Pulmonary and Extrapulmonary Manifestations of Fungal Infections Misdiagnosed as Tuberculosis: The Need for Prompt Diagnosis and Management

Abstract

Fungal infections commonly present with myriad symptoms that mimic other clinical entities, notable amongst which is tuberculosis. Besides histoplasmosis and chronic pulmonary aspergillosis, which can mimic TB, this review has identified several other fungal infections which also do. A total of 80 individual cases misdiagnosed as TB are highlighted: aspergillosis (n = 18, 22.5%), histoplasmosis (n = 16, 20%), blastomycosis (n = 14, 17.5%), cryptococcosis (n = 11, 13.8%), talaromycosis (n = 7, 8.8%), coccidioidomycosis (n = 5, 6.3%), mucormycosis (n = 4, 5%), sporotrichosis (n = 3, 3.8%), phaeohyphomycosis (n = 1, 1.3%) and chromoblastomycosis (n = 1, 1.3%). Case series from India and Pakistan reported over 100 cases of chronic and allergic bronchopulmonary aspergillosis had received anti-TB therapy before the correct diagnosis was made. Forty-five cases (56.3%) had favorable outcomes, and 25 (33.8%) died, outcome was unclear in the remainder. Seventeen (21.3%) cases were infected with human immunodeficiency virus (HIV). Diagnostic modalities were histopathology (n = 46, 57.5%), culture (n = 42, 52.5%), serology (n = 18, 22.5%), cytology (n = 2, 2.5%), gene sequencing (n = 5, 6.3%) and microscopy (n = 10, 12.5%) including Gram stain, India ink preparation, bone marrow smear and KOH mount. We conclude that the above fungal infections should always be considered or ruled out whenever a patient presents with symptoms suggestive of tuberculosis which is unconfirmed thereby reducing prolonged hospital stay and mortalities associated with a delayed or incorrect diagnosis of fungal infections.

Prevalence of Histoplasmosis and Molecular Characterization of Histoplasma species in Patients with Presumptive Pulmonary Tuberculosis in Calabar, Nigeria

“…This emphasizes the need to also investigate immunocompetent patients presenting with symptoms suggestive of TB for histoplasmosis besides patients living with HIV/AIDS. One of the challenges in our setting is the poor index of suspicion on the part of clinicians, which causes patients to be placed on anti-TB therapy despite being GeneXpert or acid-fast bacilli negative [ 2 , 6 ]. This is further corroborated by the finding from this study, which showed higher prevalence of histoplasmosis in unconfirmed TB patients (16.8%) than in confirmed TB patients (7.4%).…”

“…Concerning sensitivity, specificity, PPV, NPV, accuracy, positive likelihood ratio, and negative likelihood ratio of Histoplasma antigen test in this study, we were not keened to compare values with findings from other studies, because the standards used in those studies was not PCR [ 14–17 ]. Compared with sputum PCR, Histoplasma urinary antigen test is more feasible in our setting for the following reasons: (1) It is cheaper, quicker (turnaround time of 3–5 hours), and needs less expertise to perform; (2) sputum samples analyzed in this study were pooled and processed at the end of the study, with DNA being denatured in some of the samples; (3) although molecular assays gave excellent analytical performance, there is no consensus on PCR protocols and gene targets, which results in varying sensitivity and specificity patterns; and (4) PCR machines are not readily available in routine laboratories, especially in resource-limited settings [ 1 , 6 ]. Histoplasma urinary antigen test should therefore be deployed for the diagnosis of histoplasmosis in resource-limited settings like ours where sputum PCR is not a routine.…”

“…This underscores why histoplasmosis is commonly misdiagnosed as TB in our setting [ 1 , 2 , 7 ], with associated increased mortality, prolonged hospital stays, and unnecessary surgical interventions with attendant financial burden [ 2 , 7 , 8 ]. The pulmonary and disseminated forms of histoplasmosis present with features including fever, cough, generalized weakness, abdominal pain, abdominal swelling, nocturnal sweating, skin lesions, lymphadenopathy, hepatomegaly, and splenomegaly, which are also seen in all forms of TB [ 2 , 6 ]. Oladele et al, in a review study that spanned 6 decades, identified major features common to TB and disseminated histoplasmosis [DH] in the context of HIV infection including immunosuppression, pancytopenia, diarrhea, hepatomegaly, elevated liver enzymes, elevated C-reactive protein, skin lesions, and the involvement of organ systems (gastrointestinal tract, bone marrow, and central nervous system) [ 1 ].…”

“…Oladele et al, in a review study that spanned 6 decades, identified major features common to TB and disseminated histoplasmosis [DH] in the context of HIV infection including immunosuppression, pancytopenia, diarrhea, hepatomegaly, elevated liver enzymes, elevated C-reactive protein, skin lesions, and the involvement of organ systems (gastrointestinal tract, bone marrow, and central nervous system) [ 1 ]. In addition, the chest radiological findings in patients with pulmonary histoplasmosis include pulmonary infiltrates, hilar lymphadenopathy, opacities of the lung, and pleural effusion, which are also seen in TB patients [ 6–9 ]. While the knowledge and understanding of the prevalence and awareness of TB is high, not much can be said for histoplasmosis, and thus, clinical or presumptive diagnosis and treatment of TB may be rife in the current study setting, being mistaken for histoplasmosis due to similar clinical presentation of these two diseases.…”

Chronic cavitary pulmonary aspergillosis in an immunocompetent child

“…This index patient had anti-Koch's therapy commenced despite negative geneXpert result. Chronic pulmonary aspergillosis is most often misdiagnosed as pulmonary TB as reported in several studies [ 18 ].In China, cases of CPA misdiagnosed as pneumonia and pulmonary tuberculosis (PTB) amongst four children were reported. Their chest imaging showed lobar consolidation with adjacent pleural thickening and two of which had multiple/solitary small nodules, and another with chronic granulomatous disease [ 10 ].…”