Other Opportunistic Infections Flashcards
What are the phases of infection of herpes viruses?
Primary infection
Latency
Reactivation
Immune compromised patients increased risk of worse primary infections and reactivation
What are the three groups of herpes viruses?
1 alpha - hsv, VZV. Primary targetcmucoepithelial with latency developing in nerve cells
- Beta - cmv, hhv 6 and 7
- Gamma - ebv, KSHV (hhv8)
What is the incidence of herpes zoster (shingles) in general population?
1.5-3 per 1000 persons per year
More frequently in those over 60 and who are immunocompromised
What is the relative risk of herpes zoster in HIV patients
15 or greater compared to age matched hiv zero negative individuals
At what CD4 count are herpes zoster outbreaks more frequent?
Cd4 <200-250
Recurrences common - up to 20-30% of cases
Effect of ARVs unclear
Risk of primary zoster infection in HIV positive population?
Uncommon due to childhood infections but can result in severe disease with visceral dissemination particularly pneumonitis
How might zoster present in HIV patients?
Usually vesicles along single deratome
In HIV can be bullous, haemorrhagic, necrotic and painful
Blisters and crusts usually last 2-3 weeks - necrotic lesions may last up to 6 weeks and heal with severe scarring
Can herpes zoster be part of IRIS?
Yes - 2-4 fold increase in risk in first few months of starting HAART. Same presentation as other HIV+ pts.
What is HZO?
Herpes zoster ophthalmicus involves ophthalmic division of trigeminal nerve
Symptoms of HZO?
Skin lesions
Involvement of conjunctiva, cornea and other eye structures can result in visual loss, keratitis, anterior uveitis, severe post heretic neuralgia, necrotising retinopathy
Presentation of disseminated herpes zoster?
Multi focal leukoencephalitis, vascularised with cerebral infarcts, myelitis, ventriculitis, optic neuritis, meningitis, focal brainstem lesions
Can herpes zoster CNS disease occur in absence of neurological lesions?
Yes
Should always be considered in patients presenting with neurological disease especially if advanced immune deficiency
How is VZV diagnosed?
Usually skin lesions diagnosed in clinical appearance
VZV antigen testing using fluoroscein-conjugated monoclonal antibodies to confirm presence of VZV antigens
Culture less sensitive but may allow for aciclovir resistance to be detected
PCR rapid and more sensitive than culture
What is found on CSF testing for VZV?
Pleocytosis
Mildly raised protein
Positive PCR for VZV DNA - absence of this does not exclude
What is the treatment of primary varicella?
IV aciclovir 5-10mg/kg TDS for 7-10 days
More prolonged treatment courses may be required until all lesions are healed
If no evidence of visceral involvement can switch to 800mg po 5x day when afebrile
In patients with high CD4 counts oral aciclovir may be considered if started within 24hrs
What is the treatment of herpes zoster?
Begin within 72hrs rash
Localised dermatomal illness 800mg 5x day
If severe cutaneous disease or disseminated infection admit to hospital for iv aciclovir 10mg/kg tds for 10-14 days
Start on ART or optimise to improve immune deficiency
How to tell if patient is resistant to aciclovir?
Failure to respond to treatment
Has been reported in patients with advanced hiv disease
IV foscarnet used instead
What is the relationship between HSV and HIV?
Genital HSV2 increases acquisition risk of HIV - doubles risk of becoming infected through sexual transmission
Coinfected individuals are more likely to transmit infection - ? High titres of HIV in genital secretions during HSV2 outbreak
What is the definition of primary genital herpes?
First infection of HSV 1 or 2 in an individual with no pre-existing antibodies to either type
Non primary first episode is forst infection of hsv 1 or 2 but person has antibodies to other type
What may be different about primary HSV in immunocompromised person?
May not resolve spontaneously but persist with development of progressive, eruptive and coalescing mucocutaneous anogenital lesions
Healing may be delayed beyond 2-3 weeks
Systemic symptoms such as fever and myalgia
Rare severe systemic complications - hepatitis, pneumonia, a sceptic meningitis, autonomic neuropathy
What is the typical frequency of genital HSV recurrences in HIV zero negative population?
5 episodes per year for first 2 years and reduce in frequency after
Frequency and severity of outbreaks significantly greater in hiv infected persons with low CD4 counts
How can HSV affect the eye?
Keratoconjunctivitis
Acute retinal necrosis
Possible outcomes of
Pneumonia
Hepatitis
Oesophagitis
CNS disease
What can HSV infection of CNS cause?
Aseptic meningitis (usually a consequence of primary HSV2 infection)
Encephalitis
Myelitis
Radiculopathy
How is HSV diagnosed?
Swabs taken from base of lesion
PCR rapid and sensitive
Culture less sensitive and requires cold chain 4 degrees
How is HSV diagnosed and typed in asymptomatic individuals?
Type specific serology tests detect HSV specific gylcoproteins g1 and g2 which are specific to types 1 and 2 hsv respectively
How is HSV encephalitis or meningitis diagnosed?
CSF - PCR of HSV DNA method of choice. Lymphocytosis and elevated protein, low glucose may occur.
MRI supportive but not diagnostic
Culture not recommended
Treatment for orolabial herpes
First or severe recurrences - aciclovir 200-400mg 5x day for 7-10 days (alternatives valaciclovir, famiciclovir)
Severe oral mucocutaneous disease 5-10mg/kg every 8hrs IV aciclovir
Treatment for genital HSV ?
Aciclovir 400mg 5x day for 7-10 days
Alternatively valaciclovir 1g po bd 5-10 days or famiciclovir 250-750 TDS for 10/7
Severe disease or systemic complications - aciclovir 5-10mg/kg iv every 8 hours
Dose of aciclovir for HSV suppression
For those with >6 recurrences/year
400-800mg orally two or 3 times a day, three a day in pregnancy
Valaciclovir 500mg BD or famciclovir 500mg bd
When should suppressive aciclovir for recurrent HSV be stopped?
In hiv-ve discontinuation would happen at 12 months
If hiv+ with low cd4 - may delay this, would give episodic tx course to take home to use in event of outbreak
Treatment of systemic HSV infection
IV aciclovir 5-10mg/kg every 8 hours for 10-21 days
HSV meningitis 10mg/kg every 8 hours
HSV encephalitis 10mg/kg every 8 hours for 14-21 days and quantative PCR in CSF may be helpful to monitor response to treatment
Low threshold for ICU
Involve neurologist
What to do if aciclovir resistance suspected?
In any immunocompromised patient developing clinical hsv lesions despite adequate doses of aciclovir should have sample taken for viral culture and antiviral sensitivity.
Try increasing dose antivirals and if still new lesions after 5 days - switch - foscarnet or cidofovir
What is the most common cause of aciclovir resistance?
Mutation affecting gene encoding viral thymidine kinase (TK) - the enzyme that phosphorylates aciclovir in HSV affected cells
Foscarnet and cidofovir do not require tk dependant phosphorylation
Via where does MAC infection occur?
Respiratory and GI tracts
Can MAC be passedmperson to person?
No
In whom does disseminated MAC typically occur
<50 cells/uL
Symptoms of DMAC
Fever, night sweats, fatigue, weight loss, anorexia and diarrhoea
Signs of DMAC
Hepatomegaly
Lymphadenopathy
Anaemia
Leukopenia
Elevated alk phos
Hypoalbuminaemia
Radiological features of DMAC
Hepatosplenamegaly and infra-abdominal lymphadenopathy
How is DMAC diagnosed?
Culture in blood or bone marrow aspirate or fluid from a STERILE SITE
In the absence of radiological evidence non sterile site positive eg stool or sputum doc or stool not enough to be diagnostic
Is culture from non sterile site without supporting radiology enough to warrant anti mycobacterial tx for DMAC?
No.
Although may start tx cultures pending.
How many blood cultures needed to confirm MAC?
One will pick up 91%, two increases rate to 98%
No more than two needed
How quickly can you get a mycobacteria result using radiometric detection system?
6-12 days blood
15-20 days solid media
DNA probes can identify species within 2hrs
PCR a rapid cost effective alternative
Stains on biopsy specimens may demonstrate acid fast organisms or granulomata weeks before positive blood cultures
Preferred culture method for MAC
Lysis of peripheral blood leukocytes to release intracellular mycobacteria followed by inoculation on to solid media (eg Löwenstein-Jensen, middlebrook 7h11 agar) or into radiometric broth.
Treatment for DMAC
Macrolide and ethambutol with or without rifabutin
Which macrolide to use in treatment for DMAC
Clarithromycin better studied and more rapid clearance of MAC from blood 500mg BD
Azithromycin fewer drug drug interactions and better tolerated
How is macrolide resistance in MAC treatment detected?
Return of clinical symptoms
Increased bacterial counts
Hence addition of at least one additional class recommended
When should rifabutin be added to DMAC treatment?
Patients with advanced immunosuppression (CD4<25), marked symptoms or inability to construct effective ARV regimen
Dose of rifabutin for DMAC treatment?
Max dose 300mg/day
Or 450mg/day if given with EFV
Or 150mg 3x week if given with ritonavir
Due to risk of uveitis
What should be given if cannot tolerate first line regime?
Fluoroquinolones, amikacin
Clofazimine should not be used - excessive toxicity and higher mortality rates
When should ARVs be started in DMAC,?
Simultaneously or within 1-2 weeks
Continue if already on
When should DMAC therapy be stopped?
At least 3 months therapy
Asymptomatic with negative blood cultures 6 weeks after incubation
VL <50 on two consecutive occasions
CD4 >100 at least 3 months apart
If these are never met continue life long
What constitutes treatment failure for DMAC?
No clinical response and mycobacteria isolated from cultures after 4-8 weeks of treatment to which patient has been adherent
Treatment options if treatment failure for DMAC?
A new combo
At least 2 drugs which the isolate is susceptible to
Often keep ethambutol as facilitates penetration of other agents
Eg rifabutin if not used previously, cipro, levo, linezolid, amikacin
Primary prophylaxis DMAC
Azithro 1250mg weekly for those with CD4 <50
When can primary prophylaxis for DMAC be stopped?
Viral load <50
CD4 >50 for at least 3/12
(Pierce study - almost all MAC cases occurred at cd4 <50)
How does MAC IRIS present?
Regional lymphadenopathy, liver lesions, bone lesions, hypercalcaemia
Self limiting but can be severe
Treatment options for MAC IRIS
Oral pred 20-40mg /day for 4-8 weeks
IL2 and GMCSF used in small number of patients
Leukotriene inhibitors used in tb associated IRIS refractory/intolerant of steroids
FNA of pus
Presentation of m.kansasii
Pulmonary - fever, cough, pulmonary cavities or infiltrates, focal pulm signs on exam
Diagnosis m.kansasii
Repeated isolation and compatible clinical and radiological picture
(Can be a commensal)
Treatment of m.kansasii
Rifamycin plus ethambutol plus isoniazid for 12/12
Same for disseminated and pulmonary disease
Causes of PUO
Infection or lymphoma
HIV rarely a cause of fever
Investigation of PUO
Travel hx important - lifetime - new and reactivated tropical infections not uncommon
Consider non-HIV related illnesses if good counts
IRIS
Specific features of bartonellosis
Bacillary angiomatosis - cutaneous lesions that can be friable, red, vascular and exophytic proliferating e lesions, non descript applies or subcut nodules
Difficult to distinguish from KS
PCR of blood or biopsy
Erythromycin or doxycycline
Common diagnoses following the investigation of HIV associated PUO
Infection
DMAC
Mycobacterium tuberculosis
Bacterial infections
Leishmania
Pneumocystic Jirovecii pneumonia
Histoplasmosis
CMV end organ disease
Viral (hepatitis B, C, herpes virus, adenovirus)
Neoplastic/Lymphoproliferative Lymphoma
Kaposi’s sarcoma
Castleman’s disease
Why are PLWH more at risk of Candida infection?
Immunological response against Candida at gastrointestinal mucosa or skin surface is dependant on T helper 17 cells - this T cell subset is disproportionally depleted during early stages of HIV associated T cell decline
Vulvovaginal candidiasis less influenced by Th17 cell function and more by dye iOS is and alterations in vaginal pH
Why might PLWH on cART still be susceptible to Candida?
Impaired T cell responses to Candida can continue even after 2 years of therapy
Clinical risk factors for candidiasis other than immunosuppression in PLWH?
IVDU, TB
