Pre-biologic infection screening and vaccination

01Purpose and principlesWhat the treatment does and how it fits into care.

Screening aims to prevent three distinct events: progression of an infection already present, reactivation of a controlled latent or resolved infection, and failure to prevent a vaccine-preventable infection. A single normal blood panel cannot achieve this. The process combines clinical history, focused examination, microbiology, imaging, vaccination records and the planned drug's specific immune target.

For tuberculosis, establish whether disease is active before labelling latency. IGRA detects immune sensitisation but does not distinguish active from latent TB and can be falsely negative during glucocorticoid or other immunosuppression. Chest radiography is appropriate with positive testing, previous TB or clinical and epidemiological concern. Sputum, CT or extrapulmonary sampling follows symptoms and TB-team assessment.

A positive IGRA without evidence of active disease triggers a latent-TB pathway. NICE uses either three months of isoniazid plus rifampicin or six months of isoniazid for many adults, selected around age, hepatotoxicity and interactions. A TB specialist decides the regimen and when the planned biologic can begin. TNF inhibition is particularly associated with reactivation, but all targeted immunosuppression needs a documented plan.

HBV prevention depends on the immune target. Rituximab causes prolonged B-cell depletion and has a high reactivation risk, so anti-HBc-positive patients generally need prophylactic entecavir or tenofovir started before infusion and continued for a hepatology-defined period afterward. Lower-risk regimens may use prophylaxis or close HBV-DNA and ALT surveillance. Waiting for hepatitis symptoms is unsafe because virological rebound precedes liver injury.

Vaccination should start as early as the treatment plan. Inactivated vaccines cannot replicate and include injected influenza, COVID-19 products, pneumococcal vaccines, recombinant zoster and hepatitis vaccines. Give them before immunosuppression where possible to maximise response, commonly at least two weeks beforehand, but do not delay urgent organ-saving therapy simply to complete every dose. Continue seasonal offers during treatment.

Live attenuated vaccines include MMR, varicella, yellow fever, oral typhoid and, where still encountered, live zoster vaccine. Give a necessary live vaccine at least four weeks before starting significant biologic or targeted immunosuppression, applying the Green Book and product interval. During treatment, avoid it unless immunology or infection specialists confirm that the particular drug exposure and vaccine are permissible. Check household contacts as live oral products can occasionally shed.

Recombinant zoster vaccine is non-live and is offered to severely immunosuppressed adults from age 50 under the UK programme, with two doses usually separated by eight weeks in immunosuppressed people. It can be given during treatment but is more immunogenic beforehand. Previous shingles does not guarantee durable protection. Active zoster must resolve before a scheduled immunosuppressant is given.

Rituximab deserves special timing because it blunts new antibody responses for months. When disease permits, complete vaccines at least four weeks before an infusion course and consider timing later doses toward B-cell recovery and before the next cycle. Do not withhold an urgent rituximab induction for a life-threatening vasculitis simply to wait for vaccine response; document reduced protection and other prevention instead.

Screening is repeated when risk changes. New TB contact, travel, imprisonment, homelessness, healthcare exposure, blood-borne-virus risk, pregnancy or serious infection can justify retesting. Annual automatic IGRA in every biologic user is not required by one universal UK rule. The record should contain results, interpretation, treatment or prophylaxis, vaccines given and outstanding, and a clear authorisation to start.

Key points

Start with active infection: history, examination and symptom-directed tests come before latent-screen panels; a patient with sepsis or active TB does not proceed to biologic dosing.
Tuberculosis assessment combines exposure and residence history, symptoms, IGRA and chest imaging when indicated. Immunosuppression can produce a false-negative or indeterminate IGRA.
A positive latent-TB screen requires exclusion of active disease and referral to the TB service for preventive treatment and biologic timing; do not improvise a universal delay.
Screen hepatitis B with HBsAg, total anti-HBc and anti-HBs. Surface antigen alone misses resolved infection that can reactivate during rituximab or other potent immunosuppression.
If HBsAg or anti-HBc is positive, obtain HBV DNA and hepatology advice; B-cell depletion usually requires antiviral prophylaxis even when HBsAg is negative.
Test hepatitis C antibody with reflex RNA because antibody alone cannot distinguish cleared from active infection; active HCV is now curable and should prompt a coordinated treatment plan.
Offer HIV testing before advanced immunosuppression because undiagnosed infection changes opportunistic-infection risk, vaccine planning and the safest rheumatology regimen.
Give indicated inactivated vaccines ideally before therapy, but they cannot cause vaccine infection during treatment; immune response may be weaker, especially after rituximab.
Give a required live vaccine at least four weeks before significant immunosuppression when possible and avoid live vaccines during treatment unless an expert product-specific pathway permits one.
Build a vaccine plan covering seasonal influenza and COVID-19 offers, pneumococcal vaccination, recombinant zoster and risk-based hepatitis B, HPV, travel and occupational vaccines.

02Indications, selection and cautionsWho may benefit, who needs urgent treatment and important alternatives.

Possible active tuberculosisRed flag

Persistent cough, weight loss, sweats, fever, lymph nodes or organ-specific symptoms with epidemiological risk requires microbiological and imaging assessment, not a latency label.

Latent tuberculosis pattern

Positive IGRA with no symptoms, normal or old stable chest findings and no microbiological evidence of disease supports latent infection after TB-team assessment.

Resolved hepatitis B risk

HBsAg negative with total anti-HBc positive indicates previous natural infection and potential reactivation; anti-HBs does not remove rituximab risk.

Vaccine-only hepatitis B immunity

Anti-HBs positive with HBsAg and anti-HBc negative is consistent with vaccination rather than previous natural infection.

Active hepatitis C

HCV antibody plus detectable HCV RNA identifies current infection; antibody with undetectable RNA reflects cleared or successfully treated infection after timing is considered.

Live-vaccine exposureRed flag

Recent MMR, varicella or yellow-fever vaccination matters because replication occurs for a limited period and sets a minimum interval before significant immunosuppression.

Red flags requiring action

Cough, weight loss, fever, night sweats, haemoptysis, lymphadenopathy or TB exposure requires active-tuberculosis assessment regardless of an earlier negative IGRA.
Jaundice, right-upper-quadrant pain, marked transaminase change or detectable HBV DNA requires hepatology assessment before immunosuppression.
A painful vesicular rash involving the eye, multiple dermatomes or systemic illness may be disseminated or ophthalmic zoster and needs urgent antiviral care.
Fever, hypotension, hypoxaemia, confusion, infected wound, hot joint or focal neurological signs means the infection work-up takes priority over scheduled biologic initiation.
Live vaccination accidentally given during significant immunosuppression requires immediate specialist risk assessment rather than the next biologic dose.
Pregnancy, planned conception or late-pregnancy biologic exposure changes vaccine and infant-live-vaccine decisions and must be documented before treatment starts.

03Assessment before treatmentTests and checks that guide safe selection.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
First-line clinical infection assessmentFirst stepFirst line
Why
Identify an active focus that makes immediate immunosuppression unsafe.
Interpretation and limitations
Use history and examination to direct cultures, urine testing, dental review, joint aspiration or chest imaging; do not perform indiscriminate cultures in an asymptomatic patient.
02
IGRA with TB exposure history
Why
Detect immune sensitisation and place it within a clinical probability of latent or active TB.
Interpretation and limitations
A positive result requires active-disease exclusion; a negative or indeterminate result can be unreliable with immunosuppression, recent exposure or lymphopenia and may need repeat or TB-team review.
03
Chest radiograph and TB microbiology
Why
Find previous, latent or active pulmonary disease when history, symptoms or IGRA indicate risk.
Interpretation and limitations
Old fibrotic change raises reactivation concern; new infiltrates, cavities or nodes require sputum, molecular testing and culture, with isolation and notification for suspected active disease.
04
HBsAg, total anti-HBc and anti-HBs
Why
Classify current infection, previous natural exposure, vaccine immunity or susceptibility before immunosuppression.
Interpretation and limitations
Any HBsAg or anti-HBc positivity prompts HBV DNA and hepatology planning; anti-HBs alone reflects vaccine response, while three negative tests identify susceptibility.
05
HCV antibody with reflex RNA
Why
Distinguish past exposure from current viraemia.
Interpretation and limitations
Detectable RNA triggers specialist antiviral assessment and fibrosis staging; immunosuppression decisions account for urgency, liver function and the rheumatic disease phenotype.
06
HIV antigen-antibody test
Why
Identify infection that changes opportunistic risk, vaccines, interactions and immune interpretation.
Interpretation and limitations
A reactive screen needs confirmatory testing and prompt HIV-team linkage; effective antiretroviral control can permit carefully selected rheumatology treatment.
07
FBC, liver, renal and immunoglobulin baseline
Why
Define immune and organ reserve and create comparison values for the chosen class.
Interpretation and limitations
Lymphopenia, neutropenia, transaminase elevation, reduced eGFR or low IgG changes infection risk, dose, prophylaxis or whether rituximab and other treatments are appropriate.
08
Documented vaccine record
Why
Identify true gaps without duplicating doses or relying on recall.
Interpretation and limitations
Reconcile GP, occupational, travel and maternity records, distinguishing live from inactivated products and recording date, brand and planned timing relative to immunosuppression.

04Treatment approachPreparation, options, escalation and aftercare.

01First gateExclude active infection before latent screeningFirst stepBiologic or targeted treatment is planned and the patient enters the safety pathway.

1Take a structured symptom, exposure, travel, recurrent-infection, device, wound, dental and vaccine history and examine any likely focus.
2Investigate and treat active infection first, deferring immunosuppression when sepsis, active TB, uncontrolled hepatitis or significant untreated infection is credible.
3Proceed to latency, blood-borne-virus and vaccine assessment only when an active process has been addressed or safely excluded.

02TB branchSeparate active disease from latent infectionIGRA, exposure history, symptoms or chest imaging raises tuberculosis risk.

1Obtain chest imaging and sputum or site-specific microbiology for any possible active disease and involve the TB service urgently.
2For latent infection, select three months isoniazid plus rifampicin or six months isoniazid through the NICE and TB-specialist pathway, accounting for liver risk and interactions.
3Record the minimum preventive-treatment period before biologic initiation and the monitoring plan; do not assume one timing fits every class and organ urgency.

03Hepatitis B branchMatch prevention to serology and immune targetHBsAg or total anti-HBc is positive before immunosuppression.

1Measure HBV DNA and liver status and send the exact planned class and date to hepatology, distinguishing rituximab from lower-risk treatment.
2Start entecavir or tenofovir prophylaxis before high-risk B-cell depletion and use hepatology-defined continuation after the final course.
3For a monitoring strategy, predefine HBV DNA and ALT intervals and the viral threshold for immediate antiviral initiation rather than waiting for hepatitis symptoms.

04Vaccine sequenceGive live first and maximise inactivated responseNo active infection prevents vaccination and the planned treatment start allows preparation.

1AlternativeIdentify any required live vaccine and give it at least four weeks before significant immunosuppression, or select an alternative when treatment cannot wait.
2Give indicated influenza, COVID-19, pneumococcal, recombinant zoster and risk-based vaccines, ideally at least two weeks before therapy where feasible.
3For rituximab, maximise the interval before infusion and plan later doses around B-cell recovery; document that protection may remain incomplete.

05Authorisation and rescreeningClose every result and outstanding actionTesting and vaccines are complete enough to decide whether treatment may start.

1Record each test, interpretation, prophylaxis, vaccine date, contraindication and pending result in a single accessible initiation checklist.
2Name the clinician authorised to release the prescription and the teams responsible for TB, HBV or HIV follow-up.
3Repeat targeted screening after a new exposure, travel, serious infection or change to a higher-risk class rather than assuming the original assessment lasts indefinitely.

05Regimens, contraindications and interactionsTreatment details and the circumstances that modify them.

Shorter latent-tuberculosis treatment before or alongside timed advanced immunosuppression when interaction and hepatotoxicity profiles are acceptable.

Isoniazid plus rifampicin for latent TB

A NICE adult preventive option is isoniazid 300 mg orally once daily plus rifampicin 600 mg once daily for three months, with weight adjustment and pyridoxine prescribed when neuropathy risk warrants it under the TB service.

Exclude active TB first. Rifampicin has extensive interactions and colours secretions; both drugs can injure liver, isoniazid can cause neuropathy, and doses must follow body weight and specialist protocol.

Avoids rifampicin interactions when a longer monotherapy course offers a better balance.

Isoniazid for latent TB

Give isoniazid 300 mg orally once daily for six months, with weight adjustment and pyridoxine for relevant neuropathy risk, as an alternative NICE preventive regimen selected by the TB service.

Exclude active disease and monitor adherence, hepatitis symptoms, transaminases and neuropathy; age, alcohol, liver disease and interacting medicine affect suitability.

High-barrier antiviral prevention of hepatitis B reactivation before rituximab or another high-risk immunosuppressive regimen.

Entecavir

A usual prophylactic adult dose is 0.5 mg orally once daily on an empty stomach, adjusted for renal function and previous lamivudine resistance under hepatology direction.

Start before immunosuppression and continue for the hepatology-defined post-treatment interval; check HBV DNA, renal function and resistance history and do not stop without a surveillance plan.

Non-live prevention against shingles and post-herpetic complications before JAK inhibition and other immunosuppression.

Recombinant zoster vaccine

Give the current two-dose Shingrix course to eligible severely immunosuppressed adults, usually with the second dose around eight weeks after the first; follow the current Green Book interval when treatment urgency changes timing.

It cannot cause shingles, but fever and local reactions are common; active shingles is treated first and vaccine response may be reduced after B-cell depletion.

Prevents invasive pneumococcal disease in immunosuppressed people with an indication for vaccination.

Pneumococcal vaccination

Give the age- and risk-specific PCV or PPV23 schedule in the current Green Book after reconciling previous products and dates; do not repeat a dose solely because biologic treatment is changing.

Sequence and revaccination depend on age, splenic function, renal disease and immune category; inactivated vaccine is safe during therapy but may be less immunogenic.

06Complications, monitoring and follow-upAdverse effects, response and longer-term review.

Do not close the screening episode until every positive or indeterminate result has a documented interpretation, owner and effect on treatment timing.
During latent-TB treatment, monitor symptoms, adherence, liver risk and interactions at the TB-service interval and reassess promptly for any features of active disease.
For HBV prophylaxis or surveillance, follow HBV DNA, ALT and renal function at the hepatology-defined interval and continue after the final biologic for the class-specific risk period.
Maintain a dated vaccine record and offer each new seasonal influenza or COVID-19 programme; vaccination is an ongoing process, not a one-time pre-biologic clearance.
At biologic reviews ask about new TB contact, travel, blood-borne-virus exposure, serious infection, pregnancy and live vaccines received elsewhere, repeating only the relevant tests.
After rituximab, recognise reduced vaccine response and consider immunoglobulin and infection history before further courses; do not infer protection from vaccination date alone.

07Special situationsVariants, exceptions and circumstances that change the usual approach.

IGRA measures sensitisation, not location

A positive result does not distinguish latent from active TB, and a negative result can be false when cellular immunity is suppressed.

Core antibody records natural exposure

Vaccination does not create anti-HBc, so its presence identifies past or current infection even when HBsAg is absent.

Reactivation starts virologically

HBV DNA can rise before ALT, jaundice or symptoms, which is why prophylaxis or scheduled molecular monitoring prevents late recognition.

Non-live does not mean fully effective

Inactivated and recombinant vaccines are safe during biologic treatment, but immune response can be markedly reduced after rituximab.

Treatment urgency can outrank vaccine completion

Organ-threatening vasculitis may require immediate rituximab; prevention then relies on infection assessment, prophylaxis and later vaccine planning.

Infant exposure is part of screening

A biologic continued late in pregnancy may require a newborn live-vaccine deferral, so the initiation checklist needs a reproductive section.

08Common pitfallsFrequent interpretation and management errors.

01
Calling a patient infection-cleared because IGRA and viral serology are negative despite fever, weight loss, a wound or focal symptoms.
02
Ordering only HBsAg before rituximab and failing to identify previous infection through total anti-HBc.
03
Treating HCV antibody positivity as active infection without reflex RNA, or as immunity that prevents reinfection.
04
Giving a live vaccine after biologic initiation because all vaccines were mistakenly classified as non-live.
05
Delaying urgent organ-saving immunosuppression for months merely to complete every optional vaccine dose.
06
Listing vaccines as done without dates, products or recognition that rituximab may have prevented an adequate response.