Infectious Complications In 96 Matched-Related Bone Marrow Transplants Performed Without Positive Pressure Room Or Centralized Hepa Filtration In Lower Middle Income Countries
Authors: El Missiry Mohamed , Khaled Sadaf , Yaqub Naila , Marwa Priya , Soni Rajpreet , Ansar Saqib , Iqbal Yasir , Cornelio Uderzo , Faulkner Lawrence B. 
Published: October 2019

Abstract

Background
There is general perception that bone marrow transplant (BMT) centers need complex and costly infection control engineering standards, even more in developing countries where a greater infection-related transplant risk is often assumed in spite of lack of scientific evidence. We aim to investigate incidence of BMT-associated infectious complications in patients admitted to BMT units with no centralized air control systems in lower middle income countries (Pakistan and India).

Methods
A total of 96 consecutive patients (87 cases with thalassemia major (TM), 4 fanconi and 4 severe aplastic anemia (SAA); and 1 acute lymphoblastic leukemia (ALL); median age 3.8 years (range; 0.9 - 15.3)) transplanted in 3 centers in Pakistan (86 patients) and 1 in India (10 patients), with at least 100 days follow up from BMT where included in this analysis. All patients where admitted to single rooms with split air conditioning but no central HEPA filtration. Evidence-based infection control measures such as hand washing and daily cleaning/drying and disinfection where implemented. Mebendazole, fluconazole, and acyclovir were used as anti-infection prophylaxis. Broad-spectrum antibiotic therapy was used empirically for fever and neutropenia but not as prophylaxis. Voriconazole was used empirically for persistent fever (> 3 days) on broad spectrum antibiotic coverage and/or clinical suspicion of fungal infection.

Results
Among the 96 transplanted patients; 8 cases suffered from infections with ECOG scoring grade over 2 (i.e. ranging from severe systemic infections up to septicemia) of which 3 had clinical sepsis (one with a positive blood culture for Pseudomonas Aeruginosa and two with negative cultures). In three cases a fungal infection was suspected: One had a positive β-D-Glucan (Fungitell Assay), one had a paranasal sinusitis responding to voriconazole and one a positive blood culture for Candida, neutropenia duration (<500 neutrophils/µL) was 18, 30 and 13 days respectively. Median neutropenic days (<500 neutrophils/µL) of all 96 patients was 16 (range; 9-30). A total of 7 patients received voriconazole empirical therapy for persistent fever not responding to broad spectrum antibiotics. CMV reactivation (PCR +ve) was observed in 18 patients; of which 10 were in subclinical form (without symptoms or signs of CMV disease). A total of 3 infection-related deaths were reported: sepsis (2; one with a positive blood culture for Pseudomonas Aeruginosaand one with negative culture) and 1 CMV intersitital pneumonia.

Conclusions
Incidence and type of infection in these low-risk BMTs did not seem to be higher compared to published reports from stringent air-controlled BMT units. This may have important implications to simplify and increase access to low-risk HLA-compatible BMT in limited-resources settings.

Disclosures:
El Missiry: Cure2Children Foundation: Employment. Khaled:Cure2Children Foundation: Employment; PIDSA: Research Funding. Cornelio:Cure2Children Foundation: Employment. Faulkner:Cure2Children Foundation: Employment.