Cryptococcal Meningitis with HIV AIDS

SUKRARAJ TROPICAL AND INFECTIOUS HOSPITALBy: Dr. Saurav Poudel

On :12.18.2013At : Presentation Hall Of AHF, Teku.

Meningitis:

Inflammation of Meninges i.e Pia mater and Arachnoid mater.

Layer of Meninges: a)dura mater b)arachnoid mater c)pia materSubarachnoid space:It is the space between

arachnoid and pia mater which is filled with cerebrospinal fluid.

Infective cause of meningitis:

1)Bacteria:- Nesseria meningitidis 80% cases -Streptococcus pneumonia -Haemophilus influenza -Staphylococcus aureus -streptococcus Group B -Leisteria monocytogens -E.coli -Mycobacterium tuberculosis -Treponema Pallidum

2)Viral : -enterovirus: ECHO coxsakie -Poliomyelitis -Mumps -Herpes simplex -HIV -Epstien Barr virus

Fungal : -Cryptococcus Neoformans -Candida albicans -Coccidioides immitis -Histoplasma capsulatum

Micro-organism reaches the meninges either by direct extension from the ears,nasopharnyx,cranial injury or congenital meningeal defect or blood stream spread,immuno-compromised patient are risk of infection……………..

TYPES OF MENINGITIS

• Pyogenic or bacterial meningitis• Tubercular meningitis• Viral meningitis or Aseptic meningitis• Fungal meningitis

Clinical Features:• Fever: high fever

• Signs of Meningeal irritation: -neck rigidity -Kernigs sign -Brudzinski’s sign *signs of raised ICP:-nausea,vomiting,headache -Pappiloedema -Bradycardia *conciousness : present or not *focal neurological sign :present or not

Clinical Clues:• Petechial rash: meningococcal infection• Skull fracture Ear disease : pneumococcal infection Congenital CNS lesion *immunocompromised patient: HIV oppurtunistic infection*Rash or plueritic pain :enterovirus infection*International travel : malaria,poliomyelitisOccupational:Workers in drain,canals, :LeptospirosisPolluted water,recreational swimming

Investigation

• Cerebrospinal fluid study• Blood culture• Complete blood count• Chest x-ray for tuberculosis and pneumonia• Mountaux test• CT scan

Antibiotic in acute bacterial meningitis

antibiotic alternate*Unknown -ceftotaxime Benzylpenicillin pyogenic &chloramphenicol

*Meningococcus -Benzylpeniciilin –ceftotaxime*Pneumococcus - ceftotaxime - Peniciilin*Haemophilus – ceftotaxime - chloramphenicol

*** ceftotaxime: 2gm iv 6 hourly for 10-14 days. benzylpeniciilin:2.4gm iv 4 hourly for 5-7 days.

CRYPTOCOCCOSIS

Chronic, subacute to acute pulmonary,systemic or meningitic disease,initiated by the inhalation of the fungus.Primary pulmonary infections have no diagnostic symptoms and are usually subclinical.on dissemination,the fungus usually shows a predilection for the central nervous system,however skin, bones and other visceral organs may also become involved….

Distribution: worldwideAetiological Agent: Cryptococcus neoformans.

Cryptococcus Neoformans

*A capsulated Yeast.*Sporadic disease in the past.*Most common infection in aids patient.Morphology:-A true Yeast--round 4-10 microns--60% of the infected prove positive by India ink preparation on examination of CSF…..

Cryptococcus Neoformans Serotypes

• A true yeast• 4 serotypes –A,B,C,D A:80% clinical cases.• Many infections are caused by: C.neoformans

var neoformans.• Found in wild/domesticated birds.• Piegeons carry C.neoformans• Birds do not get infected…

CRYPTOCOCCOSIS

• C.neoformans, C.gattii• Encapsulated fungus; Inhalation

infection

immunocompromise

Disease

• Virulence factors --polysaccharide capsule :antiphagocytic,diminsh complement, enhance hiv replication. --melanin: protects from antifungal agents--ability to grow at high temperature--production of phospolipase ,urease.

MANIFESTATION• CNS - Meningitis;Dementia,abscess Granuloma,Meningoencephalitis.

• LUNG -Nodules,Cavities,ARDS,pneumonia Plueral effusion,Pneumothorax.

• SKIN -Papules,Vesicles,Purpura.

• EYE -Keratitis,Endophthalmitis, optic nerve atrophy.

• CVS -Pancarditis,Mycotic Aneurysm.

• GIT -Hepatitis,esophageal nodule.

• OTHERS -breast abscess,thyoiditis.

CRYPTOCOCCAL MENINGITIS & HIV

• Leading infectious cause of meningitis in HIVPatients-7% HIV patients (Adams neurology)• Usually in CD4<100 cells/ul;• Presentation: subacute course with fever,nausea,vomiting,altered mental

status, headache, cranial nerve palsies. • Seizures and focal neurological signs are rare..

• In HIV patients burden of yeast is higher higher antigen titers slower CSF sterilization

• Greater likelihood of second CNS event• Immune reconstitution syndrome in patients

on ART

LAB DIAGNOSIS• CSF Microscopic observation under india ink preparation.• INDIA INK: Cryptococcus neoformans, because of its large polysaccharide capsule, can be visualized by the

India stain. Organisms that possess a polysaccharide capsule exhibit a halo around the cell against the black background created by the India

• Direct microscopy- gram staining• Cultures on Sabouraud dextrose agar• Serological tests for detection of capsular antigen• CSF findings mimic like tuberculosis• In CSF-latex test for detection of antigen• Blood Cultures• ELISA

CRYPTOCOCCAL MENINGITIS & HIV @ our hospital

• From 2070/01/01-2070/09/01• Total no. of HIV +ve patient got admitted:320. total no. of death:24 CAUSE: PLHIV e C.meningitis:8 PLHIV e PTB:4 PLHIV e fever under evaluation:4 PLHIV e CLD:3 PLHIV e anaemia:1 PLHIV e chest infection:1 PLHIV e ARF:1 PLHIV e weakness:1 PLHIV e Spticaemia:1

TREATMENT

• ACUTE PHASE amphotericin B + Flucytosine: for 2 weeks

• CONSOLIDATION PHASE: Fluconazole : 10 weeks

• MAINTENANCE: fluconazole - lifelong

DOSE side effects AMPHOTERICIN B : 0.7-1.0mg/kg/day -Hypokalemia hypotension arrythmias nausea & vomiting

FLUCYTOSINE :100 mg/kg/day --anaemia,leukopenia thrombocytopenia renal and GI toxicity

• FLUCONAZOLE: 400 mg/day :CONSOLIDATION PHASE 200 mg/day:MAINTENANCE PHASE

• SIDE EFFECTS: reversible hepatotoxicity alopecia muscle weakness metallic taste

INTRACRANIAL PRESSURE(ICP)• ICP is normally 7–15 mm Hg• Raised ICP means:20–25 mm Hg

• CAUSE:• increased CSF production can occur in meningitis, subarachnoid

hemorrhage, or choroid plexus tumor• obstruction to CSF flow and/or absorption can occur

in hydrocephalus.• mass effect such as brain tumor, infarction with edema, contusions,

subdural or epidural hematoma, or abscesses.• OSMOTIC DIURETIC MANNITOL (1.5-2 g per kg intravenously) has

been used to treat signs of acutely increased ICP

ART• ART shouldnot be given during acute phase of cryptococcal meningitis

treatment because: ART

RAPID INCREASE IN CD4

DEPLETION OF VIRAL LOAD

EXAGERRATED IMMUNE RESPONSE (IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME)

• ART should be initiated after two months of initiation for treatment of cryptococcal meningitis and CD4 count >200/ul..

• BUT Once cryptococcal antigen has been significantly reduced, antiretroviral therapy can be initiated while the therapy for cryptococcal infection continues. However, newer data demonstrate improved clinical outcomes when highly active antiretroviral therapy (HAART) is initiated within 6 months of the diagnosis of cryptococcal meningitis.

PREVENTION • Primary prophylaxis To give an antifungal medication to all HIV–infected patients with low CD4+ T-

cell counts (i.e., patients with advanced HIV) in order to prevent them from getting cryptococcal meningitis.

• Targeted screening to prevent deaths "targeted screening" Research suggests that Cryptococcus is able to live in the body

undetected, especially when a person's immune system is weaker than normal. A targeted screening program would test HIV-infected patients for cryptococcal antigen (an indicator of cryptococcal infection) before they begin taking antiretroviral treatment (ART). A patient who tests positive for cryptococcal antigen can take oral fluconazole, to help the body fight the fungus before the patient starts ART. This would prevent them from developing severe cryptococcal infection.

• A new method for detecting cryptococcal antigen has recently been developed. This test is a "dipstick" test, and is simple to use on a small sample of serum (a component of blood ). The test accurately detects silent, as well as active, cryptococcal infections 95% of the time. .

PIEGONS SHOULD BE AWAY FROM IMMUNOCOMPETENT & IMMUNOCOMPROMISED PATIENT

THANK YOU

Dr.saurav poudel (saurav7utd@hotmail.com)Medical Officer @ Sukraraj Tropical & Infectious Disease

Hospital.2013.12.18