Tutorial Topics in Infection for the Combined Infection Training Programme最新文献

{"title":"Mechanism of Action of Antimicrobial Agents","authors":"R. Buchanan, A. Sefton","doi":"10.1093/oso/9780198801740.003.0053","DOIUrl":"https://doi.org/10.1093/oso/9780198801740.003.0053","url":null,"abstract":"Antibacterial and antifungal agents aim to kill pathogens, or at the very least incapacitate them. To achieve this aim these agents must have a reasonable degree of toxicity at the cellular level. If this toxicity was equally manifest against all cell types then the drugs would be unusable in patients as the side effect profile would be unacceptably severe. Selective toxicity, whereby the agents are orders of magnitude more toxic to bacteria or fungi than human cells, allows for the safe and effective administration of these agents to patients. There are a number of different mechanisms by which an antimicrobial agent can yield selective toxicity: ● Target a cellular structure that exists only in bacteria/fungi—e.g. the cell wall; ● Target a cellular structure that has a significantly different structure in bacteria/ fungi— e.g. the ribosome; the fungal cell membrane; ● Target cellular enzymes that are significantly different in bacteria/fungi e.g. topoisomerase; ● Target a synthetic pathway that exists only in bacteria e.g. folate synthesis. Broadly, antibacterial drugs can be divided into the following categories: ● Agents that target the cell wall; ● Agents that target the cell membrane; ● Agents that inhibit protein synthesis; ● Agents that inhibit DNA replication/ transcription of RNA; ● Agents that target folate synthesis; ● Agents that directly damage intracellular structures. The cell wall is unique to bacteria, and therefore an ideal target. Disrupting the complex cross-linking process required to produce the cell wall leads to loss of bacterial cell integrity and therefore to cell death. The following classes of antibiotics target the cell wall: The first class to be discovered, and still in many cases the most effective, incorporates the four-membered beta-lactam ring—its homology to d-alanyl-d-alanine allows beta-lactam-containing compounds to bind to cell wall peptidoglycans and act as chain terminators. The beta-lactam ring is fused to a five-membered sulphur-containing ring. Variations in side chains account for the differing pharmacokinetics and spectra of action of the different compounds—for example, the addition of an amino group to benzylpenicillin produces ampicillin.","PeriodicalId":274779,"journal":{"name":"Tutorial Topics in Infection for the Combined Infection Training Programme","volume":"10 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129455094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Parasites and Worms","authors":"R. Wani","doi":"10.1093/oso/9780198801740.003.0010","DOIUrl":"https://doi.org/10.1093/oso/9780198801740.003.0010","url":null,"abstract":"A parasite is an organism that lives on or in a host and gets its food from or at the expense of its host. Worms or helminths either live as parasites or free of a host in aquatic and terrestrial environments. Parasites and worms are found worldwide but mainly in the tropics. It is estimated that 20% of immigrants from endemic countries may have helminthic infections at their arrival to the UK. These people could be asymptomatic, but tend to present with unexplained symptoms, especially gastrointestinal in nature or eosinophilia. Travellers to endemic countries tend to be newly infected and have greater immune response and pronounced eosinophilia in some but not all parasitic infections. Parasites that can cause disease in humans fall under three classes: protozoa, helminths, and Ectoparasites Protozoa are microscopic, one- celled organisms that can be free living or parasitic in nature. Transmission of protozoa that live in a human’s intestine to another human typically occurs through a faeco-oral route (for example, contaminated food or water, or person- to-person contact). Protozoa that live in the blood or tissue of humans are transmitted to other humans by an arthropod vector (for example, through the bite of a mosquito or sand fly). Helminths are large, multicellular organisms that are generally visible to the naked eye in their adult stages. Like protozoa, helminths can be either free living or parasitic. There are three main groups of helminths that parasitize humans: cestodes, trematodes, and nematodes. These are flat worms that comprise Echinococcus species: intestinal tapeworms and neurocysticercosis (Taenia solium) These are leaf- shaped, and they vary in length from a few millimetres to 8 cm. They include: ■ Liver fluke: Clonorchis sinensis, Fasciola hepatica ■ Intestinal fluke: Fasciola buski, Heterophyes heterophyes, ■ Lung fluke: Paragonimus westernmani ■ Blood flukes: Schistosoma species These are cylindrical in structure. Blood- sucking arthropods such as mosquitoes are considered as ectoparasites because they depend on blood meal for their survival. Narrowly speaking, ectoparasites include organisms like ticks, fleas, lice, and mites (scabies) that attach or burrow into the skin and remain there for relatively long periods of time (e.g. weeks to months).","PeriodicalId":274779,"journal":{"name":"Tutorial Topics in Infection for the Combined Infection Training Programme","volume":"71 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132980339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunotherapy","authors":"J. Lambourne, R. Buchanan","doi":"10.1093/oso/9780198801740.003.0057","DOIUrl":"https://doi.org/10.1093/oso/9780198801740.003.0057","url":null,"abstract":"Immunotherapy implies the use of an immune-based therapy to treat infection. Broadly speaking, these therapies can be divided into antibody-based therapies (both pathogen specific and pathogen agnostic), cellular therapies (e.g. CMV-specific T cells), and immune signalling therapies (e.g. interferon-alpha in the treatment of hepatitis C infection). While agents such as corticosteroids, thalidomide, and vitamin D have profound effects on immune function and a well-established role in the treatment of some infections (e.g. corticosteroids in tuberculous and pneumococcal meningitis), in this review they are not considered as immunotherapy, as they are not directly derived from components of the immune system. When considering immunotherapy, it is important to make a distinction between therapy and prophylaxis. There are well-established indications for using immunotherapy as prophylaxis against infection, including the use of varicella immune globulin and RSV-specific monoclonal antibodies (Palivizumab) to prevent chicken pox and RSV infection respectively. In addition, immunization is a form of immunotherapy—inducing a primary immune response and immunological memory such that on exposure to the pathogen, a secondary immune response is rapidly generated, hopefully leading to the control and eradication of the pathogen before infection occurs. There are few immunotherapies currently in routine clinical use, and several experimental therapies under investigation. The aim of most immunotherapy is to replicate what should happen in an effective immune response to a pathogen, but which, due to host factors, pathogen factors, or both, has failed to occur. Antibodies exert their effect in three main ways: 1. Neutralization: Antibody binding to pathogens, or their toxins, limits the access of the pathogen or the toxin to the target cell, thereby preventing cell infection or damage. Neutralization is important for preventing viral entry into cells and preventing the actions of bacterial toxins, e.g. Staphylococcal exotoxin. Neutralization cannot prevent bacterial replication. 2. Antibody dependent cytotoxicity: Phagocytes express receptors for the Fc-portion of antibodies on their cell surface (FcRs). Ligation of phagocyte FcR with an antibody bound to a pathogen is an effective method of delivering a pathogen to a phagocyte for engulfment and destruction. Coating of pathogens with antibodies is a form of opsonization, or ‘making ready to eat’.","PeriodicalId":274779,"journal":{"name":"Tutorial Topics in Infection for the Combined Infection Training Programme","volume":"16 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132275734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pyrexia of Unknown Origin (PUO)","authors":"M. Melzer","doi":"10.1093/oso/9780198801740.003.0033","DOIUrl":"https://doi.org/10.1093/oso/9780198801740.003.0033","url":null,"abstract":"Petersdorf and Beeson defined pyrexia of unknown origin (PUO) in 1961. It is defined as an illness more than three weeks’ duration, with a fever > 38.3°C on several occasions and failure to reach a diagnosis after one week of in-patient investigation. Additional categories have now been added. These include: ● Nosocomial PUO in hospital patients: This is defined as fever of 38.3°C on several occasions caused by a process not present or incubating on admission, where initial cultures are negative and diagnosis remains unknown after three days of investigations. Fever is often related to hospital factors such as surgery, use of biomedical devices (e.g. intravascular devices/urinary catheters), C. difficile infection, and decubitus ulcers related to immobilization. ● HIV- associated PUO: This is defined as fever (as in Nosocomial PUO) for four weeks as an outpatient or three days as an in- patient. The commonest causes of fever are typical and atypical mycobacterial infections, cryptococcosis, and Cytomegalovirus (CMV). Lymphoma may cause fever in up to 25% of cases. ● Neutropenic PUO: This includes patients with a fever (as in Nosocomial PUO) with neutrophils < 1.0 x 109/L, with initial negative cultures and an uncertain diagnosis after three days. Bacterial infection is the commonest cause and should be treated empirically. The causes of a PUO can be categorized as infection (30–40%), neoplasia (20–30%), collagen-vascular and autoimmune diseases (10–20%), and miscellaneous (10–20%). The commonest causes of localized bacterial infections causing PUO are infective endocarditis, intra- abdominal or pelvic infections, oral cavity infections, osteomyelitis, and infected peripheral vessels. These conditions include: ● Infective endocarditis (IE): ■ Organisms associated with indolent onset (e.g. Streptococcus viridans, Enterococcus species, coagulase- negative staphylococci). ■ HACEK organisms (e.g. Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella). ■ Culture-negative endocarditis (e.g. Chlamydia, Coxiella, or Bartonella). ■ Non- infective endocarditis: ● Marantic endocarditis, associated with malignancy. ● Libman Sacks endocarditis, associated with systemic lupus erythematosus (SLE). ● Intra-abdominal infections. ■ Abscesses: ● Hepatic (GI tract or biliary in origin). ● Splenic (associated with IE). ● Sub-phrenic (associated with previous surgery). ● Pancreatic (post-pancreatitis).","PeriodicalId":274779,"journal":{"name":"Tutorial Topics in Infection for the Combined Infection Training Programme","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134275384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Device- Associated Infections","authors":"Mick Millar","doi":"10.1093/oso/9780198801740.003.0045","DOIUrl":"https://doi.org/10.1093/oso/9780198801740.003.0045","url":null,"abstract":"A great variety of biomedical devices are used in patient care. Almost all hospitalized patients will have a vascular catheter placed to support administration of drugs, fluids, electrolytes, blood products, feeding solutions, or for haemodynamic monitoring. Many will also be exposed to urinary catheters, or tracheal tubes. There is also increasing use of a variety of prosthetic devices. Different biomedical devices have different infection associations. Examples of associations include cardiac pacemakers with Staphylococcus aureus blood-stream infection, contact lenses with amoebic keratitis, tampons with toxic shock, and historically, intra-uterine devices with pelvic actinomycosis. The most common causative organisms associated with device infections are bacteria (less commonly fungi). For many devices coagulase-negative staphylococci are the most frequent cause of infection. It is important to remember that an enormous range of microbes have been reported to cause device-associated infection. Biomedical devices predispose to infection through a wide range of mechanisms. These may include (depending on the device) traversing of anatomical barriers (such as the skin), protected niches for microbial proliferation, inappropriate immune activation, and provision of a surface(s) for biofilm formation. Few devices are completely inert. Most devices elicit an immune response, which depletes local complement levels and reduces oxidative killing by neutrophils, some directly damage tissues, and some release biologically-active products. There is much interest in the molecular mechanisms and physical interactions that underlie the formation of communal microbial structures on biomaterial surfaces. Many difference strategies have been proposed both to prevent, and to destroy microbial biofilms associated with biomedical devices. Complications associated with devices are most likely to be mechanical or infective. It is estimated that up to 25% of patients with a central venous catheter (CVC) will suffer a serious mechanical or infection related complication. Risk factors for infection include host, device, and operator factors. Extremes of age, co-morbidities such as diabetes, active infection at the time of insertion, and loss of relevant anatomical barriers to infection are host risk factors that apply to most devices. Operator risk factors include poor compliance with insertion or post-insertion ‘best practice’.","PeriodicalId":274779,"journal":{"name":"Tutorial Topics in Infection for the Combined Infection Training Programme","volume":"43 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128021439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Post-Infection Syndrome","authors":"Sherine J Thomas","doi":"10.1093/oso/9780198801740.003.0051","DOIUrl":"https://doi.org/10.1093/oso/9780198801740.003.0051","url":null,"abstract":"Post-infection syndrome (PIS) or chronic fatigue syndrome (CFS) is a complex debilitating disorder. It is usually characterized by fatigue that is worsened by physical activity or mental exertion, and is experienced in the aftermath, or with ongoing concurrent infections. Other symptoms may also be present including myalgia, impaired concentration, impaired memory, insomnia, and post-exertion malaise that can last for more than twenty-four hours after exertion. PIS/ CFS is a complex disorder with symptoms related to cognitive, autonomous, and immune dysfunction. No single causal factor has been identified, but there is some evidence that indicates that immunological dysfunction and infections interacting with genetic and psychosocial factors probably contribute to the development of PIS/ CFS. There are no tests to diagnose PIS/ CFS. There are many conditions where the symptoms of PIS/ CFS can appear, and therefore diagnosing PIS/ CFS may rely on ruling out other conditions. There are published guidelines that are available in order to help with diagnosing these conditions. The most frequently used ones are from the CDC (the 1994 Fukuda criteria) and the 1991 Oxford criteria. The CDC case definition for CFS requires individuals to meet three criteria before receiving this diagnosis. These are: 1. Severe chronic fatigue which must have been present for six or more consecutive months, and not as a result of other medical conditions associated with fatigue. 2. Fatigue that interferes significantly with activities of daily life. 3. Four or more of the following symptoms are present: a. Post-exertion malaise that lasts for longer than twenty-four hours. b. Impairment of short-term memory. c. Myalgia. d. Unrefreshed sleep. e. Headache (of new type or severity). f. Arthralgia (without swelling or erythema around the joints). g. A frequent or recurring sore throat. h. Tender lymphadenopathy. However, the Oxford criteria differentiates CFS of unknown aetiology and CFS related to PIS, which is CFS that either follows an infection or is associated with an ongoing current infection. These guidelines suggest that in order to diagnose CFS, individuals must meet the following criteria: 1. The principle symptom experienced by patients should be fatigue that affects physical and mental functioning, and should have been present for at least six months.","PeriodicalId":274779,"journal":{"name":"Tutorial Topics in Infection for the Combined Infection Training Programme","volume":"29 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132437997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Malaria","authors":"A. Jayakumar, Zahir Osman Eltahir Babiker","doi":"10.1093/oso/9780198801740.003.0072","DOIUrl":"https://doi.org/10.1093/oso/9780198801740.003.0072","url":null,"abstract":"Malaria is a tropical parasitic infection of the red blood cells caused by the protozoal species Plasmodium falciparum, P. vivax, P. ovale, P. malariae, and P. knowlesi. It is transmitted through the bite of the female Anopheles mosquito. The average incubation period is twelve to fourteen days. Congenital and blood-borne transmissions can also occur. P. falciparum and P. vivax account for most human infections but almost all deaths are caused by P. falciparum, with children under five years of age bearing the brunt of morbidity and mortality in endemic countries. P. falciparum is dominant in sub-Saharan Africa whereas P. vivax predominates in Southeast Asia and the Western Pacific. P. ovalae and P. malaria are less common and are mainly found in sub-Saharan Africa. P. knowlesi primarily causes malaria in macaques and is geographically restricted to southeast Asia. While taking a blood meal, the female anopheline mosquito injects motile sporozoites into the bloodstream. Within half an hour, the sporozoites invade the hepatocytes and start dividing to form tissue schizonts. In P. vivax and P. ovale, some of the sporozoites that reach the liver develop into hypnozoites and stay dormant within the hepatocytes for months to years after the original infection. The schizonts eventually rupture releasing daughter merozoites into the bloodstream. The merozoites develop within the red blood cells into ring forms, trophozoites, and eventually mature schizont. This part of the life cycle takes twenty-four hours for P. knowlesi; forty-eight hours for P. falciparum, P. vivax, P. ovale; and seventy-two hours for P. malariae. In P. vivax and P. ovale, some of the sporozoites that reach the liver develop into hypnozoites and stay dormant within the hepatocytes for months to years after the original infection. The hallmark of malaria pathogenesis is parasite sequestration in major organs leading to cytoadherence, endothelial injury, coagulopathy, vascular leakage, pro-inflammatory cytokine production, and tissue inflammation. Malaria is the most frequently imported tropical disease in the UK with an annual case load of around 2000. P. falciparum is the predominant imported species, and failure to take chemoprophylaxis is the commonest risk factor.","PeriodicalId":274779,"journal":{"name":"Tutorial Topics in Infection for the Combined Infection Training Programme","volume":"2002 23","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132678331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gastro-intestinal, Hepatic, Pancreatic, and Biliary Infections","authors":"A. Riddell, C. Y. William Tong","doi":"10.1093/oso/9780198801740.003.0041","DOIUrl":"https://doi.org/10.1093/oso/9780198801740.003.0041","url":null,"abstract":"The gastro-intestinal tract (GIT) hosts the most numerous and diverse reservoir of microbes in humans. There is increasing interest in the relationship between the GIT microbiome and human health. Obesity, diabetes, allergy, and a number of inflammatory diseases have been linked with the human GIT microbiome. Infections of the GIT arise either as a result of a change in the relationship between the commensal microbes colonizing the GIT (endogenous infection) or entry in to the GIT of a micro-organism which causes disease (exogenous infection). Commensals most commonly invade host tissues as a result of compromised defensive barriers. Disease associated with exogenous infection can be toxin-mediated, or associated with local or systemic invasion of the host. Endogenous infections are usually polymicrobial. In the mouth the aetiology, presentation, and anatomical associations have led to the description of a number of syndromes. Peritonsillar infection with involvement of the internal jugular vein is Lemierre’s syndrome, which is particularly associated with infection with Fusobacterium necrophorum. ‘Trench mouth’ is a severe form of ulcerative gingivitis, so named because in the absence of oral hygiene it was a relatively common diagnosis among those in the trenches during the First World War. Ludwig’s angina is a severe infection of the floor of the mouth which spreads in to the submandibular and sub-lingual space, often following a tooth-related infection. Deep neck infections are more common in children than adults and can involve the parapharyngeal, retropharyngeal, peri-tonsillar, or sub-mandibular spaces. Children with deep neck infections are more likely than adults to present with cough and respiratory distress. Oesophagitis has a wide range of potential aetiologies. Fungi (particularly Candida species) are probably the most common microbial cause of oesophagitis. Fungal infection of the distal oesophagus is thought to play an important role in the pathogenesis of disseminated fungal infection. Risk factors for fungal infection include poor oral intake, exposure to antibiotics, immunocompromise (HIV, steroids, cancer treatments), gastric acid suppressants, and damage to mucosal integrity (naso-gastric tubes, acid reflux, varices). Bacteria (including Mycobacteria, Actinomycetes, Treponemes), parasites, and viruses (herpes simplex, cytomegalovirus) are rarer infectious causes of oesophagitis.","PeriodicalId":274779,"journal":{"name":"Tutorial Topics in Infection for the Combined Infection Training Programme","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129999563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Virological Diagnostic Methods","authors":"A. R. Oliver","doi":"10.1093/oso/9780198801740.003.0016","DOIUrl":"https://doi.org/10.1093/oso/9780198801740.003.0016","url":null,"abstract":"Every clinical virologist must step back and ask what the aim of diagnostics is, in general, i.e. the ‘who/ what/ when/ where’ questions. Broadly, the clinical virologists of today must answer a limited set of questions because that is what current technology allows: ● Is this person currently infected with a virus? ● Has this person ever been infected/ exposed to a virus? ● This person has a confirmed virus infection— how is it progressing with or without intervention? ● From whom was this virus infection contracted? However, currently many questions remain remarkably difficult to answer with existing diagnostics. Increasingly the focus of diagnostics is moving from interest solely in the virus itself to how a given virus interacts with a given host pre/ post infection, e.g. HIV host co- receptor testing. Nearly all virological diagnostic methods rely on two fundamental technical principles— target and signal amplification, which both allow the visualization of virus- specific antigen/antibody or nucleic acid. Luckily, some clinical samples, e.g. stool, do not require amplification in order to detect significant virus infections, but even in these situations it is impossible to visualize the presence of viruses or their host antibodies without highly specialized equipment and chemistry. Most viruses are < 200nm in size, and therefore it is impossible to resolve virus particles even with the best optical microscopes. Nearly all of the methodologies detect surrogate markers. It is of note that viable virus numbers do not equal nucleic acid copies, which do not equal virus capsids visible by electron microscopy: these are apples and elephants when trying to compare their quantity. Diagnostic technology operates in two phases or realms; detection or screening, and characterization. For example, asking if a patient has an Influenza A virus infection, followed by asking what is the haemagglutinin/neuraminidase type (e.g. H1N1).","PeriodicalId":274779,"journal":{"name":"Tutorial Topics in Infection for the Combined Infection Training Programme","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131100017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Laboratory Diagnosis and Monitoring of HIV Infection","authors":"Anna Jeffery- Smith, C. Y. William Tong","doi":"10.1093/oso/9780198801740.003.0067","DOIUrl":"https://doi.org/10.1093/oso/9780198801740.003.0067","url":null,"abstract":"In the majority of UK laboratories initial testing for HIV is now performed using a fourth generation test, which is a combination test for antibody to HIV and p24 antigen. These tests should be able to detect antibody to both HIV-1 and HIV-2. In addition, due to the heterogeneity of the virus they should be able to reliably detect antibody to the main circulating subtypes of HIV-1, i.e. group M (Major), O (Outlier), and N (non-M, non-O). The p24 antigen is an HIV capsid protein which is produced in large quantities during initial infection, prior to seroconversion. The sensitivity and specificity of fourth generation tests is typically > 99%. However, all positive results need further confirmation tests, as discussed below. Third generation laboratory assays only test for the presence of antibody to HIV. Though it includes the detection of IgM (which is not included in second generation assays), they do not detect early infection with isolated HIV antigen prior to seroconversion. Point-of-care testing for HIV is performed in the clinic or at bedside. Like laboratory based assays these tests can be either third or fourth generation. The sensitivity and specificity of point-of-care tests is considered lower than that of laboratory tests, and all positive results require confirmation with a laboratory assay. The window period is the length of time following infection with HIV until the appearance of laboratory markers of HIV infection in the blood. This period varies depending on which marker, i.e. antibody or antigen, is being tested for. The window period for fourth-generation tests is between eleven days and one month. Patients being counselled prior to this testing should be advised that a negative result does not cover risk exposures in the preceding month. These patients should be advised to have repeat testing if they have any further exposure risks in the preceding month prior to testing. For third-generation tests the window period is up to three months, correlating with the amount of time it may take for antibodies to HIV to develop.","PeriodicalId":274779,"journal":{"name":"Tutorial Topics in Infection for the Combined Infection Training Programme","volume":"22 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130149203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}