GIM Training Day: Infections in the Immunocompromised 27.4.21

Dr Prith Venkatesan Infectious Diseases Nottingham University Hospitals City Campus Immunocompromise Not just HIV

Individuals

Disease

Treatments Anti-inflammatory drugs NSAIDs Gold Montelukast Penicillamine Steroids Sulfasalazine Cyclophosphamide Hydroxychloroquine Azathioprine Mycophenylate Apremilast Methotrexate Tofacitinib Ciclosporin Ruxolitinib Tacrolimus Sirolimus Biologics FDA approved (a selection) IL-1 TNF a CD19 Anakinra Infliximab Blintumomab Canakinumab Adalimumab CD20 Rilonacept Certolizumab Rituximab CD25 (IL-2) Golimumab Ibritumomab Basiliximab Etanercept Obintuzumab Daclizumab CD30 Ofatumumab IL-5 Brentuximab Tositumumab Reslizumab Complement, C5 BAFF (B cells) Mepolizumab Eculizumab Belimumab IL-6 CTLA4/CD152 CD279/PD-1 Tocilizumab Abatacept Pembrolizumab IL-12/IL-23 Ipilimumab Nivolumab Ustekinumab CD52 CD274/PD-1 IL-17 Alemtuzumab Atezolizumab Secukinumab a-4 integrin Avelumab Ixekizumab Vedolizumab IgE Natalizumab Omalizumab SLAMF7/CD310 Elotuzumab Organisms

‘Anti-septics’ Physical clearance

Epithelium

B cells

Phagocytes

Inflammation T helper

T cytotoxic

Regulation 32 yr old male (Conflation of different, real cases) One week history Increased shortness of breath Dry cough Fatigue Not feverish For a few months Noticed weight loss Admission CXR 32 yr old male COVID-19 PCR positive Sats 88%, CRP 120

Dexamethasone Tocilizumab 44 yr old male Concerned about weight loss Underlying illness? Immunocompromise?

Could there be more to the chest than COVID-19? Infections and immunocompromise Respiratory Recurrent RTIs Gastrointestinal Oral thrush Persistent diarrhoea Weight loss Skin Change in skin flora Shingles at young age, HSV Generalised lymphadenopathy Chest work up Context

1. Clinical features

2. Exposures

3. Susceptibility Chest work up context Clinical features One week history of SOB, dry cough, no fever No crackles on auscultation PMH: blistering rash as a neonate Stopped 10 cigarettes/day 2 years ago No cannabis, no cocaine, no heroin Oral thrush present ‘Shotty’, generalised lymphadenopathy Exposures No travel, no animal contacts, no IVDU Male partner of 4 months well (PHE) HIV testing Raising the subject Discussion and counselling Implications of a test For patient For partner For children Chest work up context Susceptibility HIV test proves positive Infections beyond COVID-19 Viruses M,C&S CMV, HSV, Influenza Blood cultures Sputum (but unproductive) Bacteria Induced sputum (but hypoxic) St.pneumoniae, H.influenzae Bronchoscopy (but hypoxic) Atypical pneumonia pathogens Antigen tests Mycobacteria Pneumococcal Legionella • M.tuberculosis, Beta-D-Glucan (BDG) • atypical mycobacteria Aspergillus galactomannan Nocardia Cryptococcus Rhodococcus PCR Which? Fungi On what specimen? Pneumocystis jiroveci, Serology Histoplasma, Cryptococcus, Which? Aspergillus, Talaromyces marneffei Protozoa Toxoplasma Helminths Strongyloides 32 yr old male Initial improvement CRP falls On day 16 he is more SOB and his CXR shows: 32 yr old male COVID-19 progression? Should he have had other empirical treatments? Should he have had empirical PCP treatment, or should this wait till a positive result is received?

What is expected of the Med Reg? Spotting that there is something different to ‘usual’ Thinking of immunocompromise and an HIV test Pick up the phone and discuss with others 32 year old male Blood Cultures negative CMV PCR negative Sputum unproductive Throat swab PCP PCR negative From a panel • Herpes simplex PCR positive • No oral ulceration • Bystander or culprit? 32 year old male Commenced iv aciclovir Within 48 hours off oxygen Summary Natural, innate defences Epithelial surfaces Inflammatory response Adaptive, specific response B cells and humoral immunity Cell mediated immunity Suspecting immunocompromise Clinical features, exposures, susceptibility HIV testing Beware of the unexpected Thank you