Discussion:

Correct answer: 2. Although it is not possible to make a definitive diagnosis based on CT imaging alone, the characteristic pulmonary nodules surrounded by ground glass opacities in a patient with this history do suggest infection. As fungal infections are common, this CT is suggestive of pulmonary fungal disease.

Answer 1 is incorrect. The changes on the CT are quite specific (nodules with ground-glass opacities), pointing towards an infection, although other tests are required to confirm this and determine the cause of infection.¹

Answer 3 is incorrect. The reverse halo sign is seen when there is outer consolidation that surrounds an area of ground-glass opacity, and although it is suggestive of mucormycosis, it is not pathognomonic. All the areas seen on the CT scan have the consolidation in the centre with a ground-glass appearance surrounding it. So, this answer is incorrect.¹

Answer 4 is incorrect. CT alone is usually insufficient to diagnose pulmonary embolism, and CT pulmonary angiography is usually required.²

Discussion:

Correct answer: 3. This clinical picture of ALL and febrile neutropenia with the CT of the thorax showing bilateral pulmonary nodules and ground-glass opacities is highly suggestive of a fungal infection. Thus, performing rapid serological tests on serum to detect an invasive fungal infection, like Aspergillus galactomannan (GM) or Beta-D-glucan (BDG) antigen, will help establish the fungal etiology so that appropriate antifungal therapy can be started. Aspergillus GM is a specific cell-wall antigen found in Aspergillus species, and BDG is a cell-wall antigen detectable in a wide variety of pathogenic fungi except Mucorales, Cryptococcus species, and Blastomyces species.^1,3

These serological tests can give a positive result (as in this case) even if the culture is negative or the fungal species is nonculturable.

Answer 2 is reasonable but not ideal. Although sputum culture is helpful for diagnosis of lower respiratory tract infections, it is difficult to obtain in a critically ill patient with respiratory distress.

Answer 1 is incorrect. There is no need to change from a narrow-spectrum antibacterial drug to a broad-spectrum drug in this patient, as there is clearly a new source of infection that needs to be identified and treated.

Answer 4 is incorrect. The findings of the thorax CT and the duration of symptoms in this patient do not clinically indicate tuberculosis (TB). However, the World Health Organization recommends that rapid molecular tests like Xpert MTB/Rif assay be performed on the sputum or respiratory sample to rule out TB in a tuberculosis-endemic county.⁴

Discussion:

Correct answer: 2. BDG is a pan-fungal antigen present in many fungi such as Candida spp., Pneumocystis jirovecii, Aspergillus spp., Acremonium spp., and Fusarium spp. It is not found in Cryptococcus spp., Mucorales, and the yeast phase of Blastomyces dermatitidis. The Aspergillus GM ELISA detects Aspergillus cell-wall polysaccharide (GM) that is released during fungal growth and subsequently is detectable in serum and other body fluids. Since both the BDG and Aspergillus GM are positive in this patient, the most likely diagnosis is invasive aspergillosis.^1,3

Answer 1 is incorrect. Pneumocystis jirovecii is a unicellular, intracellular fungus that cannot be cultured in vitro but can only be detected in the laboratory by microscopic methods or molecular techniques such as real-time PCR. Studies have shown that PCR has better sensitivity than microscopy in diagnosing lung infection, so the disease can be ruled out in this patient as the PCR is negative.¹ While BDG can be positive with Pneumocystis jirovecii,³ the positive GM in this case lends more weight to an invasive aspergillosis diagnosis.

Answer 3 is incorrect. Xpert MTB/Rif assay is a rapid and accurate real-time PCR for the detection of pulmonary TB. In this patient, the test is negative. Also, the high-resolution CT is also not suggestive of TB.

Discussion:

Correct answer: 3. Aspergillus fumigatus is a filamentous fungus that grows on Sabouraud’s dextrose agar. Colonies are typically blue-green with a suede-like or velvety appearance.⁵ Moreover, the finding of septate fungal hyphae seen on direct microscopy from the endotracheal aspirate is more consistent with Aspergillus fumigatus than Rhizopus oryzae or Candida albicans.^6,7

Answer 2 is incorrect. Rhizopus oryzae belongs to the order Mucorales. This fungus produces sparsely septate or aseptate hyphae in tissue and grows on Sabouraud’s dextrose agar as white, woolly, or cottony colonies.⁸

Answer 3 is incorrect. Candida albicans is a yeast that produces pasty, cream-coloured, spherical, dome-shaped colonies in culture and is seen as budding oval yeasts and pseudo hyphae in tissue.⁹