A Case of Cryptococcal MeningitisPresentation Transcript
Fever in immunocompromisedpatient Dr.Jayakumar S A Prof.Dr.A.Gowrishankar unit
34 year old Mrs.Hajara ,came with c/o –fever headache 2 weeks lethargy HOPI:- Fever – intermittent ,low grade not associated with chills or rigor headache – diffuse ; - constant dull ache - progressively increasing severity
h/o increasing tiredness and inability to do daily activities h/o nausea No h/o rash/vomiting ,loose stools No h/o dysuria No h/o cough with expectoration No h/o weakness of limbs No h/o altered sensorium No h/o seizures No history suggestive of jaundice No h/o bleeding manifestations
Past history:- not a known DM/HT/TB/IHD/BA/EPILEPTIC patient Treatment history : 1 ½ months back evaluated for unexplained fever ,loss of weight and diarrhea; diagnosed HIV positive ; HAART initiated on 24.06.2010 zidovudine 300mg lamivudune 150 mg nevirapine 200 mg
Personal history mixed diet RMP 3/30 Family history husband died due to HIV six yrs back two children
o/e: conscious oriented febrile anemic no cyanosis/clubbing /pedal edema /icterus/ lymphadenopathy Vitals : Pulse – 96/mt,regular ,normal volume ,felt in all peripheral pulses BP -130/80 mmhg
CVS : S1, S2 heard no murmurs RS : normal vesicular breath sounds no crepitations / wheeze P/a : soft Bs+ no organomegaly CNS : Higher functions normal bilateral lateral rectus weakness no weakness of limbs bilateral plantar flexor minimal neck stiffness present Fundus : mild disc blurring seen ;
Impression : Retroviral disease with CNS infection cause to be evaluated
Investigatons CBC:- CXR –normal; Hb -8.5 g/dl ECG –normal; Tc -6ooo P 55 L 42 E 3 ESR -6/15 Plt – 1.7 lac PCV -28% Random blood sugar – 110mg/dl urea -18 mg/dl creatinine – 0.8mg/dl
CSF analysis : sugar – 87 mg/dl protein – 27 mg/dl cytology –acellular AFB -negative culture and sensitivity – negative cryptococcus –positive in india ink
CT BRAIN : Normal ; MRI BRAIN : 1.2 × 0.8cm T 2 hyperintensity noted in left parietal region suggestive of arachnoid cyst
Virulence factors --polysaccharide capsule --antiphagocytic ,diminish complement,enhances HIV replication --melanin --protects from antifungal agents -- ability to grow at high temperature --production of phospholipase ,urease
CryptococcAL MENINGITIS & hiv Leading infectious cause of meningitis in HIV patients -7 % HIV patients (Adam’s neurology) Usually in CD4 < 100 cells /ųl; Presentation : subacute course with Fever ,nausea ,vomiting ,altered mental status ,headache ,meningeal signs Cranial nerve palsies & cryptococcomas Seizures and focal neurologic deficits is rare
In HIV patients burden of yeast is higher higher antigen titres , slower CSF sterilization Greater likelihood of second CNS event Immune reconstitution syndrome in patients on ART
Diagnosis CSF : Normal or modest elevations in protein Microscopy : Indian ink stain mucicarmine stain fontana mason stain gomorimethanamine silver stain Culture : saboraud’s agar – 3 to 12 days staib’s birdseed ,dopa ,caffeic acid media Serology: polysaccharide Ag testing in serum CSF latex agglutination test /EIA
IMAGING CT Brain : normal /hydrocephalus /gyral enhancement /cortical atrophy MRI Brain : no pathognomonicfeature hydrocephalus /cryptococcomas lesions may’nt decrease in size for a year despite treatment
PROGNOSis High CSF pressure Low CSF glucose Low CSF pleocytosis ( < 2 /ųl) CSF /serum antigen level > 1: 32 Absence of antibody to C.neoformans Recovery of yeast cells from extraneural sites Positive CSF assay by India ink itself is a poor prognostic factor
Immune reconstitution ART RAPID INCREASE IN CD 4 & DEPLETION OF VIRAL LOAD IMPROVED /EXAGGERATED IMMUNE RESPONSE
Is immune reconstitution always beneficial?
Immune Reconstitution Inflammatory Syndromes (IRIS): Immune Reconstitution Paradox: inflammatory reaction to antigens that were previously not recognized by the immune system. can sometimes lead to worsening of a current or latent opportunistic infection. The onset of IRIS often occurs 2-8 weeks after initiation of ARV therapy but can occur earlier or later.
IRIS Case Definition Evidence of clinical response to ART with: On ART >1 log10 copies/mL decrease in HIV RNA (if available) Infectious or Inflammatory condition within 6 months of ART initiation Symptoms can not be explained by either: Expected clinical course of a previously recognized and successfully treated infectious agent Treatment failure Side effects of ART. Complete ART non-compliance
34 Practical Definition: NACO “Occurrence or manifestations of new OIs within six weeks to six months after initiating ART; with increase in CD4 count” India’s National AIDS Control Organization, Antiretroviral Therapy Guidelines for HIV-infected Adults and Adolescents Including Post-exposure Prophylaxis. May 2007
Paradoxical IRIS : the clinical worsening of an infection that was previously successfully treated and is caused by exaggerated activation of the immune system against persisting antigens present as dead organisms or debris following the initiation of ART.
Unmasking IRIS: patients with advanced immune suppression prior to ART are unable to mount an effective immune response against the viable pathogenic organisms that are present, but improving immunity after ART allows previously unrecognized pathogens to evoke an inflammatory response (unmasking).
Pathogens associated with IRIS Mycobacterium avium Mycobacterium tuberculosis Mycobacterium leprae Cryptococcus neoformans Pneumocystisjiroveci Histoplasmacapsulatum Hepatitis B virus Hepatitis C virus Varicella-zoster virus Cytomegalovirus BK Virus Parvovirus B19 JC virus Papilloma virus HHV-8 (KS)
Risk factors Risk factors at base line: Lower CD4 count prior to start of ART Higher HIV-1 RNA levels at base line Initiating ART in close proximity to starting therapy for an OI Response to therapy & the development of IRIS: Rapid fall in HIV-1 RNA level during the first 3 months of therapy Source: Journal of Antimicrobial Chemotherapy (2006) 57, 167-170;Samuel A. Shelburne, Martin Montes and Richard J.Hamill
IRIS Associated with Crytococcal Meningitis Up to 30% develop IRIS after initiation of ART Increases in headache, Increase intracranial pressure, In ≈25%, serious complications like loss of vision, cranial nerve palsies, reduced cognition death.
IRIS Management Evidence-based treatment recommendations are lacking. Identify the inciting pathogen and treat it. Most cases of IRIS are managed without stopping ARVs. In severe cases, treatment options include stopping ARVs, steroids, NSAIDS, and surgical treatment (for example drainage of abscesses).
Carry home points Cryptococcus infection is common ; disease is rare Entry route is nasal ; Treatment in HIV patients is for lifelong; Carefully watch forIRIS ; Clinical worsening after HAART doesn’t mean failure of haart; Don’t stop HAART for IRIS ;
National Institutes of Health Clinical Center (CC) ClinicalTrials.gov Identifier: NCT00286767 JAIDS Journal of Acquired Immune Deficiency Syndromes: 15 August 2007 - Volume 45 - Issue 5 - pp 595-596 Timing of Cryptococcal Immune Reconstitution Inflammatory Syndrome After Antiretroviral Therapy in Patients With AIDS and Cryptococcal Meningitis Journal of Immune Based Therapies and Vaccines 2005, 3:7doi:10.1186/1476-8518-3-7 HARRISON’S PRINCIPLES OF INTERNAL MEDICINE -17TH EDITION MANSON’S TROPICAL DISEASES -22ND EDITION MANDELL,DOUGLAS & BENNETT INFECTIOUS DISEASES -7 TH EDITION