1
Q
What are the two main types of influenza vaccines?
A
- Inactivated split vaccine
- Replication-competent attenuated (live) vaccine
- Composition updated yearly to match circulating strains
These vaccines are crucial for preventing influenza infections.
2
Q
Why could SARS-CoV-2 vaccines be developed so quickly?
A
- Existing mRNA & viral-vector platforms already in development
- Prior research on SARS-CoV-1 / MERS spike proteins
- Massive global funding and parallel clinical trial phases
- High incidence → rapid recruitment and efficacy read-outs
The rapid development was unprecedented in vaccine history.
3
Q
Why was smallpox eradication possible, but SARS-CoV-2 and influenza eradication are unlikely?
A
- Smallpox: human-only reservoir, stable DNA virus, lifelong immunity after infection/vaccine
- Clear clinical presentation → easy case detection
- Vaccines provided sterilising, durable immunity
- SARS-CoV-2 & influenza: animal reservoirs, asymptomatic transmission
- High mutation rates & antigenic change → immune escape
- Vaccines often non-sterilising, immunity wanes
The differences in virus characteristics significantly affect eradication efforts.
4
Q
Key general points about vaccines and side effects?
A
- Vaccines have saved hundreds of millions/billions of lives
- No pharmacological treatment is completely side-effect-free
- ~3,000 deaths/year estimated from aspirin
- Smallpox vaccine: ~1 death per 1,000,000 doses
- Vaccine-induced polio can occur with live polio vaccine
- Rare links to Guillain–Barré syndrome for some vaccines
Understanding the risk-benefit ratio is essential in vaccine administration.
5
Q
Rare serious adverse events of COVID-19 vaccines?
A
- Oxford/AstraZeneca: thrombosis with thrombocytopenia syndrome (TTS)
- mRNA vaccines (Pfizer/Moderna): rare myocarditis and pericarditis
Monitoring for adverse events is crucial for vaccine safety.
6
Q
How is vaccine safety ultimately judged?
A
By risk–benefit balance
The benefits in preventing severe disease and death must outweigh rare adverse events.
7
Q
How can Wolbachia bacteria help prevent viral disease?
A
- Wolbachia infecting Aedes mosquitoes reduces Dengue virus transmission
- Wolbachia-infected Aedes released in Brazil as a control strategy
This innovative approach targets the vector rather than the virus itself.
8
Q
What is the origin of HIV-1 and HIV-2?
A
- HIV-1: from SIVcpz (chimpanzee) and SIVgor (gorilla) via spill-over events
- HIV-2: from SIVsmm (sooty mangabey)
- HIV-1 group M causes the global pandemic
Understanding the origins helps in studying the virus’s evolution.
9
Q
How is HIV transmitted?
A
- Sexual transmission (body fluids)
- Vertical via breast milk
- Blood exposure: needle sharing, contaminated blood products
- Not highly contagious compared to many viruses
Awareness of transmission routes is vital for prevention strategies.
10
Q
Global HIV / AIDS pandemic figures (approximate)?
A
- ~44.1 million deaths to date
- ~40.8 million living with HIV (end of 2024)
- 2024: ~630,000 deaths, 1.3 million new infections
These statistics highlight the ongoing impact of the pandemic.
11
Q
What are the 95-95-95 UNAIDS targets and current progress (2024)?
A
- 95% of PLHIV diagnosed
- 95% of those on treatment
- 95% of those treated with suppressed viral load
- 2024 reality: 87% knew status, 77% on ART, 73% with suppressed viral load
These targets aim to improve global health outcomes for people living with HIV.
12
Q
Which cells does HIV primarily replicate in?
A
- CD4+ T helper lymphocytes
- Monocytes
- Macrophages
- Langerhans cells
Targeting these cells is crucial for effective treatment strategies.
13
Q
Outline the steps of HIV entry into host cells.
A
- gp120 binds CD4 receptor
- Conformational change exposes gp41
- gp41 inserts fusion peptide into host membrane
- Co-receptors: CCR5 (monocyte–macrophage lineage) or CXCR4 (CD4+ T cells)
- Viral envelope fuses with cell membrane; capsid enters and uncoats
Understanding these steps is essential for developing entry inhibitors.
14
Q
Which drugs target HIV entry?
A
- Maraviroc: CCR5 inhibitor (needs tropism test)
- Enfuvirtide: gp41 fusion inhibitor
These drugs are part of the antiretroviral therapy arsenal.
15
Q
Why are people lacking CCR5 relatively resistant to HIV infection?
A
- CCR5 is a key co-receptor for viral entry
- Loss-of-function CCR5 (e.g. Δ32 mutation) prevents CCR5-tropic HIV from entering cells
This genetic mutation provides a natural form of resistance.
16
Q
What are the three main classes of reverse transcriptase inhibitors?
A
- NRTIs (nucleoside RT inhibitors)
- NtRTIs (nucleotide RT inhibitor)
- NNRTIs (non-nucleoside RT inhibitors)
These classes are crucial for HIV treatment regimens.
17
Q
Give examples of NRTIs.
A
- Zidovudine (AZT)
- Didanosine
- Zalcitabine
- Stavudine
- Lamivudine
- Abacavir
- Emtricitabine
- (Also: entecavir, apricitabine)
NRTIs are foundational in HIV therapy.
18
Q
Which drug is the classic NtRTI used for HIV?
A
Tenofovir
Tenofovir is widely used due to its efficacy and safety profile.
19
Q
Give examples of NNRTIs.
A
- Efavirenz
- Nevirapine
- Delavirdine
- Etravirine
- Rilpivirine
NNRTIs are important for combination therapy in HIV treatment.
20
Q
What do integrase inhibitors do and name some examples.
A
- Block integration of viral cDNA into host genome
- Examples: raltegravir, elvitegravir, dolutegravir, cabotegravir
These inhibitors are critical in modern HIV treatment regimens.
21
Q
Role of HIV protease and examples of protease inhibitors.
A
- Cleaves Gag and Gag-Pol polyproteins during virion maturation
- Inhibitors: lopinavir, indinavir, nelfinavir, amprenavir, ritonavir, darunavir, atazanavir, saquinavir
Protease inhibitors are essential for preventing viral replication.
22
Q
Why is curing or eradicating HIV so difficult?
A
- Virus integrates into host genome → latent reservoirs
- Long-lived infected cells (memory T cells)
- Ongoing low-level replication even on ART
- No vaccine providing sterilising immunity yet
These challenges complicate treatment and eradication efforts.
23
Q
General properties of herpesviruses relevant to therapy.
A
- Enveloped dsDNA viruses with large genomes
- Cause latent, recurrent infections
- Found in many animals including humans
- Some are oncogenic (e.g. EBV, HHV-8)
Understanding these properties aids in developing antiviral therapies.
24
Q
Which human cancers are associated with herpesviruses?
A
- EBV → various lymphomas, nasopharyngeal carcinoma
- HHV-8 → Kaposi’s sarcoma
- HCMV: suspected links to several cancers (e.g. glioblastoma, prostate)
These associations highlight the importance of monitoring viral infections in cancer patients.
25
What do most **anti-herpesvirus drugs** target?
* Viral DNA polymerase (directly or indirectly)
* Especially UL54 DNA polymerase in HCMV
## Footnote
Targeting viral replication is key in herpesvirus treatment.
26
Why is **resistance** a major issue in HCMV therapy?
* Ganciclovir, cidofovir & foscarnet all target UL54
* UL54 mutations can confer cross-resistance to all three
* Used heavily in immunocompromised patients → selection pressure
## Footnote
Resistance development complicates treatment options.
27
Which newer **HCMV drugs** overcome UL54 resistance and how?
* Maribavir: UL97 kinase inhibitor
* Letermovir: terminase complex inhibitor
## Footnote
These drugs provide alternative treatment options for resistant strains.
28
Basic properties of **influenza viruses** relevant to antivirals.
* Orthomyxoviruses
* (–)ssRNA segmented genome
* Polymorphous particles (spherical or filamentous)
* Cause respiratory illness; can progress to pneumonia
## Footnote
Understanding these properties is crucial for antiviral development.
29
Why are **adamantanes (M2 inhibitors)** no longer used for influenza?
* Only act on influenza A
* Limited activity
* Rapid resistance development
* Significant side effects
## Footnote
These factors led to the discontinuation of their use.
30
Compare **zanamivir and oseltamivir** (neuraminidase inhibitors).
Zanamivir:
* Inhaled dry powder via Diskhaler
* Must start within 48 h of onset
* Difficult for very young/old, intubated, or very sick patients
Oseltamivir:
* Oral, ~80% bioavailability
* Also requires early start (<48 h)
## Footnote
Both are effective but have different administration routes and patient considerations.
31
What are the main **SARS-CoV-2 antiviral drugs** and their targets?
* Remdesivir: RNA-dependent RNA polymerase inhibitor
* Nirmatrelvir (with ritonavir): main protease (Mpro/3CLpro) inhibitor
* Molnupiravir: nucleoside analogue causing lethal mutagenesis of viral RNA
## Footnote
These drugs are pivotal in managing COVID-19.
32
Why are **antiviral drugs** of limited use in severe COVID-19?
* Severe disease driven by hyper-inflammation (“cytokine storm”)
* Viral load already declining by the time severe symptoms appear
* Antivirals only useful very early, in high-risk patients
## Footnote
Timing of administration is critical for effectiveness.
33
How are **immunosuppressants/immunomodulators** used in COVID-19?
* Reduce mortality in severe disease
* Used in patients needing oxygen or mechanical ventilation
* Target inflammatory pathways rather than the virus itself
## Footnote
These treatments focus on managing the body's response to the virus.
34
Key features of **hepatitis C virus (HCV)**.
* Flavivirus, enveloped (+)ssRNA
* Blood-borne (needles, transfusions), low sexual/vertical transmission
* ~50 million chronically infected worldwide
* Chronic infection → cirrhosis & hepatocellular carcinoma
## Footnote
Understanding HCV is crucial for public health and treatment strategies.
35
Traditional (older) **HCV treatments** and issues.
* Pegylated interferon-α
* Ribavirin
* Low efficacy
* Substantial toxicity and side-effects
## Footnote
These treatments have largely been replaced by more effective therapies.
36
What are **directly acting antiviral agents (DAAs)** for HCV and their impact?
* Target viral NS3/4A protease, NS5A, or NS5B polymerase
* High efficacy, low toxicity
* 95% of chronic HCV patients can be cured
## Footnote
DAAs represent a significant advancement in HCV treatment.
37
Give examples of **NS3/4A, NS5A, and NS5B HCV inhibitors**.
* NS3/4A: boceprevir, telaprevir, glecaprevir, paritaprevir, grazoprevir, voxilaprevir
* NS5A: daclatasvir, ledipasvir, ombitasvir, elbasvir, velpatasvir
* NS5B: sofosbuvir, dasabuvir
## Footnote
These inhibitors are key components of modern HCV therapy.
38
General final remarks on **antiviral drugs**.
* Available for only a limited number of viruses
* Work best in chronic infections; less effective in acute immunopathologic disease
* Usually target virus-specific enzymes or structures
* Resistance formation is a major concern
## Footnote
Understanding these factors is essential for effective antiviral therapy.
39
For **Ebolavirus**, what does the basic reproductive number (R0) tell us?
* Average number of secondary cases from one infected person
* Data show R0 from ~0.36 to 12; >4 at early outbreak stages
* Superspreading events can reach R0 ~20
## Footnote
R0 is crucial for understanding outbreak potential.
40
How do you calculate the **herd immunity threshold (Ic)**?
Ic = 1 – 1/R0
## Footnote
This formula helps determine the level of immunity needed to prevent disease spread.
41
What is the **critical vaccine coverage (Vc)** and its formula?
* Proportion of population that must be effectively vaccinated to achieve herd immunity
* Vc = Ic / E (E = vaccine effectiveness)
## Footnote
This calculation is essential for vaccination strategies.
42
Example: At R0 = 4 and vaccine efficacy 90%, what **Vc** is needed?
* Ic = 1 – 1/4 = 0.75 (75%)
* Vc = 0.75 / 0.9 ≈ 0.83 → >80% vaccination required
## Footnote
This example illustrates the importance of high vaccination rates.
43
Why is achieving **herd immunity** against Ebolavirus via mass vaccination unrealistic?
* Very high coverage needed in affected regions
* Limited vaccine acceptance (up to ~34% refusal in ring trials)
* High vaccine cost vs willingness/ability to pay
* Multiple Ebolavirus species; no single broadly protective vaccine yet
* Outbreak areas often resource-poor
## Footnote
These challenges complicate vaccination efforts.
44
What strategies are currently used for **Ebola outbreak control**?
* Surveillance and rapid isolation of cases
* Vaccination of healthcare workers
* Ring vaccination of patient contacts
## Footnote
These strategies are essential for controlling outbreaks.
45
Why is **Reston virus** not pathogenic in humans (current hypothesis)?
* VP24 protein has differentially conserved positions (T131S, M136L, Q139R) in karyopherin-binding site
* These changes may impair inhibition of human interferon signalling
* Weaker antagonism of STAT1 nuclear transport → stronger IFN response
## Footnote
Understanding the mechanisms of pathogenicity is crucial for public health.
46
What is **virulence** in fungal pathogenesis?
Intensity/degree of pathogenicity
## Footnote
It indicates how harmful a pathogen can be.
47
Define **virulence factor**.
Specific feature that increases virulence (e.g. capsule, toxins)
## Footnote
These factors enhance the ability of a pathogen to cause disease.
48
What is a **fitness attribute** in fungal pathogenesis?
Required for growth/survival but not directly a damage factor
## Footnote
These attributes help fungi thrive but do not necessarily cause harm.
49
Distinguish between **superficial**, **subcutaneous**, and **systemic** fungal infections.
* Superficial: outer skin/hair/nails (e.g. dermatophytes, Malassezia)
* Subcutaneous: deeper skin/soft tissue after trauma (e.g. Sporothrix, Fonsecaea)
* Systemic: internal organs/bloodstream; often from inhaled spores (e.g. Histoplasma, Cryptococcus, invasive Aspergillus)
## Footnote
Each type of infection varies in depth and severity.
50
Give examples of fungi that can cause **superficial**, **subcutaneous**, and **systemic** disease.
* Malassezia furfur: superficial
* Dermatophytes (Trichophyton, Microsporum): superficial
* Candida albicans: superficial, subcutaneous, systemic
* Sporothrix schenckii, Fonsecaea pedrosoi, mucormycetes: subcutaneous ± systemic
* Blastomyces, Histoplasma, Aspergillus, Cryptococcus, Pneumocystis, Coccidioides: systemic
## Footnote
These examples illustrate the range of fungal pathogens and the diseases they can cause.
51
Key features of **Malassezia furfur** and the disease it causes.
* Lipid-dependent dimorphic yeast; normal skin commensal
* Uses sebum; hydrolyses it into saturated & unsaturated fatty acids
* Takes up saturated FA; unsaturated FA penetrate outer skin, causing barrier disruption & itching
* Associated with dermatitis, seborrhoeic dermatitis, pityriasis versicolor, folliculitis
## Footnote
Malassezia furfur is a common skin inhabitant that can lead to various skin conditions.
52
What is **ringworm (tinea corporis)** and which fungus commonly causes it?
* Superficial dermatophyte infection of body skin
* Often due to Trichophyton mentagrophytes
* Circular, scaly, erythematous lesions with central clearing; itchy
* Spread via contact with infected humans, animals, or fomites
* Tough to eradicate; may require prolonged topical or systemic antifungals
## Footnote
Ringworm is a common fungal infection characterized by its distinctive appearance.
53
Clinical spectrum of **Candida albicans** infection.
* Superficial: oral thrush, vulvovaginal candidiasis, intertrigo
* Skin & nail infections
* Biofilm-associated catheter or line infections (nosocomial)
* Invasive candidiasis / candidaemia in immunocompromised or ICU patients
## Footnote
Candida albicans can cause a range of infections, from superficial to life-threatening.
54
Major **risk factors** and **treatment** for **Candida albicans**.
* Risks: antibiotics, diabetes, HIV, immunosuppressants, disrupted barriers
* Treatment: topical azoles or nystatin for superficial disease
* Systemic azoles (e.g. fluconazole) or echinocandins for invasive disease
## Footnote
Understanding risk factors is crucial for prevention and treatment.
55
What is **Aspergillus fumigatus** and what diseases can it cause?
* Ubiquitous filamentous mold; spores inhaled
* Diseases:
* Allergic bronchopulmonary aspergillosis (ABPA)
* Chronic pulmonary aspergillosis
* Invasive aspergillosis in severely immunocompromised patients
## Footnote
Aspergillus fumigatus is a common mold that can lead to serious respiratory diseases.
56
How is **Aspergillus fumigatus** infection diagnosed and treated?
* Diagnosis: imaging, culture, histology, galactomannan or β-D-glucan tests
* Treatment: triazoles (voriconazole, isavuconazole); amphotericin B for resistant cases
## Footnote
Accurate diagnosis and appropriate treatment are essential for managing infections.
57
Key features of **Rhizopus oryzae** and **mucormycosis**.
* Environmental mold (order Mucorales)
* Infection via inhalation, ingestion, or wound contamination
* Forms: rhinocerebral, pulmonary, cutaneous, GI, disseminated
* High mortality (50–94%)
* Strongly associated with uncontrolled diabetes (esp. ketoacidosis) & immunosuppression
## Footnote
Mucormycosis is a serious infection with high mortality rates, particularly in vulnerable populations.
58
How is **mucormycosis** treated?
* Urgent surgical debridement of necrotic tissue
* Systemic liposomal amphotericin B
* Correction of underlying factors (e.g. hyperglycaemia, acidosis, neutropenia)
## Footnote
Prompt treatment is critical for improving outcomes in mucormycosis.
59
What is **Pneumocystis jirovecii pneumonia (PCP)** and who gets it?
* AIDS-defining opportunistic fungal pneumonia
* Occurs in HIV/AIDS, transplant patients, haematological malignancies, steroid therapy
* Human-to-human transmission; cannot be cultured in standard lab conditions
## Footnote
PCP is a significant concern for immunocompromised individuals.
60
Clinical features, diagnosis, and treatment of **PCP**.
* Symptoms: progressive dyspnoea, dry cough, fever, hypoxia
* CXR: diffuse bilateral interstitial infiltrates
* Diagnosis: microscopy of BAL fluid (silver/IF stains), PCR, serum β-D-glucan
* Treatment/prophylaxis: trimethoprim–sulfamethoxazole (TMP–SMX); steroids for severe hypoxaemia
## Footnote
Early recognition and treatment are vital for managing PCP.
61
Key features of **Blastomyces dermatitidis** and **blastomycosis**.
* Dimorphic fungus; endemic in parts of North America
* Mold in environment; yeast in host
* Primary pulmonary infection → can disseminate to skin, bone, GU tract, CNS
* Diagnosis: broad-based budding yeasts in tissue
* Treatment: itraconazole (mild/moderate); amphotericin B (severe/disseminated)
## Footnote
Blastomyces dermatitidis is a significant pathogen in certain geographic areas.
62
Key features of **Histoplasma capsulatum** and **histoplasmosis**.
* Dimorphic fungus; endemic in Ohio/Mississippi River valleys
* Lives in soil enriched with bird/bat droppings
* Inhaled microconidia convert to intracellular yeasts in macrophages
* Most infections asymptomatic; can resemble pneumonia
* Disseminates in immunocompromised hosts (HIV, steroids)
## Footnote
Histoplasmosis is often underdiagnosed due to its asymptomatic nature.
63
Diagnosis and treatment of **histoplasmosis**.
* Diagnosis: intracellular yeasts on histology, culture, antigen detection, serology
* Treatment: itraconazole (mild/moderate); amphotericin B (severe/disseminated)
## Footnote
Accurate diagnosis is essential for effective treatment of histoplasmosis.
64
Key features of **Coccidioides immitis** and **coccidioidomycosis**.
* Dimorphic soil fungus; endemic in Arizona, California, Texas & other arid regions
* Arthroconidia inhaled → spherules in tissue
* ~60% asymptomatic; others get flu-like illness
* 3–5% develop chronic lung or disseminated disease
* Risk in immunocompromised & pregnant patients
## Footnote
Coccidioidomycosis can lead to severe complications in at-risk populations.
65
Diagnosis and treatment of **coccidioidomycosis**.
* Diagnosis: serology, microscopy, culture, PCR
* Treatment: fluconazole/itraconazole (mild/moderate); amphotericin B (severe/disseminated)
## Footnote
Prompt diagnosis and treatment are crucial for managing coccidioidomycosis.
66
Key facts about **Penicillium (Talaromyces) marneffei** and **penicilliosis**.
* Thermally dimorphic fungus; endemic in Southeast Asia & S. China
* Major opportunistic infection in HIV (3rd most common in some regions)
* Inhaled conidia → yeast form inside macrophages
* Symptoms: fever, weight loss, lymphadenopathy, hepatosplenomegaly, umbilicated skin lesions
* High relapse (~50%) without prophylaxis
## Footnote
Penicilliosis is a significant concern for immunocompromised individuals, particularly those with HIV.
67
How is **penicilliosis** treated?
* Induction: amphotericin B
* Maintenance: itraconazole
* Plus effective ART in HIV-positive patients
## Footnote
Effective treatment and management of HIV are essential for preventing relapses.
Pathogens
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