Secondary Immunodeficiency (Acquired)

Secondary Immunodeficiency (Acquired)

Splenectomy

·        RR of fatal infection ­ by 200 times: e.g. meningitis, bacteraemia and pneumonia ® OPSI (Overwhelming Post Splenectomy Infection) 

·        Biggest problem is encapsulated bacteria plus malaria and salmonella 

·        Treat with vaccination (e.g. for pneumoccal, negligent if you don‟t, always record in notes) + prophylactic antibiotics

·        Aggressively investigate any post splenectomy patient with infection

Diabetes

·        ¯Function of neutrophils & macrophages

·        Staph skin diseases common

·        Compounded by ketoacidosis

AIDS

·        The virus: RNA virus with reverse transcriptase.  Has p24 nuclear antigen.  Attacks CD4+ T cells.

·        Transmission: sex (­risk in receptive intercourse – male to male most significant, also in other STDs), blood and maternal transmission (¯ risk with AZT)

·        1 % of Europeans lack CXR-5 receptor: if homozygous then resistant

·        Signs & Symptoms:

o   ­Temperature, wasting (chronic ill health) 

o   Rashes: eg shingles, HSV (cold sores), candidiasis, may be drug response (heightened sensitivity to drug responses)

o   Lymph nodes

o   Signs of high risk behaviour: Injection marks, other STD

o   Mouth: infections, Kaposi‟s Sarcoma (re-purple vascular non-tender tumours – mainly on skin)

o   Chronic cough common

o   Hepatosplenomegaly (infections, lymphoma)

o   Neuropathies: eg due to intracranial lesion (eg lymphoma), peripheral sensory neuropathies

o   Fundi: cotton wool spots, scars (eg due to toxoplasmosis, CMV)

·        Early disease:

o   Seroconversion illness: in 50 – 90% of infected people.  May include macular rash

o   Debate about usefulness of early treatment

o   Good evidence of value of prophylactic treatment (e.g. following needle stick)

·        Screening:

o   3 weeks before positive after infection

o   Elisa for HIV-1 and HIV-2 antibodies

o   False positive tests: 4/1000

·        Confirmatory diagnosis: Western Blot

o   Can take up to 3 months to get Western Blot Positive

o   Can give indeterminate, weak positive or strong positive (3 bands)

·        Course: measure based on viral load and CD4 count

o   Acute illness: 4 – 8 weeks

o   Asymptomatic: 2 – 12 years

o   Symptomatic: 2+ years.  AIDS defining illness: 

§  PCP infection (treat with co-trimoxazole): can ® pneumothorax

§  Cryptococcus infection: mild headaches: lumbar puncture.  Indian ink stain positive

§  Kaposi‟s sarcoma: can present anywhere

§  Psychological: HIV related, secondary illness related, or depression

·        Viral Load:

o   High T cell turnover:  Virus replicates in 1½ days.  Infected cell lasts 2.2 days

o   HIV in sanctuary sites: e.g. brain – hard to treat

o   Measure through PCR of viral RNA: good indicator of progression.  If viral load high, treat now

·        Immune depletion: Based on CD4+ count:

o   > 500

o   200 – 500: Tb, herpes

o   <200

·        Subgroups of illness:

o   Constitutional: fever, diarrhoea, weight loss

o   Neurological: dementia, neuropathy, cognitive

o   Opportunistic infections: candida, PCP, toxoplasmosis, CMV, MAC, Tb

o   Malignancies: Kaposi‟s sarcoma, non-Hodgkin‟s lymphoma

·        Drug Treatment:

o   Combination of drugs that inhibit various points of viral replication

o   Can improve CD4+ count from very low (e.g. 50) to e.g. 500-600

o   Side-effects: non-specific rashes, „buffalo hump‟ – abnormal fat distribution

·        Leading cause of death: Respiratory infection

Testing for HIV

·        Guidelines for HIV pre-test counselling:

o   What the test for HIV antibodies means: not a test for AIDS

o   Significance of negative test (Window period)

o   Significance of positive test: medical implications (prognosis & treatment), social implications (coping, support, relationships, who needs to know, possible discrimination), notification requirements (HIV not notifiable, patient can use alias), implications for insurance

o  Safeguards to preserve confidentiality

o  Future preventative aspects: safer sex and IVDU

o  How results are obtained

o  Any costs

·        Guidelines for post test counselling:

o  Explanation of test results

o  If negative: 3-month window period – especially if recent high risk behaviour.  Future prevention 

o  If positive: repeat, confirmatory test organised, arrangement for counselling, support and specialist assessment

Other Causes of Secondary Immunodeficiency

·        Malignancy

·        Drugs e.g. steroids, cyclosporin, cytotoxics

·        Nutritional Deficiency

·        Post-viral

·        Post-transfusion

·        Alcoholism

·        Chronic renal disease