bluuebunny/crossref_metadata_2025 huggingface dataset:
Human disasters
Authors: Sen Amartya
Published: February 2020

Human disasters, as massive misfortunes long recorded over history, have great importance for medicine, rightly prompting the call for prevention, relief, and practical intervention by medical personnel. But why do human disasters happen? A sharp distinction is sometimes drawn between natural disasters (e.g. earthquakes), and social disasters (e.g. wars), but detailed knowledge often shows that this contrast is not always clear: many disasters have mixed causes. Taking the example of famines. These are popularly understood in terms of food output decline, yet many famines have occurred without any decline in food production. Such misunderstanding has been responsible for the loss of millions of lives, mainly by undermining the role of social intervention. Starvation is a characteristic of some people not having enough food to eat, not of there being not enough food in the economy. Even when nature plays a part in human disasters, society can make a huge difference.
Apoptosis in health and disease
Authors: Arends Mark J. , Gregory Christopher D.
Published: February 2020

Apoptosis is the process by which single cells die in the midst of living tissues. It is responsible for most—perhaps all—of the cell death events that occur during the formation of the early embryo and the sculpting of organs. Apoptotic cell death continues to play a critical role in the maintenance of cell numbers in those tissues in which cell turnover persists into adult life, such as the epithelium of the gastrointestinal tract, the bone marrow, and lymphoid system including both B- and T-cell lineages. This chapter gives an overview of apoptosis in health and disease. Apoptosis appears in the reactions of many tissues to injury, including mild degrees of ischaemia, exposure to ionizing and ultraviolet radiation, or treatment with cancer chemotherapeutic drugs. Excessive or too little apoptosis play a significant part in the pathogenesis of autoimmunity, infectious disease, AIDS, stroke, myocardial disease, and cancer.
Stem cells and regenerative medicine
Authors: Joannides Alexis J. , Selvaraj Bhuvaneish T. , Chandran Siddharthan
Published: February 2020

There is a great and unmet need for treatments that will deliver restorative solutions to patients with diseases hitherto considered irreparable. Advances in human pluripotent stem cell biology and gene-editing technology offer unprecedented opportunities for both drug discovery and translational therapies that will likely herald a new chapter of regenerative and personalized medicine. Consideration of three major target conditions for regenerative medicine—Parkinson’s disease, heart failure, and diabetes mellitus—emphasizes distinct and common challenges that must be overcome in order to realize the stem cell promise. Novel approaches to induce pluripotency from differentiated somatic cells and targeted genetic manipulation of stem cell populations, along with new insights derived from improved understanding of human pluripotent stem cell biology and increased recognition of endogenous stem cells, offers a range of mechanisms through which stem cells may be therapeutic.
The innate immune system
Authors: Bowness Paul
Published: February 2020

The innate immune system comprises evolutionarily ancient mechanisms that mediate first-line responses against microbial pathogens, and are also important in priming and execution of adaptive immune responses, and in defence against tumours. These responses, which recognize microbial non-self, damaged self, and absent self, are characterized by rapidity of action and they involve various different cell types, cell-associated receptors, and soluble factors. Previously thought to lack plasticity or memory, certain innate immune responses have recently been shown to be capable of ‘learning’ or ‘training’. Most cells of the innate immune system are derived from the myeloid precursors in the bone marrow. These include monocytes and their derivatives—macrophages and dendritic cells, blood granulocytes (neutrophils, basophils, and eosinophils), and tissue mast cells.
Autoimmunity
Authors: Rosen Antony
Published: February 2020

Autoimmune diseases occur when a sustained, specific, adaptive immune response is generated against self-components, and results in tissue damage or dysfunction. It is now clear that an autoimmune component is a feature of many human diseases. Indeed, there are some estimates that autoimmune diseases afflict more than 3% of Western populations, and imposes a significant personal and economic burden on individuals and nations. They probably affect more commonly women than men, and have peak incidence in the third to sixth decades. This chapter will illustrate many of the principles unifying various autoimmune states, and will present a conceptual framework within which to understand their aetiology, pathogenesis, and pathology. The rapid advances in knowledge being made in this group of disorders predict that disease mechanisms will soon be more clearly understood, and will greatly impact therapeutics.
The nature and development of cancer: Cancer mutations and their implications
Authors: Brenton James D. , Eisen Tim
Published: February 2020

Cancer is a genetic disease in which progressive accumulation of mutations in the genome of somatic cells induces abnormal biological capabilities. Cancer-inducing mutations may originate from single base substitutions or large chromosomal rearrangements; but ultimately they disrupt normal cellular processes by altering protein function or disturbing the regulation of gene expression. Loss-of-function mutations in tumour suppressor genes inactivate physiological control of cell processes, whereas gain-of-function mutations directly affect physiological networks and, for example, induce pathological activation of signalling pathways. For many common cancers, we are now close to defining unique sets of somatic alterations which confer a specific signature of the cancer type and are also highly specific to the individual patient.
Cancer immunity and immunotherapy
Authors: Drake Charles G.
Published: February 2020

The development of a cancer in an immunologically intact host leads to an interaction between the host immune system and the tumour mass. The three phases of tumour/host interactions (Elimination, Equilibrium, and Escape) form the ‘immune editing hypothesis’, which serves as a valuable framework for understanding of the immune response to cancer and the approaches by which this might be manipulated for therapeutic benefit. Immunotherapy is emerging as an important treatment modality for many tumour types, including melanoma, lung cancer, kidney cancer, lymphoma, and bladder cancer. By the time you read this chapter it is highly likely that additional monotherapy and combination regimens will be approved in multiple tumour types, but an understanding of the basic mechanisms underlying an adaptive antitumour immune response will be valuable in understanding future agents, as well as their toxicities.
Medical management of breast cancer
Authors: Crook Tim , Li Su , Harper Peter
Published: February 2020

Most patients with breast cancer are offered surgery, the main options being modified radical mastectomy, with or without immediate or delayed breast reconstruction, or breast-conserving surgery. All patients treated surgically for early breast cancer should be considered for risk-reducing neoadjuvant (before surgery) or adjuvant (after surgery) treatments. Adjuvant radiotherapy should be considered for all patients who have undergone breast-conserving surgery. Adjuvant medical therapies include (1) endocrine therapy—should be given to all oestrogen-receptor positive patients (premenopausal—tamoxifen; postmenopausal—aromatase inhibitors); (2) anti-HER2 targeted therapy (e.g. trastuzumab) in cancers that overexpress the HER2 oncogene; (3) chemotherapy—selection is informed by clinic-pathological parameters and increasingly by molecular genetic platforms such as Oncotype DX; patients with oestrogen-receptor negative, node-positive disease should receive regimens containing sequential anthracyclines and taxanes. Regimens for neoadjuvant treatment are similar to those used in the adjuvant setting.
Falls, faints, and fragility fractures
Authors: Kearney Fiona , Masud Tahir
Published: February 2020

Falls and their complications are the fifth leading cause of deaths in older adults. They typically result from the interplay of the environment, comorbidity, and age-related changes in postural stability. Recurrent falls can be debilitating in terms of physical consequences and in terms of the psychological impact of fear of falling, resulting in restriction of activity leading to a spiral of deconditioning, further loss of function, low mood, depression, and social isolation. Since some falls can be prevented, all older people in contact with healthcare professionals should be asked routinely whether they have fallen in the past year. Management requires a multifactorial approach, directed by the relevant contributors determined in the assessment process. The aim should be to prevent future falls and minimize their consequences, whilst avoiding imposing restrictions to the point that they negatively impact function, independence, and quality of life.
Symptoms other than pain
Authors: McQuillan Regina
Published: February 2020

Common symptoms in life-limiting illness include pain, fatigue, anorexia, nausea, constipation, and dyspnoea. These may be due to disease or disease progression, treatment side effects, an intercurrent acute problem, or comorbidity. Patients with life-limiting illnesses often have multiple comorbidities and might be on many medications. Effective treatment always depends on making as precise a diagnosis as possible (e.g. pharmacological management of nausea and vomiting is guided by the presumed mechanism). Symptoms can also herald an emergency (e.g. sepsis, delirium, spinal cord compression), when the patient’s frailty, likely prognosis, and own values and wishes need to be taken into account in planning management. Individualized assessment and decision-making are vital.
Clinical features and general management of patients with severe infections
Authors: Watkinson Peter , Young Duncan
Published: February 2020

This chapter examines how the host response to a severe infection involves an intricate link between the inflammatory and coagulation systems, and mechanisms designed to limit damage to normal tissues. Although originally describing both localized and disseminated infections, the term sepsis is now more commonly used to describe the systemic response to a severe infection. The symptoms and signs of sepsis include fever and rigors, flushing and vasodilation, an elevated heart and respiratory rate, confusion, hypotension, and oliguria. To these are added symptoms and signs relating to the specific infection site and pathogenic organism. The initial diagnosis of sepsis is largely clinical. The immediate treatment involves intravenous fluids, appropriate antibiotics and control of the source of infection. Culture results may allow refinement of antibiotic treatment. Treatment guidelines are available and updated regularly.
Nosocomial infections
Authors: Bowler Ian C.J.W. , Scarborough Matthew
Published: February 2020

Hospital-acquired or nosocomial infections—defined for epidemiological purposes as infections manifesting more than 48 hours after hospital admission—are common. They affect 1.4 million people worldwide, involve between 5 and 25% of hospitalized patients at any one time and are associated with considerable morbidity, mortality, and cost. The most common sites of nosocomial infection are the urinary tract, surgical wounds, and the lower respiratory tract. Most are bacterial in origin, the most common species being Escherichia coli, Staphylococcus aureus (including methicillin-resistant Staphylococcus aureus), enterococci, Pseudomonas aeruginosa, and coagulase-negative staphylococci. The principal risk factors are extremes of age, the severity of underlying acute disease (e.g. neutropenia, organ system failure), and chronic medical conditions (especially diabetes, renal failure, and alcohol abuse).
Antimicrobial chemotherapy
Authors: Albur Maha , MacGowan Alasdair , Finch Roger G.
Published: February 2020

The practice of medicine changed dramatically with the availability of effective antimicrobial agents. Often fatal diseases, such as infective endocarditis, became treatable; much minor community infectious morbidity became readily controlled; for example, urinary tract infection; many surgical procedures became much safer, and developments in solid organ and bone marrow transplantation became possible. However, the very success of antimicrobial chemotherapy has led to anti-infective overuse and misuse. In some countries, antibiotics are freely available to the public for purchase ‘over the counter’, with few controls or guidance to ensure their safe and effective use. In many others there are poorly developed antimicrobial stewardship programmes. The emergence and spread of antimicrobial resistance worldwide and the decline in development and licensing of new antimicrobials over the last 30 years has threatened the future successful treatment of bacterial infections.
Immunization
Authors: Goldblatt David , Ramsay Mary
Published: February 2020

Immunization is one of the most successful medical interventions ever developed: it prevents infectious diseases worldwide. The basis for its success is that the human immune system can respond to vaccines by producing pathogen-specific antibody and memory cells (both B and T cells) which protect the body should the pathogen be encountered. Most currently licensed vaccines contain live or killed bacterial or viral constituents, bacterial polysaccharides, or bacterial toxoids, while new types of vaccines are being developed that contain DNA. Most vaccines are delivered directly into skin or muscle via needles, or they are administered orally. New edible vaccines and vaccines delivered via the skin without the use of needles are being developed. The Expanded Programme on Immunization, set up by the World Health Organization to define which vaccines should be delivered in resource-poor countries, has done much to increase vaccination coverage among infants most at risk of infectious diseases.
Herpesviruses (excluding Epstein–Barr virus)
Authors: Sissons J.G.P.
Published: February 2020

The Herpesviridae family is widely distributed in the animal kingdom. More than 100 have been isolated from humans, primates, and other mammals, and from reptiles and fish. Eight human herpesviruses, all with a linear double-stranded DNA genome and divided into alpha-, beta-, and gamma-subfamilies on the basis of genomic and biological properties, share the capacity to produce latent infection. The diseases they cause may result from primary infection, or reactivation of the virus from latency, and tend to be more severe in immunosuppressed patients. Diagnosis of the various herpesvirus infections may be made on clinical grounds alone, by culture or demonstration of viral particles by electron microscopy of relevant samples, by serological testing, or now more routinely by polymerase chain reaction-based tests.
Poxviruses
Authors: Smith Geoffrey L.
Published: February 2020

Poxviruses are large, complex DNA viruses that have played several seminal roles in medicine and biological science. Cowpox virus was introduced by Jenner as the first human vaccine in 1796; widespread vaccination with vaccinia virus led to the global eradication of smallpox in 1977, the only human disease to have been eradicated. Smallpox is caused by variola virus, the most infamous poxvirus. Other poxviruses include molluscum contagiosum, which is the only other poxvirus that infects only humans, causing benign skin tumours that may be single or multiple, typically persisting for months before undergoing spontaneous regression. The development of vaccinia virus as an expression vector pioneered the concept of using genetically engineered viruses as live vaccines. Vaccinia virus is also being developed as an oncolytic agent. Poxviruses remain excellent models for studying virus-host interactions and virus immune evasion strategies.
Mumps: Epidemic parotitis
Authors: Rima B.K.
Published: February 2020

Mumps is an acute, systemic, highly infectious, communicable infection of children and young adults, caused by a paramyxovirus (with an RNA genome). Transmission is by airborne droplet spread. After an incubation period of 14–18 days, typical presentation is with fever, pain near the angle of the jaw, and swelling of the parotid glands. Complications include orchitis, meningitis, and encephalitis. Diagnosis is obvious clinically in cases with a contact history and parotitis, but serological (mumps-specific IgM and IgA) and RNA-based (RT-PCR) tests are used when this is not the case (e.g. the patient presenting with meningitis). Treatment is symptomatic. Prevention is by vaccination, often given as one component of a trivalent mumps/measles/rubella vaccine at 14–16 months of age. A follow-up vaccination is now recommended at 4–5 years of age.
Measles
Authors: Whittle Hilton C. , Aaby Peter
Published: February 2020

Measles is a single-stranded RNA virus that is spread by aerosolized droplets and is highly transmissible. It causes a spectrum of disease ranging from mild in the well-nourished to severe in the malnourished or immunosuppressed: mortality is 3–10% in Africa. At around 10–14 days after infection, the viral prodrome typically consists of runny nose and fever, sometimes also diarrhoea or convulsions; signs include mild conjunctivitis, red mucosae, and (on the buccal mucosa) Koplik’s spots. After 14–18 days a morbilliform rash first appears on the forehead and neck, then spreads to involve the trunk and finally the limbs. Other manifestations include severe conjunctivitis (especially in those who are vitamin A deficient), pneumonitis and enteritis (which may cause profuse diarrhoea).
Enterovirus infections
Authors: Minor Philip , Desselberger Ulrich
Published: February 2020

Enteroviruses are single-stranded, positive-sense RNA viruses comprising poliomyelitis viruses (3 types), coxsackie A viruses (23 types), coxsackie B viruses (6 types), and echoviruses (33 types). They have recently been reclassified into four human enterovirus species (A–D) on the basis of sequence comparisons. Transmission is by the faeco-oral route, with marked seasonal peaks of infection in areas of temperate climate, but infections occurring all year round in tropical regions.

Following transmission, enteroviruses undergo a first round of replication in cells of the mucosal surfaces of the gastrointestinal tract and in gut-associated lymphoid cells, followed by viraemia, which leads to infection of distant organs (brain, spinal cord, meninges, myocardium, muscle, skin, and so on), where lesions might be produced. Shedding of virus occurs from throat and faeces for many weeks.
Virus infections causing diarrhoea and vomiting
Authors: Dormitzer Philip R. , Desselberger Ulrich
Published: February 2020

Acute gastroenteritis is frequently caused by rotaviruses, human caliciviruses (noroviruses, sapoviruses), astroviruses, and enteric adenoviruses (group F): these cause much disease worldwide and considerable mortality, mainly in developing countries. Other viruses found in the human gastrointestinal tract are not regularly associated with diarrhoeal disease, except in patients who are immunosuppressed and in whom herpes simplex virus, cytomegalovirus, and picobirnaviruses can cause diarrhoea, as can HIV itself. Following an incubation period of 1–2 days, there is sudden onset of watery diarrhoea lasting between 4 and 7 days, vomiting, and varying degrees of dehydration. Other features include abdominal cramps, headache, myalgia, and fever. Treatment is supportive, mainly with oral rehydration solutions or—in more severe cases—intravenous rehydration. Continued feeding is recommended, with zinc supplementation in areas where micronutrient deficiency may be present.
Flaviviruses excluding dengue
Authors: Lee Rossi Shannan , Vasilakis Nikos
Published: February 2020

The family Flaviviridae currently consists of four recognized genera: Flavivirus, Pestivirus, Hepacivirus, and Pegivirus. Although members of the family have a large host range that includes both vertebrates and invertebrates, only members of the genus Flavivirus are known as arboviruses, vectored either by mosquitoes or ticks. The remaining genera in the family are exclusively found in mammals, and their diversity has greatly expanded with recent virus discoveries. The genus Flavivirus comprises 92 virus species, of which over 40 can cause human infection. Many of these include important human pathogens such as Zika, dengue, yellow fever, West Nile, and Japanese encephalitis virus.
Bunyaviridae
Authors: Le Duc James W. , Bente D.A.
Published: February 2020

Viruses of the family Bunyaviridae are the largest family of RNA viruses with more than 350 named isolated. They contain a three-segmented, single-stranded, negative-sense RNA genome. They are divided into five genera, of which four are known to include human pathogens—Orthobunyavirus, Phlebovirus, Hantavirus, and Nairovirus. These viruses are found throughout the world and are transmitted between vertebrate hosts and to humans through the bite of infected arthropod vectors (mosquitoes, ticks, others), or from infectious excreta of rodents and other small mammals, and rarely person to person. Many are transmitted from infected arthropod vector females to the next generation by transovarial transmission, thereby surviving adverse environmental conditions and leading to marked seasonal distribution of disease. There are few vaccines or drugs available to protect against infection. Prevention is by avoidance of exposure to potentially infected arthropod and small mammal vectors.
Parvovirus B19
Authors: Brown Kevin E.
Published: February 2020

Parvovirus B19 (B19V) is a small DNA virus that replicates in erythroid progenitor cells, with virus-induced cytotoxicity stopping red cell production. It only infects humans, is endemic in most places, and is transmitted predominantly by the respiratory route. In healthy people it causes the rash illness, erythema infectiosum, also known as ‘fifth disease’ or ‘slapped cheek disease’, associated with minimal drop in haemoglobin, but in patients with increased red cell turnover (e.g. haemolytic anaemia or haemoglobinopathy), it causes transient aplastic crisis; in immunocompromised patients it causes chronic anaemia; and following maternal infection it leads to hydrops fetalis or fetal loss. Treatment is supportive in most instances, but reduction in iatrogenic immunosuppression and/or intravenous immunoglobulin may be appropriate in some cases. No vaccine is available.
Hepatitis viruses (excluding hepatitis C virus)
Authors: Cramp Matthew , Dhanda Ashwin , Naoumov Nikolai V.
Published: February 2020

Viral hepatitis is an ancient disease which remains a major health problem worldwide. The group of hepatitis viruses includes five unrelated human viruses (A to E), which differ in their genome organization, biology, and epidemiology, while being united by their hepatotropism. About 10–15% of cases of viral hepatitis are considered as non-A to E hepatitis, whose aetiology is still unknown, but the search for which has led to the identification of several new viruses (e.g. hepatitis G virus or GB virus-C, TT, and SEN viruses) of uncertain pathogenic significance. Thus, the search for new hepatitis agents responsible for the small proportion of cases with cryptogenic hepatitis continues.
Viruses and cancer
Authors: Weiss Robin A.
Published: February 2020

Viruses are important in cancer for three main reasons: as a cause of cancer—about 15% of the worldwide cancer burden is due to viruses; in understanding of the biology of cancer-through the discovery and characterization of oncogenes and tumour suppressor genes; and in the treatment of cancer—some viruses selectively replicate in and destroy proliferating cells, viruses as foreign antigens may aid the recognition of cancer cells by the host’s immune system (‘xenogenization’), and viruses can also be used as vectors for immunization and for gene therapy. Viral cancers are prevented by early screening for tumours, screening for the virus in order to prevent transmission, and immunization as in the cases of hepatitis B virus and human papilloma virus.
Diphtheria
Authors: Bethell Delia B. , Hien Tran Tinh
Published: February 2020

Diphtheria is a potentially lethal infection caused by toxin-producing strains of Corynebacterium diphtheria, a Gram-positive bacillus. Humans are the only known reservoir, with spread via respiratory droplets or direct contact with skin lesions. Although now rare in developed countries, this vaccine-preventable disease remains an important problem in countries with poor or failing health systems, and is estimated to cause about 5,000 deaths per year worldwide, most in children under 5 years of age. Diphtheria develops when toxigenic bacteria lodge in the upper airway or on the skin of a susceptible individual. An intense inflammatory reaction develops, leading to a characteristic greyish-coloured pseudomembrane that is adherent to underlying tissues. Systemic effects are caused by release of diphtheria toxin, carried by a lysogenic corynebacteriophage, a single molecule of factor A of which can kill a eukaryotic cell.
Staphylococci
Authors: Popovich Kyle J. , Weinstein Robert A. , Hota Bala
Published: February 2020

This chapter looks at staphylococci, which are Gram-positive cocci that form clusters, but can occur singly, in pairs, chains, or tetrads. They are classically distinguished from other Gram-positive cocci by presence of catalase, an enzyme that degrades hydrogen peroxide (H2O2). S. aureus is distinguished from other coagulase-negative staphylococci, which are generally less virulent, by the presence of coagulase, an enzyme that coagulates plasma. Many toxins and regulatory elements enhance virulence in staphylococci. Staphylococci are skin commensals. About 20% of adults are persistently colonized by S. aureus, 60% are intermittently colonized, and 20% are never colonized. High-risk groups for S. aureus colonization include infants, insulin-dependent diabetics, intravenous drug users, HIV-infected patients, and renal dialysis patients. Methicillin-resistant Staphylococcus aureus (MRSA) was once predominantly seen in hospitals. However, over the past twenty years the epidemiology of MRSA has significantly changed, with MRSA infections now being observed in community settings.
Neisseria gonorrhoeae
Authors: Sherrard Jackie , Unemo Magnus
Published: February 2020

Neisseria gonorrhoeae is a Gram-negative, intracellular diplococcus that is transmitted by direct inoculation of infected secretion from one mucosa to another. It primarily colonizes the columnar epithelium of lower genital tract, only occasionally spreading to the upper genital tract or causing systemic disease. Oropharyngeal and rectal infections are common in men who have sex with men but also occur in women. N. gonorrhoeae is almost exclusively transmitted by sexual activity. Oropharyngeal and rectal infections usually produce no symptoms; disseminated gonococcal infection is a comparatively benign bacteraemia affecting joints (particularly shoulder and knee) and skin; traditionally more common in women than men. The gonococcus has adapted rapidly to prevalent antimicrobial usage, leading to resistance to all antibiotics used for treatment, notably penicillins, fluoroquinolones, macrolides, tetracycline, and cephalosporins. This development has resulted in major concerns internationally and the introduction of international and national action/response plans as well as dual antimicrobial therapy.
Enterobacteria and bacterial food poisoning
Authors: Pennington Hugh
Published: February 2020

Food poisoning denotes gastrointestinal diseases caused by microbes transmitted in food or by microbial toxins preformed there. Food spoilage by microbes also has important consequences for human health because of its impact on food supply. The worldwide impact of food poisoning is very great. Such infections kill many children in the developing world, where diarrhoeal diseases stunt their physical and cognitive development. The number of illnesses is also large elsewhere: in the United Kingdom the most common cause of food poisoning, Campylobacter, accounts for about 500,000 cases every year. The most common bacterial pathogens are Campylobacter and various members of the Enterobacteriaceae, a large family of Gram-negative organisms, of which Escherichia coli, shigella, and salmonella are considered in this chapter.
Bordetella infection
Authors: Grant Cameron C.
Published: February 2020

Bordetella are small Gram-negative coccobacilli, of which Bordetella pertussis is the most important human pathogen. Bordetella pertussis is the cause of whooping cough, which remains one of the 10 leading causes of death among children less than five years old. Transmission of this highly infectious organism is primarily by aerosolized droplets. The preferred diagnostic methods are polymerase chain reaction detection from nasopharyngeal samples and serology (IgG antibodies to pertussis toxin). Macrolide antibiotics are recommended if started within four weeks of illness onset. Preventing severe disease in young children remains the primary goal, hence schedules consist of a three-dose infant series and subsequent booster doses. Acellular vaccines enable immunization schedules to include adolescents and adults. Acellular pertussis vaccine given to pregnant women reduces the risk of pertussis in young infants. Antibiotic prophylaxis is given when there is an infant at risk of exposure.
Other Yersinia infections: Yersiniosis
Authors: Prentice Michael
Published: February 2020

Yersiniosis is caused by the enteropathogenic Gram-negative organisms Yersinia enterocolitica and Yersinia pseudotuberculosis, which are worldwide zoonotic pathogens. Disease is acquired by consumption of contaminated food or water and is commonest in childhood, and in colder climates. Presentation is with diarrhoea, fever, and abdominal pain, which may mimic appendicitis. Late complications include reactive arthritis, erythema nodosum, and erythema multiforme. Systemic infection is more likely with Y. pseudotuberculosis and a subgroup of Y. enterocolitica, and also in patients with diabetes or iron overload. Diagnosis is by culture of the organism or convalescent serology. Most cases of enteritis are self-limiting and antimicrobials are not indicated, but septicaemia or focal infection outside the gastrointestinal tract requires antibiotics (usually cefotaxime, ceftriaxone, or ciprofloxacin). Prevention is by standard food hygiene precautions.
Brucellosis
Authors: Colmenero Juan D. , Morata Pilar
Published: February 2020

Brucellosis is a worldwide zoonotic disease. It remains endemic in the Mediterranean basin, Northern Africa, the Middle East, Western Europe, Central and South America, sub-Saharan Africa, the Indian subcontinent, and Central Asia. There are three species especially pathogens for humans; Brucella melitensis (most commonly associated with goats, sheep, and camels), B. abortus (cattle) and B. suis (pigs). Brucellosis is usually transmitted by direct contact with infected animals, by ingestion of untreated dairy products, and less frequently by inhalation (laboratory workers) or inoculation (veterinary). Symptoms are very non-specific and heterogeneous, hence epidemiological information collected in the clinical history is very important. Definite diagnosis always requires laboratory confirmation, either by isolating the organism from blood, body fluids or tissues, or by demonstration of high titres of specific antibodies or seroconversion.
Botulism, gas gangrene, and clostridial gastrointestinal infections
Authors: Stevens Dennis L. , Aldape Michael J. , Bryant Amy E.
Published: February 2020

Human botulism is caused by seven serological types of C. botulinum, which is ubiquitously distributed in the soil. Poisoning usually results from ingestion of preformed toxin in food, although this is rapidly inactivated at ordinary cooking temperatures, but it can also result from contaminated wounds. C. botulinum toxin binds irreversibly to the neuromuscular junction and is the most lethal known microbial toxin. There are five forms of clinical botulism: food-borne botulism; wound botulism; infant botulism; adult enteric infectious botulism; and inhalational botulism. Clinical presentation is with symptoms suggesting gastrointestinal tract illness, followed by neurological symptoms including diplopia, blurred vision, dizziness, and difficulty with speech or swallowing, leading on to generalized flaccid paralysis. The diagnosis can be confirmed by testing for botulinum toxin in the patient’s serum, urine, or stomach contents, or in the suspect food. Treatment requires supportive care, which may continue for many months.
Tuberculosis
Authors: Chaisson Richard E. , Nachega Jean B.
Published: February 2020

Tuberculosis is caused by organisms of the Mycobacterium tuberculosis complex, including M. tuberculosis (the most important), M. bovis, and M. africanum. It has been present since antiquity and is the leading infectious cause of death ahead of HIV infection. An estimated 2 billion people worldwide carry latent infection, when M. tuberculosis persists within cells and granulomas, with the potential to reactivate to cause disease decades later. Tubercle bacilli are transmitted between people by aerosols generated when an infectious person coughs. Proximity to an infectious person determines the risk of infection. Host immunity and factors affecting it—most importantly HIV infection but also diabetes, cigarette smoking, and alcohol and drug abuse—determine the risk of active disease following infection.
Disease caused by environmental mycobacteria
Authors: van Ingen Jakko
Published: February 2020

There are over 130 species of mycobacteria; species other than M. tuberculosis complex and M. leprae are collectively referred to as the non-tuberculous or environmental mycobacteria. Non-tuberculous mycobacteria are divided into two groups, the slow growers, and the rapid growers. The most common organisms causing human disease are the slow-growing species M. avium complex and M. kansasii and, less commonly, M. marinum, M. xenopi, M. simiae, M. malmoense, and M. ulcerans. The rapid growers that are human pathogens are M. abscessus, M. fortuitum, and M. chelonae. Transmission to humans is though inhalation, ingestion, or traumatic inoculation. The prevalence of non-tuberculous mycobacteria infections is likely to have been underestimated, and appears to be increasing in developed countries.
Buruli ulcer: Mycobacterium ulcerans infection
Authors: de Jong Bouke , Portaels Françoise , Meyers Wayne M.
Published: February 2020

Buruli ulcer is caused by Mycobacterium ulcerans, which secretes a cytotoxic and immunosuppressive toxin, mycolactone. The disease is characterized by necrosis of skin, subcutaneous tissue, and bone, and is re-emerging as a potentially disabling affliction of inhabitants of tropical wetlands. Major foci are in West and Central Africa with an increasing focus in Australia, Mexico, South America, and Southeast Asia. It is not contagious; environmental sources include water, vegetation, and insects, with humans probably becoming infected by traumatic introduction of the bacillus into the skin from the overlying M. ulcerans-contaminated surface in most instances. Clinical presentation may be as a cutaneous nodule, undermined ulcer, plaque, or widely disseminated oedematous lesion. Clinical diagnosis is often accurate by experienced clinicians, and smears for acid-fast bacilli, culture, polymerase chain reaction assays, and histopathology are confirmatory. Treatment was formerly by wide surgical excision and skin grafting, yet antibiotics have now been found effective, including an all-oral regimen.
Actinomycoses
Authors: Schaal Klaus P.
Published: February 2020

Human actinomycoses are always synergistic polymicrobial infections in which fermentative actinomycetes—predominantly Actinomyces israelii, A. gerencseriae, or Propionibacterium propionicum—are the principal pathogens, usually needing the assistance of so-called concomitant microbes to produce disease. Nearly all of the members of the mixed actinomycotic microflora belong to the indigenous microbial community of human mucous membranes, hence actinomycoses present as sporadic endogenous infections which are not transmissible. Antibacterial drugs used for treatment should be active against both the causative actinomycetes and all concomitant bacteria. For cervicofacial actinomycoses, the rare cutaneous processes, and most thoracic forms of the disease, this requirement is best fulfilled by amoxicillin plus clavulanic acid in medium to high doses. The prognosis of cervicofacial and cutaneous actinomycoses is good provided that treatment is adequate; thoracic and abdominal forms are more serious, with grave prognosis without proper treatment.
Rat bite fevers (Streptobacillus moniliformis and Spirillum minus infection)
Authors: Woodhouse Andrew F.
Published: February 2020

Rat bite fever is usually attributable to Streptobacillus moniliformis in the Americas, Europe, and Australasia, and to Spirillum minus in Asia. Bites are increasingly common among children with pet rats, and pet shop and laboratory workers. Both bacteria are commensals of rats, some other rodents, and their predators. After an incubation period less than 1 week, S. moniliformis causes sudden high fever, rigors, myalgia, petechial rash, and migratory reactive or septic polyarthritis with synovial effusions. Complications can include fulminant septicaemia, endocarditis, pneumonia, and metastatic abscesses. S. minus infection (sodoku) has a longer incubation period with similarly high fever but concomitant exacerbation of the bite wound, local lymphadenopathy, papular rash, and arthralgia without effusions. In both diseases, fever subsides after a few days but may relapse repeatedly over months. Prevention is by controlling peri-domestic rats and avoiding bites by pet or laboratory rodents.
Relapsing fevers
Authors: Warrell David A.
Published: February 2020

Louse-borne relapsing fever and tick-borne relapsing fever are characterized by repeated episodes of high fever separated by afebrile periods. They are caused by Borrelia spirochaetes distinct from those responsible for Lyme borrelioses. Untreated patients may suffer as many as five (louse-borne relapsing fever) or ten (tick-borne relapsing fever) febrile relapses of decreasing severity. B. myamotoi is much less likely to relapse.

Humans are the sole reservoir of epidemic louse-borne relapsing fever caused by B. recurrentis and transmitted by body lice (Pediculus humanus corporis). Endemic tick-borne relapsing fevers are caused by at least 17 different Borrelia species and have their own particular species of soft Ornithodoros, or, in the case of B. myamotoi and B. lonestari, hard Ixodes or Ablyomma tick vectors that also act as reservoirs. Transmission transplacentally, or by needlestick, blood transfusion, or laboratory accident is also possible.
Leptospirosis
Authors: Day Nicholas P.J.
Published: February 2020

Leptospirosis, caused by pathogenic spirochetes of the genus Leptospira, is a bacterial zoonosis with a worldwide impact on human and animal health. For human infection rodents are the most important reservoir; infection follows exposure to contaminated water, soil, or urine, the organism entering through skin abrasions or mucosal surfaces.

Subclinical infection is common, but symptomatic disease usually begins with abrupt onset of fever, chills, headache, and myalgia. Most cases are undiagnosed due to the poor availability of diagnostic tests in regions where transmission occurs. Whether treatment of mild leptospirosis with antibiotics prevents more severe disease remains controversial, most experts recommend empirical treatment if leptospirosis is suspected.
Scrub typhus
Authors: Paris Daniel H. , Day Nicholas P.J.
Published: February 2020

Orientia spp. are obligate intracellular Gram-negative bacteria that cause scrub typhus, historically known as ‘tsutsugamushi disease’, a febrile illness characterized by early non-specific ‘flu-like’ symptoms, and sometimes a diffuse, macular, or maculopapular rash and/or a necrotic lesion eschar at the inoculation site. Leptotrombidium mites transmit Orientia spp. to humans via the bite of the larval stage, while all mite stages act as bacterial reservoirs through vertical transovarial and transstadial transmission. Scrub typhus is a leading cause of treatable undifferentiated febrile illness in many regions of Asia, and unfortunately remains an underappreciated neglected disease, mainly due to diagnostic difficulties and lack of awareness among medical staff. Complications include meningo-encephalitis, respiratory and renal failure, and severe multiorgan failure. Scrub typhus can be treated effectively with tetracyclines, macrolides, and chloramphenicol. Humans are dead-end hosts and do not participate in the Orientia life cycle, hence treatment does not affect overall disease incidence.
Bartonella bacilliformis infection
Authors: Llanos-Cuentas A. , Maguiña-Vargas C.
Published: February 2020

Bartonellosis (Carrión´s disease, verruga peruana, Oroya fever, Guaitará fever) is caused by the Gram-negative bacillus Bartonella bacilliformis. It is endemic in the western Andes and inter-Andean valleys of Peru, and is still occasionally reported in Ecuador and Colombia, with infection resulting from the bite of various female sandflies. Infection of red blood cells manifests with non-specific ‘viral-type’ symptoms and haemolytic anaemia in the acute stage of disease. Following an asymptomatic phase, the late ‘eruptive’ stage is characterized by dermal nodules (‘verrugas’) that frequently heal spontaneously. Secondary opportunistic infections are common. Diagnosis in areas where the disease occurs is usually by demonstration of bacteria in the blood film. Mortality is 1.1–2.4% in endemic areas and around 9% in patients admitted to hospital. There is no satisfactory prevention for people living in endemic areas; tourists can take the usual precautions against being bitten by insects.
Mycoplasmas
Authors: Jensen Jørgen Skov , Taylor-Robinson David
Published: February 2020

Mycoplasmas are the smallest self-replicating prokaryotes. They are devoid of cell walls, with the plasticity of their outer membrane favouring pleomorphism, although some have a characteristic flask-shaped appearance. Mycoplasmas recovered from humans belong to the genera Mycoplasma (14 species and one candidatus species) and Ureaplasma (two species). They are predominantly found in the respiratory and genital tracts, but sometimes invade the bloodstream and thus gain access to joints and other organs. Diagnosis is made by nucleic acid amplification tests and/or serology. Culture is slow and of limited value in clinical diagnosis. Apart from supportive care, treatment is usually with tetracyclines or macrolides, although an increasing prevalence of macrolide resistance is seen, primarily in Asia. There is no commercially available effective vaccine.
A checklist of bacteria associated with infection in humans
Authors: Paul John
Published: February 2020

In addition to a relatively small number of well-known pathogenic bacteria that infect otherwise healthy people (e.g. Staphylococcus aureus, Mycobacterium tuberculosis, and Streptococcus pyogenes), there is a steadily growing list of less well-known organisms, many of which cause disease only under special circumstances. Bacteria associated with infections in humans are listed in the table that forms the bulk of this chapter, which has been designed to serve as a single port of call for clinicians who seek concise information on the less well-known clinically significant bacteria. Every name in the table has been checked to see that it has ‘standing in nomenclature’: widely used names that do not have standing in nomenclature (at the time of writing) are included, but written in inverted commas (e.g. ‘Spirillum minus’—one of the causes of rat bite fever).
Fungal infections
Authors: Hay Roderick J.
Published: February 2020

The mycoses are disorders caused by fungi, which are saprophytic or parasitic organisms found in every continent and environment. Many are common commensals in nature, but others cause agricultural disease. The mycoses that are human infections include diseases ranging from those that are worldwide and common, such as dermatophytosis and candida infections, to those that are rare and often potentially life-threatening (e.g. histoplasmosis). In humans, fungi usually adopt one of two morphologies: (1) the yeast form—where individual cells produce daughter cells by a process of budding and subsequently separate; or (2) the hyphal form—where cells do not separate but multiply to produce chains of cells joined end to end.
Pneumocystis jirovecii
Authors: Miller Robert F. , Eades Christopher P.
Published: February 2020

The ascomycete fungus Pneumocystis jirovecii (previously called Pneumocystis carinii) is the cause of pneumocystis pneumonia in humans, which occurs largely among people with impaired CD4+ T-lymphocyte function or numbers (e.g. those infected with HIV, recipients of solid organ or haematopoietic stem cell transplants, and those taking therapeutic immunosuppressive agents). The organism is restricted to humans, and disease is now thought to arise from de novo infection by inhalation from an exogenous source. Aside from supportive care, first-line therapy of pneumocystis pneumonia is sulphamethoxazole–trimethoprim (co-trimoxazole, which has a high rate of treatment-limiting adverse drug reactions), with adjunctive corticosteroids indicated for those with severe disease (i.e. hypoxaemia). In patients whose disease is failing to respond, or those intolerant of co-trimoxazole, the main alternatives are intravenous pentamidine or clindamycin with primaquine. Among HIV-infected patients, early initiation of antiretroviral therapy (i.e. within 14 days of starting antipneumocystis pneumonia therapy) is beneficial.
Talaromyces (Penicillium) marneffei infection
Authors: Chaiwarith Romanee , Supparatpinyo Khuanchai , Sirisanthana Thira
Published: February 2020

Talaromyces (formerly Penicillium) marneffei was first isolated from bamboo rats Rhizomys sinensis in Vietnam in 1956. The fungus is endemic in Southeast Asia, north-east India, south China, Hong Kong, and Taiwan. Fewer than 40 cases of infection with T. marneffei were reported before the HIV epidemic. Since then, the incidence of disseminated T. marneffei infection has increased markedly. Talaromyces marneffei infection is very rare in the immunocompetent but one of the most common opportunistic infections in HIV-infected people in Southeast Asia, north-eastern India, southern China, Hong Kong, and Taiwan. Presentation is usually with fever, chills, lymphadenopathy, hepatomegaly, and splenomegaly, with skin lesions—most commonly papules with central necrotic umbilication—in two-thirds of cases. Diagnosis is made by microscopy of bone marrow aspirate or biopsy specimens. Standard treatment, which is usually effective, is with amphotericin B followed by itraconazole.
Microsporidiosis
Authors: Weiss Louis M.
Published: February 2020

Microsporidia are obligate intracellular eukaryotic pathogens related to the Fungi that can infect both vertebrates and invertebrates. They were first identified about 150 years ago as the cause of pebrine, a disease of silkworms, with the description of Nosema bombycis in these economically important insects. They were first described in mammalian tissue samples about 75 years ago and starting 30 years ago they were recognized as pathogenic organisms responsible for a diarrhoeal syndrome in patients with AIDS. In addition to the gastrointestinal tract, it is now appreciated that microsporidia can infect virtually any organ system. The phylum Microsporidia contains about 1,400 species, distributed in 200 genera, and 15 microsporidian species have been reported in human infections.