Infection

Unlike traditional biological research that focuses on a small set of components, systems biology studies the complex interactions among a large number of genes, proteins, and other elements of biological networks and systems. Host-pathogen systems biology examines the interactions between the components of two distinct organisms: a microbial or viral pathogen and its animal host. With the availability of complete genomic sequences of a variety of hosts and pathogens, together with breakthroughs in proteomics, metabolomics, and other experimental areas, the investigation of host-pathogen systems on a multitude of levels of detail has come within reach. This chapter introduces methods and approaches for the analysis of host-pathogen systems. We will particularly emphasize the role of biochemical networks for the study of complex relationships across species boundaries. Although the research area of host-pathogen systems biology spans multiple spatial and temporal scales, we will focus on the molecular and cellular aspects of pathogen-host interactions. We will cover the construction of biochemical networks, the identification of functional response sub-networks, and their comparative network analysis. These methods find application in the identification of host markers and drug targets for further drug development and therapeutic interventions. We will also provide a brief review of other modeling techniques and applications within host-pathogen systems biology, including rule-based modeling of signal transduction pathways, immune system models, and physiological top-down approaches.

A 24-h pretreatment of mice with diphtheria and tetanus toxoids and whole-cell pertussis vaccines depressed liver cytochrome P-450 and therefore prolonged hexobarbital-induced sleeping time in mice. The depression of liver drug metabolism by a cellular vaccine containing a mutated pertussis toxin was less marked than that induced by the wild-type vaccines, indicating that the mutated vaccine might have lower toxicity in this regard. The wild-type vaccines decreased microsomal P-450 levels by 50%, while the mutated whole-cell vaccine had a less marked effect (a decrease of 30%), paralleling the results obtained in sleeping time experiments. Furthermore, an acellular mutated vaccine did not affect liver drug metabolism, indicating a role of the whole bacterial cell in this side effect. All the cellular vaccines studied induced high serum interleukin-6 levels; on the other hand, the acellular mutated vaccine induced very low interleukin-6 levels, indicating that the whole bacterial cel...

This study described the clinical features, factors affecting the outcome of this disease, risk factors, and efficacy of ribavirin therapy for CCHF patients in Eastern Turkey.Between 2002 and 2004, 60 cases admitted to our hospital were included in this study. The diagnosis was confirmed through detection of IgM by ELISA and/or genomic segment of virus by RT-PCR.In multivariate analysis, farming (OR, 11.4), living in a rural area (OR, 10.05) and being bitten by tick (OR, 6.75) were determined as risk factors for CCHF. The rates of fever during hospitalization, confusion, neck stiffness, bleeding from multiple sites, and presence of petechia/ecchymosis were higher in the patients who died than in surviving ones. Additionally, the mean values of ALT, AST, LHD, CK, PTT, INR and urea were also higher, and the mean PLT count was lower in the patients who died. Mean recovery time was shorter in the cases treated with ribavirin than those of control. But, the need for blood and blood product, mean hospitalization duration, fatality rates, and hospital expenditure values were not significantly different between the group of patients treated with ribavirin and control groups.In Eastern Turkey, clinical features, factors influencing outcome of the disease, and risk factors were similar to other outbreaks of CCHF. Further studies are needed for the evaluation of ribavirin therapy in CCHF.

Diabetic foot is a common complication of diabetes world over. We conducted this study to determine common microbiological pathogens in Diabetic Foot Infections (DFI) at a tertiary care hospital and their management. In this observational study deep wound swabs of all admitted diabetic patients were taken, pathogens isolated, antibiotic used and its response depending on complete resolution of symptoms and biochemical markers were recorded. Data were analysed on SPSS-11. A total of 114 cases were recorded. Sixty-eight (59%) cases had ulcers on forefoot, 28 (25%) mid-foot and 18 (16%) hind-foot. One hundred and four pathogens were isolated from wound swabs after debridement. Commonest pathogen isolated was Staphylococcus aureus (52, 46%) followed by E. coli (11, 10%), MRSA was found in 10 (9%) cases, streptococcus in 6 (5%) and pseudomonas in 5 (4%) cases. Polymicrobial infection was also seen in a few cases. Surgical intervention included superficial debridement in 88 (77%) cases, t...

Immune suppression occurs frequently after major injury and undoubtedly contributes to infection and mortality in trauma patients. Prevention of such suppression may lead to decreased infection and improved survival in trauma patients surviving the immediate insult of injury. Suppressor-cell activation appears to play a key role in immune suppression after major injury. For several years we have studied the effects on immune functions after injury of various drugs which have been shown in the immunologic literature to have inhibitory effects on suppressor cell populations. H2-antagonists may inhibit suppressor cell activation by blocking surface H2-receptors, which are present in higher numbers on suppressor cells than on helper cells. Prostaglandin inhibitors may block the multiple immune suppressive effects of prostaglandins, particularly PGE2. Immunological studies suggest that low-dose cyclophosphamide selectively inhibits the proliferation of suppressor T cells. Our previous work suggested that such drugs preserve cell-mediated immune functions after injury. In experiments reported here, we utilized a standard hindlimb crush injury and amputation in mice, followed in 24 hrs by polymicrobial septic challenge using cecal ligation and 23-gauge needle puncture (CLP). Nontraumatized (control) mice had a 36.2% mortality after CLP; when crush injury/amputation was followed by CLP in 24 hrs the mortality rose to 63.8% (p less than 0.0035). When mice were given 24 hrs before crush/amputation: cimetidine, an H2-antagonist (10 mg/kg/day); ibuprofen, a prostaglandin blocker (5 mg/kg/day); or cyclophosphamide (2.5 mg/kg/day), and a second dose on the day of trauma, with CLP 24 hrs later, subsequent mortality was not different from the mortality in nontraumatized, control mice (p less than 0.0035).(ABSTRACT TRUNCATED AT 250 WORDS)

Infective endocarditis (IE) is a severe disease. Pathogen isolation is fundamental so as to treat effectively and reduce morbidity and mortality. Blood and valve culture and histopathology (HP) are routinely employed for this purpose. Valve HP is the gold standard for diagnosis. To determine the sensitivity and specificity of clinical criteria for IE (the modified Duke and the St Thomas' minor modifications, STH) of blood and valve culture compared to valve HP, and to evaluate antibiotic treatment duration. Prospective case series of patients, from 2006 to 2014 with surgically treated IE. Statistical analysis was done by the R software. There were 136 clinically definite episodes of IE in 133 patients. Mean age ± SD was 43 ± 15.6 years and IE was left sided in 81.6 %. HP was definite in 96 valves examined, which were used as gold standard. Sensitivity of blood culture was 61 % (CI 0.51, 0.71) and of valve culture 15 % (CI 0.07, 0.26). The modified Duke criteria were 65 % (CI 0.55, 0.75) sensitive and 33 % specific, while the STH's sensitivity was 72 % (CI 0.61, 0.80) with similar specificity. In multivariate analysis and logistic regression, the only variable with statistical significance was duration of antibiotic therapy postoperatively. Valve HP had high sensitivity and valve culture low sensitivity in the diagnosis of IE. The STH's criteria were more sensitive than the modified Duke criteria. Valve HP should guide duration of postoperative antibiotic treatment.

Five different species of Eimeria viz. E. acervulina, E. maxima, E. necatrix, E. tenella and E. brunetti were identified. The highest percentage (50%) was found with mixed infection. Specieswise infection with E. tenella was recorded in the present study. Monthwise highest prevalence ...

The prodromal stage of atherosclerotic lesions is already formed during human fetal development. The presence of infections during childhood may increase synergistically the progression of atherogenesis. After delivery, especially those children exposed to severe maternal hypercholesterolemia should be followed up for the onset and development of acute and chronic infections and be included in clinical and noninvasive examinations of vascular function.

Protothecosis has been reported in humans (gastroenteritis, bursitis, etc.) and in many other animal species. Bovine mastitis represents the main form of occurrence of protothecosis in cattle. Milk as well as dairy products, when contaminated with Prototheca spp., represent a potential means of transmission of this zoonosis. The purpose of this study was to evaluate the susceptibility of forty Prototheca zopfii strains isolated from milk from intramammary infections in dairy cows and also from bulk milk tanks of dairy farms, to the different ratios of temperature/time employed in the thermal treatment of milk: 72-75 degrees C/15 seconds, 72-75 degrees C/20 seconds and 62-65 degrees C/30 minutes. The samples were subjected to these different temperature/time ratios. The evaluation of the thermal susceptibility of the P. zopfii strains showed that 34 strains were resistant in at least one of the tests. The results point out the need to consider the importance of mastitis caused by Pro...

A total of 11 of 15 Streptococcus pneumoniae culture filtrates and all five bacterial autolysates produced by cell death in the stationary phase caused slowed ciliary beating and disruption of the surface integrity of human respiratory epithelium in organ culture. This effect was inhibited by cholesterol and was heat labile and reduced by standing at room temperature but was stable at -40 degrees C. The activity was detected at the late stationary phase of culture and was associated with the presence of hemolytic activity. Gel filtration of a concentrated culture filtrate and autolysate both yielded a single fraction of approximately 50 kilodaltons which slowed ciliary beating and were the only fractions with hemolytic activity. Rabbit antiserum to pneumolysin, a sulfhydryl-activated hemolytic cytotoxin released by S. pneumoniae during autolysis, neutralized the effect of the culture filtrate on respiratory epithelium. Both native and recombinant pneumolysin caused ciliary slowing a...

Translate the available knowledge on ageing and dehydration into main messages for clinical practice. Older people are more susceptible to dehydration than younger people. This is partly due to lack of thirst sensation and changes in the water and sodium balance that naturally occur as people age. It is also, to some degree, attributable to the fact that elderly people, both those living at home and those living in institutions, often have various impairments, disabilities and/or handicaps (comorbidity). They also tend to use numerous drugs and medication for these illnesses (polypharmacy). Multimorbidity and polypharmacy often overstress the normal age-related physiological changes in the water and sodium balance and therefore increase elderly people's risk of dehydration,especially during intercurrent infections or warm weather. Elderly people, whether they are living on their own or in an institution, and especially elderly people that can no longer take care of themselves be...

When the Norwegian corvette Nordstjernen was in the North Sea bound for Port Said to be present at the opening of the Suez Canal on 17 November 1869, an officer suffered a rupture of m. triceps brachii when he was drawn into the machinery during a storm. He was put ashore in Harwich; four days after the injury he was hospitalized in Colchester. The voyage was eventful in other ways too. Another officer died from typhoid fever in Ismailia. On the Swedish frigate Vanadis, also present at the opening of the Suez Canal, one of the doctors died from lung infection and was buried in Smyrna; a twelve-feet high column of white marble was taken from the ruins of Aesculap's temple and put on his grave. Denmark was represented by the frigate Sjaelland. During a storm in the North Sea, one seaman fell down on the deck from the foresail yard and suffered contusions and a fracture of the left clavicle. These cases illustrate challenges that faced our ancestors. The accident happened when the ...

Background: The clinical features, therapy and outcome of anthrax cases from the Elazig province (the eastern Anatolian region) of Turkey seen in our clinic over an 8-year period were reviewed. Patients and Methods: The records of 25 anthrax cases observed in our clinic during the period January 1994 to April 2002 were examined. Results: All cases were cutaneous; 18 (72%) patients exhibited malignant pustules and seven (28%) malignant edema. Three of the patients with a malignant pustule developed anthrax sepsis when admitted to our clinic. All cases were treated with penicillin. One patient who had penicillin allergy was treated with ciprofloxacin. In addition, patients with malignant edema were also treated with systemic corticosteroids (methylprednisolone or dexamethasone). Two patients died due to anthrax sepsis; one case with anthrax sepsis recovered. The mortality rate was 8%. Discussion: Anthrax is still a reality in Turkey. Cutaneous anthrax should be considered in any patient with a painless ulcer with vesicles, edema and a history of exposure to animals or animal products. In our series, penicillin and ciprofloxacin were effective in treatment of anthrax. Our anthrax sepsis case demonstrates that anthrax sepsis is not always fatal if antibiotic treatment is given early after diagnosis.

In highly immunised populations viruses contribute to a substantially higher proportion of meningo-encephalitis cases. This national study aimed to describe population trends in laboratory-confirmed, viral meningo-encephalitis reports in England and Wales over a ten-year period. Laboratory-confirmed, viral meningo-encephalitis cases submitted by National Health Service hospitals in England and Wales during 2004-13 were analysed. There were 9941 laboratory-confirmed reports of viral meningo-encephalitis in England and Wales over the 10-year period. Number of reports increased across all age-groups and for all viruses from 311 (incidence, 0.6/100,000) in 2004 to 2168 in 2013 (incidence, 3.9/100,000). Median age at diagnosis was 30.6 (IQR, 1.3-51.5) years, with a third of cases diagnosed in children. In 2013, infants aged <3 months accounted for 27% (588/2168) of cases, but had the highest incidence (329/100,000). Enteroviruses were responsible for 52% (5133/9941) of all cases and 9...

Three cases of severe necrotising fasciitis due to Vibrio vulnificus (two cases) and Vibrio parahaemolyticus (one case, fatal), have occurred in Caucasian tourists while fishing at a remote tropical northern Australian estuarine area. Infections were acquired over a 4-year period during the tourist fishing season (April to July 2000-2003), when water temperatures range from 23 to 30 degrees C. They are notable for their geographical clustering in the remote western aspect of the Gulf of Carpentaria, an area characterised by sedimentary stratiform zinc-lead-silver deposits and a major mining operation. Patients presented with classical bullous cellulitis with necrotising fasciitis, accompanied by severe sepsis. Underlying risk factors were identified in each patient; in one instance, previously unrecognised haemochromatosis was diagnosed. Likely reasons for Vibrio occurrence in this particular ecological niche are discussed.

Antinuclear antibody (ANA) immunofluorescence tests, using HEp-2 cells, were performed on 100 children without a history of connective tissue disease. Eighteen (18%) were positive at titres greater than or equal to 1:40, nine (9%) being greater than 1:160. Interlaboratory variability was demonstrated with some specimens. No association with possible intercurrent infection was found to account for positive results. Of 44 children with proven infections five (11%) were positive. Antinuclear antibody may be found in some normal children when using the sensitive HEp-2 cell substrate, and in the absence of clinical features should not necessarily suggest the presence of a connective tissue disease.