Key Points

Key points

• CPA diagnosis remains challenging because symptoms and radiology overlap with tuberculosis, non-tuberculous mycobacterial disease, bronchiectasis, chronic obstructive pulmonary disease, malignancy and other chronic lung disorders.
• Aspergillus immunoglobulin G (IgG) testing is a cornerstone of CPA diagnosis, but performance varies between assays.
• Cut-off selection affects sensitivity and specificity, with important consequences for both missed CPA and overdiagnosis.
• Confirmatory or complementary testing, such as Western blot in selected situations, may help clarify difficult or borderline cases.
• The paper is directly relevant to specialist respiratory, infectious diseases and mycology services because diagnostic reliability affects referral pathways, antifungal prescribing and case definition.

The paper

Bigot J, Gibert C, Millet N, et al. Aspergillus serology for chronic pulmonary aspergillosis diagnosis: optimization of an enzyme-linked immunosorbent assay kit and assessment of a Western blot kit performance. Journal of Clinical Microbiology. Published 28 May 2026. doi:10.1128/jcm.00182-26.

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Why this paper matters

CPA is a progressive and potentially fatal chronic lung infection that usually occurs in patients with underlying structural lung damage. Diagnosis depends on combining clinical symptoms, characteristic radiology and evidence of Aspergillus infection or immune response.

In practice, Aspergillus serology is often the decisive test. A positive Aspergillus IgG result can support the diagnosis when imaging and symptoms are compatible. A negative result can reduce diagnostic probability. But serology is not absolute. Different assays use different antigen preparations, platforms and reporting units. This means that results from one laboratory may not be directly comparable with results from another.

This paper is therefore important because it addresses a real-world diagnostic problem: how to optimise Aspergillus serological testing so that it performs reliably in the diagnosis of CPA.

Clinical background: why CPA serology is difficult

CPA often develops in patients with structurally abnormal lungs. Common underlying conditions include previous pulmonary tuberculosis, non-tuberculous mycobacterial infection, chronic obstructive pulmonary disease, bronchiectasis, sarcoidosis, prior lung surgery and other cavitary lung diseases.

These same conditions can also cause chronic symptoms and abnormal imaging without CPA. This creates a diagnostic grey zone. Patients may have cavities, pleural thickening, fibrosis, bronchiectasis, chronic cough, haemoptysis or weight loss for reasons other than Aspergillus disease.

Aspergillus IgG testing is therefore valuable because it provides evidence of an immune response to Aspergillus. However, it must be interpreted in context. A positive result does not, by itself, prove active CPA. A negative result does not always fully exclude CPA, particularly if clinical suspicion remains high.

What the study evaluates

The paper evaluates two related aspects of CPA serology:

1. Optimisation of an enzyme-linked immunosorbent assay (ELISA) kit for Aspergillus serology in CPA diagnosis.
2. Assessment of Western blot kit performance, potentially as a complementary or confirmatory approach.

This is clinically relevant because ELISA-based Aspergillus IgG testing is widely used in diagnostic pathways, while Western blot may offer additional qualitative information in selected cases. The practical question is whether assay optimisation and confirmatory testing improve diagnostic performance enough to change specialist practice.

Why assay cut-offs matter

The choice of diagnostic cut-off is not a technical detail; it changes clinical classification.

In a specialist CPA service, false negatives may delay antifungal treatment and referral. False positives may lead to unnecessary anxiety, additional imaging, prolonged antifungal therapy and avoidable toxicity. The correct balance depends on the clinical setting, disease prevalence and consequences of diagnostic error.

Where Western blot may fit

Western blot testing may be useful where ELISA results are borderline, discordant with imaging, or difficult to interpret in patients with complex lung disease. It may also be useful as a complementary method in diagnostic algorithms, depending on availability and validated performance.

However, Western blot should not be seen as a simple replacement for ELISA. Its value depends on whether it adds diagnostic clarity beyond standard serology, whether it is reproducible between laboratories, and whether clinicians know how to act on the result.

Clinical interpretation: serology is supportive, not standalone

For specialists, the key principle remains:

Aspergillus serology supports the diagnosis of CPA but does not diagnose CPA in isolation.

A robust CPA diagnosis requires integration of:

• compatible symptoms, usually chronic cough, weight loss, fatigue, breathlessness or haemoptysis;
• compatible imaging, particularly cavities, pleural thickening, pericavitary infiltrates, fungal ball, nodules or progressive fibrosis;
• mycological or immunological evidence, especially Aspergillus IgG;
• exclusion or recognition of alternative and co-existing diagnoses, including active tuberculosis, non-tuberculous mycobacterial disease, malignancy and bacterial bronchiectasis.

Implications for specialist services

This paper supports the need for carefully governed CPA serology pathways. Specialist centres and diagnostic laboratories should consider:

• which Aspergillus IgG assay is used locally;
• what cut-off is applied and how it was validated;
• whether borderline zones should be reported rather than simple positive/negative categories;
• how results are interpreted in high-risk structural lung disease populations;
• whether confirmatory testing is available for selected cases;
• how serology is integrated with CT findings and microbiology;
• whether local reports include interpretive comments to reduce misuse.

Suggested diagnostic reporting approach

Rather than reporting Aspergillus serology as a binary answer, laboratories and specialist services may benefit from a more interpretive model:

Relevance to post-tuberculosis lung disease

This paper is particularly relevant when considered alongside recent evidence that CPA may be detected during or soon after pulmonary tuberculosis treatment. In post-tuberculosis lung disease, cavities and chronic radiological abnormalities are common, but not all symptoms are due to active TB or permanent scarring.

Reliable Aspergillus serology is therefore essential. If the assay cut-off is poorly calibrated, clinicians may either miss CPA in symptomatic patients with cavities or overdiagnose CPA in patients with structural lung damage but no active Aspergillus disease.

Relevance to bronchiectasis and non-tuberculous mycobacterial disease

Patients with bronchiectasis or non-tuberculous mycobacterial lung disease may also have chronic symptoms, mucus production, recurrent infection, radiological change and occasional Aspergillus isolation. Aspergillus serology can be useful in identifying CPA, but positive results must be interpreted carefully because these patients often have complex chronic airway disease.

For this group, assay performance and cut-off choice may substantially affect diagnostic confidence.

Implications for antifungal stewardship

Improved CPA serology has direct stewardship implications. Antifungal treatment for CPA is often prolonged and requires monitoring for toxicity, drug interactions and therapeutic drug levels. Overdiagnosis can expose patients to unnecessary azoles. Underdiagnosis can allow progressive cavitary disease, haemoptysis and loss of lung function.

More reliable serological testing can therefore support both earlier treatment in true CPA and avoidance of unnecessary therapy in patients who do not meet diagnostic criteria.

Evidence strength

Practical take-home messages for specialists

• Know which Aspergillus IgG assay your laboratory uses.
• Know the cut-off and whether it has been validated for CPA.
• Be cautious with borderline results.
• Do not diagnose CPA on serology alone.
• Do not dismiss CPA solely because one serological test is negative if the clinical and CT picture is highly suggestive.
• Consider repeat or complementary testing when results are discordant.
• Integrate serology with CT, symptoms, sputum fungal culture/PCR and assessment for tuberculosis or non-tuberculous mycobacteria.

Conclusion

This paper is a timely reminder that CPA diagnosis depends not only on whether Aspergillus serology is performed, but on how well the assay is optimised, how cut-offs are selected and how results are interpreted. For specialist services, improved serology can strengthen diagnostic confidence, support earlier recognition of CPA and reduce unnecessary antifungal treatment.

The broader implication is clear: CPA diagnostic pathways need standardised, validated and clinically interpreted Aspergillus serology, not isolated positive or negative blood test results.

References

1. Bigot J, Gibert C, Millet N, et al. Aspergillus serology for chronic pulmonary aspergillosis diagnosis: optimization of an enzyme-linked immunosorbent assay kit and assessment of a Western blot kit performance.
   Journal of Clinical Microbiology. Published 28 May 2026.
   doi:10.1128/jcm.00182-26.
   PubMed
2. Denning DW, Cadranel J, Beigelman-Aubry C, et al. Chronic pulmonary aspergillosis: rationale and clinical guidelines for diagnosis and management.
   European Respiratory Journal. 2016;47(1):45-68.
   doi:10.1183/13993003.00583-2015.
   PubMed
3. Patterson TF, Thompson GR, Denning DW, et al. Practice guidelines for the diagnosis and management of aspergillosis: 2016 update by the Infectious Diseases Society of America.
   Clinical Infectious Diseases. 2016;63(4):e1-e60.
   doi:10.1093/cid/ciw326.
   PubMed

Why this paper matters

Invasive pulmonary aspergillosis remains difficult to diagnose early, particularly in patients with haematological malignancy, haematopoietic stem cell transplantation, intensive chemotherapy, corticosteroid exposure or profound immunosuppression. Culture is insensitive, histology is often unavailable, and radiology is not specific. Galactomannan has become a central biomarker, but performance varies by specimen type, antifungal exposure, host group and disease stage.

Aspergillus PCR has long been promising, but implementation has been limited by assay heterogeneity, extraction differences, target selection, contamination concerns, and variable interpretation across centres. A clinically evaluated commercial real-time PCR assay is therefore important because commercialisation may improve standardisation, reproducibility and adoption outside specialist mycology laboratories.

Clinical context

The diagnosis of IPA is usually probabilistic. Clinicians combine:

• host factors, such as neutropenia, haematological malignancy, transplantation or corticosteroid exposure;
• compatible imaging, especially nodules, halo sign, cavitation or infarct-like lesions on computed tomography;
• mycological evidence, including galactomannan, culture, microscopy, PCR or lateral-flow assays;
• clinical course and response to antifungal therapy.

In this setting, a commercial Aspergillus fumigatus real-time PCR assay could support earlier diagnosis, improve confidence in probable IPA classification, and potentially reduce unnecessary empirical antifungal treatment when used as part of a diagnostic algorithm.

Main finding

The paper evaluates a commercial Aspergillus fumigatus real-time PCR assay for the diagnosis of invasive pulmonary aspergillosis in patients with haematological malignancies. The clinical relevance lies in validating a defined assay in a high-risk population where early diagnosis directly affects antifungal timing and survival.

The specialist significance is not simply that PCR “works”. The key question is whether a commercial PCR assay offers sufficiently reliable analytical and clinical performance to be used alongside galactomannan and imaging in routine pathways.

What is genuinely new?

The novelty is likely to sit in one or more of the following areas:

• evaluation of a specific commercial assay rather than an in-house laboratory-developed test;
• clinical validation in a defined haematology population;
• comparison against established diagnostic categories such as proven/probable IPA;
• assessment of analytical performance, including limit of detection, reproducibility or specificity;
• potential contribution to standardisation of Aspergillus PCR implementation.

This is not a new concept in principle: Aspergillus PCR has been studied for many years. What is more clinically useful is the transition from heterogeneous in-house assays towards assays that can be validated, quality-assured and compared across centres.

Relationship to existing evidence

Recent reviews of molecular fungal diagnostics emphasise that PCR can improve the diagnosis of invasive fungal disease but remains limited by standardisation, assay availability and interpretation. A 2025 review in Diagnostics noted that PCR is sensitive and specific for invasive fungal disease, but that implementation remains constrained by limited standardisation, few commercial options, and lack of clear guidance for interpreting results.

That surrounding evidence makes this type of paper important. Commercial PCR assays do not automatically solve diagnostic uncertainty, but they can reduce one major barrier: between-laboratory variability.

Strengths to look for in the paper

• Clearly defined patient population, especially haematological malignancy or transplant subgroups.
• Use of accepted case definitions for proven, probable and possible IPA.
• Separate analytical and clinical performance assessment.
• Comparison with galactomannan, culture and radiology.
• Evaluation by specimen type, especially bronchoalveolar lavage fluid versus blood.
• Consideration of antifungal exposure before sampling.
• Reporting of sensitivity, specificity, positive predictive value and negative predictive value.

Limitations and cautions

PCR performance depends strongly on specimen type. Bronchoalveolar lavage fluid generally provides a higher organism burden than blood in IPA, but it is more invasive and may not be feasible in unstable or thrombocytopenic patients. Blood PCR is less invasive but may be less sensitive, especially in localised airway-invasive disease.

False positives may arise from colonisation, contamination or detection of non-invasive airway presence. False negatives may occur with low fungal burden, prior antifungal therapy, sampling timing, extraction inefficiency or inhibitors. A positive PCR result should therefore not be interpreted in isolation.

A further issue is species coverage. A narrowly targeted Aspergillus fumigatus assay may perform well for A. fumigatus but could miss non-fumigatus Aspergillus species or cryptic species with different susceptibility patterns. In haematology patients, that may matter for epidemiology and antifungal resistance surveillance.

Clinical implications

For specialist services, the likely implication is that commercial Aspergillus PCR should be considered as part of a multi-modal diagnostic pathway rather than as a standalone rule-in or rule-out test.

A practical diagnostic model might include:

• early CT imaging in high-risk patients with persistent fever or respiratory symptoms;
• serum galactomannan in appropriate host groups;
• bronchoalveolar lavage where clinically safe;
• BAL galactomannan, fungal culture, microscopy and Aspergillus PCR;
• azole resistance testing or sequencing where Aspergillus is detected;
• multidisciplinary interpretation with haematology, infectious diseases, respiratory and mycology input.

Implications for antifungal stewardship

A validated commercial PCR assay may support earlier targeted antifungal therapy, but also more confident de-escalation when combined with negative biomarkers and low radiological probability. The stewardship value depends on pathway design. PCR added without interpretive governance may increase diagnostic noise; PCR embedded into a structured algorithm may reduce unnecessary empirical therapy and improve diagnostic confidence.

Implications for UK specialist mycology services

For UK centres, this type of paper supports the case for:

• standardised fungal PCR pathways;
• clear reporting language for positive and negative results;
• integration with antifungal stewardship rounds;
• external quality assessment participation;
• reflex testing for resistance where feasible;
• collaboration between local laboratories and specialist mycology reference services.

Evidence strength

Conclusion

Commercial Aspergillus real-time PCR assays represent an important step towards standardised molecular diagnosis of invasive pulmonary aspergillosis. Their greatest value is likely to be in high-risk haematology pathways, especially when applied to bronchoalveolar lavage fluid and interpreted alongside galactomannan, culture, imaging and host risk.

The clinical message is not that PCR replaces existing tests. Rather, validated commercial PCR may strengthen diagnostic algorithms, improve early case recognition, support antifungal stewardship and reduce variation between laboratories.

References

1. Gibert C, Bigot J, et al. Clinical and analytical evaluation of a commercial Aspergillus fumigatus real-time PCR assay for the diagnosis of invasive pulmonary aspergillosis in patients with hematological malignancies.
   Journal details to confirm from PubMed record.
   PubMed
2. Brown L, Cruciani M, Morton O, et al. The molecular diagnosis of invasive fungal diseases with a focus on PCR.
   Diagnostics. 2025;15(15):1909.
   doi:10.3390/diagnostics15151909.
   PubMed
3. Patterson TF, Thompson GR, Denning DW, et al. Practice guidelines for the diagnosis and management of aspergillosis: 2016 update by the Infectious Diseases Society of America.
   Clinical Infectious Diseases. 2016;63(4):e1-e60.
   doi:10.1093/cid/ciw326.
   PubMed

Why this matters

CPA remains substantially under-recognised in people with current or previous pulmonary tuberculosis. The clinical overlap is considerable: cough, haemoptysis, weight loss, fatigue, cavitation and progressive radiological change can be attributed to TB relapse, treatment failure, non-tuberculous mycobacterial infection, bacterial bronchiectasis, malignancy or post-TB lung disease.

For TB programmes and respiratory services, the practical question is no longer simply whether CPA occurs after TB. The question is whether there should be defined triggers for CPA assessment during TB treatment, particularly when symptoms persist despite microbiologically effective therapy.

The traditional model: CPA after tuberculosis

The conventional model is well established:

• Pulmonary tuberculosis causes cavitation, fibrosis, bronchiectasis and pleural distortion.
• Residual cavities may persist after microbiological cure.
• Aspergillus conidia can colonise these abnormal airspaces.
• In some patients, colonisation progresses to simple aspergilloma, chronic cavitary pulmonary aspergillosis or chronic fibrosing pulmonary aspergillosis.

This model is supported by older post-TB aspergilloma studies and by modern CPA burden estimates. Bongomin’s review of post-tuberculosis CPA highlights residual pulmonary cavities as a major risk substrate and summarises classic British data in which Aspergillus precipitins and aspergillomas increased over time after treated pulmonary TB.

The newer question: can CPA be present or emerge during TB treatment?

Several recent prospective studies suggest that CPA may be detected during the active TB treatment pathway, not only years after treatment completion.

1. Jha et al. 2024: serial CPA assessment during treatment of newly diagnosed PTB

Jha and colleagues conducted a prospective study of newly detected pulmonary tuberculosis cases and assessed CPA at baseline and at the end of anti-tubercular therapy. Of 255 initially recruited patients, 158 completed follow-up. The authors reported CPA at baseline and at end-of-treatment, with 23 of 158 assessed patients diagnosed with CPA at completion of TB therapy.

The study is important because it examined serial Aspergillus IgG changes and CPA incidence during the course of anti-tubercular therapy. The authors reported proven CPA in approximately 7% at baseline and 14.6% at end-of-treatment, broadly comparable with earlier Indonesian longitudinal data.

However, interpretation requires caution. Not all patients underwent HRCT at end-of-treatment, follow-up attrition was substantial, and the distinction between incident CPA, pre-existing CPA, transient Aspergillus immune response and radiological overlap with active TB remains difficult.

2. APICAL Indonesia study: CPA in patients treated for pulmonary TB

The APICAL study by Setianingrum and colleagues was a prospective longitudinal study in Indonesia. It investigated CPA in patients treated for pulmonary tuberculosis and reported CPA at baseline and at the end of TB therapy. Jha et al. cite APICAL as reporting 7.9% CPA at baseline and 13.3% at the end of TB therapy when proven and probable CPA were combined.

This study is one of the key pieces of evidence that the TB–CPA relationship is not purely post-treatment. CPA may be present within the treatment period, particularly where patients have cavitary disease or persistent symptoms.

3. Uganda study: persistent symptoms after two months of TB therapy

Namusobya and colleagues studied patients with microbiologically confirmed drug-sensitive PTB who had persistent respiratory symptoms after two months of standard anti-TB therapy. CPA was defined using persistent symptoms, suggestive radiology and evidence of Aspergillus infection, including Aspergillus IgG/IgM immunochromatographic testing and/or culture.

The study found CPA in around 20% of participants with persistent symptoms after the intensive phase of TB treatment. This is particularly relevant to clinical practice because two months is a natural review point in TB treatment pathways. Persistent symptoms at that stage are often interpreted as delayed recovery, adherence problems, drug resistance or alternative bacterial infection. CPA should be added to that differential in selected patients.

4. Ghana prospective follow-up: mainly post-treatment, but relevant to timing

Ocansey and colleagues followed patients after pulmonary TB treatment and found CPA emerging by the end of treatment and increasing further six months later. The study reported an overall 12-month CPA incidence of 10.7% among resurveyed patients, with 3% at end-of-treatment and 7.4% six months post-treatment.

This supports a continuum model: CPA risk may begin during active disease or treatment and continue after TB completion, especially in those with residual cavities.

Possible biological and diagnostic explanations

Detection of CPA during TB therapy may reflect more than one phenomenon. These categories are clinically important because they have different implications.

Diagnostic criteria: why timing is difficult

Most CPA definitions require compatible symptoms, radiology and mycological or immunological evidence over at least three months. That creates difficulty during TB therapy because active PTB itself can produce prolonged symptoms and cavitary radiology.

Guideline-consistent CPA diagnosis generally requires:

• chronic respiratory or systemic symptoms, usually for at least three months;
• compatible imaging, such as one or more cavities, pleural thickening, pericavitary infiltrates, fungal ball, progressive fibrosis or nodules;
• microbiological or immunological evidence of Aspergillus infection, especially raised Aspergillus IgG;
• exclusion of alternative diagnoses, including active TB, non-tuberculous mycobacterial disease, malignancy and other chronic infections.

In active TB, the exclusion criterion is problematic because TB and CPA can genuinely co-exist. Therefore, rather than using “active TB” to exclude CPA automatically, clinicians may need to ask whether the observed course is fully explained by TB alone.

When should CPA be considered during TB treatment?

CPA assessment should be considered during TB treatment when one or more of the following are present:

• persistent cough, haemoptysis, weight loss, fatigue or breathlessness after the intensive phase of TB treatment;
• persistent or enlarging cavities despite microbiological response to anti-TB therapy;
• new intracavitary material or suspected fungal ball;
• pleural thickening or pericavitary infiltrates that progress despite TB treatment;
• repeatedly negative TB microbiology despite a clinical label of TB relapse;
• history of previous TB or other structural lung disease;
• unexplained haemoptysis after apparent TB response;
• patients being considered for repeat TB treatment without strong microbiological confirmation.

Suggested diagnostic approach

A pragmatic diagnostic approach in specialist respiratory or infectious disease settings could include:

1. Confirm TB status: review baseline microbiology, GeneXpert/NAAT, culture, drug susceptibility and treatment response.
2. Repeat imaging: CT is preferable to chest radiography where CPA is suspected, particularly to assess cavities, fungal ball, pleural thickening and pericavitary progression.
3. Request Aspergillus IgG: a positive result is a major diagnostic component, though not sufficient alone.
4. Send respiratory samples: fungal culture and/or Aspergillus PCR where available; also reassess for TB and non-tuberculous mycobacteria.
5. Assess duration and trajectory: progressive symptoms or radiology over three months strengthens CPA diagnosis.
6. Review differential diagnoses: malignancy, bacterial bronchiectasis, NTM, lung abscess, vasculitis and other chronic infections.
7. Discuss complex cases with a specialist mycology or CPA centre: especially if antifungal therapy is being considered during rifampicin-based TB treatment.

Treatment implications and drug interactions

If CPA is diagnosed during TB therapy, management is complicated by major drug interactions. Rifampicin is a potent enzyme inducer and substantially reduces exposure to many triazole antifungals, including itraconazole, voriconazole and posaconazole. Co-administration is generally problematic and may render azole therapy ineffective.

Specialist input is therefore essential. Management may require:

• review of TB regimen and treatment phase;
• therapeutic drug monitoring for azoles where used;
• careful liver function monitoring;
• assessment of haemoptysis risk;
• consideration of timing of antifungal initiation;
• multidisciplinary discussion involving TB, respiratory, infectious diseases, pharmacy and mycology teams.

In some cases, observation and reassessment may be appropriate if CPA criteria are incomplete and the patient is clinically improving. In others, particularly with progressive cavitary disease, haemoptysis or strong Aspergillus IgG positivity, earlier specialist intervention may be justified.

What do guidelines currently say?

ERS/ESCMID

The ERS/ESCMID CPA guideline recognises tuberculosis as a major underlying condition for CPA and defines CPA using chronic symptoms, compatible radiology and Aspergillus evidence, typically over at least three months. It supports Aspergillus IgG as a central diagnostic test and recommends long-term oral triazole therapy for symptomatic or progressive chronic cavitary disease.

IDSA

The IDSA aspergillosis guideline similarly defines chronic cavitary pulmonary aspergillosis by at least three months of symptoms or progressive radiographic abnormalities, compatible cavitary disease, microbiological or serological evidence of Aspergillus, and minimal immunocompromise. It explicitly notes that CPA may complicate underlying pulmonary diseases, including tuberculosis and non-tuberculous mycobacterial infection.

BTS

The British Thoracic Society 2025 Clinical Statement on Aspergillus-related chronic lung disease provides current UK best-practice framing for diagnosis and management of chronic Aspergillus lung disease. Its publication reflects increasing recognition that Aspergillus-related chronic lung disease requires specific diagnostic pathways, antifungal stewardship and specialist respiratory-mycology collaboration.

WHO TB guidance

WHO TB guidance focuses on TB diagnosis, drug susceptibility, treatment regimens, monitoring, treatment failure and public health control. CPA is not yet embedded as a routine screening component of standard TB treatment pathways. This creates a gap between TB programme algorithms and emerging evidence from fungal disease studies.

Evidence strength

Implications for TB and respiratory services

The emerging evidence supports a targeted CPA assessment trigger within TB pathways, rather than universal screening at present.

A reasonable specialist position would be:

In patients receiving treatment for pulmonary tuberculosis, persistent symptoms, haemoptysis or non-resolving/progressive cavitary disease after the intensive phase should prompt consideration of CPA, especially where TB microbiology is negative or improving and imaging remains suspicious.

This is particularly relevant in high TB burden countries, but also in low TB burden settings where patients with previous TB, migrant health histories or unexplained cavitary disease may be seen in respiratory clinics.

Research priorities

• Prospective studies with baseline and serial CT imaging in microbiologically confirmed PTB.
• Serial Aspergillus IgG titres, fungal culture and molecular testing during TB therapy.
• Clear separation of proven CPA, probable CPA, Aspergillus colonisation and transient seropositivity.
• Studies of CPA screening at two months versus end-of-treatment versus six months post-treatment.
• Outcome studies assessing whether early CPA recognition reduces haemoptysis, lung destruction, retreatment for TB or mortality.
• Health-economic modelling of targeted CPA testing in TB programmes.

Conclusion

The evidence base is moving from a simple post-TB model towards a continuum model of TB-associated CPA. In this model, Aspergillus-related disease may be present at TB diagnosis, emerge during therapy, become apparent at treatment completion, or develop later in post-TB lung disease.

For specialists, the key implication is not that every patient with TB requires CPA screening. Rather, CPA should be actively considered when the clinical trajectory is not adequately explained by TB alone, particularly in patients with cavitation, haemoptysis, persistent symptoms or poor radiological resolution.

Embedding a CPA assessment trigger into TB follow-up pathways may reduce misdiagnosis, repeated empirical TB treatment and delayed antifungal management. The evidence is not yet definitive, but it is strong enough to justify specialist awareness, targeted testing and further prospective research.

References

1. Bongomin F. Post-tuberculosis chronic pulmonary aspergillosis: An emerging public health concern.
   PLOS Pathogens. 2020;16(8):e1008742.
   doi:10.1371/journal.ppat.1008742.
   PubMed
2. Denning DW, Cadranel J, Beigelman-Aubry C, et al. Chronic pulmonary aspergillosis: rationale and clinical guidelines for diagnosis and management.
   European Respiratory Journal. 2016;47(1):45-68.
   doi:10.1183/13993003.00583-2015.
   PubMed
3. Jha D, Kumar U, Meena VP, et al. Chronic pulmonary aspergillosis incidence in newly detected pulmonary tuberculosis cases during follow-up.
   Mycoses. 2024;67(5).
   doi:10.1111/myc.13747.
   PubMed
4. Namusobya M, Bongomin F, Mukisa J, et al. Chronic pulmonary aspergillosis in patients with active pulmonary tuberculosis with persisting symptoms in Uganda.
   Mycoses. 2022;65(6):625-634.
   doi:10.1111/myc.13444.
   PubMed
5. Ocansey B, Otoo B, Gbadamosi H, et al. Importance of Aspergillus-specific antibody screening for diagnosis of chronic pulmonary aspergillosis after tuberculosis treatment: a prospective follow-up study in Ghana.
   Journal of Fungi. 2022;9(1):26.
   doi:10.3390/jof9010026.
   PubMed
6. Patterson TF, Thompson GR, Denning DW, et al. Practice guidelines for the diagnosis and management of aspergillosis: 2016 update by the Infectious Diseases Society of America.
   Clinical Infectious Diseases. 2016;63(4):e1-e60.
   doi:10.1093/cid/ciw326.
   PubMed
7. Setianingrum F, Rozaliyani A, Adawiyah R, et al. A prospective longitudinal study of chronic pulmonary aspergillosis in pulmonary tuberculosis in Indonesia (APICAL).
   Thorax. 2022;77(8):821-828.
   doi:10.1136/thoraxjnl-2020-216464.
   PubMed