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[Parvovirus B19 infection and pregnancy].

Parvovirus B19 was identified in 1975. It causes infections megalerythemia in adults associated with skin eruptions and joint pain (about 50% of the adult population is immunized). The risk of contamination in case of an epidemia is high in school teachers and school personnel. In 1984, the parvovirus B19 was implicated as the cause of fetal anasarca. The risk of transplacental contamination is estimated at 33% in case of maternal infection. Pregnant women with parvovirus B19 infection and confirmed serology should have an echography every 15 days. Fetal anasarca can be complicated by in utero fetal death related to erythroid stem-cell anaemia. The diagnosis of fetal infection is based on PCR techniques on fetal blood. Symptomatic antenatal treatment with in utero transfusion was proposed as early as 1988. This method does not however appear to be necessary in all cases as the outcome in several reports of untreated fetuses was delivery of a normal child. There is the possibility of myocardial damage caused by parvovirus B19 which would make in utero transfusion difficult and limit its beneficial effect. Finally associated thrombopenia is often severe and increased fetal risk.

Erythema Infectiosum↗

[Experimental study on in vivo hematopoietic regulation of interleukin-6 gene therapy].

Interleukin-6 (IL-6), a pleiotropic cytokine, is involved in extensive immune regulation and hematopoietic regulation. We observed the effect of fibroblast mediated human IL-6 gene therapy on hematopoiesis. The platelet counts started to increase at day 4 after implantation of IL-6 highly secreting fibroblast cells and peaked at day 10 and lasted at high level for 22 days. The neutrophil counts were elevated after their implantation, but WBC did not show any remarkable increase. The CFU-GM and CFU-MK in bone marrow and spleen were also increased significantly. The results demonstrated that fibroblasts mediated human IL-6 gene therapy can significantly augment in vivo hematopoietic functions in bone marrow and spleen and elevate the number of nuetrophils and platelets. This study provides a new approach to treat thrombopenia and chemotherapy or radiotherapy-induced hematopoietic suppression.

3T3 Cells↗

[Dengue epidemic in New Caledonia (1989). Environmental factors and prevention].

An extensive dengue epidemic was reported in New Caledonia en 1989. Environmental factors (temperature and rainfalls) directly controlled the mosquitos population at the end of 1988. The introduction of a new dengue virus, transmitted by Aedes aegypti, was responsible for an epidemic that occurred in January-April 1989 and lasted until July 1989. The estimated number of cases was 25,000 and the attack rate was close to 120 per thousand inhabitants for a six month-period. The epidemic involved mainly the adult population in 84% of cases and 6-8% of patients was admitted in hospital with thrombopenia, leucopenia, minor haemorrhages in 2/3 of cases and 12 patients died with severe hemorrhagic disease or shock syndrome; initial serological results from suspected cases were positive against dengue by haemaglutination inhibition. Two dengue viruses were involved (dengue 1 and dengue 3) but dengue 3 was by far the most common. Ultra-low volume aerosols of diluted insecticide (decamethrine K'Othrine, Roussel) from road vehicles and aircraft was used from February to May to kill the adult mosquitoes (adulticiding). The efficacy dependent on the interaction of the insecticide and the flying mosquitoes is relative and debated but played probably a major role on the transmission, though the reduction of breeding sites was primarily uncovered. Since the epidemic, only sporadic cases were observed in 1991 and 1992.

Animals↗

Pharmacokinetic study in carboplatin, cisplatin and 5-fluorouracil regimen for advanced oesophageal cancer.

A chemotherapy using carboplatin, cisplatin and 5-fluorouracil in continuous infusion for advanced oesophageal cancer showed a high response rate in a previous feasibility study. The overall CT-scan response rate of 85% was obtained with a haematological dose-limiting toxicity: neutropenia and thrombopenia grade 3-4 of 23% and 30% respectively. In order to correlate myelosuppression with pharmacokinetic parameters, a pharmacological study was undertaken. The area under curve (AUC) of ultrafiltrable platinum and the residual rate of total platinum in 16 patients were tested. The measured creatinine clearance was found to be predictive of the subsequent myelosuppression. Plasma samples were using daily using the atomic absorption spectrometry technique. A strong relationship in individual patients was underlined between the AUC of ultrafiltrable platinum or residual rate of total platinum and the lowest platelet count for the first 3 days of treatment (p < 0.05). Conversely, the threshold value of the AUC at day one and residual rate at days two and three were calculated to prevent a highly probable haematotoxicity. Therefore, an optimal dose of carboplatin is determined in relation to the renal function of each patient.

Adenocarcinoma↗

[Chronic lupus erythematosus in lupus disease. Retrospective study of 136 patients].

OBJECTIVES: The aim of this retrospective study of 136 patients was to specify the natural history and the systemic prognosis of chronic cutaneous lupus erythematosus. It has been stated that in most of the cases, the disease only affects the skin. METHODS: From 10 October 1980 to 31 December 1990, 136 patients with the following criteria were included in this retrospective study: clinical signs suggestive of chronic cutaneous lupus erythematosus, characteristic histology, insufficient evidence for the diagnosis of systemic lupus erythematosus. RESULTS: The prevalence of systemic clinical involvement in the population under study was nearly the same as in the general population. The following biologic or immunologic abnormalities were quite common: leukopenia, lymphopenia, thrombopenia (significantly more frequent among patients having widespread chronic cutaneous lupus erythematosus), low titers of complement levels, positive antinuclear antibodies (usually at a low titer). Eleven out of the 136 patients developed systemic lupus erythematosus, most often over 5 years after the onset of the cutaneous lesions. Four cases out of these 11 had poor prognosis: renal and/or neurologic involvement. CONCLUSION: This data suggests that patients with chronic cutaneous lupus erythematosus could benefit from long-term follow up, since the course to systemic disease occurs in only a few. Usually, antimalarials used singly or in combination with topical steroids may lead to the clearing of the lesions. Thalidomide will occasionally be useful whenever the disease is unresponsive to the preceding measures.

Adult↗

[The clinical phase I study of TNP-351. The TNP-351 Research Committee].

The clinical phase I study of TNP-351, an antifolate drug having a novel structure, was performed through a multicenter cooperative program in 40 patients with solid tumors. The test drug was used on dosage schedules of single and daily doses for 5 or 3 days (by intravenous drip over 30 minutes, respectively). From the daily administration for 5 days, severe adverse reactions such as myelosuppression, became manifest at 5 mg/m2 (1n). This schedule was then switched to daily administration for 3 days. Administration of the test drug was initiated at a dose of 5 mg/m2. On a single-dose schedule, the dose was increased up to 100 mg/m2 (20 n), and on the 3-day daily administration schedule, up to 10.8 mg/m2 (2.2 n). Consequently, 26 of the study patients received single doses; three of them the 5-day daily administration, and 11 the 3-day daily administration. The dose-limiting factors were leukopenia and thrombopenia on both the single-dose and 3-day daily administration schedules. MTD was 100 mg/m2, and MAD, 75 mg/m2 for the single-dose schedule; and 10.8 mg/m2 and 9 mg/m2 for the 3-day daily administration schedule. WBC and platelet counts fell to nadirs at 1-2 weeks on either the single-dose or 3-day daily administration schedule, and it took the respective parameters about 1 week to recover. Subjective and objective adverse reactions to the test drug consisted of digestive tract disorders manifested as stomatitis, anorexia, nausea and vomiting; and laboratory abnormalities such as elevations of GOT and GPT in addition to the myelosuppression. Many of these adverse reactions subsided within 3 weeks after initiation of TNP-351 treatment. On the single-dose schedule, the test drug occurred chiefly in unchanged form in the blood, and in this form it disappeared from the blood biphasically with an alpha phase of 0.29-0.95 hours, and a beta phase of 7.8-14.4 hours. This disappearance pattern did not vary with an increase in dose. The 24-hour urinary excretion rate of the unchanged form amounted to 42-62% of the administered doses. On the 3-day daily administration schedule, the test drug was not accumulated in vivo. In the present study, two patients with malignant fibrous histiocytoma responded to the test drug with tumor regression. The results suggested that the recommended dosage regimen for the clinical early phase II study of the test drug should comprise a course of 9 mg/m2/day (by intravenous drip infusion over 30 minutes) every day for 3 days, which should be repeated every 3 weeks.

Adult↗

[Recurrent infections, severe neutropenia and neutrophil chemotaxis defect in paroxysmal nocturnal hemoglobinuria].

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease, whose origin seems to lie in a acquired defect in the membrane of the pluri-potential hematopoietic cell. Chronic or intermittent acute hemolytic syndrome is the most frequent clinical manifestation, although in the literature there are also some references to the leukocytic and immunologic disorders of this disease. In this paper, we present the case of a 63-year-old patient with NPH who developed severe neutropenia and sustained febrile syndrome. In the past four years, she had suffered frequent episodes of fever and leukopenia, which apparently disappeared spontaneously. In the physical exploration, we observed hepatosplenomegaly. The hemogram showed mild iron deficiency anemia (hemoglobin 10.8 g/dl), severe neutropenia (neutrophil 0.3 x 10(9)/l) and significant reticulocytosis (610 x 10(9)/l). Iron deposits were greatly reduced in the marrow. Simultaneously to a new febrile episode and isolation of Escherichia coli in the urine, there was a severe anemization (hemoglobin 5 g/dl) and a significant thrombopenia (platelets 30 x 10(9)) resulting in a positive hemosiderinuria and sucrose test. The study of the leukocytic function showed a defect in the neutrophil chemotaxis, although a normal phagocytic capacity and microbicidal activity. In the following nine months, the patient had several severe infections, with intense but transitory pancytopenia, which always improved when treating the infection with antibiotics. The patient died due to a septic shock twelve months after the diagnosis. Recurrent febrile episodes and severe neutropenia are very rare in the PNH (less than 4% of the cases). The cause of these disorders is still unknown.(ABSTRACT TRUNCATED AT 250 WORDS)

Anemia, Iron-Deficiency↗

Effects of RS61443 on functional and morphological changes in chronically rejecting rat kidney allografts.

No immunosuppression agent is as yet available that prevents the process of chronic allograft rejection, the most critical cause of late organ allograft loss. RS61443 (mycophenolate mofetil) inhibits de novo DNA synthesis as well as diminishes expression of cell surface molecules and antibody production. As these factors seem important in the pathophysiology of the chronic phenomenon, we investigated the effects of the agent in an established model of chronic rejection of kidney allografts in a F344-to-Lewis rat strain combination. All recipients were treated for the first 10 days after engraftment with low-dose cyclosporine (1.5 mg/kg/day) to reverse an initial acute rejection episode. Since functional and morphological changes do not become manifest in this model until after 12 wk, treatment with RS61443 (15 mg/kg/day, p.o.) was either initiated at the day of grafting (Gp 1) or 8 wks thereafter (Gp 2), and continued throughout the follow-up period. Non-RS61443-treated allografted rats receiving vehicle only (Gp 3) developed progressive proteinuria after 12 wk. Peak cellular infiltration (particularly macrophages in glomeruli and perivascular areas) at 16 wk was associated with densely expressed adhesion molecules (ICAM-1 on endothelium), cytokines and growth factors (TNF-alpha and TGF-beta in glomeruli and PDGF on arterial smooth muscle cells). Interstitial fibrosis, with tubular atrophy, glomerulosclerosis, and varying degrees of intimal proliferation and luminal obliteration of vessels, progressed thereafter. In vitro binding of MNC from naive animals to chronically rejecting allografted kidneys generally confirmed the immunohistological observations, peaking at 12 wk; this binding was significantly inhibited by mAbs against specific adhesion molecules (CD11a, CD18, and ICAM-1). Serum-allospecific IgG and IgM peaked at 1-2 wk after engraftment in the control recipients, decreasing thereafter. Although IgM declined to baseline after 12 wk, low levels of allospecific IgG persisted throughout the follow-up period. In contrast, recipient treatment with RS61443 (both Gp 1 and Gp 2) allowed the allografts to function normally throughout follow-up period. Proteinuria was virtually absent, and morphological and immunohistological manifestations of the chronic process were markedly diminished. In addition, treated recipients developed no significant side effects, including leukopenia, anemia, thrombopenia, nephrotoxicity, and hepatotoxicity. It appears that this agent can safely prevent the changes of chronic rejection of kidney allografts in this rat model.

Animals↗

[Heparin-associated thrombocytopenia caused by low-molecular-weight heparin].

Recent studies have shown that low-molecular-weight heparins (LMWH) are not suitable for treating patients with heparin-associated thrombopenia (HAT) type 2, as they can cause the same complications as unfractionated heparin UFH. The case described ist that of concerns as female patient who died after developing HAT type 2 following LMWH given perioperatively to prevent thromboembolism. This case indicates again that LMWH can trigger HAT type 2 even if administered only once a day. For HAT to be successfully treated it is essential that the condition is diagnosed early enough by means of routine regular laboratory checks of the number of thrombocytes during any heparin treatment in order to detect the disease before clinical symptoms become apparent.

Aged↗

Results obtained with fractionated ifosfamide massive-dose treatment in generalized malignant tumours.

In 409 sufferers from various malignant tumours, we used the cytostatic Ifosfamide (ASTAZ4942) in fractionated doses. The total i.v. dose averaging 300 mg/kg bodyweight, was either spread over 5 consecutive days (5 X 60 mg/kg i.v.) or over 10 consecutive days (10 X 30 mg/kg). At the same time, most patients were irradiated, the radiation dose usually being only one tenth the antitumour dose. Infections and electrolyte imbalance were first treated before Ifosfamide therapy was instituted. Cases of advanced cerebral sclerosis, thrombopenia below 75,000/cmm, cerebral metastases, impaired renal function and inadequate cooperation of the patient were excluded from the studies. To prevent and control side effects, various premedications and adjuvants are required: Antiemetics, prevention of cystitis and infections, cardiovascular agents etc. Corticosteroids are contraindicated. Out of 360 assessable patients 101 had a full remission, 150 a partial remission, 79 were failures; 30 cases were not evaluated. Good results were seen especially in ovarian carcinoma, mammary carcinoma and microcellular bronchial carcinoma. Particularly striking is the drug's effectiveness in testicular tumours including teratomas, osteosarcomas, chondrosarcomas and myosarcomas as well as in some adenocarcinomas of the gastro-intestinal tract, particularly pancreatic carcinoma. In lymphoreticular tumours and haemoblastoses, its potency is less pronounced. The side effects of Ifosfamide are the same as those of other alkylating agents. They are reversible and can usually be controlled or even avoided by adequate preventive measures. In the order of incidence we observed: Alopecia, leukopenia, fall in haemoglobin, cystitis, intercurrent infections, nausea and vomiting as well as cerebral disorders. Since haemorrhagic cystitis considerably interferes with Ifosfamide treatment, its prevention is of essential importance. Because of possible complications and specific premedication and adjuvant measures for their control, this type of treatment should for the present only be carried out by oncologists or special cancer centres.

Adolescent↗

[Taxol (paclitaxel), first molecule of a new class of cytotoxic agents: taxanes].

Taxol is the first of the taxanes, a new class of cytotoxic agents whose cellular target is the microtubules network. Taxol induces the polymerisation of the alpha and beta sub-units of the tubulin. This mechanism of action which is different from the vinca-alkaloids explains the main cytotoxic activity of paclitaxel through the formation of abnormal and stable bundles of microtubules. Severe hypersensitivity reactions which were seen in early phase I studies are prevented by an oral corticosteroids and H1 and H2 blockers premedication. Profound neutropenia is frequent but of short duration explaining that infectious manifestations are rare and neutropenia not cumulative. Thrombopenia and anemia are rare. Neurotoxicity is dose related but severe peripheral neuropathy is rare. Conduction abnormalities are mainly asymptomatic bradycardias. In second line ovarian cancer and breast metastatic cancer a noticeable level of activity has been observed, and in lung and head and neck cancer Taxol has proved to be effective.

Breast Neoplasms↗

[Thrombotic thrombocytopenic purpura disclosing cancer: apropos of 2 cases].

Thrombotic thrombocytopenic purpura (TTP) causes severe haemolytic anaemia, thrombopenia, fever and neurological and renal involvement. Currently five large aetiologic groups have been identified: viral or bacterial infection, drugs, conjunctive tissue diseases, pregnancy and solid tumours. We observed two cases resulting from an adenocarcinoma. In the first case, a 71-year-old man with chronic silicosis, the presenting signs were asthenia, fever, epistaxis with diffus purpura and spontaneous haematomas of the lower limbs. Diagnosis of TTP was based on routine laboratory tests and the patient responded well to fresh frozen plasma. On the 5th day of treatment, haemoglobin level dropped sharply and melana occurred. Upper digestive tract endoscopy revealed a tumoural formation of the antrum-fundic junction and histology examination of the biopsy confirmed the diagnosis of adenocarcinoma. Ten months after gastrectomy the patient was in excellent health with no relapse of the TTP. In the second case, the presenting signs included spontaneous haematomas, rectorrhagia and low grade fever. Microscopic haematuria and renal failure were observed in addition to the biological syndrome of TTP. The patient responded poorly to fresh frozen plasma and packed cell transfusions. Plasma exchange was equally unsuccessful. The disease continued a fulminant course and the diagnosis of adenocarcinoma located in a pulmonary lymph nodes was made at autopsy. These rare cases of TTP caused by cancer emphasize the importance of a thorough aetiological research. Plasma exchange has been shown to be effective but mortality at 1 year approximately 85% in cancer related cases. Early diagnosis and specific anti-cancer therapy might improve prognosis. We report our personal experience with 16 other similar cases.

Adenocarcinoma↗

[Cutaneous reactions to heparin: immunological and clinical aspects].

Skin reactions to heparin are rare, the most frequent manifestation being skin necrosis. Reactions occur either as an isolated manifestation or within a context of heparin-induced thrombopenia. Urticarious and eczematous reaction, either localized at injection sites or with a general distribution, have been recently reported. In all cases, it is mandatory to withdraw heparin therapy. Such accidents can be observed with all types of heparin (standard heparin and low-molecular weight heparin). Cross-reactions between two types of heparin are frequent. Skin tests can be used to guide heparintherapy.

Drug Eruptions↗

[Parvovirus B19 and pediatric pathology].

B 19 parvovirus is a widespread virus with primary infestation generally occurring in childhood through family and community outbreaks. Its most typical manifestation is transient erythroblastopenia with aplastic crisis, often profound, mostly affecting patients with chronic hemolytic anemia, and eventually patients with defective erythropoiesis (chronic hypoplastic anemia, iron deficiency anemia). In normal individuals the primary infestation is usually asymptomatic but may give transient hematological signs for few days: moderate reticulocytopenia, thrombopenia and neutropenia. Clinically two phases of the infection are described: 1.) a first phase of viremia of 2 to 3 days which may be accompanied by fever and myalgias; 2.) a second phase which may last for several weeks with dermatological signs, the most typical being erythema infectiosum, vasculitis, arthralgias or arthritis. In pregnant women, the primary infestation with B 19 parvovirus may lead to fetal anemia and hydrops fetalis with uneven outcomes: fetal death, chronic erythroblastopenia after birth, spontaneous resolution. Although the incidence of fetal infestation in non immunized pregnant women is still unknown, the question is raised of the recognition and protection of non immunized pregnant women at high risk of exposition to infested subjects. Long term persistence of the virus in the organism may be responsible for chronic manifestation, essentially but not exclusively in immunodeficient-patients: prolonged erythroblastopenia and chronic rheumatologic manifestations. It may be also responsible for cases of juvenile arthritis, thrombocytopenic purpura and chronic neutropenia of childhood. The diagnosis of the viral infestation is mainly based upon the detection of specific IgM, then IgG, antibodies by Elisa technique.

Child↗

[Primary antiphospholipid syndrome. Clinical course features of 24 cases].

OBJECTIVES: Describe the clinico-evolutionary characteristics of cases of primary antiphospholipid syndrome (PAPLS) diagnosed at our center. PATIENTS AND METHODS: Retrospective study of all patients with circulating anticoagulant type lupus (AL) (62 patients) and/or anticardiolipin antibodies (ACLA) found in our center since 1981 and 1988, respectively. TTPA, Kaolin's test (KT), and Russel's viper venom time (RVVT) and ACLA type IgG and IgM by ELISA: Only those patients meeting the criteria for PAPLS are included. RESULTS: Twenty-four patients were diagnosed with PAPLS: Eleven patients were from the enlarged TTPA group, 11 of the total with positive ACLA, and two by KT and abnormal RVVT. As for gender, 18 were women. In the past three years, 19 patients were diagnosed. The diagnostic criteria were from the very beginning: venous thrombosis in nine patients, arterial thrombosis in four, aborted repetitions in three, and plateletopenia in eight. Six patients presented pulmonary thromboembolism, the cause of death in one patient. Thrombopenia was manifested in the evolutionary course of 14 patients, only one of which being severe. Two patients have died (one of them from neoplasia), and two others have had antiphospholipid antibodies become negative. Seven patients remain without treatment, the others undergoing anti-aggregating or anti-coagulant treatment. CONCLUSIONS: Plateletopenia, alone or accompanied by other symptoms, is the most common alteration of PAPLS in our area, followed by venous thrombosis which caused death by pulmonary thromboembolism in one patient. Arterial thrombotic events and aborted repetitions are by no means infrequent.

Abortion, Habitual↗

[Experimental chemotherapy of echinococcosis. 13. The effect of mebendazole in combination with a vegetable oil on the larval cysts of Echinococcus multilocularis and the reaction of the infested host to long-term administration of the preparation].

The use of mebendazole as a suspension in vegetable oil enhanced the efficiency of treating experimental Echinococcus granulosus infection in outbred albino rats without increasing the dose of the drug. A sharp reduction in platelet count in the blood of the infected animals treated and untreated suggests that thrombohemorrhagic complications might be in echinococcosis. Thrombopenia in the treated animals appeared to be steady-state. A decrease in a rapid immune response in the mebendazole-treated rats, as compared to the untreated ones, is likely to be a consequence of a significant fall of antigenic immune stimulation due to suppression of the parasite's viability with the drug and to be an indicator of therapeutical efficiency.

Animals↗

[Visceral form of human anthrax imported from Africa].

Widespread vaccination has largely eliminated anthrax in Europe (the last case was reported in France in 1972) but the disease remains endemic in many developing countries. The usual cutaneous presentation (malignant pustules) is much more familiar than the various visceral manifestations including digestive tract, pulmonary or meningeal signs. We report a case of a 33-year-old immigrant living in France who was hospitalized for asthenia, dyspnoea, mucopurulant expectoration and moderate diarrhoea 3 days after a 3-month stay in Senegal and Gambia. The temperature was 39 degrees C at admission and blood pressure 110/70 mmHg. Crepitants were heard at the base of the right lung and the rest of the physical examination was normal. Blood was drawn for culture. Laboratory tests and the chest X-ray led to the diagnosis of pneumopathy and a treatment of amoxicillin and clavulanic acid was given with oxygenotherapy. The patient's temperature returned to normal but over the next 48 hours the dyspnoea worsened together with the black diarrhoea. The abdomen was painful. There were no skin lesions. The chest X-ray revealed an extension of the bilateral pulmonary images and bilateral pleural effusion. Laboratory tests revealed thrombopenia (platelet count 38,000/mm3) hyperleukocytosis (WBC 48,000/mm3) and haemolysis (Hb 4 milligrams). The diagnosis was made on the basis of the initial blood cultures which were positive for Bacillus anthracis. All other samples were negative, including HIV serology. Despite adapted antibiotic therapy (penicillin G, 8MU/day, was initiated on day 2), multiple organ failure occurred with septic shock and pulmonary oedema. The patient died in the intensive care unit on day 7. Fatal outcome due to anthrax is described in 25% of the visceral forms but reaches 100% in cases of septicaemia. The haemolysis observed in this case is not mentioned in the classical descriptions of anthrax. When treating septic syndromes in patients who have returned from endemic zones, clinicians should entertain the diagnosis of anthrax since the risk of fatal outcome is increased greatly in case of delayed diagnosis.

Adult↗

[Dengue: an disease imported from the Indian subcontinent].

BACKGROUND: The febrile syndrome is one of the most frequent diseases in travellers with transient clinical pictures, not being reported on many ocassions. In Spain no cases of dengue fever has been published so far. METHODS: A prospective clinical study was carried out in travellers from endemic zones with serologic diagnosis for dengue viruses being performed: IgM/IgG by hemagglutination inhibition and ELISA enhancement. RESULTS: Six cases of dengue are described in Spanish travellers (4 tourists and 2 workers) from the Indian subcontinent (1989-1992). Serologic diagnosis: IgM/IgG by hemagglutination inhibition and ELISA enhancement was carried out. Five cases presented with classical dengue fever picture and 1 with hemorrhagic dengue. In all cases, fever and thrombopenia were reported. The clinical picture was self-limited in 2 patients, complicated with post-dengue syndrome in 3 cases and with fatal outcome in 1. CONCLUSIONS: Dengue fever should be included in the differential diagnosis of febrile syndrome in travellers coming from endemic zones. The authors present the first cases of imported dengue in Spain.

Adult↗