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Pediatric Infectious Disease Pre-Transplant Evaluation: An Opportunity to Optimize and Educate


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Blanca E. Gonzalez, MD
Cleveland Clinic
Cleveland, OH, USA
Gonzalb3@ccf.org



The main goal of the Infectious Disease pre-transplant evaluation is to identify factors that have the potential to negatively impact the outcome of the transplant and that can be prevented by treatment, vaccination or prophylaxis. It also serves as an opportunity to educate the family regarding environmental exposures and behaviors that may result in infection acquisition post transplantation.

A thorough review of the child's infectious disease history and screening for latent and active infections is performed during the evaluation. Lung transplant candidates with conditions such as cystic fibrosis are often colonized (or infected) with multi drug resistant bacteria (i.e S aureus, Pseudomonas spp, Alcaligenes, Stenotrophomonas among others) fungi (Aspergillus spp) and nontuberculous Mycobacteria (NTM) all which represent a risk for infections in the post-transplant period. Therefore, prophylaxis regimens need to be individually tailored based on microbiological and susceptibility data [1,2]. Colonization with B cenocepacia has been associated with poor outcomes after lung transplant and many centers will consider it a contraindication to transplant [3]. Careful screening of patients for tuberculosis is of extreme importance as the diagnosis and treatment of this infection post-transplant is challenging, and treatment should be provided beforehand. Screening in children is usually with a PPD but interferon gamma release assays (IGRA's) can be used in children as young as 2 years of age, especially in foreign born children vaccinated with BCG [4,5].

Heart transplant candidates are at high risk of bacterial infections in the pre transplant period as the use of central lines is common as well as the use of ventricular assist devices as bridge to transplant. LVAD infections are not a contraindication to transplant as it is difficult to clear infections until the device is explanted, but aggressive therapy is required [6].

CMV reactivation or primary infections are a significant cause of morbidity and mortality in the cardiothoracic transplant recipient. Knowledge of the recipient child's CMV status, along with the donor's status, is required to select the appropriate antiviral preventive strategy. In infants younger than 18 months, this is tricky as serology may reflect maternal immunity requiring additional test such as CMV culture from urine and saliva to prove infection [7]. Other viruses screened for in the evaluation include HSV and EBV. Many young transplant candidates, depending on country of residence, may be EBV naïve and are therefore at high risk of primary infections and of PTLD, especially if the donor is EBV positive [8].

Based on the child's exposure history, screening may also be performed for less common conditions. In the case of heart transplant candidates for example, parasitic infections with T cruzi can reactivate in the graft, and therefore, screening patients with dilated cardiomyopathy who have lived in Chagas endemic countries is warranted [9]. When there are outdoor cats in the household screening for toxoplasmosis becomes important.

Many patients will have lists of allergies in their past that need to be clarified before the transplant. Minor rashes or medication side effects may have been labeled as allergies and often parents may have misconceptions of what constitutes and allergic reaction. When in doubt, a referral to allergy for skin testing may be needed keeping in mind that reliable testing is not possible for all antimicrobials or allergy types. Alternatives regimens for treatment and prophylaxis should be crafted at this time. We often see children whose parents relate events consistent with an allergic reaction to sulfa for which alternative Pneumocystis jiroveci prophylactic regimens must be used (dapsone or pentamidine in the G6PD deficient patient).

Documenting evidence of vaccination and vaccine immunity is pivotal [10]. In industrialized nations, vaccination refusal in the community is increasing with infections such as measles and varicella making a comeback. Missed opportunity for protection through vaccination may result in high morbidity including graft loss. This is the time to catch up with vaccines as doing so post-transplantation may not result in effective immunity. Serologies should be obtained so that in the event of an exposure a prophylactic plan can be established and to determine if re administration of certain vaccines is required. This is also the time to discuss "cocooning" with the families making sure all members of the household are up-to-date with their immunizations as an indirect way of protecting the transplant recipient. Live viral vaccines are contraindicated following transplants. Physicians may have a window of opportunity to provide live viral vaccines before the transplant if they are certain that the interval to transplant will be greater than 1 month. An often forgotten opportunity is to provide MMR to children over the age of 6 months, even if the vaccine will not count toward the primary series.

We want our children to lead as normal life as possible after the transplant, and this includes allowing them to participate in everyday childhood activities such as playing outside, riding bikes and having pets, tweaked, of course, for their safety. A thorough discussion of safe living after transplantation should take place [11].

Pet ownership should be thoroughly discussed with the family at this time. Although for the most part we do not recommend that "fluffy the cat" take an indefinite vacation we do emphasize certain aspects of pet care. Some of the key aspects to review are: washing hands after playing with animals, placing cat litters in safe places away from young children or areas where food is usually prepared, discouraging older children cleaning litters, cages or fish tanks, cats should be kept indoor to minimize risk of toxoplasmosis, sick pets need to be seen by a veterinary doctor immediately (diarrhea in a pet may be due to Cryptosporidium, Giardia, Salmonella, and Campylobacter). We have seen children who have acquired severe diarrheal disease from cryptosporidium after they cared for sick calves on the farm, or fungal lung infections related to raking hay in a horse barn. There are some pets that pose a significantly increased risk to the transplanted patient. We do recommend that families find a caring home for turtles and other reptiles before the transplant. These animals are "salmonella factories" and not recommended as pets for any child by the American Academy of Pediatrics [12]. Other risky pets are exotic animals such as monkeys, chicks and ducklings. For lung transplant candidates, birds may pose an additional risk.

The household needs to be prepared for the child coming home post transplantation. Avoiding construction projects when the patient returns home is prudent as this poses a risk for invasive fungal infections, such as Aspergillus. In houses with well water, the system should be tested frequently for bacteria, and patients should be encouraged to drink bottled water.

Infectious diseases pose a significant risk to transplanted patients, but a pre-transplant consult can help reduce these and ensure a successful transplant. ■

Disclosure Statement: The author has no conflicts of interest to disclose.


References:

  1. Remund KF, Best M, Egan J. Infections Relevant to Lung Transplantation. Proc Am Thorac Soc: 6: 94-100. (2009)
  2. Westall G. Snell G, Keshavjee S, Strueber M. Infections in Lung Transplantation: Historical Perspective. In ISHLT Monograph Series 5: 11-16. Elsevier, PA (2011)
  3. De Soyza A, Meachery G, Hester KL, et al . Lung transplantation for patients with cystic fibrosis and Burkholderia cepacia complex infection: a single-center experience. J Heart Lung Transplant.;29:1395-404. (2010)
  4. Morris MI, Daly JS, Blumberg E et al. Diagnosis and management of tuberculosis in transplant donors: a donor-derived infections consensus conference report. Am J Transplant.; 12: :2288-300. (2012)
  5. Howley MM , Painter JA, Katz DJ et al. Evaluation of QuantiFERON-TB gold in-tube and tuberculin skin tests among immigrant children being screened for latent tuberculosis infection. Pediatr Infect Dis J. 34:35-9. (2015)
  6. Koval C.E , Rakita R and the AST Infectious Diseases Community of Practice. Ventricular Assist Device Related Infections and Solid Organ Transplantation. Am J Transplant. 13: 348-354 (2013)
  7. Green M , Michaels MG. Epstein-Barr virus infection and posttransplant lymphoproliferative disorder. Am J Transplant.;13 S:41-54.( 2013)
  8. Kransdorf EP, Zakowski PC, Kobashigawa JA . Chagas disease in solid organ and heart transplantation. Curr Opin Infect Dis, 27:418-424 (2014)
  9. Rubin LG, Myron L, Ljungman P, et al, 2013 IDSA Clinical Practice Guidelines for Vaccination of the Immunocompromised Host , Clin Infect Dis. 58 :e44-100. (2014)
  10. Avery RK, Michaels MG and the AST Infectious Diseases Community of Practice. Strategies for Safe Living After Solid Organ Transplantation. Am J Transplant. 13: 304-310 (2013)
  11. Pickering L, Marano N, Bocchini J, Angulo F. Exposure to Nontraditional Pets at Home and to Animals in Public Settings: Risks to Children. PEDIATRICS;122: 876-886. (2008)



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