The research, led by Josette Najjar-Pellet of the Mérieux Foundation together with colleagues from the Lebanese Ministry of Public Health, Saint Joseph University of Beirut, and collaborating hospitals, set out to do something Lebanon had not systematically done before: quantify tuberculosis infection, or TBI, among the populations considered most at risk in Beirut and Mount Lebanon, the two governorates bearing the country’s heaviest tuberculosis burden. Between September 2019 and June 2023, the team screened 860 participants drawn from four groups: healthcare workers, household and close contacts of active tuberculosis cases, migrants, and prisoners. Every participant underwent either the century-old Tuberculin Skin Test, the newer QuantiFERON-TB Gold Plus interferon-gamma release assay, or both, allowing the researchers to compare how the two diagnostic philosophies performed head to head in a real-world setting.

The headline numbers are sobering. Overall positivity for the skin test stood at 24.9 percent, while the blood-based assay returned positive results in 20.9 percent of those screened. In other words, roughly one in four people tested in these at-risk groups carried evidence of tuberculosis infection. But the aggregate figures conceal the study’s most consequential discovery: the burden is not distributed evenly. Migrants and tuberculosis contacts showed the highest prevalence of infection by a clear margin, confirming that Lebanon’s epidemic is concentrated in precisely the populations least likely to be reached by routine passive case finding. Healthcare workers, despite their occupational exposure, and prisoners occupied a lower tier of measured infection in this cohort.

That concentration matters because tuberculosis infection is the raw material of future epidemics. When Mycobacterium tuberculosis settles into a person’s lungs, it can persist in a dormant state for decades, held in check by the immune system until something—HIV infection, immunosuppressive therapy, diabetes, malnutrition, or simply the passage of time—tips the balance. Between 5 and 10 percent of infected people who never receive preventive treatment will eventually develop active disease, and each active case becomes a new engine of transmission. Screening for infection is therefore not an academic exercise; it is the front line of tuberculosis elimination, identifying the people who would benefit most from preventive therapy before they ever become contagious.

The two screening tools embody fundamentally different approaches to detecting that dormant infection. The Tuberculin Skin Test relies on a delayed-type hypersensitivity reaction: purified protein derivative, a cocktail of mycobacterial antigens, is injected into the skin, and the immune response is read as a zone of induration 48 to 72 hours later. It is cheap and requires no laboratory, but it cross-reacts with the Bacille Calmette-Guérin vaccine and with nontuberculous mycobacteria, and it demands a return visit for accurate reading. The QuantiFERON assay takes the opposite route: a blood sample is exposed to mycobacterial antigens in the laboratory, and the release of interferon-gamma by sensitized T cells is measured directly. It is more specific, unaffected by BCG vaccination, and requires only a single visit, but it costs more and depends on laboratory infrastructure that must process the sample within hours.

When the Lebanese team compared the two tests across their four population groups, the agreement between them proved anything but uniform. Kappa statistics, which measure how well two tests concur beyond what chance alone would produce, ranged from fair at 0.33 among tuberculosis contacts to moderate at 0.60 among migrants. The discrepancies were most notable among migrants and prisoners, the very groups where BCG vaccination histories, prior exposure to environmental mycobacteria, and nutritional or immunological factors are most likely to diverge from the general population. This is not a technical footnote. It means that a single national screening algorithm, applied identically to everyone, would systematically miss infections in some groups while overcalling them in others, wasting scarce resources and leaving the most vulnerable unprotected.

The multivariate logistic regression analysis sharpened the picture further. Being a tuberculosis contact emerged as the strongest independent risk factor, with an adjusted odds ratio reaching up to 5.9 for a positive result on at least one test. Migrant status carried an adjusted odds ratio of 1.8, a smaller but still meaningful elevation. These figures quantify what public health officials have long suspected but had never before measured with this precision in Lebanon: the epidemic’s future cases are already identifiable today, concentrated among people who share households or air with active cases and among displaced populations carrying infection burdens from higher-prevalence settings.

The study’s practical implications for Lebanon’s National Tuberculosis Programme are direct. Rather than a one-size-fits-all national algorithm, the data argue for tailored screening strategies matched to each population group. For tuberculosis contacts, where the skin test’s fair agreement with the blood assay suggests it may under-detect infection, the interferon-gamma release assay’s superior specificity and single-visit convenience could justify the added cost. For migrants, where the two tests agreed moderately but discrepancies remained common, the choice of test may hinge on vaccination history and the practical realities of reaching a mobile population. For healthcare workers and prisoners, the lower measured prevalence suggests that existing occupational screening may already be capturing much of the burden, though the authors caution that their convenience sampling in two governorates means these estimates describe the sampled groups rather than the nation as a whole.

The timing of this research is significant for a country navigating extraordinary pressures. Lebanon’s economic collapse has strained every layer of its health infrastructure, from medicine supply chains to laboratory reagents, while the influx and movement of displaced populations has altered the epidemiological landscape faster than surveillance systems could adapt. The study’s co-funding by the Fondation Mérieux and QIAGEN, with laboratory support from the Rodolphe Mérieux Laboratory at Saint Joseph University, reflects the kind of international partnership that has kept essential diagnostics functioning through the crisis. The collaboration with nongovernmental organizations including Amel Association International and Caritas Lebanon, and with the International Organization for Migration, was essential for reaching populations that formal health services rarely touch.

What makes this study resonate beyond Lebanon’s borders is its methodological honesty. The authors do not claim nationally representative prevalence figures; they explicitly state that their targeted convenience sampling in two governorates produces estimates that describe the sampled groups alone. Yet the study’s core finding—that screening test performance and infection burden vary systematically by population group—applies to any country designing a tuberculosis elimination strategy. As the World Health Organization pushes member states toward elimination targets, the Lebanese data offer a template: measure the burden in each at-risk population, compare the available diagnostic tools in that same population, and build the national algorithm from the ground up rather than imposing it from the top down. For a disease that has accompanied humanity for millennia, the path to elimination may depend less on any single breakthrough than on this kind of granular, population-specific evidence.

Subject of Research: Tuberculosis infection affects roughly one in four people screened in Lebanon's highest-burden regions, with contacts and migrants at greatest risk, according to a new cross-sectional study that could reshape the country's national screening strategy.

Article Title: Cross-sectional study toward optimizing the national screening strategy for tuberculosis infection in Lebanon

Article References: Cross-sectional study toward optimizing the national screening strategy for tuberculosis infection in Lebanon. (n.d.). https://doi.org/10.1186/s12879-026-14460-7

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14460-7

Keywords: tuberculosis infection, tuberculin skin test, interferon-gamma release assay, QuantiFERON-TB Gold Plus, Lebanon, national screening strategy, high-risk populations, TB contacts, migrants, prisoners, healthcare workers, BMC Infectious Diseases

The research team, led by investigators at Beijing Children’s Hospital, Capital Medical University, together with colleagues at Shenyang Chest Hospital and other Chinese institutions, enrolled 448 patients aged under 22 years who had confirmed Mycobacterium tuberculosis infection, a QuantiFERON-TB Gold Plus result, and complete clinical records. Recruitment took place between August 2022 and March 2024 at the two hospitals. Of the total cohort, 138 patients, or 30.8 percent, had active tuberculosis disease, while 310, or 69.2 percent, were diagnosed with latent tuberculosis infection, a state in which the bacteria persist in the body without causing symptoms but can reactivate into full disease later in life. This split between disease states allowed the researchers to ask a question that matters enormously in pediatric practice: does the immune signal measured by the test differ depending on whether the infection is latent or actively causing illness?

The technical logic of the assay is worth unpacking, because the study’s most interesting findings hinge on it. QuantiFERON-TB Gold Plus works by mixing a small blood sample with synthetic peptides that mimic two proteins, ESAT-6 and CFP-10, which are produced by Mycobacterium tuberculosis but absent from most environmental mycobacteria and from the BCG vaccine strain. Sensitized T cells in the blood respond by releasing interferon gamma, a signaling molecule of the immune system, and the amount released is quantified by enzyme immunoassay. The Plus version of the test splits the antigen stimulation into two tubes, TB1 and TB2. TB1 contains peptides that preferentially stimulate CD4 T cells, the classic helper cells of adaptive immunity, while TB2 adds longer peptides intended to additionally engage CD8 T cells, which are thought to play a role in controlling active tuberculosis. Comparing the responses in these two tubes therefore offers a window into different arms of the anti-tuberculosis immune response.

The headline result was a sensitivity of 82.8 percent for active tuberculosis across the whole cohort. In other words, roughly five out of six children with confirmed active disease produced a positive result. That figure places the assay in familiar territory for IGRAs in pediatric populations, where sensitivity has consistently lagged behind the near-perfect specificity these tests achieve in low-burden settings. Specificity is rarely the problem, because the tuberculosis-specific antigens virtually eliminate false positives caused by BCG vaccination or nontuberculous mycobacteria. The problem is the false negative: a child with active tuberculosis who tests negative may have treatment delayed, and in pediatric tuberculosis, where disease can progress rapidly from a small lung focus to disseminated infection, delay carries real consequences. The authors are explicit that the test should not be used as a rule-out tool, particularly in the most vulnerable patients.

Agreement between the two antigen tubes emerged as another notable finding. The percent agreement between TB1 and TB2 responses was 91.8 percent, indicating that in the vast majority of infected children the CD4-focused and CD8-inclusive stimulation tubes returned concordant results. This high concordance suggests that, in this population, adding the TB2 tube does not dramatically change who is classified as infected, although it may still contribute quantitative information about the breadth of the immune response. Notably, the researchers found no significant difference in the response to the QFT-Plus TB antigens between patients with active tuberculosis and those with latent infection. The magnitude of interferon gamma release to the antigen tubes was similar in both disease states, reinforcing the established understanding that IGRAs are tests of infection rather than tests of disease activity. A positive result tells a clinician that the immune system has encountered tuberculosis; it cannot by itself distinguish a sleeping infection from an active one.

Perhaps the most biologically revealing part of the study concerns age. The researchers measured interferon gamma production in response to both the mitogen and the tuberculosis antigens and found that children younger than one year produced lower responses to both the mitogen and the TB-specific antigens than children in other age groups. The mitogen tube, which contains a potent nonspecific stimulant of T cells, serves as a positive control: it verifies that the patient’s blood cells are capable of mounting an interferon gamma response at all. A low mitogen response in infants points to genuine immunological immaturity rather than a technical failure. This observation aligns with a well-established body of immunology showing that the neonatal and infant immune system is skewed toward tolerogenic responses, with T cells that are less effector-like and interferon gamma signaling pathways that are not yet fully developed.

The correlation analysis added further nuance. The team found a significant positive correlation between age and interferon gamma responses to the mitogen, meaning that the nonspecific immune capacity measured in the tube grows steadily as children get older. In contrast, there was a significant negative correlation between age and interferon gamma responses to the TB1 and TB2 antigen tubes. This inverse pattern is intriguing: as children age, their general T-cell responsiveness increases while their antigen-specific response to tuberculosis peptides, at least as measured in this assay, tends to decline. One plausible interpretation is that recent infection in younger children drives stronger antigen-specific responses, whereas older children and young adults in the cohort may have had more remote or more contained infections with waning antigen-specific reactivity. Whatever the mechanism, the practical implication is that a single quantitative cutoff applied across a pediatric age range from infancy to young adulthood may not capture the biology of every patient equally well.

The study also flagged comorbidities as a source of diagnostic difficulty. Children with underlying conditions showed a higher rate of indeterminate results, meaning tests that could not be interpreted because the mitogen control failed or the background interferon gamma was elevated. Indeterminate results are a well-recognized limitation of all IGRAs in immunocompromised patients, including those with malnutrition, HIV infection, malignancy, or immunosuppressive therapy, all of which can blunt T-cell function. Combined with the suboptimal sensitivity observed in infants, the authors conclude that the assay’s performance is weakest precisely in the children who are at highest risk of severe tuberculosis, including those under one year old and those with comorbidities. In these groups, clinicians must treat a negative QuantiFERON-TB Gold Plus result with skepticism and rely on a broader diagnostic toolkit, including the tuberculin skin test, microbiological culture, molecular tests such as nucleic acid amplification, radiological imaging, and careful clinical judgment.

Context matters for interpreting why this Chinese cohort is important. China carries one of the world’s largest tuberculosis burdens, and BCG vaccination at birth is universal there, which complicates the traditional tuberculin skin test because vaccine-induced immune memory can produce false-positive skin reactions. IGRAs sidestep that problem, which is a major reason they have been adopted for contact investigation and latent infection screening. At the same time, pediatric tuberculosis in high-burden settings is notoriously paucibacillary, meaning that children harbor few bacteria, making microbiological confirmation difficult and forcing clinicians to lean heavily on immunological tests. Studies like this one, grounded in a large, well-characterized cohort of confirmed infections, provide the evidence base that national guidelines need when deciding how to position IGRAs relative to skin testing and other tools.

The study, conducted under the Declaration of Helsinki with ethics approval from Beijing Children’s Hospital and informed consent from participants or their guardians, was supported by the National Natural Science Foundation of China, the Beijing Natural Science Foundation, and other national and municipal funders. Its practical message is balanced rather than dramatic. QuantiFERON-TB Gold Plus earns its place as a useful diagnostic aid for both active tuberculosis and latent infection in children and young adults, with high tube-to-tube agreement and disease-state-independent antigen responses. But the numbers also counsel humility: with sensitivity below 85 percent overall, weaker performance in infancy, and elevated indeterminate rates in children with comorbidities, the assay functions best as one instrument in a diagnostic ensemble rather than a standalone verdict. For the youngest and sickest patients, a negative result must never close the door on a tuberculosis diagnosis that clinical suspicion has opened.

Subject of Research: Diagnostic performance of the QuantiFERON-TB Gold Plus interferon gamma release assay in children and young adults with tuberculosis infection

Article Title: Analysis of QuantiFERON-TB gold plus assay in children and young adults with Mycobacterium tuberculosis infection in China

Article References: Zheng, H., Yu, Y., Wang, Y., Guo, Y., Wang, Y., Li, F., Xiao, J., Qi, H., Jiao, W., Wang, X., Chen, Y., & Sun, L. (2026). Analysis of QuantiFERON-TB gold plus assay in children and young adults with Mycobacterium tuberculosis infection in China. BMC Pediatrics. https://doi.org/10.1186/s12887-026-07717-2

Image Credits: AI Generated

DOI: 10.1186/s12887-026-07717-2

Keywords: tuberculosis, QuantiFERON-TB Gold Plus, interferon gamma release assay, children, latent tuberculosis infection, active tuberculosis, Mycobacterium tuberculosis, pediatrics, diagnostics, China, IFN-gamma, TB1 and TB2 antigens

The case, reported in the journal Respirology Case Reports, describes how a lethal cancer called sarcomatoid malignant pleural mesothelioma hid behind a convincing facade of infection. When thoracoscopy under local anesthesia revealed a purulent, pus-filled effusion with fibrin deposited across the pleural cavity, the medical team could not even obtain an adequate pleural biopsy because inflammation obscured the tissue. Acting on a clinically suspected diagnosis of tuberculosis pleurisy, physicians in January 2025 began empiric anti-tuberculosis therapy with the standard four-drug regimen of isoniazid, rifampicin, ethambutol, and pyrazinamide. The patient had a smoking history of 10 pack-years and had worked in administrative roles at construction sites, an occupation that can involve asbestos exposure, the primary known cause of mesothelioma. His history also included colon cancer, surgically treated at stage IIIA, adding another layer of complexity to the clinical picture.

For four months the treatment failed. The pleural effusion persisted, and a positron emission tomography scan fused with computed tomography, which uses a radioactive glucose analog to light up metabolically active tumors, showed no abnormal accumulation to suggest malignancy. By April 2025 the patient was referred to a second hospital, where surgeons performed a thoracoscopic biopsy at the site of pleural thickening identified on preoperative imaging. The histopathology was frustratingly non-specific: fibrous pleural thickening without any granulomatous inflammation, the clustered immune structures characteristic of tuberculosis, and no acid-fast bacilli visible under Ziehl-Neelsen staining. Cultures of the tissue for mycobacteria and ordinary bacteria were all negative. The biopsy, in other words, proved the absence of infection but could not name what was actually there.

What happened next provides the dramatic core of the report. Two months after the surgical biopsy, a routine follow-up CT scan in August 2025 revealed a new mass in the posterior right eighth rib, invading bone, and the patient had begun to feel pain at the site. A CT-guided percutaneous biopsy of that rapidly growing mass delivered tissue that was still ambiguous under the microscope. The specimen showed fibrosis mingled with a proliferation of atypical spindle cells, elongated cells with enlarged and irregular nuclei that could belong to either an aggressive cancer or a benign scarring process called fibrosing pleuritis. Even experienced pathologists cannot reliably separate these two entities on routine hematoxylin and eosin stained sections, and this case proved no exception.

The diagnostic breakthrough came from molecular testing rather than conventional histology. Immunohistochemistry showed that the spindle cells stained diffusely positive for CAM5.2, a cytokeratin marker that hints at epithelial origin and supports a mesothelial lineage, but the definitive answer required fluorescence in situ hybridization, or FISH. This technique uses fluorescently labeled DNA probes to examine tumor cells at the level of individual genes. In this patient, FISH revealed a homozygous deletion of the CDKN2A gene, also known as p16, meaning both copies of this critical tumor suppressor had been lost. The deletion of a gene whose normal function is to halt the cell cycle when DNA damage is detected is a hallmark of malignant transformation. Because homozygous CDKN2A loss is frequently found in sarcomatoid mesothelioma but is absent in benign fibrosing pleuritis, its detection confirmed the diagnosis of sarcomatoid mesothelioma. The disease had been masquerading as infection and inflammation for months, and molecular pathology finally unmasked it.

The clinical course then moved with brutal speed. Just two months after the definitive diagnosis, the patient died under best supportive care. That trajectory is characteristic of sarcomatoid mesothelioma, which carries a poorer prognosis and progresses more rapidly than the epithelioid and biphasic subtypes of the disease. Within the sarcomatoid family, the case authors note, lies an even more deceptive variant called desmoplastic mesothelioma, whose early lesions are pathologically indistinguishable from benign fibrous pleuritis. In this patient, retrospective analysis of the original surgical biopsy proved revelatory: when researchers later stained that older sample, scattered spindle cells turned out to be positive for CAM5.2, and FISH on the same archival tissue also detected the CDKN2A deletion. The cancer had been present all along, hiding in plain sight within a fibrotic pleura, in an occult phase where the tumor burden was too small and too metabolically quiet to register on FDG-PET or to catch the pathologist’s eye.

Why was tuberculosis such a plausible impostor? The report contextualizes the difficulty with sobering numbers. The sensitivity of pleural fluid smears for acid-fast bacilli in tuberculous pleurisy is below 10 percent, and cultures are positive in fewer than 30 percent of cases, meaning that a negative smear or culture never truly excludes the disease. Adenosine deaminase, while useful, has limited specificity, and in regions where tuberculosis remains common, clinicians are often justified in starting empiric therapy when the clinical constellation fits. Here, a positive interferon-gamma release assay combined with a lymphocyte-predominant exudate created a strong circumstantial case. Yet previous studies indicate that among patients who receive a diagnosis of non-specific pleuritis after invasive biopsy, between 5 and 15 percent are eventually found to have malignancy, particularly mesothelioma. That statistic transforms an initially reassuring non-specific biopsy result into a warning sign demanding surveillance rather than closure.

The British Thoracic Society guidelines recommend approximately 12 months of follow-up for patients whose pleural biopsies yield non-specific results, and this case illustrates precisely why such vigilance matters. When the effusion failed to resolve despite four months of antituberculosis drugs, the appropriate response was prompt, repeated pleural biopsy rather than continued ineffective treatment. The report argues that clinicians facing presumed tuberculous pleurisy that responds poorly to therapy must actively hunt for malignant mesothelioma. It also highlights a structural gap in clinical practice: FISH testing for CDKN2A deletion remains limited in availability and prevalence in general clinical settings, and restricted access to this powerful tool can delay mesothelioma diagnoses, sometimes fatally. Expanding access to molecular diagnostics for pleural disease emerges as an urgent unmet need.

Beyond its immediate clinical lessons, the case offers a window into how modern oncology resolves diagnostic uncertainty. A single molecular event, the loss of both copies of a tumor suppressor gene, served as the fingerprint that distinguished a rapidly lethal cancer from benign scar tissue that looked nearly identical under the microscope. The trajectory of this patient’s illness, from an occult phase invisible to imaging and pathology, through an explosive two-month emergence of a bone-invading chest wall mass, to death within weeks of diagnosis, underscores the aggressive biology of the sarcomatoid subtype. For physicians, the message is layered: treat the statistics with humility, because negative cultures and smears cannot exclude tuberculosis, and non-specific biopsies cannot exclude mesothelioma. For patients with unexplained pleural effusions that defy treatment, repeated biopsies and multidisciplinary discussion, combined with molecular tools capable of interrogating the genome rather than only the architecture of tissue, may be the difference between catching a cancer in time and discovering it only after it has claimed the advantage. This single case, reported with full clinical detail, adds a compelling data point to the growing argument that the future of pleural disease diagnosis lies as much in molecular pathology as in the pathologist’s optical microscope.

Subject of Research: A case report of sarcomatoid malignant pleural mesothelioma initially misdiagnosed and treated as tuberculous pleurisy

Article Title: Sarcomatoid Mesothelioma Revealed After Treatment for Tuberculous Pleurisy: A Case Report

Article References: Nagayama, D., Yokoo, K., Yabushita, Y., Sekikawa, M., Abe, M., Kato, H., Takayanagi, A., Takahashi, B., Kato‐Shinomiya, M., Ota, S., Yamada, G., Hiroshima, K., & Chiba, H. (2026). Sarcomatoid Mesothelioma Revealed After Treatment for Tuberculous Pleurisy: A Case Report. Respirology Case Reports, 14(9), Article e70734. https://doi.org/10.1002/rcr2.70734

Image Credits: AI Generated

DOI: 10.1002/rcr2.70734

Keywords: sarcomatoid mesothelioma, tuberculous pleurisy, pleural effusion, CDKN2A deletion, FISH testing, pleural biopsy, interferon-gamma release assay, adenosine deaminase, fibrosing pleuritis, immunohistochemistry, PET-CT, case report