Infection Flashcards
Define candidiasis
Candidiasis refers to a mucocutaneous fungal infection with a Candida species, most commonly Candida albicans*
What is the aetiology of candidiasis?
The single-celled yeast Candida albicans is a normal commensal in the mouth, GI tract and vagina. However, certain factors can contribute to excessive Candida growth and a spectrum of clinical manifestations, ranging from local symptoms to severe invasive disease.
Name some risk factors for candidiasis:
Site: moist body folds, damage to skin/mucosal barriers, indwelling medical devices
Systemic: immunosuppression, recent antibiotics, diabetes mellitus, iron deficiency anaemia, pregnancy
Exposure: hospitalisation
What are the signs and symptoms of candidiasis:
Vulvovaginal: pruritis, thick white discharge, burning sensation
Cutaneous: erythematous, scaling macules with smaller outlying lesions
Oral: mucosal erythema with white flecks
yellowish plaques on the oral mucosa that are fairly adherent to the mucosa. On scraping, there is an erythematous base and mild bleeding
Systemic: severe illness in a vulnerable patient e.g. patients
What are the investigations for candidiasis?
Swabs - fungal and/or bacterial (especially if unresponsive to treatment or severe)
Bloods - FBC, iron studies, U&E, LFT’s, clotting,CRP, HbA1c, HIV testing, ABG/VBG (if ?sepsis)
Specific investigations for differential diagnoses e.g. STI screen, urine dip
Pregnancy test if appropriate
What is the overall management for candidiasis?
If a patient is systemically unwell, adopt an A-E approach, get help early and consider initiating the sepsis six. Patients with systemic candidiasis often have underlying conditions that put them at higher risk, so escalate early. Treatment involves systemic antifungals such as echinocandin, fluconazole or amphotericin B, alongside supportive measures.
What is the management for cutaneous candidiasis?
Conservative: advice on skincare, changing nappies regularly, weight loss if appropriate
Topical imidazole which is antifungal
What is the management for vulvovaginal candidiasis?
Conservative: washing with soap substitute, avoiding tight clothing, avoiding irritants
Medical: oral fluconazole or clotrimazole cream or pessary (in pregnancy)
An induction & maintenance regime of oral fluconazole may be needed
These treatments may be given with or without topical imidazole for vulval symptoms
What is the management for oral candidiasis?
Conservative: advice on good oral hygiene
Medical: miconazole oral gel first line, nystatin suspension second line
If HIV positive: oral fluconazole 200 mg on day one, followed by 100-200mg daily for 14 days
What are the complications of candidiasis?
Worsening of symptoms
Recurrence
Secondary bacterial infection
Invasive disease, organ dysfunction & shock
If oral miconazole is contraindicated (e.g. drug interaction such as simvastatin by inhibiting CYP3A4, increasing the risk of statin-induced myopathy and rhabdomyolysis), what is the preferred treatment for oral candidiasis.
Oral nystatin suspension
Define herpes simplex virus?
Herpes simplex viruses are large double-stranded DNA viruses. They are part of the herpes virus family, and predominantly cause oral, genital and ocular manifestations.
Primary infection is the first-time exposure to HSV in a seronegative (unexposed) person.
Recurrent infection is the reactivation of HSV, causing repeated symptoms.
What are the two types of herpes simplex virus and what do they cause?
HSV-1, causing oral, genital or ocular herpes
HSV-2, which usually causes genital herpes
Following initial infection, HSV becomes latent in the sensory ganglia and can subsequently reactivate, known as shingles.
What are the signs and symptoms of herpes simplex virus?
Oral: single painful ulcer along the lip border or gingivostomatitis
Genital: multiple painful vesicular lesions progressing to ulceration & crusted lesions, dysuria
Ocular: eye pain, irritation or photophobia, eye watering, blurred vision, acute red eye, visible vesicles around the eye, corneal abnormalities
Lymphadenopathy, malaise, fever
Tingling sensation or painful before lesion appears
What are the investigations for herpes simplex virus?
Methods of diagnosis depends on the site and severity of infection. For simple oral lesions, a clinical diagnosis will usually suffice. Genital herpes infection is usually confirmed with a viral swab for PCR. Higher risk circumstances requiring further work-up are:
Recurrent or unresolving lesions - suggesting an underlying cause or alternative diagnosis
If the patient is immunocompromised
Ocular herpes - requiring an examination with fluoroscein stain and visual acuity testing with subsequent slit-lamp examination & viral culture/PCR
During pregnancy - serology may be needed to differentiate between primary infection and reactivation
What is the treatment for herpes simplex virus?
Antivirals are the mainstay of treatment. Topical treatments are available over-the-counter.
Genital herpes requires oral aciclovir and a referral to GUM services. Recurrence with no risk of complications can be managed with self-care measures alone.
Oral herpes is usually treated with topical antivirals
Ocular herpes requires specialist management typically involving oral or topical antivirals.
Symptomatic management may involve analgesia, topical lidocaine, maintaining adequate hydration and wearing loose clothing. Measures to reduce risk of transmission are also important.
What is the guidance for herpes simplex virus when pregnant?
Genital herpes during pregnancy carries a risk of neonatal herpes simplex infection, which can be very serious if left untreated. Management depends on the stage of pregnancy and whether this is a primary or recurrent infection. Below is a summary of the RCOG/BASHH guidelines (2014):
Primary infection at less than 28 weeks’ gestation: aciclovir initially and regular prophylactic aciclovir from 38 weeks. Can consider vaginal delivery (specialist decision).
Primary infection at greater than 28 weeks’ gestation: aciclovir during initial infection followed by regular prophylactic aciclovir. Usually requires caesarean section delivery.
Recurrent HSV typically carries a lower risk of neonatal infection, but it is important to avoid a prolonged rupture of membranes and prophylactic aciclovir may be considered on specialist advice.
What are the complications of herpes simplex virus?
Oral: dehydration, eczema herpeticum, adhesions, erythema multiforme, spread to trachea/lungs/oesophagus
Progressive multifocal coalescing lesions, urinary retention, increased risk of HIV infection, neonatal HSV
Ocular: corneal scarring damage & visual impairment
Secondary infection
Autoinoculation of other areas
Systemic infection including meningitis, encephalitis, hepatitis
What is a hospital acquired infection?
A hospital-acquired infection, or healthcare-associated infection, is an infection which occurs due to contact with a healthcare setting or healthcare interventions.
What are the common hospital acquired infections?
Common pathogens are:
Meticillin-resistant Staphylococcus aureus
Meticillin-sensitive Staphylococcus aureus
PVL - Staphylococcus aureus
Clostridium difficile
Escherichia coli
Pseudomonas - common cause of hospital acquired pneumonia
Which risk factors can increase the risk of healthcare associated infections?
Healthcare-specific: indwelling urinary catheters, vascular access devices
Person-specific: genetics, specific immunity, comorbidities such as malnutrition, alcoholism, immunocompromise
Specific risk factors exist for each pathogen
Name some common types of hospital acquired infections?
Common types of healthcare-associated infection are:
Respiratory, including hospital-acquired pneumonia
Urinary tract infections
Surgical site infections
There must be a temporal link between healthcare interaction and infection developing. For example, hospital-acquired pneumonia is a pneumonia with onset more than 48 hours after admission.
What do we treat hospital acquired pneumonia?
co-amoxiclav is used first-line where there is less risk of resistance. For severe cases or increased risk of resistance, options include piperacillin with tazobactam, cephalosporins or meropenem. If MRSA is a possibility, add a glycopeptide like vancomycin or teicoplanin.
What do we treat Catheter-associated urinary tract infections
can usually be managed with a 7 day course of nitrofurantoin or trimethoprim (for lower UTI’s) or cefalexin (for upper UTI’s).
What do we treat Indwelling line sepsis?
usually treated with vancomycin, with or without a broad-spectrum beta-lactam (see below).
How do we prevent healthcare associated infections?
Hand hygiene: correctly washing hands or using alcohol gel before & after any contact with a patient or healthcare environment (see the 5 steps of hand hygiene)
Personal protective equipment: use of gloves, aprons, face masks & eye protection as indicated by local protocols for patient contact
Safe use & disposal of sharps
Use of aseptic non touch technique for procedures
Correct waste disposal & laundry management
Prompt and appropriate management of blood & body fluid spillages
Equipment decontamination
Regular cleaning of the healthcare environment
Specific precautions for vascular access devices & urinary catheters
What do we treat Undifferentiated hospital-acquired septicaemia
should be treated with a broad-spectrum beta-lactam antibiotic with pseudomonas cover. Examples include piperacillin with tazobactam, ceftazidime or meropenem. Vancomycin or metronidazole may be needed for MRSA or anaerobic cover respectively.
Define Primary HIV infection
Primary HIV infection, or HIV seroconversion illness, is the phase that commences immediately after the initial exposure to the Human Immunodeficiency Virus (HIV). This phase is characterised by a surge in viral replication and often coincides with the onset of clinical symptoms.
Advanced HIV disease, also known as AIDS, is defined as very low CD4 cell levels and the development of opportunistic infections or malignancies also known as AIDS-defining illnesses.
What is the aetiology of HIV infections?
HIV, specifically HIV-1 and HIV-2, are retroviruses that cause primary HIV infection. They are predominantly transmitted through sexual contact, parenteral exposure (e.g., injection drug use, needlestick injury), or from mother to child during childbirth or breastfeeding. HIV infects the CD4+ T-cells, integrating its DNA into the host genome which is then transcribed into viral proteins.
What are the distinct stages of HIV infections?
Primary HIV infection, which is associated with symptoms and high infectivity along with immune activation.
Asymptomatic phase, associated with a low transmission risk. As viral diversity increases, the virus befins to evade the immune response.
Advanced HIV disease (AIDS) whereby the immune system is compromised giving rise to opportunistic infections and malignancies
What are some of the initial signs and symptoms of HIV infections?
Typically, individuals with primary HIV infection experience a mild flu-like illness 2-6 weeks post-exposure. The range of clinical manifestations can span from a mild glandular fever-like syndrome to an evolving encephalopathy. Classic presentations include:
Fever
Lymphadenopathy
Maculopapular rash (commonly found on the upper chest)
Mucosal ulcers
Myalgia
Arthralgia
Fatigue
Symptom onset within 3 weeks of infection, lasting longer than 2 weeks or involving the central nervous system (CNS), is associated with rapid progression to AIDS. It’s worth noting that some individuals might remain asymptomatic.
What are the long standing HIV symptoms?
Constitutional symptoms
Respiratory conditions such as pneumocystis pneumonia (classically causes reduced SpO2 on exertion), tuberculosis or recurrent respiratory infections
Neurological symptoms of cryptococcal meningitis, cerebral toxoplasmosis, cerebral lymphoma, cytomegalovirus retinitis
Malignancies including lymphoma, Kaposi’s sarcoma (dark purple/brown skin lesions), cervical cancer
Skin conditions: fungal skin & nail, viral and bacterial infections - especially severe or recurrent
Oral conditions such as candidiasis, ulcers, oral hairy leukoplakia
Gastrointestinal: oesophageal candidiasis, diarrhoea, hepatitis infections
Genital: candida, genital herpes & warts - especially if severe
Unexplained FBC abnormalities
What are the investigations for a primary HIV infection?
Laboratory tests: a venous blood sample is taken and sent to a laboratory for testing. Third-generation tests detect IgM and IgG antibodies, with highest sensitivity during the initial seroconversion period. The window period for third-generation tests is 60 days. Fourth-generation tests also detect serology as well as the p24 antigen, with a window period of 45 days.
Point of care tests: these are similar to third-generation laboratory tests but can be performed in the community with a fingerprick testing kit. The window period for these is 90 days. A confirmatory laboratory test is required for diagnosis.
Where there is uncertainty, molecular assays are sometimes used.
A range of tests are then performed to facilitate treatment decisions. These may include:
FBC, U&E, LFT’s, liver, bone profile, lipids, HbA1c, TB testing, CXR, ECG, toxoplasma serology
Sexual health screen
Viral load, genotype testing, tropism tests, HLA testing, CD4 count and CD4:8 ratio
What is the treatment for a primary HIV infection?
All patients diagnosed with primary HIV infection should be offered combination antiretroviral therapy (cART), regardless of their CD4 count. This may involve a combination of three drugs, including:
Reverse transcriptase inhibitors
Nucleoside (NRTIs) e.g. Tenofovir, Abacavir, Emtricitabine, Lamivudine, Zidovudine
Non-nucleoside (NNRTIs) e.g. Efavirenz, Nevirapine, Rilpivirine
Protease inhibitors e.g. Darunavir, Lopinavir/ritonavir, Saquinavir
Integrase inhibitors e.g. Dolutegravir, Raltegravir
CCR5 antagonist e.g. Maraviroc
Fusion inhibitors e.g. Enfuvirtide
A typical regime will include two nucleoside reverse transcriptase inhibitors and one additional drug.
Contact tracing is necessary to identify and notify individuals who may have been exposed to the virus. Regular monitoring and appropriate management of any comorbid conditions are also integral to the care of these patients.
Pre- or post- exposure prophylaxis can be offered to those who may be/have been exposed to reduce transmission risk.
Name some opportunistic infections due to HIV:
Pneumocystis pneumonia
This is a fungal infection caused by Pneumocystis Jirovecii and affects immunocompromised people, including those with HIV. Typically patients present with a subacute onset of fever, dry cough and exertional breathlessness. Patients desaturate on walking short distances, and chest X-ray may be normal or show bilateral infiltrates. Definitive diagnosis requires a sputum or broncho-alveolar lavage sample with silver staining. Management is with co-trimoxazole, with steroids for moderate-severe cases, and supportive care. Patients may be offered prophylactic co-trimoxazole if they have very low CD4 counts or have had a previous pneumocystis pneumonia.
Candidiasis
While this is a common condition in the general population, those with HIV may develop more severe or widespread infections. They may develop oesophageal candidiasis which causes painful or difficult swallowing. It is usually treated with oral fluconazole. They may require referral for biopsy if unresponsive to treatment due to malignancy risk.
Cytomegalovirus
This is a common viral infection remains latent in the body following primary infection. In immunocompromised states - such as advanced HIV - it can reactivate and cause a range of problems. Patients may experience visual changes due to CMV retinitis, polyradiculopathy, respiratory problems or gut symptoms. Ganciclovir is the first-line treatment for CMV infection.
Cryptococcal meningitis
Cryptococcus is a fungal infection that primarily affects immunocompromised people. This usually presents as a subacute meningitis involving headache, fever, altered mental status and cranial nerve deficits. Diagnosis is with CSF analysis cultured and stained with India ink. Treatment involves an induction regime with amphotericin B alongside supportive treatment, followed by a maintenance regime of fluconazole.
Cerebral toxoplasmosis
This occurs due to reactivation of a toxoplasmosis infection. It typically presents with altered mental state, headache, seizures, focal neurology and fevers. MRI is most sensitive for diagnosis and will show multiple ring enhancing lesions of toxoplasma abscesses. Treatment is with pyrimethamine, sulphadiazine and folinic acid for 6 weeks followed by a maintenance regime.
Mycobacterial disease
Patients may with severe tuberculous disease, and the two often co-exist. However, patients with HIV are also susceptible to non-tuberculous mycobacterial disease including disseminated M. avium complex. Patients often present non-specifically with fever, night sweats, gastrointestinal upset, fatigue and anorexia. Diagnosis is based on cultures and treatment is with combination antibiotic regime.
Name some HIV associated malignancies:
Kaposi’s sarcoma
This is caused by human herpes virus 8 (HHV-8). It causes multiple lesions on the skin, mucous membranes and internal organs, which may be purple, red or brown. It is often recognised clinically, though definitive diagnosis requires biopsy. Treatment generally involves combination antiretroviral therapy to manage the underlying immunodeficiency, though systemic anticancer therapy may be needed.
LANA1 (latent nuclear antigen 1) is usually expressed by Kaposi’s sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV-8).
Lymphoma
EBV-associated lymphomas are more common in HIV patients as their immune system is less effective at clearing the EBV virus. They may present with enlarging lymph nodes, night sweats, fevers and weight loss. Diagnosis is with biopsy and management is with systemic chemotherapy in conjunction with oncology.
Cervical cancer
Patients with HIV are less able to clear HPV infections that can lead to cervical cancer. As a consequence, they are at increased risk of developing cervical cancer and undergo annual cervical screening.
Name some additional complications of HIV:
Progressive muscle wasting & weakness
Diarrhoea
Neurological problems
Mental health problems
Metabolic abnormalities and cardiovascular disease
Renal disease
Osteoporosis
Define AIDS:
AIDS is the terminal stage of HIV infection where combination antiretroviral therapy (cART) has not halted the spread of the virus. It is defined by the presence of an AIDS-defining illness alongside a CD4 count of less than 200 cells/mm³.
In immunocompromised patients, such as those with HIV and a low CD4 count, Mycobacterium avium intracellulare can cause abdominal pain due to lymph node enlargement. What does this show on blood tests:
resulting in elevated levels of alkaline phosphatase and lactate dehydrogenase.
Define gastroenteritis:
Gastroenteritis: an enteric infection causing acute-onset diarrhoea, with or without associated symptoms
Define food poisoning:
Food poisoning: illness caused by eating or drinking substances contaminated with disease-causing pathogens, toxins or chemicals.
Define acute diarrhoea:
Acute diarrhoea: 3+ episodes liquid/semi-liquid stools in in a 24h period, lasting less than 14 days
Define prolonged diarrhoea:
acute-onset diarrhoea lasting over 14 days
Define dysentery:
is acute infectious diarrhoea with blood & mucus, often with associated symptoms
What are the three most common viruses causing gastroenteritis:
Most cases of infectious diarrhoea are spread by the faeco-oral route and are caused by viruses. These include:
Norovirus: most common cause in the population, and often causes outbreaks. Typically causes projectile vomiting and non-bloody diarrhoea.
Rotavirus: the most common cause of gastroenteritis in children.
Adenovirus: typically causes respiratory tract infections but may cause gastrointestinal symptoms in children.
Name some common bacterial causes of gastroenteritis:
Campylobacter: often associated with contaminated food & drink (in exams: a recent barbeque!), this is the most common cause of bacterial gastroenteritis in the UK. On microscopy, gram-negative rods are seen with characteristic ‘seagull’ shape, which release enterotoxin in the gut and invade the mucosa. Incubation period is 16-48 hours and may cause bloody diarrhoea, though vomiting is rare.
E. coli: the most common cause of traveller’s diarrhoea. In the UK, O157:H7 is the most common type and may cause bloody diarrhoea. Sources include improperly cooked meat. Associated complications include haemolytic uraemic syndrome, which typically affects the very young are old and can be fatal.
Salmonella is associated with consumption of contaminated foods, particularly poultry, eggs and milk. These are gram negative bacteria with an incubation of 16-48 hours. Salmonella can cause bloody diarrhoea and is associated with complications such as sepsis, endocarditis, mycotic aneurysm and osteomyelitis.
Cholera is associated with contaminated water supplies and causes very watery diarrhoea associated with dehydration.
Shigella and Yersinia tend to occur in children. The former can cause severe, bloody diarrhoea.
Bacillus cereus are gram-positive rods that produce two toxins causing diarrhoea and vomiting within hours of eating contaminated food (in exams, this is usually reheated rice).
Staphylococcus aureus produces a heat-stable enterotoxin that causes profuse vomiting with mild diarrhoea and abdominal pain. The incubation period is short (under 6 hours) after eating contaminated foods. The bacteria are usually introduced from the skin of the person preparing the food. Foods which do not require cooking carry greater risk.
Name some parasites causing gastroenteritis:
Cryptosporidium: a protozoal infection which may cause prolonged symptoms
Entamoeba histolytica: most cases are mild but severe cases cause dysentery
Giardia: causing diarrhoea, constitutional symptoms and bloating which may be prolonged
What are the signs and symptoms of gastroenteritis:
Sudden-onset diarrhoea, with or without blood
Faecal urgency
Nausea & vomiting
Fever, malaise
Abdominal pain
Associated symptoms specific to the cause
What are the different classifications of clostridium difficile?
What is the serology in hepatitis B:
A positive hepatitis B surface antigen (HBsAg) signifies current infection, either acute or chronic. The anti-HBc antibodies indicate at what stage the infection is. During acute infection, anti-HBc IgM is positive. Then anti-HBc IgG becomes positive in chronic infection or in resolution of infection and remains positive. The HBeAg indicates viral replication. This is negative here and the anti-HBe antibody is positive, indicating a low viral load.
