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Type E – Dr Biance Rowe – Respiratory Virus Infections in Children with Febrile Neutropenia & Tuberculosis in Children with Cancer

A travel grant was awarded to Dr Biance Rowe of Chris Hani Baragwanath Academic Hospital
and WITS Donald Gordon Medical Centre to present two posters at the Annual Society of Paediatric Oncology (SIOP) Conference in Kyoto, Japan from 16 to 19 November 2018.


Project 1: Respiratory Virus Infections in Children with Febrile Neutropenia – Experience from a South African Center


The role of respiratory viruses(RV) as infecting or co-infecting pathogens in patients with febrile neutropenia(FN) has not been extensively characterized. The aim was to (i) document the incidence of RV-infections in children with hematologic malignancies and solid tumours, and to assess whether there was a difference between these groups, (ii) to identify the most common RV’s occurring in children with FN and (iii) document the incidence of RV-infections in those children that died.

All children diagnosed with cancer between 01/04/2010 and 31/03/2012 at a paediatric oncology unit at a tertiary center in South Africa were enrolled in a prospective cohort study. A suspected septic episode(SSE) was defined according to the standard definition of FN. During a SSE, blood investigations and nasopharyngeal aspirates were done and various parameters recorded.

There were 169 patients, 82/169(48.5%) with hematologic malignancies and 87/169(51.5%) with solid tumours. A total of 528 SSE’s occurred. The number of SSE’s associated with RV were 147/330(44.5%) in hematologic malignancies and 64/198(32.3%) in solid tumours(p=0.007). The number of SSE’s with bacterial-viral co-infections were 112/330(33.9%) in hematologic malignancies vs 45/198(22.7%;p=0.01). The overall incidence per 100 child years of RV-associated SSE’s was 61.2 with 92.4 in hematologic malignancies vs 35.1 in solid tumours(p<0.001). Human rhinovirus(HRV) was identified in 96/368(26.1%). Viral-viral co-infections occurred in 17.5% and RV-bacterial co-infection in 35%. Twelve children (7.1%) died due to sepsis. Eighteen RV’s were isolated in the 12 deceased patients; Human Coronavirus in 44.4% and HRV in 27.8%.

RV-infections and bacterial-viral co-infections in SSE’s were more common among children with hematologic malignancies compared to those with solid tumours. The most common RV identified was HRV. Viral-viral co-infections were lower than bacterial-viral co-infections. The patients who died had bacterial and fungal co-infections in addition to the identified RV’s. The presence of RV-infection and its clinical significance and relationship with outcome remains uncertain.

Project 2: Tuberculosis in Children with Cancer – Experience from a South African Center

Tuberculosis(TB) has been reported in children undergoing chemotherapy. The objective of this study is to (i) describe the incidence of latent TB-infection and TB-disease in children with cancer, (ii) to compare the Tuberculin Skin Test(TST) with the Interferon Gamma Release Assay(IGRA-T-SPOT.TB) for diagnosing latent TB-infection and (iii) to describe the characteristics and outcome of children with TB-disease and cancer .

A prospective cohort study was conducted at a tertiary center in South Africa from 1 April 2010 to 31 March 2012. Newly diagnosed children with cancer were enrolled and screened for latent TB-infection with a TST and T-SPOT.TB test. Where TB-disease was suspected during chemotherapy sputum was sent for culture.

A total of 169 patients were enrolled. Latent TB-infection was documented in 5 patients (2.9%). The T-SPOT.TB assay yielded negative results. Twenty-four(14.2%) patients were diagnosed with TB-disease during chemotherapy. The incidence of TB-disease was 4.7 per 100 child years. Those that developed TB-disease during chemotherapy had a higher number of high-dose corticosteroid courses (397.4 per 100 child years) compared to those who did not develop TB (40.7 per 100 child years;p<0.001). Children who developed TB-disease had more septic episodes associated with profound neutropenia (319.5 vs 46.6;p<0.001), profound lymphopenia (264.9 vs 41;p<0.001) and profound monocytopenia (389.6 vs 63.7;p<0.001). Children who developed TB had more septic episodes with prolonged neutropenia (350.6 vs 51.1;p<0.001), prolonged lymphopenia (335.1 vs 59.2;p<0.001) and prolonged monocytopenia (444.2 vs 70.7;p<0.001). There were 4/24(16.7%) deaths.

The incidence of latent TB-infection in children with cancer was low. The TST and T-SPOT.TB tests have limited value in diagnosing TB-infection in immuno-compromised patients. Risk factors for developing active TB-disease in patients with hematological malignancies are the use of numerous courses of high-dose corticosteroids and profound, prolonged neutropenia, lymphopenia and monocytopenia. Mortality in patients with TB and cancer are due to complex factors.

The major areas of study and how the visit have contributed to the understanding and/or management of cancer

The major areas of study that these 2 papers contributed to was in the sphere of supportive care in children with cancer, and in specific in the management of infectious complications including both respiratory viral infections and tuberculosis in children with cancer.

The setting in which these studies were done is in a developing country and the infectious challenges in a developing country is of particular interest as other influencing factors are also at play namely malnutrition, exposure to other infectious diseases eg. HIV etc. and other co-morbidities. These studies highlighted the burden of infectious disease in addition to a cancer diagnosis.

In particular, it was shown that children with hematologic malignancies have more bacterial-viral co-infections than viral-viral co-infections. This knowledge may inform the type of antibiotic (if any) chosen for a patient. Certain risk factors for children with cancer to also develop tuberculosis were identified as prolonged steroid use and prolonged, profound cytopaenias. A high index of suspicion should be maintained for tuberculosis in these patients.

Overall, the visit contributed to the understanding and management of various childhood cancers from chronic myeloid leukaemia, neuroblastoma, brain tumours and haematologic malignancies that were discussed specifically. Research was presented including papers detailing advances in molecular diagnosis to protocol development and supportive care in developing countries (PODC sessions).

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