#ClinicSpeak & #NeuroSpeak: alemtuzumab and opportunistic infections

Calling all alemtuzumabers please be extra-vigilant about infections when your lymphocyte counts are low. #ClinicSpeak #NeuroSpeak #MSBlog

I was at a meeting on Friday and heard about a patient who had died of Listeria meningitis after receiving alemtuzumab. Listeria is an opportunistic infection and tends to occur more often in people who are immuno-compromised. Nocardia is another opportunistic infection that has been described post-alemtuzumab (see below). These cases are likely to be at the vanguard and are not 'unexpected'; a case of Listeria meningitis was described in the clinical trial programme and we know from basic principles that immunosuppressive therapies are associated with opportunistic infections. Importantly, you need to know that you can de-risk Listeria to some extent by being on a 'pregnancy diet' post-treatment for the first 3-4 months until your lymphocyte counts have recovered. We recommend that all our patients follow the pregnancy diet for 3 months, which can be found on the NHS Preventing Listeria web-page. 

Preventing Listeriosis (adapted from the NHS website) 

The best way to prevent getting listeriosis is to always ensure that you follow good basic food hygiene. This includes:

• Peeling raw vegetables, salads or fruit, or washing them thoroughly before eating.
• Washing your hands before preparing food, before eating and after going to the toilet.
• Washing kitchen surfaces and utensils regularly, particularly after preparing raw meat, poultry and eggs.
• Always separating raw foods from ready-to-eat foods. Don't store raw meat above ready-to-eat foods, because there's a risk that juice containing harmful bacteria may leak from the raw meat.
• Always cooking food thoroughly and checking cooking instructions carefully, including the cooking time.

For foods that are "ready to eat", the most important ways of reducing the risk of listeriosis are to:

• not use food after its "use by" date
• make sure that the temperature of your fridge is 0-5C
• follow storage instructions on food labels

As an alemtuzumabers' are high-risk group for catching listeriosis, you should avoid eating foods known to be at risk of listeria contamination. Foods to avoid include:

• soft mould-ripened cheese – such as Brie, Camembert and chèvre (a type of goat's cheese)
• soft blue-veined cheese – such as Danish blue and gorgonzola 
• all types of pâté – including vegetable pâté
• unpasteurised milk
• undercooked food

It's safe to eat hard blue-veined cheese , such as Stilton, as well as other types of hard cheese, including Cheddar and Parmesan – even if these are made from unpasteurised milk.

Read more about foods to avoid after alemtuzumab and during pregnancy.

Farm animals: Alemtuzumabers should avoid close contact with farm animals that are giving birth or have recently given birth. This is to avoid the small, but serious, risk of an infection.

Read more about the potential risks of close contact with farm animals on GOV.UK.

Please note that alemtuzumab is an induction therapy and is irreversible. Based on its mode of action there will be complications. The only way to de-risk the opportunistic infections is to be vigilant and to take symptoms of infection seriously. If in doubt seek advice. Please note that once your immune systems have reconstituted the risk of opportunistic infections is very low. 

Penkert et al. Fulminant Central Nervous System Nocardiosis in a Patient Treated With Alemtuzumab for Relapsing-Remitting Multiple Sclerosis. JAMA Neurol. 2016 Jun 1;73(6):757-9.

Rau et al. Listeria Meningitis Complicating Alemtuzumab Treatment in Multiple Sclerosis--Report of Two Cases. Int J Mol Sci. 2015 Jun 29;16(7):14669-76.

Alemtuzumab, a humanized monoclonal antibody targeting the surface molecule CD52, leads to a rapid depletion of immune cells in the innate and adaptive immune system. In phase 2 and 3 trials in multiple sclerosis (MS), infections have been reported more frequently inalemtuzumab than in interferon beta treated patients. Here we report two patients treated with alemtuzumab for MS developing Listeriameningitis few days after the first infusion cycle. Both patients recovered completely after prompt diagnosis and adequate treatment. Physicians and patients should be aware of this serious, but treatable complication.