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Location of the gene causing hyperimmunoglobulinemia D and periodic fever syndrome differs from that for familial Mediterranean fever. International Hyper-IgD Study Group.

The hyperimmunoglobulinemia D and periodic fever (hyper-IgD) syndrome is typified by recurrent febrile attacks with abdominal distress, joint involvement (arthralgias/arthritis), headache, skin lesions, and an elevated serum IgD level (> 100 U/ml). This familial disorder has been diagnosed in 56 subjects worldwide. As the hyper-IgD syndrome resembles familial Mediterranean fever, one could speculate that both result from mutations in the same gene. The gene causing familial Mediterranean fever (MEF) has been located on chromosome 16p. We have studied 10 families with 19 affected and 28 non-affected subjects. The clinical findings and IgD determinations from these families are compatible with autosomal recessive inheritance. Using highly polymorphic markers surrounding the MEF gene, only negative Lod scores were obtained, whereas haplotype analysis excluded this locus as the cause of the hyper-IgD syndrome. In addition, no indication for linkage was obtained with markers from other candidate gene regions on chromosomes 17q and 14q.

Chromosome Mapping↗

Isolation and characterization of wild type yellow fever virus in cases temporally associated with 17DD vaccination during an outbreak of yellow fever in Brazil.

A mass vaccination was carried out in the state of Minas Gerais, Southeast region of Brazil, to control an outbreak of sylvatic yellow fever in 2001. During the outbreak the surveillance system identified two fatal cases temporally associated with YF vaccination. Virus recovered from blood and postmortem samples of both cases was identified as yellow fever virus. Partial nucleotide sequence of parts of prM/E and the non-structural (NS) 5 genes and 3' non-coding region (3' NCR) was employed to characterize the origin of yellow fever virus (YFV) involved in both cases. Wild-type YFV was identified as the etiologic agent responsible for the disease.

Adult↗

Serosurvey of wild rodents for Rickettsioses (spotted fever, murine typhus and Q fever) in Java Island, Indonesia.

The prevalence of antibodies against spotted fever group rickettsia (SFGR), murine typhus and Q fever were investigated in wild rats captured in Indonesia. Sera of 327 rats were collected from Jakarta and Boyolali on Java Island. The prevalences of antibodies against SFGR and murine typhus were 128 (39.1%) and 48 (14.7%), respectively. Antibodies against Q fever were not detected in these serum samples. Antibodies against SFGR were found in all species of rats (20.8-51.9%). The antibody positive rate against murine typhus in Rattus norvegicus (38.0%) was significantly higher than that in other rat species (0-4.8%, p<0.01). The antibody positive rates against SFGR and murine typhus in rats captured in Jakarta were significantly higher than those in rats captured in Boyolali (p<0.01). In this survey, all species of rats had antibodies against SFGR, indicating that the 4 species of tested rats (R. norvegicus, R. rattus, R. exulans, R. tiomanicus) were infected with SFGR and that SFGR may infest the whole of Java Island. Most of the rats that were antibody-positive against murine typhus were captured in Jakarta. Therefore, R. norvegicus and R. rattus are likely to be important hosts of murine typhus in Jakarta. The antibody-positive rates against SFGR and murine typhus in rats captured in the dry season were significantly higher than those in rats captured in the rainy season. This may coincide with the active periods of ticks and fleas in Indonesia.

Animals↗

[Fever of unknown origin and colchicine-sensitive amyloidosis: familial Mediterranean fever?].

A 39-year-old man who had for 20 years suffered from recurrent fever, abdominal pain and joint pains was diagnosed to have generalized amyloidosis type AA. Suspected of having familial mediterranean fever (FMF) he was treated with colchicine, 2 mg daily. Within four years the fever bouts became milder and the amyloidosis no longer progressed. Since the patient was a foundling it was impossible to prove FMF, despite the typical signs and the successful treatment.

Adult↗

The Duke criteria for diagnosing infective endocarditis are specific: analysis of 100 patients with acute fever or fever of unknown origin.

The recently proposed Duke criteria were confirmed to be more sensitive than the former Beth Israel criteria for the diagnosis of infective endocarditis (IE). To assess the specificity of the Duke criteria, we reviewed the records of 100 patients admitted to two internal medicine wards because of acute fever or fever of unknown origin (FUO). IE was considered a possible diagnosis for all patients who had had at least two blood cultures performed and one transthoracic echocardiogram obtained. The diagnosis of IE was rejected in all cases in accordance with the Duke criteria (i.e., a firm alternate diagnosis [n = 23], resolution of symptoms with no antibiotics [n = 39], or both reasons [n = 38]). To calculate the specificity of the Duke criteria, all 100 cases were then reclassified according to these criteria as if the diagnosis of IE had not been rejected. Only one patient, who probably did not have IE, was reclassified as having clinically definite IE. The specificity of the Duke criteria could therefore be calculated to 0.99 (95% confidence interval, 0.97-1). Although the design of the study may have resulted in a slight overestimation of the specificity rate, we conclude that the Duke criteria are highly specific for ruling out IE in patients with acute fever or FUO who are at low risk for IE.

Adult↗

[Typhoid fever with intestinal hemorrhage, drug-induced fever, DIC, ARDS and psychiatric disorder (a case report)].

A 40-year-old poor nutritional Japanese male was admitted to our hospital on June 5, 1989, with a 31-day history of fever. He had been working as a crew member of a ship in South East Asia. Salmonella typhi was isolated from his blood culture. In the course of the disease, intestinal hemorrhage, drug-induced fever and liver dysfunction, DIC, ARDS, and psychiatric disorder were identified. Intestinal hemorrhage occurred after the coagulation test became normal, so it was thought that the intestinal hemorrhage did not correlate with DIC. The patient was treated with CP, ABPC and supportive therapy. He became well, and ARDS and psychiatric disorder were disappeared. He was discharged on the 118th day of illness. Drug-induced fever was thought as one of the allergic reaction and the causative drug was not identified by LST. It was suspected that psychiatric disorder correlated with poor nutrition. Supportive therapy such as mandatory bed rest, intravenous hyperalimentation and low-volume blood transfusions, as well as an antimicrobial treatment were important for the inhibition of shock and/or intestinal perforation.

Adult↗

[Serologic survey for yellow fever and other arboviruses among inhabitants of Rio Branco, Brazil, before and three months after receiving the yellow fever 17D vaccine].

During a yellow fever vaccination campaign among residents of Rio Branco (Acre State), the frequency of HI antibodies to the most prevalent arboviruses in the Amazon region and to yellow fever virus was determined before and three months after immunization with YF 17D vaccine. From 390 inhabitants included in the first phase of serologic survey (August 1999), only 190 provided a second serum sample, after the use of 17D vaccine (January 2000). Among first phase samples, the frequency of HI antibodies was: 17D (27.2%); Ilheus (5.9%); Mayaro (5.4%); Caraparu (4.9%); Dengue-2 (4.1%); Oropouche (2.3%); and Dengue-1 (0.3%). In the second study phase, the serologic conversion to YF reached 89.7% among previously negative persons. Serologic conversions were also observed to Ilheus (6.2%); Dengue-3 (3.2%); Mayaro (1.1%); and Oropouche (1.1%) viruses. In conclusion, considering the high YF antibody rate after vaccination, the risk of urban yellow fever seems insignificant, although the lower prevalence of HI antibodies to dengue viruses, is of concern and inhabitants are under high risk of dengue outbreaks, especially to DEN-3 recently introduced in Brazil, as was observed in 2000 and 2001 with DEN-1 and DEN-2.

Antibodies, Viral↗

Combined vaccination against yellow fever and typhoid fever: a comparative trial.

In order to evaluate a combination of yellow fever and typhoid fever vaccine, we conducted a controlled trial comparing reactogenicity and immunogenicity of Vi polysaccharide (ViPS) vaccine and yellow fever 17D (YF) vaccine after single, simultaneous and combined administration. The combined YF/ViPS vaccine was prepared by using the liquid ViPS vaccine as a diluent for the YF vaccine. The stability of such a reconstitution had been assessed in vitro. Safety was evaluated using a self-surveillance form and by repeated clinical visits. Immunogenicity was evaluated by a plaque reduction test for YF and by radioimmunoassay for ViPS. Tolerability was satisfactory in all groups. There was no increase in local or general reactions in groups receiving both vaccines, whether given simultaneously or combined. The serological response to ViPS was similar after single and simultaneous or combined administration. Interestingly, the immune response to YF was significantly enhanced in groups receiving the vaccines simultaneously or combined, suggesting a potential adjuvant effect of ViPS.

Adult↗

Fever induced by platelet-derived growth factor, in contrast to fever induced by lipopolysaccharide, depends only on nitric oxide, but not on carbon monoxide pathway.

Platelet-derived growth factor (PDGF) is a multifunctional protein which is known to induce a febrile response when injected intracerebroventricularly. The gaseous neurotransmitters, nitric oxide (NO) and carbon monoxide (CO), are both known to exert thermoregulatory effects and to participate in lipopolysaccharide-induced fever. In this study, we investigated the role of NO and CO in the febrile response to PDGF-BB in rats. Intracerebroventricular (i.c.v.) injection of PDGF-BB produced a dose-dependent increase in body temperature. This increase in body temperature induced by PDGF-BB was exacerbated by N(G)-nitro-L-arginine methyl ester (L-NAME-a nonselective NO synthase inhibitor) and S-methyl-L-thiocitrulline treatment [SMTC-a neuronal NOS (nNOS) selective inhibitor], but not by aminoguanidine treatment [an inducible NOS (iNOS) selective inhibitor]. Zinc deuteroporphyrin 2,4-bis glycol treatment (ZnDPBG-a nonselective heme oxygenase (HO) blocker) did not affect PDGF-BB fever. Our data indicate that the NO but not the CO pathway participates in PDGF-BB fever. Furthermore, our data show that nNOS is the NOS isoform responsible for NO synthesis in this response.

Animals↗

Clinical predictors of malaria in Gambian children with fever or a history of fever.

Diagnosis of malaria in children is difficult without laboratory support because the symptoms and signs of malaria overlap with those of other febrile illnesses such as pneumonia. Nevertheless, in many parts of Africa diagnosis of malaria must be made without laboratory investigation. Therefore, a scoring system has been developed to assist peripheral health care workers in making this diagnosis. Four hundred and seven Gambian children aged 6 months to 9 years who presented to a rural clinic with fever or a recent history of fever were investigated. A diagnosis of malaria was made in 159 children who had a fever of 38 degrees C or more and malaria parasitaemia of 5000 parasites/microL or more. Symptoms and signs in children with malaria were compared with those in children with other febrile illnesses to identify features which predicted malaria. Symptoms and signs were incorporated into various logistic regression models to test which were best independent predictors of malaria and these regression models were used to construct simple scoring systems which predicted malaria. A nine terms model predicted clinical malaria with a sensitivity of 89% and a specificity of 61%, values comparable to those obtained by an experienced paediatrician without laboratory support. The ability of peripheral health care workers to diagnose malaria using this approach is now being investigated in a prospective study.

Antimalarials↗

Studies on the pathogenesis of fever. V. The relation of circulating endogenous pyrogen to the fever of acute bacterial infections.

An endogenous pyrogen, which is indistinguishable from leucocytic pyrogen, has been demonstrated in the blood streams of rabbits with fevers caused by experimental pneumococcal and streptococcal infections. Like the endogenous pyrogen previously detected in the serum of animals with fever produced by the intravenous injection of typhoid vaccine, the newly discovered circulating factor acts directly upon the thermoregulatory centers of the brain. Its origin from polymorphonuclear leucocytes at the site of infection appears to have been established. The possible relationship of this circulating endogenous pyrogen to the pathogenesis of other forms of fever is discussed.

Animals↗

Studies on the pathogenesis of fever. VIII. Further observations on the role of endogenous pyrogen in endotoxin fever.

Rabbits made granulocytopenic with nitrogen mustard have been shown to generate serum endogenous pyrogen when given a fever-producing dose of bacterial endotoxin. This finding is in accord with the hypothesis that endogenous pyrogen plays a central role in the pathogenesis of endotoxin fever. The fact that leucopenic animals produce less serum-endogenous pyrogen than normal animals given the same dose of endotoxin has also been confirmed and suggests that polymorphonuclear leucocytes constitute a major source of the endogenous pyrogen which is demonstrable in the circulation during endotoxin fever.

Animals↗

Cellular immunity in Q fever: specific lymphocyte unresponsiveness in Q fever endocarditis.

Human infection with the rickettsia Coxiella burnetii presents as acute influenza-like primary Q fever, subacute granulomatous hepatitis, or chronic endocarditis with hepatitis. To investigate whether persistent infection is associated with a possible immunologic defect, we tested lymphocyte proliferation specific for Coxiella in vitro in peripheral blood mononuclear cells from patients and controls. All four patients with endocarditis had profound lymphocyte unresponsiveness to Coxiella antigens with normal proliferation to control antigens. Hepatitis and primary Q fever were associated with vigorous responses in vitro to Coxiella antigens. Suppression of lymphocyte unresponsiveness was in part mediated by an antigen-nonspecific, glass-adherent cell. We hypothesize that specific T cell unresponsiveness is an important factor in persistent infection with C. burnetii and offer in vitro lymphocyte stimulation as a more specific diagnostic test to distinguish cases of endocarditis among those with chronic hepatitis due to Q fever.

Adult↗

Antibody responses in acute and chronic Q fever and in subjects vaccinated against Q fever.

An analysis is made of the antibody response to Coxiella burnettii Phase-1 and Phase-2 antigens, as measured by immunofluorescence in the IgM, IgG or IgA immunoglobulin classes, or by complement-fixation, in patients with acute and chronic Q fever and in vaccinated or skin-tested subjects. In acute (primary) Q fever, IgM specific antibodies to Phase-1 antigen are present in early convalescence together with IgM, IgG, IgA and CF antibodies to Phase-2 antigen. IgM specific antibody may persist for at least 678 days after onset of the acute illness. Patients with chronic Q fever have no IgM specific antibody to Phase-1 or -2 antigens, or only at very low levels; high levels of specific antibody in the IgG and IgA classes, together with CF antibody to both antigenic phases, appear to be characteristic. The serological response in initially seronegative, vaccinated subjects is mainly to Phase-1 antigen in the IgM fraction, and to a lesser degree to Phase-2 antigen by CF and in IgM and IgG classes. Subjects who were equivocally seropositive before vaccination showed IgA and IgG specific antibody responses to Phase-1 antigen and CF and IgG class responses to Phase-2 antigen. Similar antibody profiles were observed in patients who seroconverted after a positive skin-test. Data are also presented on the suitability of C. burnettii antigens for use in immunofluorescence and on the binding of IgM specific antibody by Phase-1 antigen but its failure to fix complement.

Acute Disease↗

Antibody to a 145-kilodalton outer membrane protein has bactericidal activity and protective activity against experimental bacteremia caused by a Brazilian purpuric fever isolate of Haemophilus influenzae biogroup aegyptius. The Brazilian Purpuric Fever Study Group.

The immunologic basis for protection against Brazilian purpuric fever, a septicemic infection associated with Haemophilus influenzae biogroup aegyptius bacteremia, is unknown. Passive immunization of infant rats with antiserum to whole bacterial cells of the homologous strain protects them from experimental bacteremia following bacterial challenge. In immunoblotting, antibody to a 145-kDa protein (P145) was present in protective antisera but not in nonprotective antisera. As judged by analysis of the antibodies eluted from whole bacterial cells and the agglutination of bacteria by antisera to P145, this protein is surface exposed. We prepared monospecific rat antisera to this protein by three methods: (i) immunization with whole bacterial cells and absorption with a Brazilian purpuric fever strain not expressing P145, (ii) immunization with gel-purified P145, and (iii) immunization with a P145-expressing transformant of a laboratory H. influenzae strain expressing this protein and absorption of the antiserum with the laboratory H. influenzae strain. These antisera had low antilipooligosaccharide antibody titers, were reactive only with P145, and had bactericidal activity in vitro. Following passive immunization, these antisera partially protected infant rats from bacteremia resulting from intraperitoneal challenge with bacteria. As assessed by immunoblotting, pooled adult human sera contained antibodies reactive with P145. Antibody to P145 may contribute to protection against Brazilian purpuric fever.

Animals↗

"Periodic fever" without fever: two cases of non-febrile TRAPS with mutations in the TNFRSF1A gene presenting with episodes of inflammation or monosymptomatic amyloidosis.

BACKGROUND: Tumour necrosis factor (TNF) receptor associated periodic syndrome (TRAPS) is caused by dominant mutations in the TNFRSF1A gene. In typical cases TRAPS begins early in childhood and is characterised by high and remittent fever over a period of 1-4 weeks or longer, accompanied by systemic and local inflammation. CASE REPORTS: Patient 1 presented with recurrent episodes of weakness, migrating myalgias, arthralgias, exanthema, and chest pain lasting for 1-4 weeks, but without any fever over an initial period of 4 years at least. Diagnosis of TRAPS was confirmed by the heterozygous mutation Y20H in TNFRSF1A. Patient 2, a 23 year old woman never had any symptoms indicative of TRAPS. Genetic evaluation of all members of her family with a TRAPS index patient disclosed the T50M mutation in TNFRSF1A. A medical check up showed proteinuria, and renal biopsy disclosed AA amyloidosis. CONCLUSIONS: TRAPS associated mutations can induce considerable inflammation that is not necessarily accompanied by fever. Even monosymptomatic severe amyloidosis can occur in these patients. Genetic counselling and appropriate management to prevent or mitigate amyloidosis may be necessary.

Adult↗

Rat bite fever without fever.

Rat bite fever is a rarely reported acute febrile bacterial illness caused by Streptobacillus moniliformis or Spirillum minus following a rat bite. It is classically characterised by abrupt onset of fever with rigors, myalgias, headache, and the appearance of a generalised maculopapular petechial skin rash. Polyarthritis complicates the course of the disease in up to 50% of infected patients, and numerous hurdles can make the diagnosis particularly difficult in the absence of fever or rash, as in the present case. A high degree of awareness is necessary to make the correct diagnosis in such cases. Diagnosis has important prognostic implications as the disease is potentially lethal, but easily treatable.

Aged↗

Methodology of fever research: why are polyphasic fevers often thought to be biphasic?

This study explains why the recently described triphasic lipopolysaccharide (LPS) fevers have been repeatedly mistaken for biphasic fevers. Experiments were performed in loosely restrained male Wistar rats with a catheter implanted into the right jugular vein. Each animal was injected with Escherichia coli LPS, and its colonic (Tc) and tail skin temperatures were monitored. The results are presented as time graphs and phase-plane plots; in the latter case the rate of change of Tc is plotted against Tc. At an ambient temperature (Ta) of 30.0 degrees C, the response to the 10 microg/kg dose of LPS was triphasic, as is obvious from time graphs of Tc (3 peaks), time graphs of effector activity (3 waves of tail skin vasoconstriction), and phase-plane plots (3 complete loops). When the Ta was below neutral (22.0 degrees C) or the LPS dose was higher (100 or 1,000 microg/kg), the time graph of Tc did not allow for the reliable detection of all three febrile phases, but the phase-plane plot and time graph of effector activity clearly revealed the triphasic pattern. In a separate experiment, LPS (10 microg/kg) or saline was injected via one of two different procedures: in the first group the injection was performed through the jugular catheter, from outside the experimental chamber; in the second group the same nonstressing injection was combined with opening the chamber and pricking the animal in its lower abdomen with a needle. In the first group the febrile response was obviously triphasic, and none of the phases was due to the procedure of injection per se (injection of saline did not affect Tc). In the second group the fever similarly consisted of three Tc rises, but it might have been readily mistaken for biphasic because the first rise was indistinguishable from stress hyperthermia occurring in the saline-injected (and needle-pricked) controls. We conclude that several methodological factors (dose of LPS, procedure of its injection, and Ta) have contributed, although each in a different way, to the common misbelief that there are only two febrile phases.

Activity Cycles↗