ID I Flashcards
Define HIV
Retrovirus that destory CD4 T cells
Acquired immunodeficiency syndrome (AIDS)
The virus is capable of reverse transcription
Incorporated into host cells
Two types exist
HIV I is the global epidemic
Pathophysiology of HIV
- HIV enters cells through binding of the viral envelope glycoprotein (GP120)
Links to specific receptors on the cells (CD4 present on T helper cellsm MP and glial cells) - Conformatational change in GP120
- CD4 cells migrate to lymphoid tissue. Viral replication. New virons to new T cells
- Depletion or impaired function CD4 cells. Decreased immune function
Discuss how new virons are generated
Attachment Entry Uncoating Reverse transcription Genomic integration (integrase) Transcription viral mRNA Splicing of mRNA and translation into proteins (GAG) New virons = budding
Outline the reasons the body struggles to develop an immune response towards to virus
Neutralising antibodies of low magnitude
Envelope glycoprotein is poorly immunogenic
Mutation (error prone): viral escape
Where are the reservoirs of HIV replication
CNS (glial)
Testes (genital tract)
Macrophage (long lived cell population)
Resting CD4 T Cells (latently infected
How is HIV transmitted
Blood
Sexual
Vertical
Certain symptoms should make you suspicious of a possible HIV dx. List the symptoms
Generalised lymphadenopathy Acute generalised rash Flu like illness/ Glandular fever Prolonged herpes simplex Frequent candidiasis Odd looking mouth lesions Unexplained night sweats, weight loss Recurrent bacterial infection
Discuss the investigations involved in the dx of HIV
- Simple serology:
- detect antibodies and antigens of the virus
- pre and post testing counselling
- negative results will require re testing in the window period
- positive result can be reactive will require re testing - ELISA
- can give false negatives
- +ve result western blot - Western blot
- Confirmation - Serum p24 antigen: present during high viral replication
- Serum CD4 count, serum HIV RNA (PCR) for viral load
What other investigations might you like to consider in a patient recently tested +ve for HIV
Pregnancy test Serum Hep B serology Serum Hep C serology TB skin test CXR
Who should be contacted in the case of a HIV +ve result
Partner notification
Criminally liable if know status and transmit infection
May disclose to partner if known risk and unaware
Discuss the monitoring of HIV
CD4 and viral load are used as parameters to determine how advanced the disease is
Monitor treatment response
Treatment aim of HIV
CD4 > 400cells/mm3
Viral load = 0
Discuss the natural history of HIV
SEROCONVERSION/PRIMARY HIV
- Short illness, flu like post infection
- highly infective
- blotchy red rash
- mouth ulcers
ASYMPTOMATIC HIV INFECTION
- last several years
- generalised lymphadenopathy
SYMPTOMATIC HIV INFECTION
- Opportunistic infection
- Certain cancers
LATE STAGE HIV INFECTION
- Opportunistic infection
- AIDS related complex
- CD4<200
What make up AIDS related complex
Pyrexia Night sweats Diarrhoea Weight loss - oral hairy leukoplakia - oral candida - herpes zoster - herpes simplex
List AIDS defining illnesses
PCP CMV TB Sentinel tumours (Kaposi's sarcoma, lymphoma) HIV becomes AIDS in 5-10 years
AIDS is associated with many opportunistic infections. List some of them
Tuberculosis Pneumocystic jirovecci pneumonia (BAL) Candidiasis: candidia albicans Cryptococcal meningitis: cryptococcus neoformans Toxoplasmosis: Toxoplasma gondii CMV Mycobacterium avium complex HSV/VZV at multiple dermatomes Kaposi sarcoma (HHV8) Oral hairy leukoplakia Burkitt's lymphoma
HIV is now a treatable disease. List the treatment available for HIV +ve people
Nucleoside reverse transcriptase inhibitors (NRTI): Prevent elongation of DNA chain from the RNA template
Non nucleoside reverse transcriptase (NNRT): Act near site of reverse transcriptase to block viral replication
Protease inhibitors: Block cleavage of active proteins from polyprotein formed by viral transcription
Fusion inhibitors (FI): Block virus entering the CD4 cells
Outline the treatment regimens that are generally offered to people that are HIV +Ve
Used at least 3 different antiretroviral drugs
1 NNRTI + 2 NRTI
2 NNRTI + 1 PI
Name and state the side effects of NRTI
Lamivudine (AZT): Haemolytic anaemia
Zidovudine (AZT): Haemolytic anaemia
Tenofovir: Renal impairment
Name and state the side effects of NNRTI
Nevirapine
Rash
Liver toxicity
Drug interactions
Name and state the side effects of PI
Lopinavir
GI disturbance
Diarrhoea
Peripheral neuropathy
What is given as prophylaxis exposure for HIV
4 week course
Tenofovir
Emtricitabine
Raltegravir
Must be given between 1hr and 3 days
Barriers to compliance with HIV
Social Ecconomic class
Social support
Stigma of HIV
How is vertical transmission of HIV reduced
Can be transmitted via delivery or breast milk
Antenatal antiretroviral therapy from the end of T1
HAART
Zidovudine monotherapy
VL<50 can be vaginal delivery
Postnatal: zidovudine monotherapy for 4W
Exclusively forumla fed
Name the types of malaria
P.Falciparum P.Vivax P.Ovale P.Malariae P.Knowlesi
Outline the pathology associated with Malaria
- Infected female anopheles inject: SPOROZITES
- Sporozoites enter hepatocytes
- Reproduce to form shizonts (asexual). Remain asymptomatic until this
- Many merozoites released into the blood to penetrate erythrocytes. Pre-patent period
- Merozoites undergo schizonts. They rupture to produce merozoites. Invasion of new erythrocytes
- Fever paroxysms occurs
- Rupture of erythrocytes. Release toxins that induce CK release from MP.
Primary prevention in Malaria
Avoid outdoor after sunset Insect repellent Long sleeves Insecticide treated bed nets Antimalarial chemoprophylaxis
P.Falciparum
- Chloroquine or hydroxychloroquine
1 week prior, during, 4 weeks post
If resistant to the above
- Doxycycline
- Atovaquone/proguanil
Malaria symptoms
Fever paroxysms Chill and rigors followed by fever and sweats Headache Weakness Myalgia Arthralgia Anorexia Diarrhoea Jaundice HSM Pallor Tacycardia Hypotension
Investigations in Malaria
- Giemsa stained thick (parasite number) and thin blood films (species)
- trophozoites in RBC
- gametocytes in RBC - Rapid dx test
- detection of parasite antigen or enzymes - FBC (pancytopenia)
- Blood sugar as treatment can drop this
Management of Malaria
Primaquine single dose
Falciparum
- Chloroquine (sensitive)
- Artesunate + mefloquine
- Quinine sulfate + doxycycline
IV Severe Infection
- Artesunate + fluid management + airway support
Ovale/Vivax
- Choroquine
- Hydroxychloroquine
Complication of Malaria
Acute renal failure Hypoglycaemia Metabolic acidosis Seizure Acute resp distress syndrome due to pulmonary oedema
What organism causes syphilis
Spirochaete treponema pallidum
Classify syphilis
- Primary syphilis
- Local macule/ papule/ulcer
- chancre at 14-21 days
- lymphadenopathy (rubbery) - Secondary syphilis
- 4-8 weeks characterised by spirochetemia and dissemination to skin
- Diffuse rash on palms of hands and soles of feet
- trunk with mucous membrane involvement
- Alopecia
- Condylomata lata (warty) - Tertiary syphilis
- chronic end organ complications years after the infection
- CVS, neuro, gummatous
- Memory impairment, dementia, argyll-robertson pupil, ataxia, rombergs, visual disturbances
- Diastolic murmur due to aortic regurgitation (aortic root affected)
Investigations for syphilis
Dark ground microscopy of swab: coiled spirochaete
Serum T pallidum particle agglutination (+ve lifelong)
LP/CSF analysis
CXR (widened aortic root)
ECHO (aortic regurgitation)
Treatment of syphilis
IM benzylpenicillin + prednisolone
What causes viral haemorrhagic fevers
5 types of RNA virus Filovirus: Ebola and Marburg Flavivirus: - Yellow fever - Zika virus - Japanese encephalitis - Tick borne encephalitis
Pathology of viral haemorrhagic fevers
Ebola and Marburg = Spread from BATS 2-21 days incubation Vascular affects - Flushing - Conjunctival injection - Petechial haemorrhage - Fever - Myalgia
Central pathological process leading to increased vascular permeability
Mucous membrane haemorrhage
Hypovolaemia with hypotension
Shock and circulatory collapse
Warning signs of a potential viral haemorrhagic fever
Febrile illness
Foreign travel or contact
Exposure to rodents, bats, insects
Flu-like symptoms
Presentation of a viral haemorrhagic fever
Sudden headache Pleuritic pain Backache Myalgia Conjunctivitis Dehydration Facial flushing High temperature Bleeding Renal failure Encephalitis Coma
Investigations for viral haemorrhagic fever
FBC - leukopenia - thrombocytopenia LFT - elevated transaminases
Coagulation screen
- PTT
- INR
- clotting times prolonged
- evidence of DIC (high D dimer and fibrinogen low)
PT-PCR
Signs of altered vascular permeability
Coagulopathy Haemorrhagic complications (hepatic damage) Myocarditis Encephalitis Multi-system organ failure
Management of viral haemorrhagic fevers
Notify public health and proper officer Seek advice on prevention transmission Barrier nursing and vistor restriction Supportive management - Blood volume - Clotting - Care of major organs Antivirals - Ribavirin not for ebola
What organism causes Dengue fever and how is it spread
Arbovirus
Spread by the aides mosquitp
Classify the different types of Dengue fever
Primary infection
- Benign in nature
Secondary infection
- Dengue haemorrhagic fever
- Dengue shock syndrome
- Vascular leak (hypoalbuminaemia and pleural effusions, ascites)
Presentation of Dengue fever
Flu-like illness (>40 degree)
Rash (maculopapular)
Flushing
Retro-orbital pain
Presentation of Dengue haemorrhage fever
Widespread effusions
- pleuritis CP
- Dyspnoea
- Cough
DIC
Hepatomegaly
Can cause circulatory collapse
Investigations of Dengue fever
FBC
- Elevated HCT
- Leukopenia
- Thrombocytopenia
LFT
- Deranged (high)
- Albumin (low)
Serology
- +ve IgM
- +ve IgG
Treatment of Dengue fever
Oral/ IV fluids Supportive care Antipyretics Notification Beware of fluid overload
Exclusion criteria for Dengue
Symptoms start > 2 weeks post leaving a Dengue area
Fever lasts > 2 weeks
What causes Leishmaniasis
Sandflies
Classify the types of Leishmaniasis
Cutaneous
- Skin ulcers
- Chiclero’s ulcer
Mucocutaneous
- Respiratory system (Upper)
- Cause scarring
Visceral
- Black sickness
- Deadly disease
- Spread via lymphatics
- Leishman-Donovan bodies
Presentation of Leishmaniasis
Prolonged fever Wt loss and night sweats Ulcerative lesions Skin nodules (warty) Mucosal infiltration Hyperpigmentation Pancytopenia
Investigations to confirm Leishmaniasis
Microscopy biopsy/aspirate
- amastigote
Leishmania skin test
- >5mm
rK39 Dipstick
- antibodies against rK39
Management of Leishmaniasis
Cutaneous: Sodium stibogluconate
Visceral: Amphotericin B
Name the types of trypanosomiasis
African
- T Brucei
- Sleeping sickness
South American
- T cruzi
- Chagas disease
- Incurable
Outline the stages of African trypanosomiasis
Stage I: Haemolymphatic
- Rash
- Fever
- Flu like illness
- Painless chancre
- Lymphadenopathy
- Winterbottom’s sign
Stage II: Meningoencephalitis
- Headahce
- Drowsiness
- Convulsions
- Coma
Presentation of South American Trypanosomiasis
Local sore Orbital/ Generlaised oedema Heart - Cardiomegaly - CCF - Arhythmia Megaoesohagus Megacolon
Destruction of the enteric nerves
Investigations of Trypanosomiasis
Giemsa statin on blood film
FBC
- pancytopenia
ESR
- elevated
Serum immunoglobulins elevated (Chagas IgG ELISA)
Rapid diagnostic tests
- presence of specific antibodies
Treatment of sleeping sickness
Seek expert help
Treat anaemia and infections first
EARLY
- IV suramin
Late
- Melarsopol
Chagas
- no cure
- symptomatic
What causes schistosomiasis
Schistoma
Blood flukes
Transmitted from contaminated fresh water
Types of schistosomiasis
S. Haematobium (GU symptoms)
S.Japonicum (intestinal and portal hypertension symptoms)
S.Mansoni (as above)
Diagnosis of schistosomiasis
Microscopic visualisation of eggs in stool or urine
Treatment of schistosomiasis
Praziquantel
Anti-helminthic
Outline the pathology of schistosomiasis
- Contaminated water and skin contact
- Penetrate skin
- cercarial dermatitis
- swimmer’s itch
3.Migration to the blood stream
- flu like symptoms
- abdo pain
eggs laid in tissues
- Hypersensitivity reaction
- Eosinophilia - Chronic infection
- Anaemia
- Malnutrition
- Obstructive uropathy
- portal HTN
Fibrosis, obstruction, granulomas
Outline the signs seen in chronic schistosomiasis
Haematuria Dysuria Frequency HSM Chronic bowel disease Blood stained stool
Investigations in schistosomiasis
Stool or urine microscopy
- visualisation of the eggs
Tissue biopsy
- granulomas sure eggs
Urinanalysis
- haematuria
FBC
- eosinophillia
Thickening of the bladder wall
Treatment of schistosomiasis
Praziquantel
Corticosteriods
What organism is responsible for amoebiasis
Entamoeba histolytica
Tropics
Spreads through ingestion of cysts in faecally contaminated food and water
Presentation of amoebiasis
Diarrhoea Dysentery (blood + mucus) Abdo tenderness Weight loss Sweating Fever Cough due to phrenic nerve irritation
Pathology of amoebiasis cess (E whistle
Cyst passes to small intestine Excyst to invasive trophozoite Cellular damage at the invasion site Intestinal epithelium is invaded Extra intestinal spread to the peritoneum and liver Haematogenous dissemination via portal venous system Amoebic liver abscess and brain
Investigations in amoebiasis
Stool antigen detection
PCR stool or liver abscess (E histolytica DNA)
Serum antibody test
Stool microscopy (x3)
- trophozoite and cyst with 4 nuclei
- motile amoeba
Liver USS
- hypo echoic round lesion
CXR
- oval lesion
Treatment of amoebiasis
Nitromidazole
(metronidazole + luminal agenet
If abscess must aspirate
What organism causes Giardiasis
Giardia lambia (flagellated protozoan Tropical
How is giardiasis transmitted
Oral ingestion of cyst via faec-oral route
Swallowing water from swimming
Tap water
Eating lettuce
A patient presents with diarrhoea which they describe as greasy and foul smelling. They also complain of frequent belching , ado bloating and pain.
What do you suspect as the diagnosis?
Giardiasis
What investigations would you order in a case of suspected giardiasis
Stool microscopy (x3) cysts and trophozoites
Stool antigen tests (ELISA) +ve cell wall
String test (mucus examined for trophozoites
Baseline FBC
Treatment of giardiasis
Metronidazole
Tinidazole
List the presenting symptoms of typhoid
High fever Dull frontal headache Dry cough Malaise Prostration Diarrhoea
Outline the investigations you would order in cases of suspected Typhoid
FBC: mild anaemia LFt: transaminase x2/3 Blood culture +ve Stool culture +ve Bone marrow culture+ve
List the potential complications of Typhoid fever
Chronic biliary carriage
Typhoid hepatitis
Bowel perforation
Treatment of Typhoid
ABX: Ceftriaxone and azithromycin
Fluids
Antipyretics
Complications of malaria
Acute renal failure Hypoglycaemia Metabolic acidosis Seizure Acute respiratory distress ssyndrome
What diseases are linked to bats
Histoplasmosis
Leptospirosis
VHF
Rabies
What is MRSA
Methicillin Resistant staphylococcus aureus
Resistant to beta lactams
What do you treat MRSA with
Vancomycin
Teicoplanin
What antibiotics cause C.diff
Ciprofloxacin Co-amoxiclav Carbepenems Clindamycin Cephalosporins Also caused by PPI change in gut flora
What is the organism that cause glandular fever
EBV Mononucleosis syndrome (CMV, HIV, HSV, HBV,HCV, VZV)
Presentation of glandular fever
Fever Pharyngitis Lymphadenopathy Atypical lymphocytosis Fever Fatigue Depression Splenomegaly
Diagnostic test for glandular fever
Blood film: Lymphocytosis
Heterophil antibody test (Monospot test): +ve at three weeks
Serology for EBV
IgM and IgG
Complications of glandular fever
Thromboytopenia
Haemolytic anaemia
Fulminant hepatitis
Acute renal failure
Pathology of EBV
DNA herpes virus
Predilection for B lymphocytes in the tonsils
B cells spread the infection to the liver and the spleen
Antibodies are produced
Rapid response to T cells
(atypical mononuclear cells)
Management of glandular fever
- Supportive care
2. Do not give ampicillin or amoxicillin
Outline the manifestations of primary herpes simplex virus
- Genital herpes (HSV-2)
- Ginivostomatitis
- Eczema herpeticum
- Herpes simplex encephalitis
- HSV keratitis
Presentation of genital herpes
Flu-like prodrome
Grouped vesicles and papillose around the genitals and anus
Shallow ulcers (generally clear in 3 weeks)
Urethral discharge
Dysuria (females)
Urinary retention
Management of genital herpes
Aciclovir
If immunocompromised
Famiciclovir
What causes chickenpox
Varicella zooster virus
Contagious febrile illness with crops of blisters at various stages
Outline the natural history of chickenpox
Incubation prior: 11-21d
Infectivity: 4d before the rash appears and lasts until all the lesions are scabbed over (~1 week)
Post infection the virus remains dormant in the dorsal root ganglion
VZV can remain dormant in the dorsal root ganglion for years prior to reactivation. What is this condition called and how does it present?
Shingles
Pain in a dermatomal distribution
Malaise
Fever
Treatment of Shingles
Acute zoster: acyclovir 800mg 5 times/d PO 7 days
Post shingles pain
- Amitriptyline
Where is affected in ophthalmic shingles
CN V branch 1
Presentation of ophthalmic shingles
Pain Keratitis Iritis Hutchinson's sign - Nose tip involvement Blistering rash
Treatment of ophthalmic shingles
3% aciclovir ointment
What is the mode of transmission of CMV
Direct contact
Blood transfusion
Organ transplantation
Diagnostic tests for CMV
Serology: specific IgM (acute infection)
CMV PCR
Treatment of CMV
Supportive care
Serious infection (immunocompromised)
- Ganciclovir
How is CMV prevented post transplant
Weekly PCR to detect CMV antigens
or
Pre emptive ganciclovir
Name the types of TB infection
Pulmonary Tb
- Active
- Latent
Extra Pulmonary TB
Outline the pathophysiology of TB
Primary TB
- Naive infection with TB
- Organisms multiple = GHON FOCUS
- Macrophages take TB to LNS
- Node + lung lesion = GHON COMPLEX
- Cell mediated immunity = RANKE COMPLEX
Primary Progressive TB
- Appears like acute bacterial pneumonia
- Mid and lower lobe consolidation
- Hilar lymphadenopathy
- Lymphogematgenous spread: extra pul and milary TB
Latent TB
- Infected but no X-ray or clinical signs
Secondary TB
- Reactivation of latent TB
- Reduced host immunity
- @ upper lobes
- Casating granulomas due to hypersensitivity
Diagnostic tests in HIV
Latent TB
- Mantoux test
- cell mediated response 48-72hrs
Active TB
- CXR: Consolidation, Cavitation, Calcification and Fibrosis
- BAL: Ziehl nielson stain, Lowstein-Jensen culture
Quantiferon TB Gold
- IFN gamma if previously exposed
Presentation of pulmonary TB
Cough Sputum Malaise Fever Haemotypsis Pleural effusion
Discuss the systems affected in extra pulmonary TB
Meningitis GU Bone (Potts) Lymph nodes Skin Peritoneal
Management of TB
- Check colour vision, FBC, U&Es and LFT’s prior to starting treatment
- Initial phase
- 8 wks 4 drugs
- Rifampacin
- Isoniazid
- Pyrazinamide
- Ethabutamol - Continuation phase
- 16 wks 2 drugs
- Rifampacin
- Isoniazid
DOTS
Discuss the side effects associated with the TB drugs in turn
RIFAMPACIN
- Hepatitis ( increase LFT)
- Orange discolouration of the urine and tears
ISONIAZID
- Hepatitis
- Low WCC
- Peripheral neuropathy
PYRAZINAMIDE
- Hepatitis
- Arthalgia
ETHANUTAMOL
- Optic neuritis
What type of virus is Hep A and how is it spread
RNA virus
Faeco-oral route
In a patient infected with HepA what would their blood work show
HAV IgM HAV IgG LFT - ALT: AST (2:1 ratio) - Raised bilirubin
What type of virus is Hep E and how is it spread
RNA
Faeco-oral route
In a patient infected with HepE what would their blood work show
HEV IgM
HEV IgM
Viral PCR
How is Hep C spread
Blood or bodily fluid
IVDU
Needle stick injury
What investigations would you do in a patient suspected of having HepC
HCV serology
- anti HCV ab
- HCV IgM
- HCV IgG
PCR HCV RNA: treat if still detectable at >2 months
LFTs
- Raised AST
- Rasied ALT (ratio will be greater than 1)
Biopsy of the liver: degree of inflammation
Management of Hepatits C
- Prevention of needle exchange programme. Alcohol avoidance
- Screen for HCC
- Dual therapy: pegylated IFN alpha and Ribavrin
- Direct acting antiretrovirals
Leading cause of a liver transplant in the UK
How is Hep B spread
DNA virus
Blood and bodily fluids
Vertical transmission
Sexual contact
Outline the relation of the following components to the Hep B virus
- HBsAg
- Anti-HBs
- HBcAG
- Anti-HBc
- HBeAG
- Anti-HBe
HBsAg
- Surface antigen
- Current infection
Anti-HBs
- Surface antibody
- indicate immunity from post exposure or immunisation
HBcAg
- core antigen
- not used
HBeAg
- Envelope antigen
- assessment of phase of infection
Anti-HBe
- evidence of immune response
Presentation of Hep B
Acute
- prodromal
- VANFAM
Hepatic
- can become fulminate, watch INR
- hepatomegaly
- jaundice
- RUQ pain
Chronic
- > 6months
- Fibrosis
- Cirrohosis
- HCC
Management of Hep B
Some people clear the acute infection. Chronic infection requires treatment. It is treated to control the disease not to cure .
- Prevention
- Blood screening
- Safe sex
- Partner notification - Acute
- Supportive
- Notify proper officer - Chronic
- 48 wks IFN alpha
(can also give tenofovir)
- 6 monthly screen for HCC
