LO: List the most common important viral pathogens that affect particular groups of patients

Influenza viruses

• Acute viral infection of the respiratory tract
• Three types: A, B and C
• A and B are responsible for most clinical illness
• Highly infectious with usual incubation period of 1-3 days
• Frequent antigenic changes, seasonality and impact on general population
• Explosive outbreaks of febrile respiratory illness
• Substantive morbidity and mortality - particularly in people with chronic diseases

Risk of complications

• Lower respiratory tract infection
• Admission to hospital
• Death
• Depends on factors such as age and the type of comorbidity

'At risk groups'

• Influenza in 'at risk groups' means infection in people who are more likely than others to develop severe disease if they should be infected
• Chronic respiratory system diseases
• Cardiovascular system diseases
• Endocrine system diseases
• Hepatic system diseases
• Renal system diseases
• Neurological/neuromuscular conditions
• Any condition compromising respiratory functions
• Immunosuppression
• Antenatal women

Management

• Immunisation with inactivated influenza vaccine
• Exposure prophylaxis - prevent serious infection

Treatment

• Oseltamivir, Zanamivir - neuraminidase inhibitors
• Polymerase acidic protein (subunit of the influenza virus RNA polymerase complex) inhibitor - baloxavir

Vaccines

• Live attenuated vaccine
• Inactivated influenza vaccine
• Trivalent adjuvanted inactivated vaccine
• New mRNA vaccines

Respiratory syncitial virus (RSV)

• Major cause of lower respiratory tract infection in young children and adults
• Commonest cause of severe respiratory infection in infants
• 3.4 million hospitalisations and 66'000 deaths worldwide each year
• Very infectious and spreads with ease

Impact

• Life threatening lower respiratory tract infections in the first two years of life
• Healthcare costs of hospital admission due to RSV - millions

Epidemiology

• Prematurity - low birth weight
• Congenital cardiopulmonary disease
• Immunodeficiency
• Maternal smoking
• Male sex
• Overcrowding
• Lack of breastfeeding
• Low socio-economic status

Virology

• Paramyxoviridae family
• RSV/A and RSV/B

Transmission

• Small inoculum needed to infect
• Transmitted by respiratory secretions
• Direct contact
• Via fomites
• Large droplets
• Entry occurs through contact with nasal mucosa or eyes
• Incubation period varies from 2-8 days

Pathogenesis

• Earliest lesion - necrosis of the bronchiolar epithelium with denudation of ciliated epithelial cells
• Lymphocytes migrate into affected tissue
• Submucosa and adventitia become oedematous
• Increased secretion from mucous-producing cells
• Plugs consisting of mucous, cellular debris, fibrin strands occlude the smaller bronchioles

Manifestations

• Bronchiolitis
• Bronchitis
• Pneumonia
• Laryngitis
• Expiratory wheezing
• Cough and coryza
• Air trapping
• Nasal flaring
• Subcostal retractions
• Cyanosis
• Fever

Diagnosis

• Clinical
• Nasopharyngeal aspirate
• Nasal swabs
• Endotracheal aspirate
• Nucleic acid detection (Rt-PCR)
• Antibody

Prophylaxis

• Active immunoprophylaxis - maternal immunisation with RSV vaccine
• Passive immunoprophylaxis - long-acting recombinant human monoclonal antibodies blocking the fusion protein of RSV

Recommendations for the use of passive immunisation

• High risk due to bronchopulmonary dysplasia (BPD) - chronic lung disease
• High risk due to congenital heart disease (CHD)
• High risk due to severe combined immunodeficiency syndrome (SCID)

Treatment

• Healthy children and immunocompetent healthy adults require supportive treatment only
• Hypoxemia, apnoea and poor oral intake in children under 1 years require hospitalisation
• Inspired O₂ concentration and IV fluid may be required
• Antibiotics only if bacterial superinfection
• Antiviral treatment:
  • Ribavirin aerosol for treatment of RSV in children
• Duration of therapy in immunocompromised ~ 5 days

Other respiratory viral infections

• Seasonal human coronaviruses
• Seasonality unpredictable
• URI symptoms, sore throat, dry cough, rarely pneumonia
• URI viruses: rhinovirus, adenovirus, parainfluenza 1-4

SARS-CoV-2

• Causative agent of the COVID 19 pandemic

Transmission

• Arial droplets
• Incubation 2-10 days
• Symptom onset median: day 4-5 from exposure
• High viral shedding occurs early in disease course even those with mild symptoms
• Prolonged shedding noted
• Reinfection possible
• Asymptotic cases
• Hand-to-mucus-membrane contact, sticks to skin easily
• Airborne, fecal

Symptoms and course

• Fever or chills, cough, difficulty breathing, fatigue, muscle/body aches, headache, lost of taste or smell, sore throat, runny nose, nausea, vomitting, diarrhoea
• Week 2: ~15-20% develop severe dyspnoea requiring hospitilisation
• Week 2-3: 1/3 will need ITU care
• Rapidly decline from mild hypoxia to frank ARDS
• Cytokine storm, multi-organ failure
• Late stage sudden cardiomyopathy/viral myocarditis, cardiac shock

Comorbidities and risk conditions

• Age
• Hypertension
• Diabetes mellitus
• Coronary heart disease
• COPD
• Immunosuppression

Diagnosis

• Presenting symptoms
• Chest - rales or rhonchi
• Tachycardia and tachypnoea
• Present as severe asthma or COPD exacerbation
• Hypoxia
• High CRP, high ferritin associated with greater illness severity

Radiography

• Bilateral air space consolidation on CXR
• Unremarkable chest radiographs early in disease
• Bilateral, peripheral ground glass opacities in CT
• CT imaging pattern is non-specific

Diagnostic tests

• Nose and throat swab for RT-PCR
• POCT (point of care testing) - RT-PCR
• Antigen tests - lateral flow

Treatment

• Asymptomatic and very mild symptoms - no treatment
• Antiviral therapy - molnupiravir, remdesivir
• MAB - ronapreve
• Glucocorticosteroid, oxygen

Human immunodeficiency virus (HIV)

• HIV-1 and HIV-2 are enveloped viruses
• Family Retroviridae, genus Lentivirus
• RNA viruses
• Reverse transcribe their genome to form double stranded DNA which integrates into host genome
• Four genetic groups of HIV-1 (M, M, O and P)
• HIV-1 group M viruses dominate the pandemic

Transmission

• Blood
• Semen
• Vaginal secretions
• Breast milk
• Comes into contact with mucous membranes, damaged tissues or injected into body
• Vaginal, anal or oral sex
• Contaminated needles
• IV drug use
• Key populations: yaoi sex, drug injectors, prisoners, sex workers/clients and trasngender people
  
• Perinatal transmission during pregnancy, labour and delivery or breastfeeding
• Occupational exposure via needle stick or eyes, nose or open wound
• Blood transfusion/organ donation from HIV infected donor

Manifestations

• Symptomatic primary infection occurs in 30-70% of the infected
• Fever, Pharyngitis, Headache, Myalgia, Arthralgia, Malaise, Non-pruritic, Generalised lymphadenopathy
• Dermatological disorders - dermatitis
• CNS disorders - HIV dementia complex
• PNS - toxic neuropathy
• Respiratory - interstitial pneumonitis
• Mouth - xerostomia
• Blood - anaemia, neutropenia

CD4 count

• Laboratory test
• Measures state of a person's immune function
• 500-1300 in adults
• Determine stage of HIV progression
• Determine risk of opportunistic infection
• Guided decisions about antiretroviral therapy

Virological tests

• Serological diagnosis: combines antibody/antigen detection
• HIV-1 RNA virus load after serology
• Detects amount of virus
• Monitors effectiveness of antiretroviral therapy (ART)
• Used in acute infection to detect virus
• Measured by HIV-1 RNA RT-PCR
• All HIV testing services must follow the WHO-recommended principles "5 Cs":
  • Informed consent
  • Confidentiality
  • Counselling pre and post testing
  • Correct test results
  • Connection (link to care, treatment and other HIV services)

Management

• No cure for HIV
• Effective antiretroviral drugs (ARVs) can control the virus and help prevent onward transmission to other people
• If HIV-positive person adheres to an effective ART, risk of transmitting the virus reduced by 96%
• Oral pre-exposure prophylaxis (PrEP) fo HIV is the daily use of ARVS by HIV-negative people to block the acquisition of HIV

Antiretroviral treatment

• Nucleoside reverse transcriptase inhibitors (NRTIs)
• Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
• Protease inhibitors (PIs)
• Integrase inhibitors (INSTIs)
• Fusion inhibitors (FIs)
• Chemokine receptor antagonists (CCR5 antagonists)
• Always use 3 or more different ARV medications for therapy

Acquired immunodeficiency syndrome (AIDS)

• HIV infected patients develop AIDS in the absence of treatment
• Median time: 8-10 years
• Average loss of 30-60 CD4+ cells/$\mu$l per year in the absence of treatment
• Opportunistic infections
• Oncological complications
• Cardiovascular complications
• CNS complications

Diagnosis

• HIV positive patient has a CD4 count of less than 200 or 14% if the patient is diagnosed with an AIDS defining condition
• Combined treatment with 3 antiretroviral drugs is essential in preventing the onset of AIDS

LO: Mechanism of disease, treatment and prevention