Possible Donor‐Derived Tuberculosis in an Orthotopic Heart Transplant Recipient

To the Editor: We report a case of possible donor-derived TB in a heart transplant recipient which highlights the inherent limitations of immunocompromised donor screening and classification framework for donor derived infections. A 60-year-old woman with non-ischemic cardiomyopathy (ejection fraction of 15%) was evaluated for heart transplantation %) in June 2023. Pre-transplant infectious disease (ID) evaluation revealed no prior travel or occupational exposure to tuberculosis (TB). Workup was positive for IgG antibodies to cytomegalovirus (CMV), Epstein–Barr virus (EBV), herpes simplex virus-1 (HSV-1), and varicella zoster virus (VZV), while herpes simplex virus-2 (HSV-2) IgG was negative. Immunity was noted to mumps and rubella but not to measles, hepatitis A or B. Hepatitis C antibody was negative. She had two negative TB screens, one T-spot test and one Quantiferon Gold. Remaining ID evaluation was negative. She received recommended pre-transplant vaccines. She was reevaluated by ID in October 2023 for chronic hypereosinophilia. Computed tomography (CT) of the sinuses demonstrated mucosal thickening suggestive of chronic congestion. CT chest revealed peripheral nodular consolidation suggestive of scarring versus atelectasis, a stable 4 mm left lower lobe subpleural nodule as noted on CT chest six weeks prior. Parasitic and fungal workup including Strongyloides antibody, Toxocara canis antibody, serum Aspergillus galactomannan, beta-D-1,3 glucan, Coccidioides antibody, Histoplasma serum, and urine antigen was negative. She underwent orthotopic heart transplantation (OHT) on March 11, 2024, from a CMV, EBV seropositive, and Toxoplasma seronegative donor. Endomyocardial biopsy on postoperative Day 7 demonstrated antibody-mediated rejection (AMR) (Grade 2 pAMR), which was treated with intravenous steroids and accelerated taper. She was discharged with standard antimicrobial prophylaxis and immunosuppression. Repeat endomyocardial biopsy two weeks post-OHT demonstrated persistent AMR and Grade 1R acute cellular rejection (ACR) needing treatment with plasmapheresis, intravenous immunoglobulin (IVIG) and steroids. About three weeks post OHT, she developed fever, lactic acidosis, and hypotension. Infectious workup including blood cultures, respiratory pathogen PCR panel, and urinalysis was negative. Lumbar puncture was normal. CT of the chest demonstrated multiple new small pulmonary nodules, distinct from the 4 mm left lower lobe subpleural nodule noted on pre-transplant imaging. Bronchoscopy with broncho-alveolar lavage (BAL) was performed. BAL cultures were negative, acid-fast bacilli (AFB) stain was negative, AFB and fungal cultures were pending. Fever resolved with broad-spectrum antibiotics, and she was discharged on empiric oral antibiotics. She was readmitted two weeks later, approximately five weeks from OHT, with recurrent fevers, fatigue, and headache. CT of the chest demonstrated interval increase in size and number of pulmonary nodules. Echocardiogram revealed an incidental mobile mass in the mid to distal left ventricular (LV) cavity. Repeat bronchoscopy with BAL was positive for AFB stain and Mycobacterium tuberculosis (MTB) PCR. Notably, AFB cultures from prior BAL also resulted positive for mycobacteria. Positron emission tomography-computed tomography (PET-CT) demonstrated increased uptake in the pericardium, raising concern for disseminated TB with pericardial involvement. Treatment for TB was initiated with rifabutin, ethambutol, pyrazinamide, isoniazid, and pyridoxine (RIPE) under direct observation by the health department. MTB susceptibility testing demonstrated no antimicrobial resistance. Six weeks after initiation of TB therapy, follow up CT imaging revealed incidental pneumoperitoneum without signs of acute abdomen, suggestive of gastrointestinal involvement of disseminated TB. After 10 weeks of treatment, she was transitioned to Isoniazid and rifabutin. Investigation into donor history revealed that the donor was originally from Philippines, an endemic region for TB and received a kidney transplant, six months prior to cardiac organ donation. The donor's terminal hospitalization was attributed to Enterococcus faecalis bacteremia, with unexplained abdominal pain and seizures. It remains unknown whether the donor was ever screened for TB prior to receiving the kidney transplant and initiation of immunosuppression. TB is a known post-transplant complication, with an attributable mortality of 9.5% [1]. Solid organ transplant (SOT) recipients are at risk of TB either through a new exposure post-transplant, reactivation of latent TB (LTBI) after immunosuppression or through donor-derived infection. Clinical presentation of post-transplant TB can be difficult to diagnose, while drug interactions add further challenges to treatment [2]. Most post-transplant TB is due to reactivation of latent infection, while donor-derived tuberculosis (DD-TB) accounts for fewer than 5% of cases [3, 4]. DD-TB is uncommon in OHT recipients, with isolated reports in the literature [5]. In the United States, potential donor-derived transmission events are reported to the Organ Procurement and Transplantation Network (OPTN) for investigation by the Disease Transmission Advisory Committee (DTAC) [6]. Select cases are reviewed, categorized and referred to the Centers for Disease Control and Prevention (CDC) for further laboratory or epidemiologic assistance [7]. Several features support donor-derived transmission in this case. The recipient had no epidemiological risk factors for TB, no known exposures and negative interferon gamma release assay (IGRA) testing prior to transplant. The rapid onset of TB disease within weeks of transplantation is far earlier than typical reactivation, which generally presents later in the post-transplant course [5]. The donor originated from the Philippines, a TB-endemic country, and had recently undergone kidney transplantation, both of which heightened risk [8, 9]. In addition, the donor presented with unexplained abdominal pain and seizures which suggest that donor may have harbored unrecognized disseminated TB at the time of organ procurement. In the TB pathogenesis, primary pulmonary infection may involve early hematogenous spread seeding extrapulmonary sites such as lymph nodes, meninges, pericardium, and gastrointestinal tract [10]. Pericardial TB itself is an uncommon extrapulmonary manifestation, accounting for ∼1%–2% of all TB cases worldwide and poses significant diagnostic challenges [11]. DD-TB presents as fever or involvement of the transplanted organ in most SOT recipients with pulmonary disease predominantly in lung transplant recipients and extrapulmonary or disseminated disease in non-lung SOT recipients [5, 8]. The diffuse pericardial uptake observed on recipient's cardiac PET-CT within weeks of transplantation suggests that the pericardium may have served as a primary nidus of infection, with subsequent dissemination to the lungs and the gastrointestinal tract upon initiation of immunosuppression. Our patient's clinical history of fever with progressive pulmonary nodules, pericardial involvement on pet CT and subsequently identified pneumatosis coli is suggestive of disseminated TB rather than isolated pulmonary disease. This case also underscores the inherent limitations of donor evaluation. Time constraints during organ procurement, nonspecific donor presentations make TB detection difficult. Screening practices vary across countries and transplant systems [12]. Migration from TB endemic regions to low incidence areas adds complexity to risk stratification. Scientific societies have created guidelines for prevention of donor derived infections but are largely based on expert opinion [13]. This case was reported to OPTN and reviewed for potential DD-TB. Corroborative evidence from additional recipients which typically strengthens the classification of donor derived transmission was unavailable as no other organs were procured from this donor. Review of all available diagnostic data from the donor at the time of organ procurement revealed no microbiological evidence of TB. The case could not be classified as proven or probable donor derived transmission per established criteria [7] despite the compelling clinical and epidemiological evidence in the recipient. This highlights a recognized limitation in the current classification framework, whereby cases involving single organ donors, or donors without antemortem TB testing, may remain categorized as possible transmission despite strong circumstantial evidence. This case reinforces the need for enhanced vigilance regarding DD-TB, particularly when donors originate from endemic regions or have undergone prior transplantation as immunocompromised donors such as the donor in our case may pose a higher risk of donor derided infections. Sincerely, Phani V Akella, Rachel Sigler Phani V AKella: Conceptualization, Writing – original draft, Writing – review & editing. Rachel Sigler: conceptualization, writing – review and editing, supervision. The authors have no funding sources to disclose. During the preparation of this work, ChatGPT-5.2 and Claude Sonnet 4.6 were used to assist with grammar and general editing. All content was created, written and edited by the authors, who take full responsibility for the published work. The authors declare no conflicts of interest.