Screening for and Prevention of Infectious Diseases inSpecial PopulationsCLINICALDefinition•Immune suppression (IS) has potential therapeutic implications for those with underlying conditions requiring the need to alter the immune response (examples include, but are not limited to, inflammatory bowel conditions, autoimmune disorders, connective tissue diseases, and other inflammatory conditions). [13]•Screening for and vaccinating against infectious diseases prior to initiation of IS when feasible, is critical to help lower potential infectious complications.•The opportunity to update vaccinations and screen for infectious diseases prior to initiation of IS may be missed. In most scenarios, there is time prior to initiation of IS to take the necessary steps to foster prevention of infectious complications down the road.•The definition of “immune suppression” for this module is:▫The use of corticosteroids such as prednisone > 20mg/day (or 2mg/kg/day if < 10kg) for 2 weeks or more and within 3 months of stopping.▫Effective doses of immunomodulators, methotrexate, or biologics within 3 months of stopping these agents▫Any combination of therapies above.•The purpose of this module is to help guide physicians to optimize patient outcomes when initiating IS. Many of these recommendations are evidence-based, and others based upon expert opinion.Screening for infectious diseases:A thorough history and physical exam are required with close attention paid to the following historical details:•Travel history, area of residence, occupational exposures and exposures through hobbies, water and food exposures, sick contacts, and animal exposures.•History of bacterial infections (e.g., recurrent UTIs)•History of fungal infections (e.g., oral and vaginal candidiasis)•Risk of active or latent tuberculosis•Prior history of chickenpox and/or shingles•History of recurrent herpes simplex virus infection•Vaccination history•Travel history and area of residence may be telling of endemic fungal infections and/or Strongyloides exposure, as well as tuberculosis exposure risks.▫Traveling after receiving IS would benefit from assistance of a Travel Medicine/Infectious Diseases specialist.▫If your patient is anticipating travel after the initiation of IS, it would be prudent to refer to a Travel Medicine/Infectious Diseases specialist prior to starting IS as many travel related vaccinations are live vaccines that can be given prior to ISinitiation, but are contraindicated after IS initiation.•Occupational exposure and exposure through hobbies may indicate exposure to various fungal infections, such as Cryptococcus and Aspergillus.•Water exposures▫Often, patients’ homes are supplied through untreated well water, which increases their risks for Giardia, Legionella, Cryptosporidium, Microsporidium, as well as non-tuberculous mycobacterial infections.▫If well water is supplying a patient’s home, they should be advised to either obtaina water treatment system, boil the water for at least one minute prior to use orconsumption, or use bottled water routinely for consumption purposes.•Food exposures▫Raw and undercooked eggs, poultry, and meat carries Salmonella and E.colirisks.‣Avoidance of unpasteurized products is necessary to avoid infections, such as Listeria.‣Similarly, soft cheeses and cold cuts of meat (i.e. delicatessen processed meats, hot dogs, and refrigerated pates) should be avoided for risk ofListeria.•Animal exposures▫All patients who are to receive IS should avoid sick animals and live vaccinations in their animals (such as the kennel cough vaccine, which protects against Bordetella bronchiseptica. This live vaccine has been reported as having the potential to infect immunocompromised individuals.). [12]▫If a cat is present, it is essential that your patient does not handle the cat litter for possible exposure to various bacterial and parasitic exposures, such as Toxoplasma.▫Turtles, snakes, and other reptiles have a risk of carrying Salmonella.▫New animals should not be acquired while on IS.•Bacteria▫Active bacterial infections, including UTI, cellulitis, and pneumonia should halt the initiation of IS until the infection has cleared and all necessary therapies for the infection are completed.▫Routine dental care should be performed prior to starting IS.•Mycobacteria▫M. tuberculosis‣Patients on steroids or other IS may not mount a response (anergy) to a tuberculin skin test (such as the Protein Purified Derivative [PPD]assay).[13][15]‣Patients who have received a bacilli de Calmette-Guerin (BCG) vaccine will test positive on a PPD assay in the early years after administration,but typically wanes after 15-20 years.‣Therefore, the PPD assay can both under- and over- estimate the incidence of latent TB in these circumstances. A more reliable assay to use wouldbe the interferon-gamma release cellular assay.[13][15]‣T-SPOT TB and QuantiFERON TB Gold are two availableinterferon-gamma release assays in the U.S.‣All patients should have an interferon-gamma release assay performed prior to initiating IS, especially immunomodulators and biologics.‣ A positive TB test is not a contraindication for IS as long as the patient is started on isoniazide or other appropriate latent TB therapy (such asrifampin, isoniazide plus rifapentine) for at least 4 weeks prior to startingIS.•Viruses▫Viruses of concern include the following:‣HIV, HA V, HBV, HCV, HSV, VZV, CMV, EBV, HPV, and Influenza ▫Human immunodeficiency virus (HIV), hepatitis A virus (HA V), hepatitis B virus (HBV), and hepatitis C virus (HCV)‣Prior to starting IS, the following should be considered:‣Serum HIV screening should be performed on all individuals ages 15-64 (as per the U.S. Preventative Services Task Force)[6]‣If positive, refer to Infectious Diseases to initiate onappropriate antiretroviral therapy prior to starting any IS‣If negative, counsel against engaging in risky behaviors thatmay increase one’s risk of acquiring HIV‣Serum HA V IgG should be sent, if negative would advise vaccination.‣HBV has been known to progress in the context of IS.[13]‣Screening for HBV should be performed even if one has beenvaccinated in the past. Some immunocompetent individuals donot mount biologically adequate antibody levels without abooster vaccination.⁎Serum serologies to send: Hepatitis B surface antigen,surface antibody, core total antibody (IgG + IgM)‣If negative and deemed HBV susceptible, should vaccinateagainst HBV. Would also educate against engaging in riskybehaviors that may increase one’s risk of acquiring HBV.‣If serologic testing reveals acute infection, chronic infection,or resolving infection, would refer to Infectious Diseases orGastroenterology for evaluation of treatment for HBV prior tostarting IS.⁎Treatment is necessary at minimum 3 weeks prior tostarting IS.‣HCV Antibody (serum IgG) should be screened prior to starting IS.‣If positive, would refer to Infectious Diseases orGastroenterology for evaluation of treatment for HCV prior tostarting any IS.‣If negative, would counsel against engaging in risky behaviorsthat may increase one’s risk of acquiring HCV ▫Herpes simplex virus (HSV), varicella zoster virus (VZV), and cytomegalovirus (CMV)‣Serum antibodies (IgG) to each of these should be evaluated for todetermine prior exposure.‣If HSV and/or VZV positive, then should monitor for reactivation.‣HSV: If a patient has frequent (>4 episodes) and/or severeHSV outbreaks, would provide prophylaxis againstreactivation while on IS.⁎Prophylaxis: Valacyclovir 500mg po twice-daily orAcyclovir 400mg po twice-daily‣VZV: If a patient develops shingles, would provideprophylaxis after treatment course while on IS.⁎Prophylaxis: Valacyclovir 500mg po twice-daily orAcyclovir 400mg po twice-daily⁎See VZV module for treatment of active infection.‣If reactivation of either virus is severe, it may be necessary tostop IS until infection resolves.‣If CMV IgG positive, closely monitor for signs/symptoms consistent with CMV reactivation.‣Fevers, chills, diarrhea, vision changes, hepatitis, etc.‣Outside of the solid organ transplant and hematopoietic stemcell transplant populations, there is no clear role for pre-emptive monitoring for CMV reactivation.‣If IgG negative, patient is at risk for primary CMV Infectionwhile on IS.▫Human papilloma virus (HPV)‣Women should have documentation of an updated Pap smear to rule out active HPV infection or abnormal cytology prior to starting IS.‣If positive, evaluation by Gynecology should be performedprior to starting IS.‣There may be data to suggest that immunosuppressed women should undergo more frequent screening with Pap smears.‣Current guidelines recommend routine Pap smears every 3years.‣Literature suggests that for the immunocompromised woman,Pap smears every year would improve early detection ofabnormal cytology and/or HPV infection.‣If appropriate based on age, vaccination against HPV is warranted prior to starting IS.▫Influenza‣Each respiratory virus season, those receiving IS should receive the inactivated influenza vaccine.‣Avoid giving the live intranasal vaccine to theimmunosuppressed patient and their close contacts as this canlead to transmission of the attenuated influenza strain.‣If a live, intranasal vaccine is given to a household/closecontact, the immunosuppressed individual should avoid thevaccine recipient for 7 days at minimum after receiving thevaccine.•Fungi▫Endemic fungi have the potential to reactivate in the setting of IS.▫Fungi of concern: Coccidiomycosis, Histoplasma, Blastomycoses, Cryptococcus, Pneumocystis jirovecii (PJP), Aspergillus.▫Exposure to endemic fungi should be determined based upon history acquired from patient (see exposure history above).▫Based upon historical information, send serum for Coccidiomycosis antibodies and/or Histoplasmaantibodies to determine if evidence of prior infection.‣If a patient presents with fever and pulmonary symptoms, it may be necessary to rule out active/acute hisotplasmosis - send urine Histoplasmaantigen.▫If determined as necessary based upon history obtained regarding occupational and hobbies exposures, send cryptococcal antigen to determine if any evidence of active cryptococcal infection exists/is present prior to starting IS.‣If positive, would delay initiation of IS by at least 4-6 weeks, during which time, the patient should receive the appropriate work up and treatment foractive cryptococcus.▫PJP prophylaxis: Treatment with either steroids (20mg or greater (or the equivalent) for longer than 2 weeks), a biologic or an immunomodulatory agent requires PJP prophylaxis.‣First line: Bactrim 1 SS tab po daily or 1 DS tab po qMWF‣Second line: Dapsone 100mg po daily‣If using dapsone, would check G6PD levels prior to starting.If deficient should avoid dapsone for risk of developinghemolytic anemia‣In pediatric patients, IV pentamidine is often used as a secondline agent.‣Third line: Atovaquone 750mg po twice-daily or inhaled pentamidine •Parasitic infections▫Risks depend on historical data acquired from the patient‣It is important to obtain a travel history as well as a history of areas of residence over one’s lifetime▫Strongyloidesis ubiquitous on all continents, except Antarctica. It is most commonly found in the tropics, subtropics, and in warm temperate regions (such as Southeast Asia and rural Appalachia)▫If traveled or lived in a strongyloides endemic area, would send strongylides IgG.‣If positive, then patient is at risk for strongyloides hyperinfection syndrome while on IS.‣Thus if positive, treat with Ivermectin 200mcg/kg po x 2 doses (each dose given 2 weeks apart). Treatment should be completed prior to starting IS. Vaccinations•All patients should undergo a thorough vaccination history with documentation ofvaccinations, if possible.•Based upon small studies, patients with chronic immunologic diseases will respond to vaccinations and produce adequate antibodies.▫Vaccinations in these populations is not a risk factor for flare of clinical disease.•All vaccinations that require updating or boosters as per the CDC Adult Immunization Schedule should be administered prior to starting IS.[2]▫Any killed (inactivated) vaccine should be given at least 2 weeks prior to starting any IS.▫Any live vaccinations should be given at least 4-6 weeks prior to starting any IS.▫All live vaccines in the immunosuppressed individual should be avoided after IS has begun.▫Live vaccinations in household/close contacts:‣As noted above, influenza live vaccine (intranasal) can be given to household/close contacts if needed, but should be avoided when possible.‣If given, the immunosuppressed individual should avoid thevaccinated recipient for 7 days at minimum after receiving thevaccine.‣VZV and MMR vaccines can be given to household/close contacts of immunosuppressed individuals.[4]‣If a VZV vaccine (ZOSTA V AX, V ARIV AX or PROQUAD) isgiven and a herpetic lesion/rash develops at the site ofvaccination, the immunosuppressed individual should avoidcontact with the VZV vaccine recipient until the lesion hasfully healed.‣Rotavirus vaccine can be given, but immunosuppressed individuals should avoid changing diapers for at least 14 days after vaccination hasbeen given.‣Oral polio vaccine should not be given under any circumstances to household or close contacts.‣Live typhoid and yellow fever vaccines can be given to household/close contacts.▫Tetanus and diphtheria (Td) vaccine should be given once ever 10 years, with the tetanus, diphtheria, and acellular pertussis vaccine (Tdap) given at least once during this period.▫Travel vaccinations should be given under the direction of a Travel Medicine or Infectious Diseases specialist.‣In some instances avoidance of travel may be necessary while on IS. OTHER INFORMATIONMonitoring while on immunosuppressive therapy[19]•Patient education is vital for the prevention and treatment of infections while on IS.•Patients should be counseled about monitoring for the development of infections while receiving immunosuppressive therapies.▫Fever is often the first and only sign of a serious infectious complication.•Vaccinations should remain up to date.•Routine CBC should be monitored while on IS.If neutropenia and/or lymphopenia develop, this will increase one’s risk for infectious complications.。