Infectious diseases Flashcards
HIV symposium: How is HIV transferred?
Sexual contact
Blood- blood contact, IVDU
Infected blood products
In utero - cross placental drugs now stop this and in birth
Breast milk
HIV symposium: What are the HIV types and strains?
HIV 1 and HIV 2
HIV 1 most common
HIV 2 less easily transmitted and less pathogenic - some drugs do not work against HIV2
HIV mutates readily- Reverse Transcriptase does not proofread
Three main groups of HIV-1:
- Main (M- pandemic trains), New (N) and Outlier (O- confined to Cameroon area), many subtypes
- Infected individuals contain a heterogeneous viral population
HIV symposium: How did HIV-1 start?
The most commonly accepted theory is that of the ‘hunter’. In this scenario, SIVcpz was transferred to humans as a result of chimps being killed and eaten, or their blood getting into cuts or wounds on people in the course of hunting.5 Normally, the hunter’s body would have fought off SIV, but on a few occasions the virus adapted itself within its new human host and became HIV-1.
HIV symposium: How did HIV-2 start?
HIV-2 comes from SIVsmm in sooty mangabey monkeys rather than chimpanzees.7 The crossover to humans is believed to have happened in a similar way (through the butchering and consumption of monkey meat).
It is far rarer, and less infectious than HIV-1. As a result, it infects far fewer people, and is mainly found in a few countries in West Africa like Mali, Mauritania, Nigeria and Sierra Leone
HIV symposium: What are the main features of HIV virus?
adhesions on the outside of the virus - gps 120-41 which binds to the cell receptor
lipid coat the virion - enveloped - actually makes it less resistant to survival outside host
ssRNA - has RNA and RT enzyme to convert RAN to DNA
also has p24gag protein - target for HIV tests (major structural core protein)
HIV symposium: What cells does hIV infect?
CD4 CELLS - include T cells, macrophages means viral load increase can be triggered by 2’ infections and actually promoted by humoral response to HIV and dendritic cells- aid dissemination since they act as a reservoir for virus move slowly round the body and stimulate cvells in plymph nodes to produce ,,, this helps infection and dissemination
HIV symposium: How does hIV initially bind to cd4 CELLSs?
Initial attachment via gp120 binding to CD4
followed by co-receptor binding
membrane fusion and internalisation - gp41 dependent which released both the viral mRNA and RT and integrate enzymes
this then converts RNA to DNA in nucleus and then integrates into the chromosome - retrovirus
When cells are activated viral proteins are produced
And thousands of new virus progeny synthesized
HIV symposium: Which people are resistant to HIV?
People with CCR5 mutations are resistant
Occurs in 2-14% europeans (caucasian) , and 15% of Icelandic
HIV symposium: How does the virus vary during HIV infection?
Isolates from early in infection- CCR5 (M)
macrophage tropic and low cytopathic effect- more transmissable
Isolates from late infection- CXCR4 (T)
high cytopathic ability – less transmissable
i.e. at start good at transmission and finding macrophage and cd4 cells, to aid dissemination and get established in the body, but over time isolates from same person become more pathogenic and less transmissable in the progression to AIDS
HIV symposium: What are the symptoms of primary infection?
tnsient glandular fever like illness, malaise, muscle pain, throat pain, rash,
High plasma hiv levels, and transient cd4 cell depletion. Then antibodies build up and cd4 levels partially recover.
Cd4 cell continue to deplete while viral load remains largely unchaned until cd4 levels get too low
Later constitutiuonal symptoms such as diarrhoea, fevers, night sweats, weight loss. And minor infections usually of mucous membranes- candidosis, shingles, herpes. lymphomas
These often signal the onset of serious AIDS, more opp inf and tumours start
Such as kaposis sarcoma, b cell lymphomas- brain, and encephalitis- casued by release of neurotoxins by macrophages that are infected by the virus
Pneumonia is common, pneumocystis infection often diagnostic of AIDS full blown. TB, fungal- aspergillus, cyrptosporid, toxoplasmosis, cyrptococcus, oral hairy leukoplakia
HIV symposium: What opportunistic infections can you get in AIDS?
Bacterial-
- Mycobacterium tuberculosis
- Salmonella
- Haemophilus, Streptococcus, Pneumococcus- Pyogenic infections (pus formers)- recurrent
Protozoa-
- Cryptosporidum (chronic diaarhoea)
- Toxoplasma gondii (disseminated, including CNS- from Cats)
Fungal-
- Aspergillus - pneumonia
- Candida- oral presentation
- Cryptococcus neoformans- CNS
- Pneumocystis jiroveci/ carinii- pneumonia
Viruses-
- HSV- Herpes simplex virus- chronic oral infection
- EBV- Hairy leukoplakia, and B- cell lymphomas
- HHV-8 – Kaposis Sarcoma
HIV symposium: What are some oral manifestations of HIV?
thrush
gingival erythema
erythematous candidiasis
hairy leukoplakia
HIV symposium: how many people with hIV progress too AIDS?
10% of HIV-infected subjects progress within 2-3 years
5-10% are clinically asymptomatic after 10 years
Remaining subjects progress to AIDS within 10 years- DEATH
Situation drastically improved by antiretroviral therapy
HIV symposium: What drug targets are there for HIV drugs?
Fusion inhibitors
integrase inhibitors
PI (protease inhibitors)
CCR5 entry inhibitors
NNRTI (non-nucleoside reverse transcriptase inhibitor) - Nucleotide analogues cause chain termination when RT builds DNA from RNA
HIV symposium: What is the treatment for HIV?
Highly Active Anti-Retroviral Therapy
First line regimen
- 2 NRTIs (side-effects must be managed)
- e.g. zidovudine (AZT), lamivudine (3TC), emtricatabaine (FTC), stavudine (d4T)
- 1 NNRTI- inactive against HIV-2
- e.g. Efavirenz, Nevirapine
OR a Protease Inhibitor (PI) – high turnover in the body= many pills> boosted with Ritonavir to improve efficacy
- e.g.Indinavir (IDV), Fos-amprenavir (FPV)
OR an Integrase inhibitor
HIV symposium: What are the side effects of HIV drugs?
NRTIs
- AZT- headaches and nausea, anaemia, neutropenia
- Stavudine-lactic acidosis, lipoatrophy (loss from face and limbs – gain to neck and tummy) and peripheral neuropathy- possibly via mitochondrial toxicity
- rashes
NNRTIs
- Stevens Johnson Syndrome: a severe disorder of mucous membranes
- teratogenecity
PIs
- lipodystrophy- fat loss from legs, fat gain-pot belly
RESISTANCE-
- increasing problem
- drug-holidays- ineffective, compliance an issue also
HIV symposium: What is an alternative first line drug?
DTG or dolutegravir used with tenofovir disoproxil fumarate (NtRTI) & lamivudine (NRTI)
DTG – Integrase inhibitor, first used in 2014 btu becoming more and more widely used, in OK also.
HIV symposium: What is the dental transmission control for hIV?
VERY LOW RISK- even with risk contact only 1/300 chance of infection
Normal infectious control procedures Gloves Sterilise instruments Dispose of sharps Suction Care if blood spillage
If at risk- contact Occupational health physician for prophylactic HAART and HIV testing
If needlestick of HIV + patient» PEP administration ASAP and within 72 hours at longest. (using this method NO NHS employee was infected (last 10y- no sero conversions – out of around 600 incidents).
HIV symposium: How is hIV tested for?
Most testing is ELISA based blood test- detects HIV antibodies in the blood.
antibody takes 6-12 weeks to develop
most reliable testing at 3 months (re-test at 6 months)
Babies may test positive from maternal antibody- PCR test.
Home test kits exist but blood test most reliable
HIV testing and clinical management: What are the problems with late diagnosis?
More likely to die
Transmission to others
HIV testing and clinical management: What are the clinical indicator diseases for adult HIV infection?
TB cerebral abscess kaposi's sarcoma non Hodgkin's lymphoma cervical cancer oral candidacies hairy leukoplaia head and neckk cancer chronic parotitis lymphadonopathy etc
HIV testing and clinical management: check slide 13
slide 13
HIV testing and clinical management: What would you do if a patient said no to testing?
Address any issues raised by the patient
If patient refuses, explore why
? Incorrect beliefs re virus/testing
HIV testing and clinical management: How do you test for HIV?
Verbal consent Send clotted blood to lab “4th generation” test antibody/antigen Window period 1 month Costs 99.9% PPV
other ways: “Point of care” tests – finger prick, mouth swab, saliva Antibody only tests Antigen only tests HIV RNA PCR – “viral load"
