was the early infusion of specific antivenom, which led to 100% recovery in our series.
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