Preventing infections in immunosuppressed patients

SUMMARY

Immunosuppressed patients are vulnerable to infections which can cause significant mortality and morbidity. A dedicated evaluation, performed prior to immunosuppression where possible, can improve infection-related outcomes for these complex patients. Strategies to reduce infection risk include individualised risk assessment, targeted screening investigations, antimicrobial prophylaxis, vaccination and education to reduce future exposures to infectious pathogens.

 

Introduction

An increasing number of people living in Australia are immunocompromised. This includes patients with primary immunodeficiencies, acquired immunodeficiencies (e.g. human immunodeficiency virus [HIV] infection, asplenia), and most commonly those receiving immunosuppressive drugs for conditions such as cancer and autoimmune diseases, and transplantation. These range from traditional immunosuppressants like prednisone to an expanding number of newer biologics, immunomodulators and small-molecule inhibitors, with annual expenditure in Australia now over $7 billion and growing.¹ Immunosuppression can lead to significant improvements in quality of life and survival; however, patients also have an elevated risk of infection.² While infections can contribute to significant morbidity and mortality, many are predictable and preventable.³

Careful evaluation before starting immunosuppression, or shortly after and while on treatment, can reduce risks related to infection.⁴ This practice is well established in solid organ and bone marrow transplantation, and principles can be extended to the growing population of other immunocompromised patients.^5,6 While some circumstances exist where involvement by an infectious diseases specialist is warranted, many of these interventions can be effectively provided in primary care.

This article provides an overview of the key components of a pre-immunosuppression evaluation, which include an individualised risk assessment, targeted screening investigations, antimicrobial prophylaxis, vaccinations, and education on safe living strategies, and aims to provide guidance and encouragement for these evaluations to be increasingly conducted in primary care.

 

Individualised risk assessment

Every patient prescribed immunosuppression therapy is likely to benefit from an individualised risk assessment. Infection risk is determined by factors including the type and degree of immunosuppression, underlying disease complications, and prior exposure to infections. The specific types of infections experienced are influenced by the depth and duration of immunosuppression and epidemiological exposures from travel, occupation, or other environmental sources.

Medical history and immunosuppression

Risk assessment begins with a detailed medical history (Box 1). Elements that contribute to infection risk include the underlying disease (e.g. autoimmune disease, malignancy, end-organ failure), its complications and treatments. Common secondary complications that increase risk of infection include malabsorption and malnutrition, diabetes, end-organ dysfunction (e.g. cirrhosis, chronic kidney disease), and asplenia or hyposplenia.^2,7

Treatment history includes previous, current, and planned or potential future immunosuppression. For many patients, immunosuppression will fluctuate over time and the cumulative impact of previous treatments may be important. For example, patients treated with rituximab may have reduced B-cell function between 6 and 24 months or longer after their last dose.⁸ Periods of intensive immunosuppression increase infection risk, for example induction therapy early post-transplant, initiation of treatment for autoimmune disease, treatment of flares or relapse in autoimmune disease and malignancy, and treatment of rejection in transplant recipients.

A detailed antimicrobial allergy assessment can help inform future therapeutic choices. This includes an allergy history, de-labelling in the outpatient setting if safe to do so, or referral to a dedicated allergy service for formalised testing.^9-11

Previous infections

A comprehensive history of prior infections can help identify ongoing risks and includes childhood illnesses, infections resulting in hospitalisation, and previous opportunistic infections. A history of previous multidrug-resistant organisms may indicate ongoing colonisation, which could inform prophylactic or therapeutic antimicrobial choices and infection control practices. For patients undergoing surgery including transplant, perioperative screening for Staphylococcus aureus may be performed, and decolonisation can reduce the risk of surgical site infections.¹²

Epidemiological risk stratification

Epidemiological risk stratification helps characterise the risk of specific infections based on previous exposures. This requires a detailed history of travel-related, occupational and other environmental exposures.⁶

A travel history includes places of residence and travel for vocation or leisure. Extended stays or residence beyond several months at a given location increase the risk of exposure to or acquiring infections endemic to a region, such as tuberculosis or parasitic infections. Current and previous residence in rural, regional and remote settings should be assessed, focusing on infections known to be endemic to the region, such as Strongyloides, as well as agricultural and wildlife exposures (e.g. in northern or central Australia). In contrast, history taking for holidays and shorter trips should focus on higher risk activities such as trekking, wildlife exposure, water or adventure sports. Epidemiological risk may vary within different regions of the same country and over time, particularly in the setting of climate change.^4,13

Occupational exposures can be associated with specific infectious risks. Examples of higher risk occupations include humanitarian or aid work, military service, healthcare (particularly overseas), childcare, agricultural and construction work. For instance, farmers may have greater exposure to zoonoses such as Coxiella burnetii (Q fever), Brucella and Listeria, outdoor or construction workers are exposed to environmental organisms including fungi, and childcare workers are regularly exposed to circulating viral infections such as norovirus, cytomegalovirus and respiratory viruses.

 

Targeted screening investigations

Laboratory testing, predominantly with serology assays for immunoglobulin G (IgG), can be used to identify latent infections that may reactivate with immunosuppression and to assess immunity from vaccination or past infection.² Many infections remain latent and asymptomatic, with exposures sometimes innocuous or far removed and difficult to identify by history alone.^4,13 Reactivation can be difficult to diagnose and can result in more severe disease in immunosuppressed patients; pre-emptive treatment can prevent morbidity.² Serologies are relatively inexpensive and allow for risk profiling to inform prophylaxis and pre-immunosuppression vaccination.

Serology is best tested before starting treatment, as interpretation can be more difficult on treatment, for example an increase in false negative results with immunosuppression and false positive antibody results with administration of intravenous immunoglobulin. Immunoglobulin M assays are only needed if acute infection is suspected.

Routine screening for bloodborne viruses, including HIV, hepatitis B and hepatitis C, as well as evaluation of serological status for measles, mumps, rubella and varicella, is recommended. Screening for tuberculosis is recommended for patients with potential exposure to tuberculosis at any time in their life. This includes those who have lived or travelled in endemic regions, and older patients from high-income countries including Australia who may have been exposed to tuberculosis in childhood. Strongyloides screening is recommended in patients who have lived or travelled in endemic areas, either overseas or within Australia. Additional serologies may be required for select patients depending on their epidemiological risk factors and the type of planned immunosuppression (Table 1).

Table 1 Screening investigations and actions that can follow depending on results [NB1]

Pathogen or disease	Whom to test	Recommended test	Result	Action
HIV	All patients prior to starting immunosuppression	Serology	Positive	Viral load testing, treatment
Hepatitis B	All patients prior to starting immunosuppression	HBV surface antigen	Nonimmune	Vaccination and repeated serology to document immune responses
		HBV surface antibody HBV core antibody	Past or current infection	Variable; may include antiviral treatment, prophylaxis or viral load testing guided by infectious diseases or gastroenterology team
Hepatitis C	All patients prior to starting immunosuppression	Serology	Positive	Viral load testing; if viral load is positive, refer to gastroenterology or infectious diseases for treatment
Measles, mumps, rubella	All patients prior to starting immunosuppression	Serology (IgG only)	Negative	Vaccination prior to immunosuppression if possible, unless individual has already received 2 documented doses (live vaccine contraindicated after immunosuppression)
Varicella-zoster virus	All patients prior to starting immunosuppression	Serology (IgG only)	Positive	Antiviral prophylaxis may be used in select situations; inactivated shingles vaccine recommended (serology results not required for administration)
			Negative	Primary vaccination prior to immunosuppression if possible, unless individual has already received 2 documented doses (live vaccine contraindicated after immunosuppression)
Cytomegalovirus	Patients planned for solid organ or bone marrow transplantation	Serology (IgG only)	Positive	Variable; may include risk stratification, antiviral prophylaxis or viral load monitoring, guided by transplant or infectious diseases specialists
Epstein–Barr virus	Patients planned for solid organ or bone marrow transplantation	Serology (IgG only)	Positive	Variable; may include risk stratification, antiviral prophylaxis or viral load monitoring, guided by transplant or infectious diseases specialists
Hepatitis A	Patients likely to travel to an endemic area, or with higher lifestyle or occupational risk	Serology (IgG only)	Negative	Vaccination if there is current or potential future exposure risk, or liver disease
Helicobacter pylori	Patients with relevant exposures or symptoms	Stool antigen Breath test	Positive	Treatment
Schistosomiasis	Patients with relevant freshwater exposures in endemic areas, eosinophilia or symptoms	Serology	Positive	Treatment Examination of stool and urine for ova
Strongyloidiasis	Patients with relevant exposures (e.g. residence in or travel to endemic areas), eosinophilia or symptoms	Serology	Positive	Treatment
Syphilis	Patients planned for solid organ or bone marrow transplantation or with relevant exposures	Serology	Positive	Stage-appropriate treatment
Toxoplasmosis	Patients planned for solid organ or bone marrow transplantation	Serology (IgG only)	Positive	Risk stratification, prophylaxis
Tuberculosis	Patients with risk factors for exposure, including known contact with a person with active tuberculosis (including in childhood), residence or travel in an endemic area, incarceration, and refugee status Older patients from high-income countries including Australia who may have been exposed to tuberculosis in childhood	Interferon gamma release assay or tuberculin skin test Chest imaging (X-ray, CT scan)	Positive	Assessment to distinguish active from latent infection, followed by treatment or prophylaxis
			Indeterminate	Careful consideration of harms and benefits of prophylaxis
Enteric parasites	Patients with relevant exposures (e.g. residence in or travel to endemic areas), eosinophilia or symptoms	Stool ova, cysts and parasites microscopy or molecular testing	Positive	Treatment
Herpes simplex virus	Not routinely recommended	Serology IgG	–	Prophylaxis may be recommended regardless of serological status, so testing is not useful
CT = computed tomography; HBV = hepatitis B virus; HIV = human immunodeficiency virus; IgG = immunoglobulin G NB1: Other specialised testing may be recommended for specific patient groups on specialist advice (e.g. infectious disease). This may include testing for human T-lymphotrophic virus type 1, Chagas disease and endemic mycoses.

 

Antimicrobial prophylaxis

Antimicrobial prophylaxis may be recommended in some patients receiving higher intensity immunosuppression, such as transplant recipients or patients on higher doses of prednisone, and in patients with specific epidemiological risk factors for preventable infections.¹⁴ This includes the administration of antimicrobials to prevent the de novo acquisition of new infections, as well as the treatment or suppression of latent infections to prevent reactivation and subsequent disease. The most common infections for which routine prophylaxis is used include Pneumocystis jirovecii, herpes simplex and varicella-zoster viruses, latent tuberculosis and hepatitis B (Table 2).

Table 2 Infections that can be prevented using antimicrobial prophylaxis

Infection	Prophylaxis options
Pneumocystis jirovecii pneumonia	Trimethoprim+sulfamethoxazole, inhaled pentamidine, dapsone, atovaquone
Toxoplasmosis	Trimethoprim+sulfamethoxazole, pyrimethamine, atovaquone
Herpes simplex, varicella-zoster viruses	Valaciclovir, famciclovir, aciclovir
Cytomegalovirus	Valganciclovir, letermovir
Yeasts (Candida)	Fluconazole
Mould	Voriconazole, posaconazole, itraconazole
Tuberculosis	Isoniazid, rifampicin
Hepatitis B	Entecavir, tenofovir, lamivudine
Strongyloidiasis	Ivermectin

The duration and choice of prophylaxis is dependent on patient factors, type, degree and duration of immunosuppression, epidemiological exposures, tolerance and toxicities.^15-17 Sometimes prophylaxis is limited to periods of intense immunosuppression such as the early post-transplant period, while other times may be continued lifelong. The decision to use prophylaxis balances risk of infection, efficacy of prophylaxis, and risks of antimicrobial exposure. Protocols are well established for patients undergoing transplantation, certain malignancies, and those receiving prolonged courses of higher dose corticosteroids.^18,19 For example, Pneumocystis jirovecii pneumonia prophylaxis is recommended for all patients receiving at least 20 mg of prednisone daily for more than 4 weeks.¹⁴ For other immunocompromised patients, principles are often extrapolated, and prophylactic regimens can be recommended following discussion with infectious diseases clinicians based on individual risk factors.

 

Vaccination

Patients who are immunosuppressed have an increased risk of morbidity and mortality from vaccine-preventable diseases. Optimisation of vaccination prior to immunosuppression is ideal where possible, as vaccine responses can be less robust afterwards. Live vaccinations are contraindicated in most immunosuppressed patients, although they can be considered in some patients on very low-level immunosuppression if benefits outweigh harms, with guidance from infectious diseases specialists. The Australian Immunisation Handbook provides detailed and updated recommendations on specific conditions, doses and timing of administration of vaccines.²⁰ There are also jurisdiction- and disease-specific guidelines available.^21,22

A personalised vaccination plan can be developed based on a detailed review of vaccination records, serology results, history of childhood infections, future travel plans and timing of immunosuppression.²³ After starting immunosuppression, an annual review of vaccine status ensures that patients remain up to date, and regular alerts placed on the patient's medical record can aid ongoing administration of required vaccines. The Australian National Immunisation Program funds certain vaccines against many common circulating infections. Other vaccinations are available, but some carry out-of-pocket costs. Table 3 summarises key vaccine recommendations in Australia at the time of writing.

Table 3 Vaccine recommendations for immunocompromised patients [NB1]²⁰

Vaccine	When to administer
Routinely recommended
Influenza	Annually
COVID‑19	6 to 12-monthly based on individual risk, age, level of immunosuppression, epidemiology and local guidance
Pneumococcal conjugate vaccine (13vPCV)	Single dose
Pneumococcal polysaccharide vaccine (PPV23)	2 to 12 months after 13vPCV 2 lifetime doses, 5 years apart If a person received a PPV23 dose prior to their 13vPCV dose, the second dose of PPV23 should be given 5 years after the previous dose of PPV23, or 2 to 12 months after the dose of 13vPCV – whichever is later
Tetanus, diphtheria, pertussis	Booster dose every 10 years
Hepatitis B	3-dose regimen (at 0, 1 and 6 months) Adults with HIV, severely impaired renal function or who are on haemodialysis should receive a high dose (40 micrograms) with a 4-dose schedule at 0, 1, 2 and 6 months; accelerated schedule (days 0, 7, 21 and 365) is an alternative Vaccine response can be confirmed with surface antibody testing 4 to 8 weeks after the final dose
Extended schedule based on risk factors and serology
Measles, mumps, rubella [NB2]	2 doses, 1 month apart, if nonimmune and fewer than 2 documented prior doses
Varicella (primary – monovalent live-attenuated varicella vaccine) [NB2]	2 doses, 1 month apart, if nonimmune
Varicella (secondary – recombinant varicella-zoster virus subunit vaccine)	2 doses, 1 to 2 months apart, if seropositive, over 65 years old or greater than 1 year post-transplant
Haemophilus influenzae type B	Splenectomy, complement inhibitors (e.g. eculizumab) Incomplete childhood vaccination
Meningococcal ACWY	Splenectomy, complement inhibitors (e.g. eculizumab) Incomplete childhood vaccination (Highest risk in those under 24 years old)
Meningococcal B	Splenectomy, complement inhibitors (e.g. eculizumab) (Highest risk in those under 24 years old)
Hepatitis A	2 doses, 6 months apart, if nonimmune and with a higher lifestyle or occupational exposure risk, liver disease or likely future travel to endemic areas
Human papilloma virus	3-dose schedule if 26 years old or above, or already immunocompromised 1 dose if 9 to 25 years old and immunocompetent
Yellow fever [NB2]	Planned or likely future travel to endemic regions of Africa or South America
Typhoid [NB2]	Single intramuscular dose if planned travel to endemic region in next 1 to 2 years
Polio (inactivated) [NB3]	Consider 3-dose schedule in those with incomplete childhood vaccination history Booster dose every 10 years if planned or likely future travel to endemic areas
Japanese encephalitis [NB2]	2 doses of the inactivated formulation, 28 days apart, in those with residence in or likely travel to endemic areas in Australia or overseas
Rabies	Regular or extended travel to endemic areas outside of Australia Occupational exposure (e.g. veterinarians)
Q fever	Occupational exposures (e.g. farm or abattoir workers)
Respiratory syncytial virus	Aged 60 years or above
Limited data available
BCG [NB2]	Not routinely recommended
Mpox [NB2]	Consider in patients with high exposure risk
BCG = Bacille Calmette–Guérin; HIV = human immunodeficiency virus NB1: Refer to the Australian Immunisation Handbook page on 'Vaccination for people who are immunocompromised' for more detailed recommendations. NB2: Live vaccines must be administered at least 30 days prior to immunosuppression; otherwise, they are generally contraindicated. NB3: Oral polio vaccine is not recommended in immunocompromised patients. Inactivated polio vaccine is safe to use.

For patients born overseas who may not have access to vaccination records, the country-specific vaccine recommendations, schedules and coverage can be reviewed through the World Health Organization Immunisation Data portal. In some cases, a full catch-up schedule may be warranted.²⁴

 

Patients who warrant a more detailed evaluation

Some patients would benefit from a more detailed evaluation, which may include consultation with an infectious diseases physician (Box 2).

 

Safe living advice

There are several lifestyle measures that can significantly reduce the risk of exposure to infectious pathogens after starting immunosuppression (Box 3).⁵ This is particularly relevant for patients whose functional status improves with immunosuppression, allowing return to work and other activities. Infection risks, which can be dynamic over time, need to be balanced against patient goals and quality of life, with recommendations tailored to a patient's individual circumstances, risk profile and overall prognosis.⁵

Elements of safe living advice include food and water safety, advice for safe hobbies, pet care, travel, safe sex practices and vaccination of household members and close contacts.

Gardening and exposure to dusty or dirty environments carries an often-underappreciated risk of fungal infections, as spores are present in soil or surfaces and can be easily inhaled if aerosolised. Use of appropriate personal protective equipment while gardening or cleaning reduces these risks (Box 3).

Mosquito avoidance (protective clothing, repellent, avoiding areas of high mosquito activity) reduces the risk of vector-borne infections, both in Australia and overseas. Patients wishing to travel overseas are likely to benefit from dedicated assessment in a travel medicine or infectious diseases clinic.²⁵ Additional vaccines and specific risk mitigation strategies may be recommended depending on the destination.²⁶

Finally, all patients should be educated on the importance of seeking prompt medical attention if signs or symptoms of infection occur to ensure timely evaluation and treatment or hospitalisation if required.

 

Conclusion

Clinicians can support immunosuppressed patients by performing individualised pre-immunosuppression evaluation. Some more complex or higher risk patients may benefit from a more detailed evaluation, which may include consultation with an infectious diseases physician. This can help minimise ongoing infection risk by identifying and treating latent infections, optimising protection against vaccine-preventable diseases, and targeted education on lifestyle changes which reduce future exposures.

This article was finalised on 10 December 2025.

Conflicts of interest: Michelle Giles is a principal investigator on vaccine trials (phase 3 and registered products) sponsored by Moderna, CSL, Sanofi, GSK and Arcturus. Michelle was a member of the Australian Technical Advisory Group on Immunisation (2016 to 2025).

Bradley Gardiner has received travel support, speaker fees and advisory fees from Takeda and Biotest (2021 to 2025) and consulting fees from Qiagen.

Aadith Ashok and Aleece MacPhail have no conflicts of interest to declare.

This article is peer reviewed.