RETINAL MANIFESTATIONS IN ADULT T-CELL LEUKEMIA/LYMPHOMA RELATED TO INFECTION BY THE HUMAN T-CELL LYMPHOTROPIC VIRUS TYPE-1.

PURPOSE: To describe the retinal manifestations in adult T-cell leukemia (ATL) related to an infection by the human T-cell lymphotropic virus type-1 (HTLV-1). METHODS: Retrospective case series of patients with ATL with retinal findings. RESULTS: A total of 175 patients were diagnosed with ATL in Martinique between 1983 and 2013. Three of them showed intraocular findings related to ATL. They were bilateral deep retinal infiltrates associated with intermediate uveitis. In two cases, the ATL diagnosis was known. In the third, fluorescein angiography was remarkable for deep retinal infiltrates although fundus examination was unremarkable. The ATL cells were found in the blood of this patient. Despite chemotherapy, infiltrates progressed from the retinal periphery to the posterior pole in two patients, thus reducing visual acuity to light perception. They were associated with vasculitis. CONCLUSION: Retinal involvement in ATL is very rare. It can occur at any point during the natural course of the disease. Human T-cell lymphotropic virus type-1 carriers should benefit from a regular ophthalmic examination, and a fluorescein angiography must be performed in all patients with human T-cell lymphotropic virus type-1 with vitreous cells. The presence of deep retinal infiltrates must raise suspicion for ATL in a patient with human T-cell lymphotropic virus type-1.

Highly active antiretroviral treatment against STLV-1 infection combining reverse transcriptase and HDAC inhibitors.

Approximately 3% of all human T-lymphotropic virus type 1 (HTLV-1)-infected persons will develop a disabling inflammatory disease of the central nervous system known as HTLV-1-associated myelopathy/tropical spastic paraparesis, against which there is currently no efficient treatment. As correlation exists between the proviral load (PVL) and the clinical status of the carrier, it is thought that diminishing the PVL could prevent later occurrence of the disease. We have conducted a study combining valproate, an inhibitor of histone deacetylases, and azidothymidine, an inhibitor of reverse transcriptase, in a series of baboons naturally infected with simian T-lymphotropic virus type 1 (STLV-1), whose PVL was equivalent to that of HTLV-1 asymptomatic carriers. We show that the combination of drugs caused a strong decrease in the PVL and prevented the transient rise in PVL that is seen after treatment with histone deacetylases alone. We then demonstrate that the PVL decline was associated with an increase in the STLV-1-specific cytotoxic T-cell population. We conclude that combined treatment with valproate to induce viral expression and azidothymidine to prevent viral propagation is a safe and effective means to decrease PVL in vivo. Such treatments may be useful to reduce the risk of HAM/TSP in asymptomatic carriers with a high PVL.

Analysis of the ten-eleven translocation 2 (TET2) gene in familial myeloproliferative neoplasms.

The JAK2(V617F) mutation does not elucidate the phenotypic variability observed in myeloproliferative neoplasm (MPN) families. A putative tumor suppressor gene, TET2, was recently implicated in MPN and myelodysplastic syndromes through the identification of acquired mutations affecting hematopoietic stem cells. The present study analyzed the TET2 gene in 61 MPN cases from 42 families. Fifteen distinct mutations were identified in 12 (20%) JAK2(V617F)-positive or -negative patients. In a patient with 2 TET2 mutations, the analysis of 5 blood samples at different phases of her disease showed the sequential occurrence of JAK2(V617F) and TET2 mutations concomitantly to the disease evolution. Analysis of familial segregation confirmed that TET2 mutations were not inherited but somatically acquired. TET2 mutations were mainly observed (10 of 12) in patients with primary myelofibrosis or patients with polycythemia vera or essential thrombocythemia who secondarily evolved toward myelofibrosis or acute myeloid leukemia.

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. STUDY DESIGN AND METHODS: An emergency department-based prospective observational study was conducted in Martinique during a dengue outbreak in adult patients presenting with an acute febrile illness. Patients with severe bleeding and/or who underwent invasive intensive care procedures or emergency surgery were given PLT transfusion to achieve PLT counts of more than 50 x 10(9)/L. PLT transfusion was also considered for patients with PLT counts of less than 5 x 10(9)/L and for those with associated risk factors and PLT counts of less than 20 x 10(9)/L. RESULTS: A total of 350 patients were admitted with confirmed dengue infections. Most of them had secondary serotype-2 infections. PLT counts of less than 50 x 10(9)/L were recorded in 165 patients (47.1%). PLT transfusion was administered to 9 patients with thrombocytopenia. The indications included severe bleeding (5 cases), invasive procedures (3 cases), emergency surgery (1 case), and/or associated risk factors (2 cases). The median time duration from the onset of fever to PLT transfusion was 6 days (range, 4-10 days). The median amount of PLTs transfused was 3.66 x 10(11) (range, 2.8 x 10(11)-13.2 x 10(11)). The median PLT yield was +12.4% (range, -3.9% to +67.1%). Three patients died. All other patients recovered during the second week after the onset of fever. CONCLUSION: A restrictive strategy for PLT transfusion based on clinical features and low PLT count thresholds proved to be feasible and safe for adult dengue patients.

Occipital infarction revealed by quadranopsia following snakebite by Bothrops lanceolatus.

We report a case of snakebite in which envenomation was manifested through impairment of the visual field. The patient, a 46-year-old man, was bitten on the right thumb by Bothrops lanceolatus. Treatment with a specific equine antivenom (Bothrofav) was administered one hour after the bite. With the exception of fang marks, the results of a clinical examination, particularly the neurologic component, were normal. The day after the bite, the patient developed an inferior left lateral homonymous quadranopsia with macular epargne. T2 magnetic resonance imaging showed a right occipital infarction. His condition improved clinically and biologically. This observation of snakebite is the first in which envenomation was accompanied exclusively by an impairment of the visual field. Envenomation by B. lanceolatus is distinct in its incidence of significant thrombotic complications at a distance from the site of the bite.

Retinal vasculitis caused by adult T-cell leukemia/lymphoma.

BACKGROUND: To report a case of lymphomatous infiltration and bilateral retinal vasculitis observed among 83 cases of adult T-cell leukemia (ATL) treated in the University Hospital Center in Fort-de-France (Martinique, French West Indies) between 1984 and 2003. CASE: A complete clinical ophthalmologic examination was performed in this patient along with fluorescein angiography. OBSERVATIONS: After being checked for diffuse adenopathies, myodesopsias, and phosphenes, the 35-year-old patient was diagnosed with ATL. The ocular impairment, present since the onset of ATL as peripheral subretinal infiltrates, spread progressively and afferently to the rest of the retina in the form of an essentially venous vasculitis. Impairment of the vitreous was noted only in the end stages of disease progression. As ocular lesions progressed, the general state of the patient degraded at the same time despite chemotherapeutic measures. CONCLUSION: Among the more than 300 seropositive for human T-cell lymphotropic virus type 1 (HTLV-1) or patients with HTLV-1-associated myelopathy/tropical spastic paraparesis treated at our hospital in the last 20 years, and among the 83 cases of ATL, only this single case of retinal vasculitis associated with HTLV-1 was observed (1/83, 1.2%) in Martinique, confirming the geographic variability of the clinical phenotype of HTLV-1 infection. The incidence of retinal vasculitis in ATL patients may signify an even worse prognosis than initially indicated.

First case of visceral leishmaniasis caused by Leishmania martiniquensis.

We report the first case of visceral leishmaniasis (VL) caused by Leishmania martiniquensis in the Caribbean, which until now, was known only to cause cutaneous leishmaniasis. The disease presented with fatigue, anemia, and hepatosplenomegaly in a 61-year-old man with human immunodeficiency virus (HIV) infection who was receiving antiretroviral therapy. Diagnosis was made by bone marrow biopsy. VL is life-threatening, and its emergence in the Caribbean is of concern.

Quantitation of HTLV-I proviral load by a TaqMan real-time PCR assay.

A quantitative real-time PCR assay was developed to measure the proviral load of human T-lymphotropic virus type I (HTLV-I) in peripheral blood mononuclear cells (PBMCs). The HTLV-I copy number was referred to the actual amount of cellular DNA by means of the quantitation of the albumin gene. Ten copies of HTLV-I DNA could be detected with 100% sensitivity, and the assay had a wide range of at least 5 log(10). Intra- and inter-assay reproducibility was evaluated using independent extractions of PBMCs from an HTLV-I-infected patient (coefficients of variation, 24 and 7% respectively). The performance of this TaqMan PCR assay, coupled with its high throughput, thus allows reliable routine follow-up of HTLV-I proviral load in infected patients. Preliminary results using clinical samples indicate a higher proviral load in patients with HTLV-I-associated myelopathy/tropical spastic paraparesis than in asymptomatic carriers, and also suggest the usefulness of this quantitative measurement to assess the etiological link between HTLV-I and adult T-cell leukaemia/lymphoma-like syndromes.

Treatment of adult T-cell leukemia-lymphoma by CHOP followed by therapy with antinucleosides, alpha interferon and oral etoposide.

UNLABELLED: Adult T-cell leukemia-lymphoma (ATLL) has a very bad prognosis and remains resistant to conventional therapy. Promising results have been reported with the combination of zidovudine (AZT) and alpha-interferon (IFN). METHOD: A combination with IFN and antinucleoside [AZT or zalcitabine (ddC)] was applied since 1995 in Martinique (French West Indies). An initial treatment with two cycles of CHOP was added to reduce initial tumoral burden, followed by antiretroviral (ARV) therapy associated with etoposide. We report the characteristics and outcomes of 29 patients diagnosed with an ATLL between 1990 and 1999. The overall median survival was 8 months. A striking improvement of survival was observed when comparing the periods between 1990-1994 and 1995-1999 (17 months versus 3 months, p = 0.004). During the second period, seven patients received a therapy with oral etoposide, antinucleoside and IFN, among which, six patients received an initial induction CHOP chemotherapy. No major toxicity was observed with this strategy. In conclusion, the progression of survival since 1995 suggests that a therapeutic approach combining initial polychemotherapy with CHOP followed by ARV drugs, IFN and oral etoposide is an interesting option in treating patients with ATLL.

HIV, 'an evolving species'. Roles of cellular activation and co-infections.

Each small variation of the genome of a species can be preserved if it is useful for the survival of the species in a given environment. Within this framework, the finality of the biological cycle of HIV consists in a search for harmony (biological coherence) with man, which is to say a stable condition. Cellular activation appears to be the strategy developed by HIV in order to achieve this coherence. The price of this strategy is the AIDS. The first contact between HIV and immune system appears to determine the subsequent clinical outcome and the future of HIV. Lymphocytic activation varies during the course of the vital cycle of HIV. For each individual, this lymphocytic activation depends on both the HLA repertoire acquired during thymic ontogenesis and the antigenic experience before and after HIV infection. Thus intercurrent infections alter the immune condition of the organism and influence the outcome of HIV. We described a synthetic analysis of the effects of HIV on the surface protein expression and the cellular activation pathways which should provide insights in the evolutionary relationship between HIV and man and should permit to do a more physiological therapeutic approach.

[Evolution in the prevalence of intestinal parasitosis in the Fort de France University Hospital (Martinique)]. / Evolution de la prévalence des parasitoses digestives au CHU de Fort-de-France (Martinique).

OBJECTIVE: Determine the prevalence of intestinal parasitosis between January 1, 1997 and December 31, 1999 in the microbiology laboratory of the Fort de France University Hospital. METHOD: Retrospective study of the results of 4684 parasitological examinations of stools performed in 2704 patients between January 1, 1997 and December 31, 1999 in this laboratory. RESULTS: This survey showed the high prevalence of anguillulosis, found in 51.69% of infested patients and in 4.56% of the population studied, the ever high prevalence of non or scarcely pathogenic amoebas (Endolimax nanus, Dientamoeba fragilis, Entamoeba coli) found in 27.19% of infested patients and 1.88% of the population studied, together with that of hookworms (12.80% of infested patients and 1.13% of the population), and the persistence of lambliasis. This study also revealed the presence of cryptosporidies (7 cases) and microsporidies (4 cases) in the patients infected by the human immunodeficiency virus. DISCUSSION: These results confirm the trend of the past twenty Years and the results of surveys initiated by the national statistics board (INSERM) in 1978, 1988 and 1995-1995, with the regression of bilharziosis and the persistence of anguillulosis and hookworms. CONCLUSION: The improvement in living conditions and hygiene, the combined efforts of the health care workers and Authorities in Martinique over the past 30 Years in the fight against parasites have led to a great reduction in the prevalence of classical intestinal parasitosis. However, new parasites associated with HIV infection have appeared.

Meta-analysis on the use of zidovudine and interferon-alfa in adult T-cell leukemia/lymphoma showing improved survival in the leukemic subtypes.

PURPOSE: Human T-cell lymphotropic virus type-I-associated adult T-cell leukemia/lymphoma (ATL) is an aggressive, chemotherapy-resistant malignancy. Multiple small studies using zidovudine (AZT) and interferon-alfa (IFN-α) have shown response in patients with ATL. However, the impact of this innovative antiviral treatment strategy on long-term survival remains undetermined. PATIENTS AND METHODS: We report a meta-analysis of antiviral therapy of ATL. Medical records of 254 patients with ATL who were treated in the United States, the United Kingdom, Martinique, and continental France were individually reviewed. RESULTS: According to Shimoyama classification, there were 116 patients with acute ATL, 18 patients with chronic ATL, 11 patients with smoldering ATL, and 100 patients with ATL lymphoma. In 231 patients with available survival data, first-line therapy was recorded in 207 patients. Five-year overall survival rates were 46% for 75 patients who received first-line antiviral therapy (P = .004), 20% for 77 patients who received first-line chemotherapy, and 12% for 55 patients who received first-line chemotherapy followed by antiviral therapy. Patients with acute, chronic, and smoldering ATL significantly benefited from first-line antiviral therapy, whereas patients with ATL lymphoma experienced a better outcome with chemotherapy. In acute ATL, achievement of complete remission with antiviral therapy resulted in 82% 5-year survival. Antiviral therapy in chronic and smoldering ATL resulted in 100% 5-year survival. Multivariate analysis confirmed that first-line antiviral therapy significantly improves overall survival of patients with ATL (hazard ratio, 0.47; 95% CI, 0.27 to 0.83; P = .021). CONCLUSION: These results confirm the high efficacy of AZT and IFN, which should now be considered the gold standard first-line therapy in leukemic subtypes of ATL.

Influence of the dengue serotype, previous dengue infection, and plasma viral load on clinical presentation and outcome during a dengue-2 and dengue-4 co-epidemic.

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.