Infectious Diseases

Viral Infections

AIDS This is a condition caused by the human immunodeficiency virus (HIV). The virus gains entry in CD4+ T cells. As the infection progresses, it leads to depletion of the CD4 cells, leading to a decrease in immune function. This leads to acquired immunodeficiency syndrome (AIDS).   Transmission Sexual Transmission Vertical (mother to baby) IVDU   Symptoms Seroconversion (3–12 weeks following infection) Flu-like symptoms with fatigue, fever, lymphadenopathy, sore throat, and arthralgia Erythematous papular rash and mouth ulcers Persistent generalised lymphadenopathy (swollen lymph nodes lasting > 3 months)   Chronic infection This is usually asymptomatic until complications of immunosuppression develop

Gut Infections

Short incubation periods   Staphylococcus Aureus A Gram-positive bacterium which produces toxins causing intestinal inflammation. The bacteria makes enterotoxins to compete with other bacteria in cooked and processed foods, but these end up being ingested by humans, causing symptoms The symptoms are due to the toxin rather than the bacteria, which gives the short incubation period of 1–6 hours.   Symptoms Nausea and explosive vomiting up to 24 hours Abdominal pain, weakness and headache   Key tests Stool culture to assess if bacterium is present Management Fluid and electrolyte replacement as illness quickly resolves within a couple days   Bacillus

Sexually Transmitted Diseases (STDs)

Chlamydia This is a condition which is caused by the bacteria Chlamydia trachomatis. It is the commonest sexually transmitted disease in the UK. It is spread through all types of sex and can be passed to the baby during childbir   Symptoms  Often the infection is asymptomatic In females, can cause vaginal bleeding, discharge and deep dyspareunia In males, can cause urethritis (dysuria and discharge) Eye disease – can cause blindness Joints – often a cause of reactive arthritis Risk factor for pelvic inflammatory disease (PID) in women, leading to infertility   Key tests Investigation of choice is nuclear acid

Bacterial Infections

Lyme disease This is a condition which is caused by the bacteria Borrelia burgdorferi. Transmission occurs via the Ixodes tick bite, so it is important to ask a detailed travel history to places where these ticks live e.g., forests, parks (e.g., Richmond Park in London has a higher incidence). It initially causes an expanding area of redness on the skin at the site of the tick bite. The bacteria can become systemic and spread to the heart, joints and CNS where they can persist for years. It is thought that the bacteria induce an autoimmune disease secondary to molecular mimicry,

Parasitic Infections

Malaria This is a mosquito borne infection which injects the parasite Plasmodium into the blood. There are 4 main variants of the parasite and the natural vector is the female anopheles’ mosquito Pre-erythrocytic stage Mosquito injects sporozoites into human blood These migrate to liver and infect hepatocytes, multiplying by mitosis They can stage in the liver for up to 2 years remaining immature as hypnozoites These differentiate into merozoites which are released from the liver into the bloodstream   Erythrocytic stage Trophozoites infect RBCs, feeding on haemoglobin using the enzyme haem polymerase These form a schizont and multiply asexually, and

Fungal Infections

Pneumocystis Jirovecci This is a fungal infection that is seen in immunocompromised patients. It is an AIDS-defining disease, typically causing a pneumonia in HIV positive patients.   Symptoms Atypical pneumonia (SOB, dry cough, fever) but very few chest signs The classic symptom is desaturation of SpO2 during exercise/exertion Can lead to secondary pneumothorax, hepatosplenomegaly and lymphadenopathy   Key tests Blood tests show raised inflammatory markers and fungal markers (beta-glucan) CXR/HRCT shows bilateral interstitial pulmonary opacifications Sputum culture – this can be taken directly or from bronchoalveolar lavage if needed Lung biopsy may be required if diagnostic doubt   Management Co-trimoxazole is

Parasitic Infections

Malaria This is a mosquito borne infection which injects the parasite Plasmodium into the blood. There are 4 main variants of the parasite and the natural vector is the female anopheles’ mosquito Pre-erythrocytic stage Mosquito injects sporozoites into human blood These migrate to liver and infect hepatocytes, multiplying by mitosis They can stage in the liver for up to 2 years remaining immature as hypnozoites These differentiate into merozoites which are released from the liver into the bloodstream   Erythrocytic stage Trophozoites infect RBCs, feeding on haemoglobin using the enzyme haem polymerase These form a schizont and multiply asexually, and

Bacterial Infections

Lyme disease This is a condition which is caused by the bacteria Borrelia burgdorferi. Transmission occurs via the Ixodes tick bite, so it is important to ask a detailed travel history to places where these ticks live e.g., forests, parks (e.g., Richmond Park in London has a higher incidence). It initially causes an expanding area of redness on the skin at the site of the tick bite. The bacteria can become systemic and spread to the heart, joints and CNS where they can persist for years. It is thought that the bacteria induce an autoimmune disease secondary to molecular mimicry,

Viral Infections

AIDS This is a condition caused by the human immunodeficiency virus (HIV). The virus gains entry in CD4+ T cells. As the infection progresses, it leads to depletion of the CD4 cells, leading to a decrease in immune function. This leads to acquired immunodeficiency syndrome (AIDS).   Transmission Sexual Transmission Vertical (mother to baby) IVDU   Symptoms Seroconversion (3–12 weeks following infection) Flu-like symptoms with fatigue, fever, lymphadenopathy, sore throat, and arthralgia Erythematous papular rash and mouth ulcers Persistent generalised lymphadenopathy (swollen lymph nodes lasting > 3 months)   Chronic infection This is usually asymptomatic until complications of immunosuppression develop

Sexually Transmitted Diseases (STDs)

Chlamydia This is a condition which is caused by the bacteria Chlamydia trachomatis. It is the commonest sexually transmitted disease in the UK. It is spread through all types of sex and can be passed to the baby during childbir   Symptoms  Often the infection is asymptomatic In females, can cause vaginal bleeding, discharge and deep dyspareunia In males, can cause urethritis (dysuria and discharge) Eye disease – can cause blindness Joints – often a cause of reactive arthritis Risk factor for pelvic inflammatory disease (PID) in women, leading to infertility   Key tests Investigation of choice is nuclear acid

Gut Infections

Short incubation periods   Staphylococcus Aureus A Gram-positive bacterium which produces toxins causing intestinal inflammation. The bacteria makes enterotoxins to compete with other bacteria in cooked and processed foods, but these end up being ingested by humans, causing symptoms The symptoms are due to the toxin rather than the bacteria, which gives the short incubation period of 1–6 hours.   Symptoms Nausea and explosive vomiting up to 24 hours Abdominal pain, weakness and headache   Key tests Stool culture to assess if bacterium is present Management Fluid and electrolyte replacement as illness quickly resolves within a couple days   Bacillus

Resistant Bacterial Infections

C. difficile This is a Gram-positive bacterium which colonises the gut in the absence of one’s commensal harmless bacteria. The commensal flora in the gut can be killed due to the use of broad-spectrum antibiotics, leaving the individual vulnerable to a C. diff infection. The bacteria make a toxin which leads to inflammation in the colon, causing pseudomembranous colitis. It is a common hospital-acquired infection and can spread rapidly between patients.   Causes Most commonly secondary to antibiotics beginning with the letter “C” like cephalosporins, clindamycin. Also associated with PPI use.   Symptoms Diarrhoea, abdominal pain, fever If severe, can

Gut Infections

Short incubation periods   Staphylococcus Aureus A Gram-positive bacterium which produces toxins causing intestinal inflammation. The bacteria makes enterotoxins to compete with other bacteria in cooked and processed foods, but these end up being ingested by humans, causing symptoms The symptoms are due to the toxin rather than the bacteria, which gives the short incubation period of 1–6 hours.   Symptoms Nausea and explosive vomiting up to 24 hours Abdominal pain, weakness and headache   Key tests Stool culture to assess if bacterium is present Management Fluid and electrolyte replacement as illness quickly resolves within a couple days   Bacillus

Sexually Transmitted Diseases (STDs)

Chlamydia This is a condition which is caused by the bacteria Chlamydia trachomatis. It is the commonest sexually transmitted disease in the UK. It is spread through all types of sex and can be passed to the baby during childbir   Symptoms  Often the infection is asymptomatic In females, can cause vaginal bleeding, discharge and deep dyspareunia In males, can cause urethritis (dysuria and discharge) Eye disease – can cause blindness Joints – often a cause of reactive arthritis Risk factor for pelvic inflammatory disease (PID) in women, leading to infertility   Key tests Investigation of choice is nuclear acid

Principles of Fungi

Fungi are eukaryotes with a nucleus, cytoplasm and a cell membrane made of ergosterol. – They also have a cell wall made of an outer matrix of B-1,3-linked glucans and inner layer of chitin, which is made up of chains of B-1,4-linked n-acetyl glucosamine. Fungi can exist in many different forms: Yeasts: These are round unicellular organisms which multiply asexually by a process called budding   Filamentous moulds: These form hyphae, which form an interwoven mass called a mycelium   Dimorphic: These change morphologies depending on the external environment.   Fungi classically are grouped into 2 types of pathogens: Systemic

Principles of Viruses

Viruses are composed of a genome (nucleic acid) with a protein shell (capsid). This is sometimes surrounded by a phospholipid membrane called an envelope. – The most important part of the life cycle is being able to replicate the viral DNA within host cells. DNA viruses These use a host DNA-dependent RNA polymerase to make mRNA – The mRNA is translated in cytoplasm and used to make protein components – These protein components are put together in the cytoplasm to make new virus particles which can be released from the cell.     RNA viruses These can be subdivided according

Principles of Bacteria

Bacteria are unicellular microorganisms which are composed of a naked DNA chromosome, cytoplasm, cell membrane and cell wall. They can be divided into Gram Positive and Negative bacteria i) Gram Positive: These have a cell wall made of peptidoglycan, take up Gram stain   ii)Gram Negative: These have a cell wall of peptidoglycan but then an additional outer membrane too, do not take up Gram Stain Bacteria can be classified by Gram Stain, shape, enzymes and whether they are aerobic or anaerobic. This will all affect diagnosis and treatment options.   Gram Positive Bacteria   Cocci These look like round

The Immune System

The immune response can be split into the innate and adaptive system:   Innate Immunity This is immunity which is dependent on antigen receptors that are germline encoded   The innate immune system recognizes 3 types of stimulants, which activate the innate response: – Pathogen associated molecular patterns (PAMPs) – molecular shapes specific to the pathogen – Danger associated molecular patterns (DAMPs) – self-molecules released by host stressed cells – Missing-self – Infected cells do not show normal self-antigens which protect host cells from NK cells.   The activation of these receptors gives acute inflammation and activation of the following

Gut Infections

Short incubation periods   Staphylococcus Aureus A Gram-positive bacterium which produces toxins causing intestinal inflammation. The bacteria makes enterotoxins to compete with other bacteria in cooked and processed foods, but these end up being ingested by humans, causing symptoms The symptoms are due to the toxin rather than the bacteria, which gives the short incubation period of 1–6 hours.   Symptoms Nausea and explosive vomiting up to 24 hours Abdominal pain, weakness and headache   Key tests Stool culture to assess if bacterium is present Management Fluid and electrolyte replacement as illness quickly resolves within a couple days   Bacillus

Sexually Transmitted Diseases (STDs)

Chlamydia This is a condition which is caused by the bacteria Chlamydia trachomatis. It is the commonest sexually transmitted disease in the UK. It is spread through all types of sex and can be passed to the baby during childbir   Symptoms  Often the infection is asymptomatic In females, can cause vaginal bleeding, discharge and deep dyspareunia In males, can cause urethritis (dysuria and discharge) Eye disease – can cause blindness Joints – often a cause of reactive arthritis Risk factor for pelvic inflammatory disease (PID) in women, leading to infertility   Key tests Investigation of choice is nuclear acid

Parasitic Infections

Malaria This is a mosquito borne infection which injects the parasite Plasmodium into the blood. There are 4 main variants of the parasite and the natural vector is the female anopheles’ mosquito Pre-erythrocytic stage Mosquito injects sporozoites into human blood These migrate to liver and infect hepatocytes, multiplying by mitosis They can stage in the liver for up to 2 years remaining immature as hypnozoites These differentiate into merozoites which are released from the liver into the bloodstream   Erythrocytic stage Trophozoites infect RBCs, feeding on haemoglobin using the enzyme haem polymerase These form a schizont and multiply asexually, and

Fungal Infections

Pneumocystis Jirovecci This is a fungal infection that is seen in immunocompromised patients. It is an AIDS-defining disease, typically causing a pneumonia in HIV positive patients.   Symptoms Atypical pneumonia (SOB, dry cough, fever) but very few chest signs The classic symptom is desaturation of SpO2 during exercise/exertion Can lead to secondary pneumothorax, hepatosplenomegaly and lymphadenopathy   Key tests Blood tests show raised inflammatory markers and fungal markers (beta-glucan) CXR/HRCT shows bilateral interstitial pulmonary opacifications Sputum culture – this can be taken directly or from bronchoalveolar lavage if needed Lung biopsy may be required if diagnostic doubt   Management Co-trimoxazole is

Viral Infections

AIDS This is a condition caused by the human immunodeficiency virus (HIV). The virus gains entry in CD4+ T cells. As the infection progresses, it leads to depletion of the CD4 cells, leading to a decrease in immune function. This leads to acquired immunodeficiency syndrome (AIDS).   Transmission Sexual Transmission Vertical (mother to baby) IVDU   Symptoms Seroconversion (3–12 weeks following infection) Flu-like symptoms with fatigue, fever, lymphadenopathy, sore throat, and arthralgia Erythematous papular rash and mouth ulcers Persistent generalised lymphadenopathy (swollen lymph nodes lasting > 3 months)   Chronic infection This is usually asymptomatic until complications of immunosuppression develop

Resistant Bacterial Infections

C. difficile This is a Gram-positive bacterium which colonises the gut in the absence of one’s commensal harmless bacteria. The commensal flora in the gut can be killed due to the use of broad-spectrum antibiotics, leaving the individual vulnerable to a C. diff infection. The bacteria make a toxin which leads to inflammation in the colon, causing pseudomembranous colitis. It is a common hospital-acquired infection and can spread rapidly between patients.   Causes Most commonly secondary to antibiotics beginning with the letter “C” like cephalosporins, clindamycin. Also associated with PPI use.   Symptoms Diarrhoea, abdominal pain, fever If severe, can

Bacterial Infections

Lyme disease This is a condition which is caused by the bacteria Borrelia burgdorferi. Transmission occurs via the Ixodes tick bite, so it is important to ask a detailed travel history to places where these ticks live e.g., forests, parks (e.g., Richmond Park in London has a higher incidence). It initially causes an expanding area of redness on the skin at the site of the tick bite. The bacteria can become systemic and spread to the heart, joints and CNS where they can persist for years. It is thought that the bacteria induce an autoimmune disease secondary to molecular mimicry,

URTI

Overview Upper respiratory tract infections (URTIs) are common self-limiting illnesses that present with coryzal symptoms. An upper respiratory tract infection (URTI) refers to inflammation of the mucosa of the nostrils, nasal cavity, mouth, throat (i.e. pharynx), and larynx that all constitute the upper respiratory tract. URTIs are very common and lead to symptoms of nasal stuffiness, runny nose, sneezing, sore throat, and cough. This collection of symptoms is often referred to as ‘coryza’. URTI is caused by a viral infection and there are numerous causative viruses including rhinovirus, adenovirus, and many others. URTI is colloquially known as the ‘common cold’ or more

Shingles

Overview Sepsis is a dysregulated host response to infection leading to life-threatening organ dysfunction. Sepsis is a commonly encountered problem in the healthcare setting and a major cause of morbidity and mortality. In its most simplistic form, sepsis is organ dysfunction secondary to an infection. It is regarded as a dysregulated host response to infection that is associated with both clinical and biochemical abnormalities. It can be difficult to understand sepsis because the terminology used to define the condition has changed over the years and there is no universal agreement. In addition, in clinical practice, we see organ dysfunction in many systemic diseases.

Sepsis

Overview Sepsis is a dysregulated host response to infection leading to life-threatening organ dysfunction. Sepsis is a commonly encountered problem in the healthcare setting and a major cause of morbidity and mortality. In its most simplistic form, sepsis is organ dysfunction secondary to an infection. It is regarded as a dysregulated host response to infection that is associated with both clinical and biochemical abnormalities. It can be difficult to understand sepsis because the terminology used to define the condition has changed over the years and there is no universal agreement. In addition, in clinical practice, we see organ dysfunction in many systemic diseases.

Meningitis

Overview Meningitis refers to inflammation of the meninges, which are the outer membranes covering the brain and spinal cord. Meningitis broadly refers to inflammation of the meninges, which may be due to a number of infectious and non-infective aetiologies. The most devastating of these is bacterial meningitis, which is a life-threatening condition and one of the major causes of infection-related deaths worldwide. In these notes, we predominantly focus on bacterial meningitis. Epidemiology The annual incidence of bacterial meningitis in developed countries is estimated at 2-5 per 100,000 population. Further epidemiological data is dependent on the underlying aetiology. Meningitis has been reported to

Malaria

Overview Malaria is a potentially life-threatening illness that is caused by the Plasmodium protozoa. Malaria is one of the most well known tropical diseases worldwide. In the UK, malaria is characterised by fever in travellers returning from endemic areas. Malaria is caused by the Plasmodium protozoa, which are transmitted to humans by Anopheles mosquitoes. These insects transmit the parasite following the bite of an infected female. There are five different types of Plasmodium protozoa that can cause malaria in humans. P. vivax P. falciparum P. ovale P. malariae P. knowlesi P. falciparum is associated with the most severe form of malaria, which can lead to multi-organ

Gram-positive infections

Introduction Bacteria are prokaryotic (single-celled) microorganisms that are found in both human health and disease. Bacteria range in size from approximately 0.5-5.0 micrometers in length and different in morphology. Typical shapes of bacteria include spheres (i.e. cocci) and rods (i.e. bacilli) . The human body is colonised with trillions of bacteria in normal health. This collective is known as the human microbiota and is important for normal functioning. Bacteria are also the cause of many clinically relevant infections in humans. Cell wall structure The general structure of a bacterium includes the cell wall, cell membrane, capsule, flagella, fimbriae, nuclear material, cytoplasm and other intracellular components.

Gram-negative infections

Introduction Bacteria are prokaryotic (single-celled) microorganisms that are found in both human health and disease. Bacteria range in size from approximately 0.5-5.0 micrometers in length and different in morphology. Typical shapes of bacteria include spheres (i.e. cocci) and rods (i.e. bacilli) . The human body is colonised with trillions of bacteria in normal health. This collective is known as the human microbiota and is important for normal functioning. Bacteria are also the cause of many clinically relevant infections in humans. Cell wall structure The general structure of a bacterium includes the cell wall, cell membrane, capsule, flagella, fimbriae, nuclear material, cytoplasm and other intracellular components. 

Gastroenteritis

Overview Gastroenteritis is a diarrhoea and/or vomiting illness due to an enteric infection. Gastroenteritis is an acute transient diarrhoeal illness with or without vomiting due to an enteric infection that may be viral, bacterial or parasitic. Common additional symptoms include nausea, fever and abdominal pain. Worldwide, acute infective diarrhoea is a major cause of mortality, particularly in children under 5 years old. In resource-rich settings (e.g. UK), gastroenteritis is usually a self-limiting illness with symptomatic treatment only. There are several terms used to describe gastroenteritis illnesses: Diarrhoea: ≥ 3 loose/watery stools per day Acute diarrhoea: diarrhoea that lasts < 14 days Persistent or

COVID-19

Introduction Coronavirus disease 2019 is a respiratory disease caused by the virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Coronavirus disease 2019 (COVID-19) emerged in 2019 in Wuhan, the capital of Hubei Province in China. On 8th December 2019, there were initial reports of an unusual pneumonia which following investigation was reported to the World Health Organisation (WHO) by the Chinese authorities on 31st December 2019. By January 2020, the causative organism of COVID-19 was identified as a novel coronavirus and termed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Unfortunately, the virus spread significantly throughout the world and was declared a pandemic on

Clostridium difficile

Overview Clostridium (now Clostridioides) difficile infection is one of the most well-recognised hospital-acquired infections. C. difficile (CD) is a gram-positive bacillus (rod-shaped), which is both spore-forming and toxin-producing. It is found in < 2% of healthy adults as a commensal organism within the bowel. This increases to 7% in patients within long-term care facilities and 3-26% among inpatient populations. There are two important strains of C. difficile: Toxigenic (70-90%): produce and release two exotoxins (A & B). Central to pathogenicity. Nontoxigenic (10-30%): cannot produce exotoxins. Colonises colon without causing disease. C. difficile infection (CDI) is an important hospital-acquired (nosocomial) infection that is responsible for 20-30% of

Cellulitis

Overview Cellulitis is an acute bacterial infection of the skin. Cellulitis refers to an acute bacterial skin infection that affects both the dermis and subcutaneous tissue. It may occur anywhere on the body and ranges form a self-limiting infection to severe necrotising infection. Cellulitis is a very common condition. It can occur at any age, but is mostly seen in middle-aged to older adults and usually affects the lower limbs. Aetiology & pathophysiology Cellulitis is commonly caused by both Streptococcus and Staphylococcus species. Cellulitis occurs due to disruption of the skin barrier (e.g. cut, abrasion), which allows entry of microorganisms. Both Streptococcus and Staphylococcus are common skin commensal organisms that can enter

Cellulitis

Overview Cellulitis is an acute bacterial infection of the skin. Cellulitis refers to an acute bacterial skin infection that affects both the dermis and subcutaneous tissue. It may occur anywhere on the body and ranges form a self-limiting infection to severe necrotising infection. Cellulitis is a very common condition. It can occur at any age, but is mostly seen in middle-aged to older adults and usually affects the lower limbs.     Aetiology & pathophysiology Cellulitis is commonly caused by both Streptococcus and Staphylococcus species. Cellulitis occurs due to disruption of the skin barrier (e.g. cut, abrasion), which allows entry