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Almost two of three tourists developed traveller's diarrhoea during 2-week stays at high-risk destinations. Large differences in infection rates between hotels were seen. Patients with milder forms of diarrhoea show a similar chronology to those more severely affected. Although enterotoxigenic Escherichia coil was the most frequent cause, viral pathogens were detected more often than in other studies.
During 1974 in the West Midlands of England, 38% of children less than 6 years old with enteritis were excreting rotaviruses. Children aged from 6 months to 3 years were those most commonly infected. Rotavirus infections were most common during winter with only a few sporadic cases during summer. A possible pathogen was detected in 59% of patients examined.
BACKGROUND: Enterocytozoon bieneusi and Cryptosporidium parvum cause chronic antimicrobial-resistant gastrointestinal infections in HIV-1-infected individuals. HIV-1 reverse transcriptase inhibitors delay the onset of opportunistic infections, but are not known to reverse established infections. HIV-1 protease inhibitors are more effective across a broader range of HIV-1-infected immune cells. Combination antiretroviral therapy that includes a protease inhibitor could improve immunity to E bieneusi and C parvum. METHODS: HIV-1 infected patients with chronic microsporidiosis (five), cryptosporidiosis (three), or dual infection (one), were treated with combination therapy that included at least one HIV-1 protease inhibitor. Outcome measures were symptoms, weight, use of antidiarrhoeal and antimicrobial drugs, T-lymphocyte subsets, HIV-1 viraemia, stool microscopy, and biopsy by endoscopy. FINDINGS: All patients had complete clinical responses, gained a median 15 kg in weight, and ceased all antidiarrhoeal and antimicrobial therapies. Biliary cryptosporidiosis responded in both affected patients. Neither pathogen was detected in follow-up stool microscopy (eight of eight patients) or in biopsy samples by endoscopy (five of five). Intestinal architecture returned to normal in three patients. There was a dense CD8 lymphocyte and macrophage infiltrate and staining of intraepithelial E bieneusi with interferon-gamma before and after treatment, but little staining for CD4 or B lymphocytes, interleukin 10, or HIV-1 gp41. Five patients remained symptom-free after a median 13 months follow-up. Four patients had recurrent diarrhoea at 7-13 months (one with positive stool microscopy), associated with declining CD4 counts. INTERPRETATION: Combination antiretroviral therapy that includes a protease inhibitor can restore immunity to E bieneusi or C parvum in HIV-1 infected individuals, and result in complete clinical, microbiological, and histological responses. The persistent CD8 cell and macrophage infiltrate, and the rapid time to relapse in patients with declining CD4 lymphocyte counts, suggest that neither infection was eradicated.
Chronic suppurative otitis media in young children is a major problem in Africa, with socio-economic consequences at a later age. Common treatment regimens with antibiotics are expensive and often not practically feasible. Therefore, a project was started to develop a low-cost and effective treatment in a rural area of Malawi by studying the clinical efficacy of an inexpensive application regimen of ofloxacin (0.075%) in hydroxypropyl methylcellulose (1.5%) ear drops. In earlier studies with this treatment regimen, it was possible to cure approximately 70% of ears. The aim of this study was to find out whether the bacteriological spectrum cultured from wet ears before and after treatment, and patterns of resistance to antibiotics, played a role in the percentage of cures. Patients with long-standing chronic suppurative otitis media were clinically assessed and treated with suction cleaning and instillation of ear drops on days 1, 3, 7 and 10. Bacterial swabs were taken for culture and sensitivity tests for ofloxacin were on days 1 and 10 from the ears that were still discharging. After 21 weeks, the ears were assessed again clinically. Clinical cure was considered to be complete cessation of otorrhea. Ninety of 104 tested patients (124 ears) completed the study. About 73% of the ears had become dry by day 10. This dropped to 42% after 21 weeks. Before treatment, most ears (91%) harbored fecal bacteria, Proteus mirabilis (74%) and enterococci (60%) being the most frequently isolated microbes. The second group of frequently cultured bacteria were water bacteria e.g. Pseudomonas species and other non-fermenters (69%), whereas the classical otitis media pathogens were detected only in 15% of ears. Before treatment, 9.7% of strains were resistant to ofloxacin, most (30/35) of which were cultured from ears that were eventually cured. After treatment, fecal and water bacteria were still the most frequently found, with 36% new strains and an overall sensitivity to ofloxacin of 58%. Bacterial resistance did not appear to play an important role in the outcome of treatment. These data rather suggest a very high risk of infection due to poor hygiene conditions. Medical treatment can only have a longer-lasting effect if accompanied by community-based programs that focus on improvement of hygiene. A public health approach is necessary alongside a medical approach for the management of CSOM.
The detection of pathogenic bacteria directly in human fecal specimens by PCR, requires removal of PCR-inhibitory substances. To investigate whether five different macroporous filters (polypropylene, nylon, polyester, polyethylene, fluorocarbon) could retain polysaccharides, major PCR inhibitors, an in vitro model and human fecal samples were used. The in vitro model consisted of Xanthum gum solutions (3 mg/ml PBS), a bacterial polysaccharide, to which Helicobacter pylori cells were added. Fecal samples from healthy volunteers were spiked with H. pylori and Mycobacterium paratuberculosis cells. Polysaccharide concentrations were significantly reduced only by the polypropylene but not by the other filters. Accordingly, both Xanthum gum solutions and spiked fecal specimens became PCR positive only after filtration with the polypropylene filter. We conclude that this filter can be used to prepare a bacterial DNA template suitable for PCR analysis from human feces.
The use of microbiological testing in systems for assuring the safety of beef was considered at a meeting arranged by the International Livestock Educational Foundation as part of the International Livestock Congress, TX, USA, during February, 2000. The 11 invited participants from industry and government research organizations concurred in concluding that microbiological testing is necessary for the implementation and maintenance of effective Hazard Analysis Critical Control Point (HACCP) systems, which are the only means of assuring the microbiological safety of beef; that microbiological testing for HACCP purposes must involve the enumeration of indicator organisms rather than the detection of pathogens; that the efficacy of process control should be assessed against performance criteria and food safety objectives that refer to the numbers of indicator organisms in product; that sampling procedures should allow indicator organisms to be enumerated at very low numbers; and that food safety objectives and microbiological criteria are better related to variables, rather than attributes sampling plans.
The presence of Escherichia coli O157:H7 in various foods of animal origin was surveyed in northwestern Greece. Six hundred samples of unpasteurized cows', ewes' and goats' milk, raw minced meat, uncooked frozen beef hamburgers, sandwiches (containing ham or turkey, mixed vegetable salad with mayonnaise and lettuce), fresh traditional Greek pork sausages and swine intestines appropriate for traditional Greek kokoretsi were assayed for E. coli serogroup O157:H7 using the standard cultural method and the immunomagnetic separation technique. The pathogen was detected in 1 out of 100 (1.0%) samples of ewes' milk, 1 out of 75 (1.3%) fresh sausages and 1 out of 50 (2.0%) swine intestines prepared for kokoretsi. The isolated strains were nonsorbitol fermenters, MUG-negative, O157 agglutinating, verotoxin-producing and carried both VT1 and VT2 genes. The three isolated strains were tested for antibiotic resistance and were found to be susceptible to eight antimicrobial agents (ampicillin, chloramphenicol, kanamycin, nalidixic acid, norfloxacin, streptomycin, sulfamethoxazole-trimethoprim and tetracycline).
Five grams of seafood products were inoculated with one to 500 viable or 10(9) heat-killed cells of Listeria monocytogenes. The presence of the pathogen was detected by the polymerase chain reaction (PCR) with primers specific for fragments of the listeriolysin O (hly) gene (two sets) and for the invasion-associated protein (iap) gene (one set). For DNA preparation, boiling, either alone or in combination with lysozyme and proteinase K treatment, was not always sufficient to lyse L. monocytogenes, while treatment with Triton X-100 produced consistently good DNA suitable for amplification. To avoid false-negative and false-positive results, 48 h incubations were necessary and a subculturing step after an initial 24 h incubation greatly improved the results. The primers that amplified regions of the listeriolysin O gene gave clearer and stronger products than primers for the invasion-associated protein gene. Using this method we were able to detect one to five L. monocytogenes cells in 5 g of product in a total of 55 h.
A retrospective study was performed in 117 children with head and neck space infections treated at the Children's Hospital of Pittsburgh from January 1986 through June 1992. Peritonsillar space infections were the most common (49%), followed by retropharyngeal (22%), submandibular (14%), buccal (11%), parapharyngeal (2%), and canine (2%) space infections. The most common pathogens isolated (N = 78) were the aerobes beta-hemolytic streptococcus (18%) and Staphylococcus aureus (18%), the anaerobes Bacteroides melaninogenicus (17%) and Veillonella (14%), and the gram-negative organism Haemophilus parainfluenzae (14%). beta-Lactamase production by aerobic pathogens was detected in 22% of cultures. Computed tomography scans (N = 16) were reviewed in blinded fashion and compared with operative findings. The sensitivity of computed tomography scan in detecting the presence of an abscess vs. cellulitis was high (91%), whereas the specificity was rather low (60%). Treatment of head and neck space infections in children should consist of accurate physical diagnosis aided by imaging studies, empiric antibiotic therapy that covers gram-negative and beta-lactamase--producing organisms as well as gram-positive organisms and anaerobes, and timely surgical intervention, when indicated.
We have compared the efficiency of biotinylated DNA probes and various visualization techniques with 35S-labeled DNA probes in routine paraffin sections from the pathology service; both autopsy and biopsy tissue were investigated. Probes included DNA genomic fragments from cytomegalovirus (CMV), Epstein-Barr-Virus (EBV) and human immunodeficiency virus (HIV). Methods of detection by Pathogene II kit (ENZO) and Blue Gene kit (BRL) with visualization by AEC, NBT/BCIP, Immunogold (Janssen) and autoradiography were used. The study shows most satisfactory results by applying the Blue Gene-NBT/BCIP combination followed by the Immunogold technique. Data obtained by these techniques compare well to those of using radioactive DNA probes and autoradiography.
Infectious uveitis is a serious condition requiring rapid diagnosis and therapeutic management. Molecular tools, such as PCR and its variants, have significantly changed the diagnostic approach during the last 10 years. Presumed and empirical diagnosis should be excluded in the face of atypical clinical presentations, but also inadequate response to anti-inflammatory drugs. It is of particular importance to note that most of these tests need to be processed in specialized central laboratories to ensure the best sensitivity and specificity. Molecular techniques have their own limits, sometimes caused by inadequate primers or PCR-inhibitors and contaminants. PCR positivity means detection of pathogen DNA, but does not confirm a productive infection. Cultures from ocular fluids should be improved to obtain complementary data about pathogen life cycles and resistance to antibiotics or antivirals. Furthermore, diagnostic yield is significantly increased when PCR and local antibody production are associated, especially in viral infections. This step is of particular importance to identify new infectious entities in cases that are presently considered to be idiopathic or autoimmune disorders.
Explosion of knowledge both in human genomics and in host inflammatory response explains the increasing interest in infectious disease genetics over the last 5 years. However, twin and adoptee studies have suggested more than 15 years ago, that host genetic factors are major determinants of susceptibility to infectious diseases in humans. Recently, candidate gene studies (association studies) and human genomewide analysis have been used to identify infectious diseases susceptibility and resistance genes. Rarely, a single gene defect has been directly related to devastating consequences such as interferon-gamma receptor mutations leading to fatal infections with ubiquitous mycobacteria. For clinical practice, gene polymorphisms of specific host immune defence elements appear to be of major importance. These genetic variants, which modify the regulation or function of the mediators, have been associated with susceptibility and/or outcome of severe sepsis and septic shock. All steps of the host response to bacteria may be affected by genetic factors. For example, Fc gamma receptor, Toll like receptor or mannose binding protein mutations have been shown to modify the detection of pathogens leading to pneumococcal severe infections, Gram-negative bacteria septic shock, and meningococcal disease, respectively. Polymorphisms of cytokine genes (TNF-alpha, TNF-beta, IL-1-ra) have been reported to influence the level of secreted mediators and to unbalance the inflammatory cascade. Coagulation response to sepsis may also be affected by gene variants such as the plaminogen activator inhibitor 1 (PAI-1) common functional polymorphism which increases the risk of death from meningococcal infection or severe trauma. The impact of these findings on the understanding of infectious disease pathogenesis and on the design of future preventive and therapeutic strategies should be considerable.
Developments in the rapid detection of pathogens (PCR and its variations) and molecular typing of strains isolated from the ecosystem illustrate the stimulation of research due to the recent foodborne and waterborne disease outbreaks.
The detection of pathogens by plants is often described as a 'gene-for -gene' interaction. However, recent work from several laboratories indicates that, in some instances, a single gene product in the plant can mediate the recognition of multiple pathogen signals, and that multiple plant genes are required for the recognition of, and response to, a single pathogen signal.
Significant advances have occurred in the knowledge of the pathogenesis of ARDS. It is now recognized that ARDS is a manifestation of a diffuse process that results from a complicated cascade of events following an initial insult or injury. Mechanical ventilation and PEEP are still important components of supportive therapy. To avoid ventilator-associated lung injury there is emphasis on targeting ventilator management based on measurement of pulmonary mechanics. For those with resistant hypoxia and severe pulmonary hypertension adjunctive modalities, such as prone positioning and low-dose iNO, may provide important benefit. Alternative modes of supporting gas exchange, such as with partial liquid ventilation and extracorporeal gas-exchange, may serve as rescue therapies. Advances in cell and molecular biology have contributed to a better understanding of the role of inflammatory cells and mediators that contribute to the acute lung injury and the pathophysiology of the syndrome that manifests as ARDS. Based on this new understanding, the potential targets for intervention to ameliorate the systemic inflammatory response have proliferated. Examples include the cytokine network and its receptors, antioxidants, and endothelins. Apart from the challenge of testing these agents in experimental models, it seems likely that determination of the optimum combination of agents will become an equally important endeavor. A particular challenge is to develop better methods of predicting which of the many at-risk patients will go on to full-blown ARDS and MODS, thereby targeting subgroups of patients most likely to benefit from anti-inflammatory therapies. Similarly, the adverse effects of immunosuppressive therapy may be diminished by improved, perhaps molecular, techniques to detect microbial pathogens and permit differentiation between Systemic inflammatory response syndrome and sepsis.
BACKGROUND: With society's rapidly increasing mobility, patients infected with severe viral infections can become seriously ill at any place in Europe and elsewhere. Improving the diagnostics of these infections is the most important step in detecting the pathogens and dealing with them, and for this purpose, quality control measures are essential tools. OBJECTIVES: To assess the diagnostic reality for rare hantavirus infections in Europe by (1) running a pre-evaluation panel (four samples, sent out in 1999) to optimise sample preparation and shipping procedure and afterwards (2) starting an External Quality Assurance (EQA) program (20 samples, sent out in 2001). STUDY DESIGN: All samples sent out had to be tested for the presence of specific IgG and IgM antibodies against hantavirus. For the pre-evaluation panel, four samples were distributed (two samples IgG+/IgM-, one sample IgG-borderline/IgM-, one sample IgG-/IgM-), for the EQA 20 samples (six samples IgG+/IgM+, eight samples IgG+/IgM-, one sample IgG-borderline/IgM-, five samples IgG-/IgM-). Thirteen laboratories took part in the pre-evaluation panel, 18 laboratories participated in the first EQA run. RESULTS: For the pre-evaluation panel, the participants reported correct results for 64% of the IgG-positive samples (85% excluding borderline-positive sample), and 92% for the IgG-negative sample. IgM testing was correctly negative in all laboratories. For the EQA, the participants reported correct results for 76% of the IgG-positive samples, and 97% correct results for the IgG-negative samples. For the IgM-positive samples, 53% correct results were reported, and 98% correct results for the IgM-negative samples. CONCLUSIONS: The results presented here prove the importance of quality measures also for viruses only rarely suspected, like hantavirus, and they clearly demonstrate the need for improvement of the existing test systems.
Dendritic cells (DCs) detect different pathogens and elicit tailored anti-microbial immune responses. They express C-type lectins that recognise carbohydrate profiles on microorganisms, resulting in internalisation, processing and presentation. Intracellular sequences of distinct DC-specific lectins point to differences in intracellular routing that influence antigen presentation. Moreover, putative signalling motifs hint to the activation of DCs on carbohydrate recognition. Recent evidence shows that not only pathogens, but also tumour antigens, exploit C-type lectins to escape intracellular degradation resulting in abortive immunity. More insight into ligand specificity, intracellular targeting and signalling will reveal the pathways by which pathogens modulate immunity through C-type lectins.
Molecular methods have been used increasingly over the past ten years to improve the sensitivity and speed of diagnosis in infectious diseases. Although their routine use is still limited to the detection of pathogens that are difficult to culture in vitro,'real-time' methods, commercial kits, quantification and automation will increase potential applications. Molecular methods are now widely used for epidemiological fingerprinting of isolates of public health importance. Sequence-based identification and strain typing, together with the development of tools that can probe for thousands of markers, will allow detailed strain fingerprinting to assist in disease management and control.