{"title":"Mechanisms of Antibiotic Resistance","authors":"Ruaridh Buchanan, David Wareham","doi":"10.1093/oso/9780198801740.003.0055","DOIUrl":"https://doi.org/10.1093/oso/9780198801740.003.0055","url":null,"abstract":"Although antibiotic resistance has come to the fore in the media and clinical practice relatively recently, it is by no means a new issue; Alexander Fleming discussed the risks of penicillin resistance more than sixty years ago, but even he was behind the times. Bacteria have been competing with each other for millions of years, producing compounds which kill or inhibit other species—it is not surprising that bacteria have evolved defence mechanisms. Current major concerns are the rise of pan-drug resistant gram-negative organisms and the spread of multi-drug resistant TB. Bacterial cells turn over rapidly—this rate of reproduction leads to many errors in DNA replication. Many of these mutations are deleterious to the organism, but others confer new properties, such as changing the structure of an enzyme. The application of selection pressure in the form of antimicrobial therapy leads to the survival of mutants that have randomly acquired resistance mechanisms. There are two useful ways to categorize resistance mechanisms: by how bacterial cells acquire them and by the physical mechanism of action. The types of acquisition have important infection control ramifications. Resistance can be subdivided into three separate categories: ● Intrinsic resistance— mechanisms hard coded into all members of a bacterial species at the chromosomal level. If an organism’s antibiogram suggests susceptibility to an agent to which it should be intrinsically resistant, further work should be done to check that the identification is correct. Examples include gram-negative bacteria being resistant to glycopeptides due to the outer cell membrane, anaerobes being resistant to aminoglycosides due to lack of an uptake mechanism, and amoxicillin resistance in Klebsiella due to beta-lactamase production. ● Mutational resistance—resistance that arises randomly due to DNA replication errors in conjunction with selection pressure applied by antimicrobial agents. This is the basis of the majority of the mechanisms detailed in this chapter. ● Transferrable resistance— mutational resistance that is passed horizontally from the bacterium in which it arose to another cell, possibly of a different species entirely. This happens through either transposons (DNA that incorporates into the bacterial chromosome) or plasmids (rings of DNA that replicate independent of the main chromosome).","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":"126307272","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":"Detecting Antimicrobial Resistance","authors":"L. Phee, D. Wareham","doi":"10.1093/oso/9780198801740.003.0056","DOIUrl":"https://doi.org/10.1093/oso/9780198801740.003.0056","url":null,"abstract":"● To optimize antimicrobial therapy for the management of individual patient’s infection. ● For surveillance purposes, which in turn inform local/national/international clinical guidelines. ● For the management of infection control and prevention. Broadly speaking, resistance is detected by observing its phenotypic expression (activity of the candidate drug(s) against the target bacterium) or detecting the underlying genotypic determinant (resistance genes). Commonly used methods in clinical diagnostic laboratories generally fall under the ‘phenotypic’ category. These share similar traits— ease of use, reproducibility, scalability, quick turnaround of results and relative low cost of materials/reagents required. Moreover, decades of experience and fine-tuning have seen them established as methods of choice in most microbiology laboratories. Most phenotypic test methods are reliant on the use of clinical breakpoints set by national and international bodies (e.g. EUCAST and CLSI) to determine susceptibility/resistance. These guidelines are regularly subject to updates with input from leading experts and latest research findings. It is important for clinical diagnostic laboratories to adhere to best practice guidance set out by these bodies and keep up-to-date with the latest guidelines. Growth characteristics (on artificial media) of the bacterium of interest are extremely important in conventional phenotypic methods. As this presents a big obstacle for slow growers and ‘unculturable’ pathogens (e.g. Mycobacterium tuberculosis, Mycoplasma spp.) it has led to the introduction of genotypic methods of resistance detection in the clinical diagnostic laboratory. meteoric rise in the world of microbiology. Compared with conventional phenotypic methods, molecular genotypic-based tests are better suited for automation and reduce dependence on skilled workers for result interpretation. They therefore deliver the rapid turnaround demanded by modern medicine. Antimicrobial susceptibility tests (ASTs) is a term used to describe a range of phenotypic methods that employ direct observation of the action of antimicrobials against a target microorganism. This is the most commonly used method in clinical diagnostic laboratories for detecting resistance in bacteria. A. Disc diffusion Growth medium: Standardized agar plates (usually unsupplemented, but addition(s) may be necessary for bacteria with specific growth requirements). Antibacterial component: Fixed dose in standard size circular paper discs or tablets.","PeriodicalId":274779,"journal":{"name":"Tutorial Topics in Infection for the Combined Infection Training Programme","volume":"17 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":"126428199","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":"Biosafety Categorisations and Containment Levels","authors":"C. Y. William Tong","doi":"10.1093/oso/9780198801740.003.0021","DOIUrl":"https://doi.org/10.1093/oso/9780198801740.003.0021","url":null,"abstract":"The Control of Substances Hazardous to Health Regulations 2002 (COSHH) classifies biological agents into four categories (Hazard Groups) according to an approved list by the Health and Safety Executive (HSE). Biological agents are bacteria, viruses, parasites, and fungi that can cause harm to human health, usually due to infection, although some are toxic or can cause an allergy. The approved list is relevant to risk assessment for work with biological agents and the application of appropriate control measures. Hazard Group 1 agents are not considered to pose a risk to human health, while Hazard Group 4 agents present the greatest risk. The principle of the categorization is laid down by the Advisory Committee on Dangerous Pathogens (ACDP) based on the following (see also Table 13.1): ● the likelihood that it will cause disease by infection or toxicity in humans; ● how likely it is that the infection would spread to the community; and ● the availability of any prophylaxis or treatment. The ACDP only considers the risks to human health when deciding appropriate classification. Some listed agents can also cause disease in animals (zoonoses) and have also been assigned a hazard classification under the Specified Animal Pathogens Order (SAPO). In allocating human pathogens to a hazard group, no account is taken of particular effects on those whose susceptibility to infection may be affected, for example, because of pre-existing disease, medication, compromised immunity, pregnancy, or breastfeeding. Type 2 polio virus has been reclassified from Hazard Group 2 to Hazard Group 3 to bring the UK in line with the expectations of World Health Organization’s global polio eradication programme. This reclassification also applies to attenuated type 2 polio viruses once this component is no longer used as part of the trivalent polio vaccine. Zika virus has been reclassified from Hazard Group 3 to Hazard Group 2 as there is substantial evidence that while it can cause human disease, this is generally mild. It is also unlikely to spread to the community from the laboratory. COSHH regulations specify four containment levels for activities which involve working with biological agents.","PeriodicalId":274779,"journal":{"name":"Tutorial Topics in Infection for the Combined Infection Training Programme","volume":"27 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":"121797675","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":"The Use of the Laboratory in the Investigation, Management, and Prevention of Infection","authors":"C. Rosmarin","doi":"10.1093/oso/9780198801740.003.0014","DOIUrl":"https://doi.org/10.1093/oso/9780198801740.003.0014","url":null,"abstract":"The pre-analytical stage is broadly classified into four elements: 1. Appropriate selection and use of diagnostic tests; 2. Proper filling in of request forms (paper or electronic); 3. Collection and transport of specimens; and 4. Checks made when the specimen and request form reach the laboratory to ensure the correct patient, sample, and request have been made. A large part of the laboratory role is to advise on the collection of appropriate samples in order to ensure the best chance of diagnosing a suspected infection syndrome or specific pathogen. This requires having a working knowledge of the range and processes of tests available in the laboratory for each clinical syndrome, and the ability to appreciate their strengths and weaknesses, sensitivities and specificities. In addition, advice on the sampling technique may need to be provided regarding the timing of the sample, the type of sample, number or volume of samples, and optimal storage and transport conditions that are required for the specific test. Failure to take sufficient amount of the correct sample, at the correct time, and using the correct container, or storing it in a suboptimal manner, may lead to falsely negative or positive results. Most laboratories have manuals for guidance on sampling details and the tests performed. It is vital that this information is available to clinical staff. Microbiologists and virologists contribute to this guide and assist in ensuring it is communicated to the clinicians taking the samples. This is particularly important for precious samples that cannot easily be repeated, e.g surgical biopsies, CSF from lumbar punctures. Ensuring the correct completion of the request form is vital. Important clinical details should be included on the request to help guide the most appropriate tests. Examples of important information to be documented on the request include travel history, antibiotic history, immune status, underlying diseases, and site of suspected infection. The analytical stage consists of the actual testing of the sample. Examples of common tests performed in this stage include microscopy, culture, sensitivity testing, serology, and molecular detection, as well as more novel techniques such as mass spectrometry, bioinformatics, and sequencing.","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":"129114176","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":"The Biology of Bacteria","authors":"A. Sefton","doi":"10.1093/oso/9780198801740.003.0007","DOIUrl":"https://doi.org/10.1093/oso/9780198801740.003.0007","url":null,"abstract":"Bacterial infections and infestations of man can be caused by both microbes and non-microbes. Microbes include bacteria, viruses, fungi, and protozoa. Non-microbes include worms, insects, and arachnids. This chapter concentrates on the basic biology of bacteria. A pathogen is an organism that is able to cause disease in its host and the pathogenicity of any organism is its ability to produce disease. Microbes express their pathogenicity by means of their virulence. The virulence of any pathogen is determined by any of its structural, biochemical, or genetic features that enable it to cause disease in the host. The relationship between a host and a potential pathogen is non- static; the likelihood of any pathogen causing disease in its host depends both on the virulence of the pathogen and the degree of resistance or susceptibility of the host, due mainly to the effectiveness of the host’s defence mechanisms. Two of the main factors influencing a bacteria’s pathogenicity are its ability to invade and it ability to produce toxins—either exotoxins or endotoxins. Bacteria are unicellular prokaryotic micro-organisms, unlike human cells, which are eukaryotic. Fungi, protozoa, helminths, and arthropods are also eukaryotic. Prokaryotic organisms contain both DNA and RNA, but their genetic material exists unbound in the cytoplasm of the cell as, unlike eukaryotic cells, they have no nuclear membrane. Sometimes bacteria contain additional smaller circular DNA molecules, called plasmids. The main features of a bacterium are the cell wall, cytoplasm, and cell membrane. However, some bacteria have additional features such as spores, capsules, fimbriae (pili), and flagellae. The construction of the cell wall is different in different bacteria, but all cell walls contain peptidoglycan. The structure of the cell wall determines the staining characteristics when stained using the Gram stain. Although its first use was over a hundred and fifty years ago, is still the standard method for primary classification of bacteria. Occasionally, bacteria do not have a cell wall. Gram staining of a fixed smear of bacteria is used to separate bacteria into Gram positive or Gram negative, and also to demonstrate their shape. Bacteria with a thick peptidoglycan layer but with no outer membrane stain purple and are called Gram positive.","PeriodicalId":274779,"journal":{"name":"Tutorial Topics in Infection for the Combined Infection Training Programme","volume":"7 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":"117264738","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":"Epidemiology and Natural History of HIV","authors":"P. Khan, S. Parry","doi":"10.1093/oso/9780198801740.003.0066","DOIUrl":"https://doi.org/10.1093/oso/9780198801740.003.0066","url":null,"abstract":"The human immunodeficiency virus (HIV) is a member of the genus Lentivirus, a subgroup of retrovirus (Retroviridae), that causes HIV infection, which, if untreated, results in acquired immunodeficiency syndrome (AIDS) and death. It was first described in 1981 during an epidemic of a previously unknown immunodeficiency syndrome in the US. The term HIV was accepted in 1986. HIV is thought to originate from simian immune deficiency virus (SIV). HIV-1 was discovered first, with the epidemic of AIDS in the US in 1981. In 1986, a related virus subsequently known as HIV-2, was identified in West Africa. The viruses differ in several aspects; HIV-1 is found worldwide, whereas HIV-2 is predominantly found in West Africa. HIV-1 is a more virulent and rapidly progressive virus; HIV-2 tends to be present in lower viral quantities and progresses more slowly. The number of people living with HIV (PLWH) rose from an estimated 9.0 million in 1990 to 36.9 million in 2014, due in part to a substantial improvement in survival rates as a result of effective anti-retroviral treatment. By 2014, annual new HIV infections had dropped to 2.0 million, down from 3.1 million in 2000, representing a decline of about 35%, although there remain an estimated 5600 people newly infected with HIV every day. It is estimated that without the global response that was mounted in 2000, notably the ‘Combatting of HIV/AIDS’ (the 6th Millennium Development Goal, which focused on halting and reversing trends for HIV by the end of 2015) there would have been six million new infections in 2013 alone. The main driver of progress has been widespread roll-out of antiretroviral treatment (ART) and behavioural change interventions, resulting in increased condom use, fewer multiple sexual partnerships, and delayed sexual debut. HIV-related deaths peaked in 2004–2005, and deaths fell by 24% between 2000 and 2014 from 1.2 million (0.98–1.6 million) in 2014 compared to 1.6 million (1.3–2.1 million) in 2000. The drop in AIDS-related mortality has been even steeper among children aged under fifteen years of age due to the enormous progress made with prevention of mother-to-child transmission (PMTCT).","PeriodicalId":274779,"journal":{"name":"Tutorial Topics in Infection for the Combined Infection Training Programme","volume":"19 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":"127996306","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":"Fever in Returned Travellers","authors":"Desmond Hsu, Z. Babiker","doi":"10.1093/oso/9780198801740.003.0073","DOIUrl":"https://doi.org/10.1093/oso/9780198801740.003.0073","url":null,"abstract":"Travel-related problems have been reported in up to two-thirds of travellers to developing countries and approximately 10% of them seek medical advice during or after return from abroad. Furthermore, global migration from the developing to the developed world has increased over the past decades and these individuals may present with tropical infections soon after arrival in non-endemic settings. Fever, with or without localizing symptoms or signs, is a common presenting symptom in returning travellers. Most unwell travellers seek medical attention within one month of return from abroad. Travellers who visit friends and relatives (VFRs) in their countries of origin are disproportionately affected by the burden of imported infections, e.g. 70% of patients with imported malaria in the United Kingdom (UK) are VFRs. While most febrile travellers have common infections such as respiratory or urinary tract infection, it is of paramount importance not to miss potentially life-threatening tropical infections. Evaluation of fever in returning travellers requires an understanding of the geographical distribution of infectious diseases, risk factors for acquisition, incubation periods, and major clinical syndromes of travel-associated infections. The following points should be considered when assessing febrile international travellers: A. Travel dates: the relationship between the timing of the onset of symptoms and travel dates should be assessed. B. Geography: ● travel destination: a detailed itinerary is required. ● local setting: urban vs rural locations; type of accommodation, e.g. air-conditioned hotel room, outdoor camping, etc. C. Risk factors for acquiring infectious diseases: ● purpose of travel: visiting friends and family; social gatherings (e.g. funerals and weddings); mass gatherings (e.g. Hajj pilgrimage, Kumbh Mela religious festival, Olympic games, etc.); tourism; business; voluntary work. ● contact with unwell individuals. ● activities while abroad (examples): ■ food consumption: street food, seafood, raw food, unpasteurized dairy products, exotic foods, bush meat, etc. ■ contact with animals: visits to game parks, farms, caves, bites or scratches by bats or terrestrial animals, visits to ‘wet markets’, birding events, etc. ■ bites: ticks, insects, snakes, spiders, etc. ■ use of local healthcare system: dental or surgical procedures, blood transfusion, dialysis, tattoos, acupuncture.","PeriodicalId":274779,"journal":{"name":"Tutorial Topics in Infection for the Combined Infection Training Programme","volume":"49 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":"134229219","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":"The Biology of Fungi","authors":"Stephanie J. Smith, R. Manuel","doi":"10.1093/oso/9780198801740.003.0009","DOIUrl":"https://doi.org/10.1093/oso/9780198801740.003.0009","url":null,"abstract":"Fungi are found ubiquitously in the environment such as soil, water, and food. There are an estimated 1.5 million fungal species worldwide, although this number is felt to be grossly underestimated and is regularly updated. Of these vast numbers, around 500 fungi to date have been implicated in human disease. As opposed to bacteria, which are prokaryotes, fungi are eukaryotes, meaning they have a well-defined nucleus and have membrane- bound organelles in the cytoplasm, including an endoplasmic reticulum and a golgi apparatus. In 1969, the scientist R. H. Whittaker first proposed that organisms be classified into five kingdoms: Monera (Bacteria), Protista (Algae and Protozoans), Plantae (Plants), Mycetae (Fungi), and Animalia (Animals). Since then, there have been dramatic changes to the classifications of fungi, largely due to the appliance of phylogenetic molecular techniques. This has resulted in variances to the number of phylums, and the species assigned to them. Table 3.1 shows the seven phyla of the Fungi Kingdom. The majority of fungi pathogenic to humans inhabit the Ascomycota and Basidiomycota phyla. Fungi used to be dually named if they had a pleomorphic life cycle with sexual/ asexual stages (teleomorph/ anamorph, respectively), which meant that fungi often had two names and were classed differently. This practice was discontinued in January 2013 after the International Commission on the Taxonomy of Fungi decided that a ‘one fungus, one name’ approach should be followed. Fungi can be unicellular (yeast) or multicellular (fungi). Yeasts may look globose in nature when grown, whereas multicellular fungi grow as tubular, filamentous material called hyphae that can create a branching, hyphal network called a mycelium. Hyphae may have septa that cross their walls or be nonseptate, which is a method of differentiating fungi. An early hyphal outgrowth from a spore is called a germ tube. The germ tube test can be used to differentiate the yeasts Candida albicans and Candida dubliniensis from other Candida species. The fungal cell wall is composed of chitin and glucans, which are different components to the human cell wall. This means that they can be an effective target for antifungal therapy.","PeriodicalId":274779,"journal":{"name":"Tutorial Topics in Infection for the Combined Infection Training Programme","volume":"137 ","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"113984115","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":"Infection of the Central Nervous System","authors":"C. Rosmarin","doi":"10.1093/oso/9780198801740.003.0043","DOIUrl":"https://doi.org/10.1093/oso/9780198801740.003.0043","url":null,"abstract":"Meningism is the syndrome of the triad of symptoms of headache, neck stiffness, and photophobia caused by irritation of the meninges. While it is often associated with a diagnosis of meningitis, it is also present in other conditions causing meningeal irritation such as subarachnoid haemorrhage, trigeminal neuralgia, migraine, or febrile illness in children. Meningitis is process of inflammation of the meninges, which may or may not be due to an infectious agent. Strictly speaking, it is a pathological diagnosis, but in lieu of the impracticability of biopsying the meninges, surrogate markers are used to infer inflammation. These include raised cerebrospinal fluid (CSF) white cell count and protein; and meningeal enhancement using contrast enhanced MRI or CT of the brain. Encephalitis is process of inflammation of the brain parenchyma. Strictly speaking, it is again a pathological diagnosis, and again surrogate markers are used to infer this inflammation, although it is slightly more difficult due to the protected nature of the brain. CSF white cell count and protein are expected to be elevated and parenchymal inflammation may be seen on contrast enhanced MRI. Meningoencephalitis is a combination of the above with inflammation of both the meninges and the adjoining brain parenchyma. Aseptic meningitis is said to be present when there is meningism and signs of meningeal inflammation on CSF and imaging, but no bacterial cause is found on culture or molecular diagnostics. Viral meningitis is the commonest cause, although post-neurosurgical aseptic meningitis is often chemical in nature. Meningism plus fever are the classic symptoms of meningitis. The onset may be acute, subacute, or chronic, depending on the cause. Neck stiffness may range from mild discomfort to an almost rigid neck and is not a sensitive test in young children or elderly. While not used routinely and with low sensitivity particularly in young children and elderly, Kernig’s and Brudkzinski’s signs, both of which stretch the meninges worsening the irritation and increasing pain, have a good positive predictive value. Non-specific signs of intracranial pathology may be present, such as signs of raised intracranial pressure (ICP), vomiting, reduced level of consciousness, focal neurological signs, seizures, or irritability, especially in the immunocompromised, elderly, and young children who may not have classic signs and symptoms.","PeriodicalId":274779,"journal":{"name":"Tutorial Topics in Infection for the Combined Infection Training Programme","volume":"114 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":"116019623","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":"Tuberculosis and Other Mycobacterial Infections","authors":"Simon Tiberi","doi":"10.1093/oso/9780198801740.003.0035","DOIUrl":"https://doi.org/10.1093/oso/9780198801740.003.0035","url":null,"abstract":"Mycobacterium tuberculosis (MTB) is a thin, aerobic, non-spore forming, slow-growing (doubling time twelve hours) non-motile rod-shaped bacteria, belonging to the family Mycobacteriaceae. Mycobacterium tuberculosis complex is made up of several species, including M. tuberculosis, M. bovis, Bacillus Calmette-Guerin (BCG), M. africanum, M. canetii, M.caprae, M. microti, and others. Transmission is via inhalation of aerosolized respiratory secretions. After inhalation, majority of bacilli are captured in the upper respiratory tract by mucus and removed through a process called clearance, although bacteria in small droplets can reach the alveoli where the bacilli are ingested by macrophages. If clearance is not effective infection may result. With the involvement of CD4 lymphocytes, interferon-γ and tumour necrosis factor-α, a granuloma is formed, and bacilli may be destroyed. In many cases, the bacilli are not destroyed and can spread into lymphatics or via blood to other sites (any organs) where it can lie dormant for years. This asymptomatic situation is called latent TB infection (LTBI). It may reactivate in 10% of people throughout their lifetime; this increases with immunosuppression and HIV infection. The course of illness is chronic and indolent. However, rapid progression to fulminant disease may result if the host is immunocompromised. Pulmonary TB is the most common and important form of TB because it is the infectious form of the disease. In areas where reactivation predominates (like the UK), there is a higher proportion of extrapulmonary TB. Tuberculosis bacilli resist destaining with acid alcohol treatment hence the term. This retention is due to complexing of the carbolfuschin Ziehl-Neelsen stain with mycolic acids present in the waxy cell wall, including lipoarabinomannan (which facilitates survival in macrophages). Microscopy will diagnose TB in 80% of smear-positive patients with a first sputum sample, a further 15% with the second, and 5% with a third. In endemic areas finding acid-fast bacilli in sputum has a 98% specificity, but this is not the case in the UK, a low-prevalence setting, where atypical mycobacteria can have a similar prevalence. In the best settings only 60% of culture-positive patients are also sputum smear-positive as liquid culture, the gold standard, and most sensitive test.","PeriodicalId":274779,"journal":{"name":"Tutorial Topics in Infection for the Combined Infection Training Programme","volume":"21 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":"116505952","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}