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“Mais le SIDA n’existe plus quand même..?!”

[But AIDS has disappeared, not so…?!]

Filip MoermanCHR Citadelle Lüttich, BelgiumInstitute of Tropical Medicine, Antwerp

EUREGIO 2018 (Aachen, Germany)

Overview of the presentation 13 cases of clinical AIDS last 18 months in CHR

Liège! (9 Afr, 4 Europeans) So we may not forget the clinical spectrum of

AIDS (cfr in Africa still very prevalent) We’ll present 2 clinical cases of this year,

emphasizing on the Se / PPV (Prevalence!) of symptoms, AND a short summary on diagnosis and treatment of other AIDS-def. illnesses.

Renaud, 27yrs old (nurse). Never been tested, no relevant med history Emergencies June 2018 with longstanding

headache, loss of apetite and fever on and off Mother says: “becomes slow and bizarre and

can no longer concentrate” CLIN/LAB: cachectic (BMI=16), weak, pale,

tachycardia, tachypnoe, photophobia, HIV+ [CD4]=20/mm³, (SGOT/PT)↑, Hb = 8,2 g/dl with a HIV-1 VL of nearly 6 log

WHAT IS YOUR (D) DIAGNOSIS?

Cryptococcal meningitis Most common life-threatening fungal infection in

PLWHA CD4 < 50 Insidious onset: fever + headache (Se↑, NPV↑) Confusion, behavioral change (mother!) Papilledema,+/- neck stiffness, seizures, cranial

nerve paralysis

Lumbar puncture, even if no meningeal signs

Even when papiloedema, LP does not carry excessive risk of cerebral herniation

Diagnosis (clinical suspicion, Pre- test-Prob)

Microscopy, Culture, Antigen, PCR Se of India-ink-staining in CSF < 86% (CAVE low

fungal burden) CSF culture = gold standard (but takes 7 days!) (!): detection of Cryptococcal Ag in CSF and serum

both have high Se & Spe and are fast techniques. Additionally PCR

Usually several approaches result in quick diagnosis.

Cryptococcal meningitis

India ink preparation (85% sens.) : Cryptococcus neoformans

Treatment of cryptococcal meningitis

Induction phase Amphotericin B lip 3 mg/kg/24h, IV, 2 weeks + Flucytosine 25 mg/kg q6h p.o. for 2 weeks at least, followed byà Prolongation phase Fluconazole 800 mg 8-10

weeks, then 200 mg / day (2° prophyl)

Fungicidal rate decline about 0,4 log/day

Repeated LP as part of the therapyUp to 30 cc daily until ICP< 20 cm or 50% initial

P.

CAVE: wait with HAART!!Very intensive CRYPTO-IRIS

Smilnak, et al. Novel treatment of cryptococcal

meningitis via neurapheresis therapy JID 2018

designed as adjunctive treatment to standard care

The Journal of Infectious Diseases , Volume 218, Issue 7, 24 August 2018, Pages 1147–1154,

https://doi.org/10.1093/infdis/jiy286

Would result in a 5 log reduction of yeasts in 24h!

Follow-up of treatment success

Clinical

India Ink: capsula disappearing

Cryptococcal Ag: only useful when titers! And still…low evaluation power

Culture (probably ‘better’ than Ag)

How is Renaud? Hospitalized from June 10th – September 28th During the course of his crypto-treatment he

developped MAC characterised by fever+++ (possibly as IRIS since prompt VL-decrease to VL<20 copies/ml after 10 weeks!)

Developed severe AKI as well, now improved He is ‘relatively’ well now and followed-up

fortnightly.

Jane, 38 yrs old, Ivory Coast Slow loss of weight with diarrea Progressive increase of headache and apathy Vesperal fevers H. zoster recidivans Difficulties in walking with right hemiparesis Progressive dysphagia that forced Jane finally

to the hospital

Cerebral toxoplasmosis

Cerebral Toxo

Cerebral toxoplasmosisCause : T. Gondii (oocysts in cat stools and undercooked meat) – invasion of lungs, heart, retinitis, brainSYMPTOMS: Fever: 50% Headache: 50-70% Hemiparesis: 50% Seizures: 30% NO symptoms (!): MRI as screening in AIDS-

analyses!Diagnosis : IgG (IgG- = NPV↑), scan, MRI more Se than CT (CSF normal, exclude TB-meningitis, Lymphoma, Crypto, PMLE)à Response to empirical therapy in poor settingsà Go to brain biopsy if no improvement (TB-abcess of

brain!)

Cerebral toxoplasmosisTREATMENT: (steroids NOT systematically, but often later)

First choice: Sulphadiazine + pyrimethamine* 6w*inhibit folates synthesis

à hematologic toxicity (+ Sulphadiazine may cause crystaluria: hydration!)

+ Folinic acid

Cheap

Monitor Kidney

COTRIMOXAZOLE TMP/SMX 10/50 mg/kg daily divided over 2 dosesFor 4 weeks (patients 50 kg 3 tablets of TMP80/SMX400 twice daily)Followed by maintenance therapy

AFRICAN setting: If referral difficult

Focal neurological signs + fever + headache and CSF normal therapeutic trial with cotrimoxazole Response in 1-2 week if it is toxo

Altern treatments include: dara + Azithro 1000 OR ‘dara+dala’

Treat intracranial hypertension (prednisolone 40 mg 4x daily) and seizures (phenytoine 100 mg 2-3 daily) if necessary

Jane…(0 CD4)Jane denied her diagnosis established in Africa in 1998, she did not reveal it to her husband and 2 children. On admission, following active diagnoses were withheld: Cerebral Toxoplasmosis, H. zoster+++, slim disease with µ-sporidium, candida oesophagitis, CxCA in situ, PMLE (JC virus), probable AIDS-dementiaShe died of multipathology, drug-related toxicity and severe IRIS …

Diarrhea 50% of patients will develop diarrhea in the

course of their HIV disease Significant effect on quality of life

HAART / Paromomycin empirical to consider

In 50% of patients we can not identify a cause

Causes of diarrhea Infectious agents Other causes Bacteria

ProtozoaToxin inducedMycobacteriaHelminthicFungal Viral

AIDS enteropathyKaposi’s sarcomaLymphoma of the gutMedications

Isospora belli (‘cryptoisosporiasis’)

Direct stool exam Large oocysts (20-30

µm) R/ Cotri 1DS x 4/day

for 10 days Followed by 1 DS x

2/day for 3 weeks Secondary prophylaxis

with cotrimoxazole 1DS

Microsporidiosis Modified

trichrome stain Small spores: 1-3

µm: survive for years outs host

Usually faeco-oral

Albendazole 400 mg Bid 2-4w (relapse) HAART !!! (response in 1-15w, average 6w)

Case: chronic diarrhea Patient presents

with respiratory symptoms

Skin lesions ~ creeping eruption

Diarrhea, HIV+

Strongyloides hyperinfection syndromeR/ Ivermectin (Stromectol®) 200 µg/kg (+ repeat in 1 week)Poor setting: Albendazole 2 x 400 mg dd

PCP (Pneumocystis Carinii = Pneumocystis Jiroveci)

Symptoms: Sub-acute onset Dry cough Fever, first low & vesperal, later continuously DYSPNEA (on exertion): parabolic

deterioration at one point with desaturation. At this point, Steroids to add

Cfr LDH rather high NPV! Less frequent in Afr!

PCP, diagnosis ‘Typical’ chest X-ray – CT:

Bilateral interstitial infiltrates beginning in the perihilar regions/ ground glass appearance/ Butterfly wings

25% normal at initial presentation

Diagnosis mostly by clinical presentation

and chest X-ray/CT/BAL + PCR

Typical CT-scan

Bronchoalveolar ‘washing’

Treatment of PCP TMP-SMX: 20 mg/kg/day SMX and TMP 5 mg/kg/day

divided over 4 doses for 21 days, initially mostly IV (4 x 4 amp of Eusaprim IV/day)

In case of hypoxemia *(P02<70mmHg): Prednisone before Ǿ

40 mg 2x/day for 5 days40 mg 1x/day for 5 days20 mg for 11 days*Decomposition of many dead parasites aggravates inflammation worsening of hypoxemia

ALTERNATIVE TREATMENT: Atovaquone or DDS+TMP or Clinda+PQ

à Improvement in 7-10 daysà Secondary prophylaxis 1DS TMP/SMX

Average 4x3 tablets of CTX F per day

CMV retinitis (low CD4, CMV viraemia, Leucopenia, vision

disturbances)

Cerebral lymphoma

But don’t forget simpler diagnoses

S. Pneumoniae Pneumonia

Streptococcus pneumoniae Often positive blood

cultures Acutely ill, high

fever Productive cough Pleuritic type chest

pain Gram stain + culture

75% diagnostic

Vaccinate your patients!

Nocardiosis Rare in immune

competent DD TB Gram stain + AFB

Histoplasmosis (published)

Deep fungal infection Rare Histoplasmosis, coccidiomycosis, aspergillosis,

cryptococcosis, Penicillium Marneffei (OI frequent in Thailand)

Diagnosis: blood and sputum culture, BAwashing

Amphotericin B during 14 days, followed by itraconazole 200 mg twice daily (10 weeks), followed by secondary prophylaxis with itraconazole once daily

ORAL HAIRY LEUKOPLAKIA Vertical folds Non-removable Not painful

No treatment (HAART)

Sign of immune suppression

WHO stage III

Caused by EBV replication in the epithelium of the surface of the tongue

Severe forms of OHL

Disturbance of taste

Difficulties to eat Regression is seen

when treated with Acyclovir and HAART

Ulcers of unkown origin

Solitary big ulcers

What to consider?

Clinical approach

Histoplasma

Necrotising gingivitis Inflammation of the

gums Extensive and

necrotic Tooth loss

Anaerobic infection R/ metronidazole

3x500 mg

Kaposi’s Sarcoma

Solitary big ulcers CMV Deep mycosis: histoplasma, cryptococcosis

In single big ulcers:Before prednisone 40 mg daily

èTrial with fluconazole or itraconazoleèRule out treatables (clinical approach)èDon’t forget SYPHILIS !

TB meningitis 10% of AIDS patients who present with TB will

show involvement of the meninges. Symptoms: sub-acute meningitisü Gradual onset of headacheü Low grade feverü Neck stiffness

Cranial nerve palsies Seizures, focal neurological deficits, altered consciousness

Diagnosis of TB meningitis: difficult!

IMAGING: MRI/CT may show leptomeningeal enhancement, hydrocephalus, tuberculoma, abcess

LAB: hypoNa+, QFR (CAVE AIDS), VS +/- CSF microbiology: smear, culture, PCR

(multiple [>3] samples required to increase Se) CSF analysis: lympho pleio preceded by PMN

predominance in early infection, high proteinorachia, low glucose: consider when glu low, prot high and negative bact cultures AND ‘pre-test’ high (HIV, Afr origin, Epidemiol context, …)

TB brain abcess (DD: biopsy!)

Tuberculous granuloma of the brain

Treatment of TB meningitis TB treatment according to protocol

(INH+PZA+RIF+EMB), prolonged: 2 + 7-10 months.

Furthermore, Prednisolone 1 mg/kg for 2-4 weeks in case of severe neurological signs (always if IRIS)*

Timing to introduction of HAART depends on CD4 count; if possible (> 100 CD4/mm³), wait until end of initial phase.

Steroids in TB-HIV: pericarditis, meningitis *early mortality decrease: Marx G, et al. Tuberc Res Treat 2014