Retno Wahyuningsih

Pulmonary histoplasmosis is often misdiagnosed as or coinfected with pulmonary tuberculosis (TB). This study aims to analyze the misdiagnosis or co-occurrence of published cases of pulmonary TB and pulmonary histoplasmosis. Cases of histoplasmosis with dissemination were excluded, as it affects other organs. Systematic research was conducted using PubMed, EBSCOhost, ProQuest, BioRxiv, and MedRxiv databases. Twenty-seven articles were included, covering a total of 51 cases. Males were predominantly affected, with a median age of 54 years. Exposure to caves and farming occupations were identified as the primary sources of infection (61.9%). The most common clinical symptoms were fever (80%) and cough (82.5%). Laboratory tests revealed culture positivity in 77.1% of cases, with sputum being the most frequently used specimens. In proven pulmonary histoplasmosis, antibody tests were positive in 18 out of 24 cases. Chest X-rays commonly showed cavities, infiltrates, and nodules, with an increase in nodular pattern in recent cases. The number of pulmonary nodules detected was higher on chest computed tomography (CT). Radiologic abnormality could occur in any lung region. This review suggests the potential for misdiagnosis and/or coinfection of pulmonary histoplasmosis and pulmonary TB. The combination of clinical suspicion, radiological findings, antibody and/or antigen testing could improve the diagnosis of pulmonary histoplasmosis.

Background: Indonesia is endemic for histoplasmosis, yet there is limited research on the Indonesian strain of H. capsulatum. This study aims to convert H. capsulatum to its yeast phase and provides detailed morphological descriptions and information about this phase. Method: Two Indonesian strains of H. capsulatum were analyzed using various media. The solid media employed were MLGema, potato starch-egg medium, and modified brain heart infusion (BHI) semisolid medium. For liquid media, modified Müeller Hinton broth (MHB) and modified BHI broth (BHIB) were utilized. The mold phase of H. capsulatum was inoculated and incubated at 37°C, with the colony and microscopic appearances observed. Fungal microscopic morphology was examined using lactophenol cotton blue (LPCB) and 3% Giemsa staining. Results: The complete conversion of H. capsulatum to the yeast phase was achieved in solid MLGema medium and potato starch-egg medium for both strains after one month in both media. MLGema outperformed potato starch-egg medium in both number and size of colonies. H. capsulatum appeared as oval-shaped yeast cells measuring 2-7 μm with budding. Our strain was identified as H. capsulatum, not Histoplasma duboisii. Cysteine, egg, and glucose were found to be crucial nutrients for successful conversion. Conclusion: Our study successfully converted the Indonesian strain of Histoplasma using MLGema and potato starch-egg media. This is the first to provide a morphological description of the yeast phase of the Indonesian strain, confirming it as H. capsulatum. For the analyzed strain, thorough genetic analysis of the strains is necessary to confirm the unique pattern.

In Indonesia, 2.4% of all new tuberculosis patients had multi-drug resistant disease (MDR-TB); an estimated 24,000 incidences. Historical case series of MDR-TB described a high frequency of cavitation and poor prognosis. The diagnosis of chronic pulmonary aspergillosis (CPA) relies on raised levels of Aspergillus IgG antibodies, and detectable Histoplasma IgG antibodies are suspicious for chronic pulmonary histoplasmosis (CPH). We investigated whether MDR-TB patients might have concurrent CPH or CPA. This was a cross-sectional study with 50 MDR-TB patients. ELISA was used to detect Histoplasma IgG antibodies and lateral flow assay was used to detect Aspergillus IgG/IgM antibodies. Several other possible disease determinants were assessed by multivariate analysis. Of the 50 MDR-TB patients, 14 (28%) and 16 (32%) had positive Histoplasma or Aspergillus serology; six patients (12%) had dual antibody reactivity. Radiological abnormalities in positive patients included diffuse or local infiltrates, nodules, consolidation, and apical cavities, consistent with CPH and CPA. Patients with detectable fungal antibodies tended to have worse disease, and 4 of 26 (15.3%) died in the first 5 months of dual infection (p = 0.11 compared with no deaths in those with only MDR-TB). The criteria for the diagnosis of CPH and CPA were fulfilled in those with moderately and far advanced disease (13 of 14 or 93%) and 12 of 16 (75%), respectively. Damp housing was the only determinant associated with Histoplasma antibodies (PR 2.01; 95%CI 0.56–7.19), while pets were associated with the Aspergillus antibody (PR 18.024; 95%CI 1.594–203.744). CPA or CPH are probably frequent in MDR-TB patients in Indonesia and may carry a worse prognosis.