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PubMed2004

Role of actin filaments in targeting of Crimean Congo hemorrhagic fever virus nucleocapsid protein to perinuclear regions of mammalian cells.

Crimean-Congo hemorrhagic fever virus is the causative agent of a severe disease throughout Africa, Europe, and Asia. Like other members of the genus Nairovirus, the Crimean-Congo hemorrhagic fever virus contains three genomic RNA segments, the small (S), medium (M), and large (L) segments. The S segment encodes the viral nucleocapsid protein (NP), while the M and L segments encode the glycoproteins and the RNA-dependent RNA polymerase, respectively. In this study, the site of expression and assembly of Crimean-Congo hemorrhagic fever virus NP in mammalian cells have been investigated. It was found that the NP is localized in the perinuclear region of infected cells. By using the Semliki forest virus expression system, it was shown that the Crimean-Congo hemorrhagic fever virus NP is targeted to the perinuclear region of cells in the absence of native RNA segments and virally encoded glycoproteins. It was also demonstrated that the Crimean-Congo hemorrhagic fever virus NP was not expressed as a Golgi-membrane associated protein. By using Cytochalasin D, an agent that disrupts actin filaments, it was found that actin filaments are involved in targeting the viral NP to perinuclear regions. We also demonstrated that disruption of actin filaments reduced the assembly of infectious Crimean-Congo hemorrhagic fever virus up to 97%. Furthermore, we showed that the NP of Crimean-Congo hemorrhagic fever virus NP interacts with actin.

Actin Cytoskeleton↗
PubMed1986

Simultaneous administration of hepatitis B and yellow fever vaccines.

In most developing countries, hepatitis B prevention is carried out early in life. In these countries, mobile immunization teams have a limited number of sessions to devote to each rural community; simultaneous administration of multiple antigens is thus normal practice. We compared the immune responses of Senegalese children to the separate or simultaneous injections of yellow fever and hepatitis B vaccines. Injections were given at the time of booster injection for hepatitis B vaccine. Yellow fever antibodies were detected in similar proportions in infants immunized with either yellow fever vaccine alone or yellow fever and hepatitis B vaccines simultaneously. However, a lower proportion of high yellow fever antibody levels were observed when the two vaccines were injected simultaneously. No reduction in the anamnestic response of antibodies against the surface antigen of hepatitis B virus (anti-HBs) was observed when yellow fever vaccine was injected at the same time as the booster dose of hepatitis B vaccine. Since no untoward reactions were noted, it is concluded that hepatitis B and yellow fever vaccines can be administered at the same time.

Antibodies, Viral↗
PubMed1988

Hematologic dysfunction in Lassa fever.

Lassa fever is widespread in West Africa, where the case fatality is about 16% in hospitalized adult patients. The clinical course is highly variable, with a few patients developing severe disease with bleeding, adult respiratory distress syndrome, encephalopathy and hypovolemic shock. We studied 70 patients admitted with suspected Lassa fever to a hospital in Sierra Leone, West Africa. Fourteen patients classified as having severe Lassa fever on the basis of serum aspartate amino transferase (AST) greater than 150 IU/L or viremia of greater than 10(3.6) tissue culture infective dose (TCID) 50/ml were found to have statistically significantly depressed lymphocyte counts when compared with patients with mild Lassa fever (AST less than 150 IU/L or viremia, less than 10(3.6)TCID50/ml), (P less than 0.0001) and with febrile control patients, in whom Lassa infection had been excluded by laboratory criteria (P less than 0.0008). Maximum depression occurred a mean of 10.9 days post onset. Patients with severe Lassa fever also had moderate thrombocytopenia, which was statistically significant when compared with febrile control patients (P less than 0.0003) and this occurred a mean of 10.8 days postonset. The most significant changes were in platelet function, which was markedly depressed in patients with severe Lassa fever (P less than 0.0035 in response to ADP and P = 0.0081 for collagen) when compared with patients with mild Lassa fever, and when compared with febrile controls, (P = 0.0013 for ADP and P less than 0.00001 for collagen). This abnormality was usually maximal on admission to hospital, and probably is an early event, preceding hospitalization in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗
PubMedDate not supplied

Mother's knowledge of, attitudes toward, and management of fever in preschool children in Italy.

BACKGROUND: We examined mothers' knowledge of, attitudes toward, and management of fever in their children. METHODS: Interviews of mothers of preschool children were performed using a structured questionnaire administered by interviewers with no specific medical competence. RESULTS: Of a total of 1,237 mothers who were interviewed, data were analyzed for the 707 mothers who had coped with a febrile episode in their children during the previous month. Of these, 59% were concerned about fever in their children and 17% were very worried. At the onset of fever, 48% of the mothers gave their child an antipyretic and 18% called the physician immediately. In logistic regression analysis, five variables were significantly associated with mothers' concern: the absence of previous information on the management of fever, temperature > 39 degrees C, an only child, mother's low educational level, and mother's residency in the south of Italy. For the request for a physician's visit, of the variables entered, the only explanatory ones were the mother's concern and the absence of previous information on the management of fever. CONCLUSIONS: These findings suggest that informing mothers on the definition, consequences, and treatment of fever can significantly improve their confidence in managing fever, as reflected by fewer requests for physicians' visits.

Child, Preschool↗
PubMed1996

Sandfly fever viruses in Italy.

Two serologically distinct agents, the sandfly fever Sicilian and the sandfly fever Naples viruses, were isolated by Sabin from blood samples taken during an Italian epidemic of febrile illness. Since then, several different viruses have been isolated from sandflies and/or humans in both the Old and New World. Toscana virus, a new virus closely antigenically related to sandfly fever Naples virus, was isolated in 1971 from the sandfly Phlebotomus perniciosus in Italy. Extensive studies on the importance of Toscana virus as a human pathogen demonstrated its association with acute neurologic diseases. A serosurvey for the presence of antibodies to sandfly fever Sicilian, sandfly fever Naples and Toscana viruses indicated that, as in other Mediterranean areas, both sandfly fever Sicilian and sandfly fever Naples viral infections decreased or disappeared after the 1940s in countries performing insecticide-spraying malaria eradication campaigns. In contrast, clinical cases of aseptic meningitis or meningoencephalitis caused by Toscana virus are observed annually in Central Italy during the summer. Toscana virus may be present in other Mediterranean countries where sandflies of the genus Phlebotomus are present.

Animals↗
PubMed1990

Fever response induced by intravenous and intracerebroventricular injection of pyrogen in thyroidectomised and protein-calorie malnourished rabbits.

The development of a fever in response to intravenous (IV, 1.5 micrograms/kg body mass) and intracerebroventricular (ICV, 1.5 micrograms/animal) injections of Escherichia coli lipopolysaccharide (LPS) was studied in control, thyroidectomised and protein-calorie malnourished rabbits (New Zealand Whites, n = 55). ICV injection of LPS in control rabbits produced a fever response, the characteristics of which differed from those obtained after IV pyrogen injection. Thyroid deficiency caused an attenuated fever response, irrespective of whether LPS had been administered by IV or ICV injection. Protein-calorie malnourished rabbits showed a smaller fever response after IV or ICV pyrogen injections. Malnourished rabbits, refed over a period of 15 days, showed a typical biphasic fever response, but with lower magnitude than controls. The results of these experiments suggest that ICV injection of LPS is not an appropriate model for the study of fever mechanisms in disease states, and that the attenuated fever response observed in protein-calorie malnourished rabbits may be related, at least in part, to a decreased ability to produce the endogenous pyrogen interleukin-1.

Animals↗
PubMed1990

Participation of interleukin-1 and tumor necrosis factor in the responses of the sympathetic nervous system during lipopolysaccharide-induced fever.

The regional sympathetic responses during fevers induced by an exogenous pyrogen, lipopolysaccharide, and by two endogenous pyrogens, interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF-alpha), were compared in urethane-anesthetized rabbits. Rectal temperature (Tre), ear skin temperature (Tear) as an index for cutaneous sympathetic activity, renal sympathetic nerve activity (RSNA) representing visceral efferents, arterial blood pressure, and heart rate were recorded during fever caused by intravenous injections of each of the three pyrogens. Lipopolysaccharide (1 micrograms/kg i.v.) caused prolonged fever of more than 3 h duration with a tendency towards a biphasic course of temperature, whereas fevers induced by IL-1 beta (1 microgram/kg i.v.) and TNF-alpha (10 micrograms/kg i.v.) were monophasic with a maximum between the 45th and 60th min. Each of the three pyrogens typically induced a decrease in Tear, indicative of cutaneous sympathetic activation, and simultaneous inhibition of RSNA during the first phase of rising Tre. RSNA tended to increase again approximately to its control level when the maximum Tre had been attained after the injection of each pyrogen. When the second rising phase of lipopolysaccharide fever started, Tear decreased once more, but RSNA remained at its control level. Taken together with the enhancement of IL-1 and TNF production during lipopolysaccharide-induced fever, the present results suggest the participation of these endogenous pyrogens in the responses of the sympathetic nervous system during the early phase of the lipopolysaccharide induced fever.

Animals↗
PubMedDate not supplied

Fever in hospitalized medical patients: characteristics and significance.

The occurrence of fever and the clinical profile of febrile patients on the medical service of a teaching hospital were studied prospectively. Thirty-six per cent of 972 patients developed fever (temperature exceeding 38 degrees C). Their 13% mortality rate and 13.2-day average hospital stay exceeded the 3% mortality and seven-day hospitalization for afebrile patients (p less than 0.0001 for both). Most fever episodes occurred during the first two hospital days. Approximately 30% of first and subsequent fever episodes were caused by bacterial infections; illnesses involving tissue necrosis (e.g., stroke, myocardial infarction) accounted for 20%. Five conditions comprised 53% of diagnoses: respiratory and urinary tract infections, neoplasm, myocardial infarction, and drug reaction. Only one patient had a fever of uncertain origin. Several clinical clues used frequently to identify bacterial infections were reevaluated. Patients with bacterial infections had higher temperatures on the first febrile day (mean 38.9 degrees C) and were more likely to have had prior infections than those with other causes of fever (mean 38.3 degrees C, p less than 0.001). Older patients (greater than 75 years) had a lower febrile response to bacterial infections than younger patients. Fever in hospitalized medical patients is a common and important concomitant of increased mortality and length of hospitalization.

Bacterial Infections↗
PubMed2003

Importance of the vagus nerve for fever and neutrophil migration induced by intraperitoneal LPS injection.

OBJECTIVE: We investigated the importance of the vagus nerve in fever, neutrophil migration and neutrophilia simultaneously induced by intraperitoneal injection of endotoxin (lipopolysaccharide, LPS) and in terms of the production of pre-formed pyrogenic factor (PFPF) and of the fever induced by this factor. METHODS: Naïve, sham-operated or subdiaphragmatically vagotomized male Wistar rats received either LPS (i.p. or i.pl.) or PFPF (i.v., i.c.v., i.p.). The number of neutrophils was evaluated in peritoneal or pleural fluid and in blood. Fever was monitored using a rectal probe. RESULTS: In naïve animals, LPS (0.02-200 microg kg(-1), i.p.) induced dose-related neutrophilia and fever while on neutrophil migration it resulted in a bell-shaped curve. Vagotomy reduced the peritoneal resident cell population (56%), fever (71%) and neutrophil migration (43%) but not the neutrophilia or neutrophil migration to the pleural cavity. Vagotomy did not affect the PFPF production or PFPF-induced fever. CONCLUSIONS: Vagus nerve integrity is important not only for fever but also for the neutrophil influx to the peritoneal cavity by controlling the number of resident cells in this cavity.

Animals↗
PubMed2000

Involvement of CRH in fever induced by a distinct pre-formed pyrogenic factor (PFPF).

OBJECTIVE: This study investigated the role of corticotrophin-releasing hormone (CRH) in mediating the fever induced by a novel pre-formed pyrogenic factor (PFPF), using a CRF antagonist in vivo and evaluating the capacity of PFPF to stimulate CRH release from the hypothalamus in vitro. MATERIALS AND METHODS: Male Wistar rats were used. The PFPF, induced following brief incubation of rat peritoneal macrophages with LPS and retained on 10 or 20 kDa MW cut-off membranes, was injected intracerebroventricularly. Fever was monitored using a rectal probe. Hypothalamus tissue was incubated with PFPF to establish its ability to induce CRH release. The CRH was measured by ELISA. RESULTS: PFPF induced a dose-dependent fever that was abolished by boiling or pronase treatment. Whereas both dexamethasone and indomethacin were effective in reducing interleukin- (IL) 1beta-induced fever, only dexamethasone abolished the fever induced by PFPF. The CRH antagonist, a-helical CRH9-41, abolished the fever induced by synthetic CRH, IL-8 and PFPF but not tumour necrosis factor-a (TNF-alpha). Like IL-1, PFPF was able to induce the release of CRH from rat hypothalamic tissue in vitro. CONCLUSIONS: These results suggest that the fever induced by PFPF depends on CRH release but not prostaglandin synthesis.

Animals↗
PubMed2001

[Fever as etiology of temporary infertility in the man].

BACKGROUND AND OBJECTIVE: Fever of > or = 39 degrees C for > or = 3 days can lead to severely impaired semen quality and even azoospermia. Among spermatogenic cells, pachytene spermatocytes and spermatids are particularly sensitive to temperature. Because of the nature of a spermatogenic cycle, impairment of semen quality becomes obvious after a latent period of several weeks. The changes are usually reversible within a few months. Therefore, a careful history with regard to fever episodes during preceding 3 months is mandatory for interpretation of semen analysis. PATIENTS/METHODS: Five patients are reported who desired a child and had experienced high fever of > or = 39 degrees C for > or = 3 days. The results of semen analyses are presented in relation to fever episodes. RESULTS: Sperm concentration declined to 0.4-7% and fast progressive motility to 0-23% 3-6 weeks after the fever episodes and returned to base line levels within 4-6 months. In patients without semen analysis before the fever episode, semen quality remarkably improved thereafter. CONCLUSIONS: Investigating patients for a history of fever during the 3 months preceding fertility work-up avoids unreasonable treatment recommendations based on transient impairment of semen quality.

Fever↗
PubMed2002

Antibiotic prescription for fever episodes in hospice patients.

Bacterial infection usually plays an important part in the fever episodes that are common in patients in the hospice palliative care unit. The physicians' attitude to use of antibiotics in such cases is usually complex. We retrospectively studied 535 admissions to a hospice and palliative care unit in a medical center in Taiwan. Ninety-three fever episodes (16.7%) were identified among these admissions, and 79 fever episodes (84.9%) were treated with antibiotics. The Karnofsky performance status (KPS), verbal communication ability (VCA) and Glasgow Coma Scale (GCS) were all significantly compromised in these febrile patients. Although KPS, VCA and GCS were similar among all patients at the date of admission, these parameters became significantly worse in fever episodes that were left untreated than in those treated with antibiotics. Patients without antibiotic treatment showed a shorter mean survival (8.7 +/- 9.9 days vs 14.6 +/- 13.1 days; P = 0.03) and a higher 3-day mortality rate than those patients with antibiotic treatment (50% vs 15.2%; P = 0.015). In conclusion, appropriate antibiotic use may cause fever to subside and thus decrease the fever-related discomfort. Physicians may tend to withhold antibiotic treatment because of the poorer KPS, VCA, and GCS and poorer estimated prognosis of patients at the time of fever.

Aged↗
PubMed1998

No specific brain protection against thermal stress in fever.

Knowledge about human brain temperature is still very limited, despite evidence demonstrating the critical influence of mild increases in temperature on the ischaemic brain. It has been suggested that in passive and exercise hyperthermia the brain may be protected against thermal damage by a mechanism of selective brain cooling (SBC). It is said to bring about suppression of the temperature of the brain, rendering it significantly lower than trunk and arterial blood temperature. Yet very little is known about the possible role of this mechanism in fever, a condition fundamentally different from "physiological" hyperthermia, especially when it occurs in brain-damaged patients. In our investigation we retrospectively analysed the results of direct recordings of cerebral temperature within the subdural space (Tsd) and within the brain parenchyma (Tbr-16 cases) in 63 unanaesthetized patients following neurosurgical procedures, including 23 with fever > 38 degrees C. The difference between trunk temperature, measured in the rectum (Tre) or in the oesophagus (Tes), and the intracranial temperature, were calculated in all subjects. A statistically significant reduction of these differences, in step with increasing fever, would be compatible with demonstrating a process of selective brain cooling. The offsets Tre-Tsd, Tre-Tbr, and Tes-Tsd were plotted against Tre over a wide range of body temperature and near zero correlation was found. This finding suggests that brain temperature in fever was not selectively suppressed by any specific thermolytic mechanism and that dissipation of the main bulk of cerebral metabolic heat both in normothermia and in fever depends on heat uptake by arterial blood. The results suggest that the brain in fever can be seriously jeopardized by heat stress and no specific cooling mechanism exists, to reduce it below body temperature in feverish neurosurgical patients. Tbr and/or Tsd remained the highest body temperature in 14 out of the 23 patients during fever.

Aged↗
PubMed2004

Clinical implication of prolonged fever in children with cat scratch disease.

Cat scratch disease, caused by Bartonella henselae, typically presents with a localized lymphadenopathy with a brief period of fever and general symptoms. However, there are atypical cases with a wide spectrum of clinical manifestations including prolonged fever (> or =37.5 degrees C, for more than 7 days), or with systemic complication, or without lymphadenopathy. We analyzed relationships among those manifestations in children with cat scratch disease. A total of 127 patients were serologically diagnosed as having Bartonella infection between 1997 and 2003. Relationships among clinical manifestations were analyzed by use of multiple regression and multiple logistic regression analyses. Of the 127 seropositive cases, 75 (59.1%) had typical cat scratch disease and 52 (40.9%) had an atypical one. As atypical manifestations, 46 (36.2%) had prolonged fever, 23 (18.1%) had no lymphadenopathy, and 21 (16.5%) had complications: hepatic/splenic abscesses or low-echoic lesions, hepatic granuloma, and central nervous system involvements. Prolonged fever was observed in 20 (87%) of the 23 cases without lymphadenopathy and 16 (76.2%) of the 21 cases with complications. By multiple regression analysis, the duration of fever was significantly associated with both the absence of lymphadenopathy and the presence of complications. The child suffering from cat scratch disease without lymphadenopathy or with complication tends to have prolonged fever. Conversely, when a child has a prolonged fever of unknown origin, possibility of cat scratch disease should be considered, and a search for underlying systemic complications is recommended for prompt diagnosis and appropriate treatment.

Adolescent↗
PubMed1981

Fever in renal transplant recipients: causes, prognostic significance and changing patterns at the University of Minnesota Hospital.

During a three year period in which 433 renal transplants were performed, 194 episodes of fever were documented in allograft recipients hospitalized at the University of Minnesota. Viral infections were responsible for over half of the febrile episodes, and 98 (51 percent) of the fevers were associated with cytomegalovirus (CMV), either occurring alone or in conjunction with allograft rejection or another systemic infection. Bacterial infections, fungal infections and rejection were other important causes of fever, accounting for 14 percent, 5 percent and 13 percent of the febrile episodes, respectively. Most fevers occurred in the first four months after transplantation; although about two thirds of these fevers were due to CMV, only 17 percent of fevers that occurred more than one year after the renal transplant were due to CMV. Bacterial and fungal infections and malignancy were important causes of these fevers. Of the febrile illnesses associated with transplant nephrectomy or death, a majority occurred in patients with CMV disease. Secondary bacterial and/or fungal infections were observed in a large majority of patients with lethal CMV disease. During the third year of this study there was a significant decrease in the proportion of febrile episodes due to CMV.

Adolescent↗
PubMed1982

Molecular basis of fever in humans.

This review presents several areas of research on the pathogenesis of fever in humans and updates new information concerning the role of fever in host defense mechanisms. Fever is mediated by a polypeptide of phagocytic cell origin called leukocytic pyrogen. Several agents and disease processes are associated with the synthesis and release of leukocytic pyrogen. Although the original studies on leukocytic pyrogen suggested that the neutrophil was the primary source, recent experiments indicate the mononuclear phagocyte to be the major producer of leukocytic pyrogen. The mechanism by which human monocytes are stimulated to produce leukocytic pyrogen is discussed, including the effects of corticosteroids, estrogens and antipyretics on the synthesis of leukocytic pyrogen in vitro. The ability of leukocytic pyrogen to alter the hypothalamic thermoregulatory center by increasing arachidonic acid metabolite levels is the most likely mechanism by which leukocytic pyrogen initiates fever. Antipyretics prevent the synthesis of certain cyclooxygenase metabolites, which accounts for their ability to reduce fever. Studies on the chemical and physical properties of human leukocytic pyrogen are reviewed and form the basis for current experiments on the similarities between leukocytic pyrogen and lymphocyte activating factor. These studies suggest that leukocytic pyrogen, in addition to producing fever, also stimulates non-hypothalamic cells involved in aspects of the acute-phase response. In this regard, leukocytic pyrogen may be an important mechanism for host defenses. Hyperthermia may also be beneficial to the host but is distinct from fever; the role of leukocytic pyrogen as well as hyperthermia as a defense mechanism is discussed.

Adjuvants, Immunologic↗
PubMed1992

Epidemiologic features and clinical presentation of acute Q fever in hospitalized patients: 323 French cases.

PURPOSE: To contribute to the knowledge of epidemiologic and clinical features of patients hospitalized with Q fever in France. METHODS: We conducted a retrospective analysis of 22,496 sera submitted between 1982 and 1990 to the French National Reference Center for Rickettsial Diseases (NRC). The diagnosis of acute Q fever was based on an IgG titer greater than or equal to 1:200 and an IgM titer greater than or equal to 1:25 against phase II Coxiella burnetii antigen on an indirect immunofluorescence test (IFA). Fifteen cases prior to 1985 were diagnosed on the basis of a complement fixation titer greater than or equal to 1:8. A serosurvey of blood donors from Marseille was also conducted in 1988 on 924 sera, using IFA with a cutoff titer of 1:25. RESULTS: The serosurvey conducted in 1988 showed a seroprevalence of 4.03%, without age or sex prediction. The incidence rate of acute Q fever detection at the NRC was 0.58 per 100,000 inhabitants over the 9-year period. Three hundred twenty-three clinical cases were diagnosed, rising from 1 in 1982 to 107 in 1990. In patients hospitalized for acute Q fever, there was a significantly higher sex ratio of males to females (2.3), which, coupled with the age distribution, indicated that elder males, who are overrepresented due to our recruitment bias, are more susceptible to C. burnetii infections. The mean age of the patients was 45.5 years, while the risk was increased in the 30 to 39 age group as well as in the 60 to 69 age group. Usual epidemiologic risk factors were found in 20.1% of the cases. Hepatitis (61.9%) was a more common clinical presentation in our patients with Q fever than pneumonia (45.8%). This might reflect differences in strains of C. burnetii or the biology of the host. However, French farmers and stock breeders commonly drink unpasteurized raw milk from their cattle, which might indicate a relationship between hepatitis and infection via the digestive tract. CONCLUSION: Our results indicate that many cases of acute Q fever are undiagnosed. A greater awareness of the disease and more extensive serologic testing of patients with symptoms compatible with Q fever may improve the situation.

Acute Disease↗
PubMed1993

Interleukin-6 and tumor necrosis factor in cerebrospinal fluid: changes during pyrogen fever.

Several peptides (cytokines), viz., interleukin-1 (IL-1), interferon-alpha (IFN-alpha), interleukin-6 (IL-6), tumor necrosis factor (TNF), are formed in response to conditions causing tissue inflammation or damage and are implicated in reactive changes of the host, including fever, while IL-1 has been considered an important mediator of fever, the other cytokines, specifically IL-6 and TNF, have recently acquired prominence. The present study extends earlier research on IL-1 and addresses the question of the role of IL-6 and TNF in the genesis of fever. Experiments were conducted in the conscious cat, and IL-6 and TNF were assayed concomitantly in cerebrospinal fluid (CSF) from the third ventricle using specific bioassays. In the absence of fever, IL-6 was usually below the threshold of the assay (4-32 pg/ml), while TNF appeared measurable (424 +/- 57 pg/ml) in most experiments. A single intravenous injection of endotoxin (bolus) or continuous infusion of IL-1 at doses eliciting a sustained fever increased CSF levels of IL-6, but had no effect on concentrations of TNF. Intracerebroventricular injection of a pyrogenic dose of endotoxin led to an elevation of TNF and IL-6 and, in either case, the effect was manifest during the latent period before the fever. In addition, by the same route, IL-1 caused a rise in IL-6. We conclude that brain is intrinsically capable of producing both IL-6 and TNF depending on the site of challenge. However, since IL-6 CSF levels are elevated regardless of the site of pyrogen injection, IL-6 lends itself better to a role in the pathogenesis of fever.

Animals↗