Fungal infections in immunocompetent and immunocompromised children — formative SAQs

SAQ 1 (10 marks)

A 7-year-old boy with acute lymphoblastic leukaemia is on day 12 of induction chemotherapy. His absolute neutrophil count is 0.1, and he has a central venous catheter in situ. He has been febrile for six days despite appropriate broad-spectrum anti-pseudomonal beta-lactam therapy; blood cultures remain negative. He now reports pleuritic chest pain. [1]

Question: Outline your assessment and management of this child, including the differential diagnosis, the investigations, the empirical and definitive therapy, and the principles of source control and prophylaxis. (10 marks) [14]

Model answer

Differential diagnosis and risk framing (2 marks). Persistent febrile neutropenia beyond four to seven days on appropriate broad-spectrum antibiotics, in a profoundly neutropenic child with a central line, raises invasive fungal disease to the top of the differential — invasive candidiasis, invasive pulmonary aspergillosis, and mucormycosis — alongside unresolving bacterial infection and viral reactivation. The pleuritic chest pain points toward an invasive pulmonary mould process. The error to avoid is attributing the persistent fever to bacterial infection alone; the day-four-to-seven persistent fever is the trigger to add empirical antifungal therapy and to image the chest and sinuses. [14] [1]

Investigations (3 marks). Send blood cultures from a peripheral site and from each lumen of the central line, a serum galactomannan (Aspergillus) and a serum beta-D-glucan (Candida and Pneumocystis). Obtain an urgent high-resolution chest computed tomogram, looking for pulmonary nodules with the halo sign (early invasive aspergillosis) or the reversed-halo sign (mucormycosis) — a plain chest radiograph is insensitive in the neutropenic patient. Pursue bronchoalveolar-lavage galactomannan and, where feasible, biopsy histopathology for tissue invasion by hyphae. The principle is to investigate before, not instead of, empirical therapy. [2] [14]

Empirical and definitive therapy (3 marks). Start empirical antifungal therapy without delay — an echinocandin (caspofungin or micafungin) or liposomal amphotericin B, selected by the suspected organism and the local mould epidemiology; if invasive aspergillosis is confirmed, voriconazole becomes first-line, and if mucormycosis is confirmed, high-dose liposomal amphotericin B is the backbone. Give a minimum of two weeks of therapy after the first negative culture in candidaemia, maintain hydration and electrolytes (amphotericin nephrotoxicity), and arrange therapeutic drug monitoring for voriconazole or posaconazole given the interactions with chemotherapy and calcineurin inhibitors. [2] [14]

Source control, reversal of immunosuppression and prophylaxis (2 marks). Remove the central line if candidaemia is confirmed — line removal shortens the bacteraemia and reduces metastatic seeding. Reverse the immunosuppression where possible, and treat the underlying graft-versus-host disease or the haematological malignancy. For the next cycle, consider antifungal prophylaxis — fluconazole or caspofungin in acute myeloid leukaemia induction (the Fisher JAMA trial showed caspofungin reduced invasive fungal disease versus fluconazole), or posaconazole in graft-versus-host disease. The lesson is that host-tier recognition, empirical cover and source control together determine survival in this child. [1] [14]