In April 2011, a 68-year-old man presented himself at our research clinic in rural Tanzania with a three-month persistent productive cough, chest pain, night sweats, and recurrent nonmassive haemoptysis. He denied fever, night sweats, weight loss, and any recent contact with a known tuberculosis case. A prior treatment with a broad-spectrum antibiotic had not been successful. The patient reported having been treated for tuberculosis, diagnosed by sputum smear ten years ago. On examination he was afebrile, in a reduced general condition with a body mass index of 17.1 kg/m2. Other findings were bilateral reduced breath sounds and mild clubbing. Testing for HIV with two rapid tests (SD Bioline HIV 1/2 3.0 and Determine HIV-1/2) was negative. Posteroanterior chest radiography in an erect position showed a cavity of 60 mmx73 mm diameter in the right upper lobe containing an intracavitary focal mass of 47 mmx31 mm diameter with adjacent moon-shaped radiolucency (Figure 1). A second radiography in a supine position showed a changed position of this focal mass (Figure 2). A chest x-ray of the previous TB episode was not available for comparison. Smear microscopy of early morning and spot sputum after Ziehl-Neelsen stain was negative for acid-fast bacilli. A nucleic acid amplification test (Xpert MTB/RIF) did not detect Mycobacterium tuberculosis. Both the early morning and spot sputum samples were subsequently cultured on solid (Lowenstein Jensen) and in liquid (MGIT) media, neither of which showed mycobacterial growth after eight and six weeks, respectively. In order to isolate Aspergillus, a sabouraud dextrose agar was inoculated directly with sputum, but only Enterobacter cloacae could be found. Due to lack of facilities, neither an ELISA for IgG antibodies to Aspergillus nor an Aspergillus precipitin test could be performed.

There is no epidemiological data on pulmonary aspergilloma in Tanzania and sub-Saharan Africa. However, the high burden of tuberculosis in these countries suggests a considerable number of unreported cases. The case described here should not illustrate a new treatment approach but emphasize the limitations and challenges in diagnosis and treatment due to resource limitations, the tuberculosis epidemic, and lack of consensus on therapeutic approach. The means used in this case surpassed the resources of an average rural setting, where we would have encountered even more limitations. Our initial diagnosis was purely based on the typical radiological findings illustrated in Figure 1 and Figure 2. Recurrent nonmassive haemoptysis and other clinical symptoms at the first consultation were consistent with pulmonary aspergilloma and other pulmonary conditions, including tuberculosis. Unfortunately, we could not compare radiographies with the tuberculosis episode that the patient had ten years before and distinguish between new and old radiological manifestations. Consequently, our case fulfilled all criteria for a sputum smear-negative case according to national standards and the international standards for tuberculosis care in high epidemic countries, and the NTLP decided to start treatment despite of the unavailability of mycobacterial cultures at this point. If we had attributed the symptoms purely to pulmonary aspergilloma, surgical resection would have been the best treatment choice. Missing options of surgical treatment due to lack of resources and epidemiological concerns led to the decision to treat pharmacologically, first for tuberculosis and subsequently for pulmonary aspergilloma. With total treatment duration of at least 12 months, it was difficult to guarantee proper adherence to both treatments. In our case, insufficient drug supply, as well as logistical difficulties in making the antifungal drugs available for the patient, led us to extend the antifungal therapy for another six months. It remains unclear if the treatment with tuberculostatica, antifungal medication, or the natural history of pulmonary aspergilloma caused the clinical improvement of the patient, whose symptoms disappeared except residual chest pain. Retrospectively, although it was initially not possible to exclude a smear-negative tuberculosis case, treatment of pulmonary aspergilloma should have been given priority while TB treatment should have been started only in the case of positive cultures.
The challenges in differential diagnosis and therapy of pulmonary aspergilloma demonstrated in this case underline the necessity for incorporating management of this frequently neglected TB-associated disease into national TB treatment guidelines in endemic countries.