Dengue and dengue haemorrhagic fever: implications of host genetics

Little is known of the role of human leucocyte antigen (HLA) alleles or non-HLA alleles in determining resistance, susceptibility or the severity of acute viral infections. Dengue fever (DF) and dengue haemorrhagic fever (DHF) are suitable models for immunogenetic studies, yet only superficial efforts have been made to study dengue disease to date. DF and DHF can be caused by both primary and secondary infection by any of the four serotypes of the dengue virus. Differences in host susceptibility to infectious disease and disease severity cannot be attributed solely to the virus virulence. Variations in immune response, often associated with polymorphism in the human genome, can now be detected. Data on the influence of human genes in DF and DHF are discussed here in relation to (1) associations between HLA polymorphism and dengue disease susceptibility or resistance, (2) protective alleles influencing progression to severe disease, (3) alleles restricting CD4(+) and CD8(+) T lymphocytes, and (4) non-HLA genetic factors that may contribute to DHF evolution. Recent discoveries regarding genetic associations in other viral infections may provide clues to understanding the development of end-stage complications in dengue disease. The scanty positive data presented here indicate a need for detailed genetic studies in different ethnic groups in different countries during the acute phase of DF and DHF on a larger number of patients.     

Filovirus haemorrhagic fevers: Ebola fever

Epidemiological issues, clinical course and laboratory diagnostics of Ebola haemorrhagic fever are reviewed. The structural features of virions and genetic variants of the virus are described along with ecology of Ebola virus. The data on Ebola fever global morbidity are also presented.     

Crimean-Congo haemorrhagic fever in southern Russia

At the end of the 20th--the beginning of the 21st century activation of a natural focus of Crimean-Congo haemorrhagic fever (CCHF) in southern Russia was noted. As a consequence, in 2002 outbreaks and sporadic cases of this disease were registered on the territory of 6 out of 13 administrative units of the Southern Federal District. To minimize the epidemiological consequences of the aggravating epidemiological situation considerable efforts and means were required from health care organs and institutions of the state sanitary and epidemiological service, including essential financial expenditures. The results of natural foci of CCHF survey, obtained by 2002, as well as main trends of prophylactic and antiepidemic interventions are presented. Scientific research and practical observations made it possible to work out a number of methodological regulations concerning the diagnostics, treatment and prophylaxis of CCHF.     

Bromocriptine treatment in tall adolescents: two years of clinical experience

34 adolescents referred for excessive height prediction (HP) (11 boys with HP greater than 196 cm, 23 girls with HP greater than 180 cm) were treated for 9-15 months with bromocriptine (5-7.5 mg/day). Minor and transient side effects were observed in 20% of the subjects at the beginning of the treatment. Treatment had to be stopped in 1 boy complaining of asthenia and headache. Puberty developed normally, 19 girls experienced menarche during treatment and 1 continued regular menses. Bromocriptine treatment induced: (1) a significant decrease (p less than 0.001) in growth velocity from (mean +/- SEM) 8.6 +/- 0.4 to 5.3 +/- 1.5 cm/year in boys and from 7.1 +/- 0.2 to 4.6 +/- 0.6 cm/year in girls; (2) a twofold mean increase in skeletal maturation rate. Adult HP was reduced significantly from 202 +/- 1.4 to 195.4 +/- 1.2 cm in boys, and from 184 +/- 0.7 to 179.8 +/- 0.7 in girls. These results confirm our previous report suggesting that bromocriptine is a valuable alternative to sex steroid treatment in order to limit the final height in excessively tall adolescents.     

Spermine oxidase: ten years after

Spermine oxidase (SMO) was discovered much more recently than other enzymes involved in polyamine metabolism; this review summarizes 10?years of researches on this enzyme. Spermine oxidase (SMO) is a FAD-dependent enzyme that specifically oxidizes spermine (Spm) and plays a dominant role in the highly regulated mammalian polyamines catabolism. SMO participates in drug response, apoptosis, response to stressful stimuli and etiology of several pathological conditions, including cancer. SMO is a highly inducible enzyme, its deregulation can alter polyamine homeostasis, and dysregulation of polyamine catabolism is often associated with several disease states. The oxidative products of SMO activity are spermidine, and the reactive oxygen species H₂O₂ and the aldehyde 3-aminopropanal each with the potential to produce cellular damages and pathologies. The SMO substrate Spm is a tetramine that plays mandatory roles in several cell functions, such as DNA synthesis, cellular proliferation, modulation of ion channels function, cellular signaling, nitric oxide synthesis and inhibition of immune responses. The goal of this review is to cover the main biochemical, cellular and physiological processes in which SMO is involved.     

Changing pattern of antibiotic susceptibility in intensive care units: ten years experience of a university hospital

The study was performed to assess microorganisms and antibiotic susceptibility patterns during ten years in intensive care units of a University Hospital. Infection Control Committee has active, prospective surveillance in ICUs for thirteen years. Ten years data of ICUs was evaluated retrospectively from surveillance forms. Microorganisms and their antibiotic resistance were recorded according to the years. During ten years, gram negative microorganisms were the most frequent isolated microorganisms from clinical specimens. Acinetobacter baumannii (21.8%), Pseudomonas aerigunosa (16%), Escherichia coli (10.4%) and Klebsiella pneumoniae (8%) were the most common gram negative microorganisms. However, Staphylococcus aureus was the most prevalent gram positive microorganism, the incidence decreased from 18.6% to 4.8% during ten years. Also antibiotic susceptibility of microorganisms changed during ten years. Carbapenem resistance increased from 44% to 92% in A. baumannii and ciprofloxacin resistance increased in E. coli from 28% to 60% and in K. pneumoniae from 21% to 55% during ten years. However, methicilin resistance decreased in S. aureus from 96% to 54%. In conclusion, antibiotic resistance is growing problem in ICUs. Rationale antibiotic policies and infection control measures will prevent the development of resistance.     

Cytotoxic factor-autoantibodies: possible role in the pathogenesis of dengue haemorrhagic fever

During dengue virus infection a unique cytokine, cytotoxic factor (hCF), is produced that is pathogenesis-related and plays a key role in the development of dengue haemorrhagic fever (DHF). However, what regulates the adverse effects of hCF is not known. We have previously shown that anti-hCF antibodies raised in mice, neutralise the pathogenic effects of hCF. In this study we have investigated the presence and levels of hCF-autoantibodies in sera of patients with various severity of dengue illness (n=136) and normal healthy controls (n=50). The highest levels of hCF-autoantibodies (mean+/-S.D.=36+/-20 U ml(-1)) were seen in patients with mild illness, the dengue fever (DF), and 48 out of 50 (96%) of the sera were positive. On the other hand the hCF-autoantibody levels declined sharply with the development of DHF and the levels were lowest in patients with DHF grade IV (mean+/-S.D.=5+/-2 U ml(-1); P=<0.001 as compared to DF). Only one of the 13 DHF grade IV patients had an antibody level above the 'cut-off' value (mean plus 3 S.D. of the control sera). The analysis of data with respect to different days of illness further showed that the highest levels of hCF-autoantibodies were present in DF patients at >9 days of illness. Moreover, the DF patients at all time points, i.e. 1-4, 5-8 and >9 days of illness had significantly higher levels of hCF-autoantibodies (P<0.001) than patients with DHF grade I, II, III and IV. In addition DHF grade I and grade II patients had significantly more positive specimens than DHF grade III and grade IV patients at all time points. These results suggest that elevated levels of hCF-autoantibodies protect the patients against the development of severe forms of DHF and, therefore, it may be useful as a prognostic indicator.     

Dengue hemorrhagic fever epidemiology in Thailand: description and forecasting of epidemics

Despite the use of a variety of control strategies, dengue hemorrhagic fever (DHF) control is a major and permanent challenge for public health services in Thailand and in Southeast Asia. In order to improve the efficiency of DHF control in Thailand, these activities have to concentrate on areas and populations at higher risk, which implies early identification of higher incidence periods. A retrospective study of spatial and temporal variations of DHF incidence in all 73 provinces of Thailand (1983-1995) allowed discrimination between seasonal (endemic) transmission dependent on climatic variations and vector density and non-seasonal (epidemic) transmission, mainly due to the occurrence of a new virus serotype in a population with low immunity. To identify epidemic months, which appear significantly clustered, a significant deviation from the monthly average incidence was defined. The occurrence of two consecutive epidemic months in a given area has a high probability (P = 0.66) of being followed by a cluster of 2-18 epidemic months (average: 7.7 months). This observation is proposed as a warning of epidemic outbreak enabling an early launch of control activities. As an example, when this method is retrospectively applied to the studied period, 11,388 province months (73 provinces x 156 months), 579 epidemic outbreaks (5.1% of the total) are identified. Control activities can thus be improved through early management and prevention of the 308,636 supplementary cases occurring during epidemics (37.0% of the total recorded).     

Interferons in multiple sclerosis: ten years' experience

Interferons (IFNs) were considered for the treatment of patients with multiple sclerosis (MS) after the demonstration, based on small studies, of the efficacy of type IFN beta in decreasing the frequency of exacerbations in relapsing-remitting multiple sclerosis when administered intrathecally, subcutaneously, or intramuscularly. Three preparations of IFN beta are now approved in Europe and North America: chronologically IFN beta-1b (Berlex/Schering), IFN beta-1a given intramuscularly (Biogen), and IFN beta-1a given subcutaneously (Ares Serono). These treatments have now been in use for more than 10 years, and are supposed to decrease relapse rates. However a lot of questions remain unanswered: it is difficult to compare the various preparations; there remain controversies about the effects of different routes of administration and of different dosage preparations; the role of neutralizing antibodies remains partially understood; and the long term effect on disability has not yet been demonstrated.     

Meiosis in plants: ten years of gene discovery

Plants have always been at the forefront of genetic and cytogenetic studies, but it was only following the explosion of genomic tools linked to the development of Arabidopsis thaliana as a model, that the first genes involved in plant meiosis were cloned in the late 1990s. Since then, in less than 10 years, close to fifty plant meiotic genes have been functionally characterized, mainly in Arabidopsis but also in rice and maize. In this review, we give an overview of this decade of discovery, with emphasis on the strategies that have been used for meiotic gene identification. We also highlight particularly interesting breakthroughs that these mutant and gene screens made possible.     

Protocols for simulating the thermal component of fever: preclinical and clinical experience

An increase in body temperature in association with inflammation or infection has been evolutionarily conserved in all cold and warm-blooded vertebrates and even in several invertebrates thus far examined. This change in temperature is strongly correlated with survival from infection in many animal models. Although the means by which body temperature is increased and maintained differs between cold- versus warm-blooded species, there are strong similarities in terms of the magnitude of temperature change and its duration. Despite these intriguing observations and significant biological sequelae, temperature manipulation is rarely considered in the context of most experimental immunological investigations. We have hypothesized that the thermal microenvironment plays a critical role in regulating events in the immune response and that an increase in ambient temperature can serve as a natural trigger or "danger signal" to the immune system. To examine the direct effects of fever-like temperatures on immunological parameters, we have designed and characterized protocols for performing whole body heating of mice and humans in vivo, and heating of cultured cells in vitro. Our studies have now progressed to the development of therapeutic uses of fever-range hyperthermia in combination with other therapies. This chapter describes the experimental procedures that have been developed for these studies and summarizes several of the immunologically relevant effects that we have noticed following mild heat treatments in vivo and in vitro.     

Cerebral malaria in children in South Sudan: 8 years experience in 261 cases

Two hundred-sixty-one (261) cases of cerebral malaria within last 8 years from 3 tropical clinics in South Sudan were analyzed. Coma was present at 79.8% and convulsions at 25.6%. However 90.5% of children were cured. Commonest antimalarial drugs used were intravenous quinine, clindamycin, artesunate and artemeter.