Clinical Profiles
Clinical Profiles
com/scientificreports
Keywords Gene xpert, Sputum smear positive, Pulmonary tuberculosis, Infectivity, China
Pulmonary tuberculosis (TB) is an infectious disease. In 2022, tuberculosis stands as the second leading cause
of death from a single source of infection, surpassing only by coronavirus (COVID-19). The estimated number
of individuals affected by tuberculosis in 2022 is 20.6 million, surpassing the figures of 10.3 million in 2021 and
10 million in 2020. Additionally, about 7.5 million new diagnoses are anticipated in 2022, surpassing the figures
of 5.8 million in 2020 and 6.4 million in 2021. The global incidence rate of tuberculosis is expected to increase
by 3.9% between 2020 and 2022, reversing the trend of an annual decline of about 2% observed over the past
20 years1,2.
1
Department of Radiology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology
of China, Chengdu, People’s Republic of China. 2Department of Radiology, The First People’s Hospital of
Liangshan Yi Autonomous Prefecture, Xichang, Sichuan, People’s Republic of China. 3School of Medicine,
University of Electronic Science and Technology of China, Chengdu, People’s Republic of China. 4CT Collaboration,
Siemens-Healthineers, Chengdu, People’s Republic of China. 5These authors contributed equally: Shiqing Yu, Yan
Gao, Weifang Kong and Lan Shang. *email: kongweifang@med.uestc.edu.cn; shanglan8282@163.com
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Pulmonary tuberculosis is caused by Mycobacterium tuberculosis (MTB), which spreads when patients
release bacteria into the air, such as during coughing. It is estimated that approximately a quarter of the world’s
population, nearly 2 billion people, are infected with Mycobacterium t uberculosis3.
The World Health Organization (WHO) Stop tuberculosis Strategy mandates a yearly reduction of 10% in the
tuberculosis incidence rate by 2025. An integral aspect of this strategy is the attainment of swift detection and
early diagnosis of tuberculosis. Currently, the conventional methods for detecting tuberculosis include micro-
scopic smear examination, culture, drug sensitivity test and chest X-ray examination. Among these methods,
the culture and drug sensitivity test for tuberculosis bacteria are the gold standard for diagnosing tuberculosis,
with microscopic examination of sputum smear being a crucial diagnostic method. While a positive result in
sputum smear indicates high infectiousness, its sensitivity is low4. Gene Xpert, a rapid detection method for
Mycobacterium tuberculosis recommended by the WHO, is based on real-time PCR detection and molecular
technology. This method boasts high sensitivity, accuracy and speed (results obtainable within 2 h). Importantly,
it can detect Mycobacterium tuberculosis even when the sputum smear results are negative. This capability aids
in the early intervention of tuberculosis patients, preventing severe consequences and delaying the optimal
treatment of p atients5.
While some literatures reported on the clinical characteristics of patients with positive Gene Xpert test and
positive sputum smear t est6–11, few articles have conducted a comparative analysis of these characteristics. This
scarcity of comparative studies limits the understanding of the clinical features and associated factors related to
the development and infectivity of tuberculosis in patients who tested positive in smear Mycobacterium tuber-
culosis tests compared with those who tested negative in smear mycobacterium tests but positive in sputum
Gene Xpert tests. To address this, we analyzed the data of hospitalized patients with newly diagnosed pulmo-
nary tuberculosis to understand the clinical characteristics of Gene Xpert positive and sputum smear positive
pulmonary tuberculosis patients. As with smear positive pulmonary tuberculosis patients can directly discharge
Mycobacterium tuberculosis into the air through coughing, leading to the potential infection of others and
further spread, they are considered highly i nfectious12.
Methods
Patients
We conducted a retrospective cross-sectional study on hospitalized patients with suspected pulmonary tuber-
culosis at Sichuan Provincial People’s Hospital from January 1, 2018 to August 5, 2023. Data for this study were
collected from patients’ hospitalization medical records and anonymized for analysis. All methods were carried
out comply with the ethical standards of Sichuan Academy of Medical Sciences and Sichuan Provincial People’s
Hospital, as well as the 1964 Helsinki declaration and its later amendments or comparable ethical standards. All
clinical data and laboratory results, as well as the waiver of patient informed consent has been approved by the
Ethics Review Committee of Sichuan Provincial Academy of Medical Sciences and Sichuan Provincial People’s
Hospital (Protocol 20220-254).
In accordance with the diagnostic criteria for pulmonary tuberculosis outlined in the Health Industry Stand-
ards of the People’s Republic of China (ws 288-2017), the inclusion criteria are as follows: (a) confirmation of
pulmonary tuberculosis through bacteriology (sputum smear); (b) Confirmation of Pulmonary tuberculosis
through polymerase chain reaction in respiratory specimens (sputum, bronchoalveolar lavage fluid). The exclu-
sion criteria are as follows: (a) previous diagnosis or treatment for pulmonary tuberculosis; (b) presence of
human immunodeficiency virus infection, undergoing immunosuppressive therapy, potential malignant tumors,
or concurrent lung diseases (including lung cancer, pneumoconiosis, or other lung infections). Details of the
inclusion and exclusion data are presented in Fig. 1.
Parameter collection
Clinical information for all patients encompasses gender, age, nationality, BMI, smoking history, drinking his-
tory, and clinical symptoms (cough, expectoration, hemoptysis, night sweats, fever, tightness of breath, dyspnea,
etc.). Additionally, extrapulmonary tuberculosis status (tuberculous pleurisy, tuberculous peritonitis, intestinal
tuberculosis, joint tuberculosis, urinary tuberculosis, etc.). And other concurrent disease conditions (diabetes,
hypertension, anemia, rheumatoid arthritis, malnutrition, etc.) are also included in the data collection.
Patients grouping
• Based on their body mass index (BMI): underweight:BMI below 18.5; normal weight:BMI between 18.5 and
24.9; overweight: BMI great than or equal to 2 513.
• Age groups: Minors: 0–17 years old; Young adults: 18–44 years old; Middle-aged individuals:45–59 years
old; Young and elderly individuals: 60–74 years old; Elderly individuals:75–89 years old; Individuals over
90 years old.
• According to the diagnostic criteria of pulmonary tuberculosis: “Smear negative but geneXpert positive”
groups; “Sputum smear positive” group.
Statistical analysis
A descriptive analysis was conducted on the clinical data collected from all GeneXpert positive and sputum
smear positive pulmonary tuberculosis inpatients. Frequencies and percentages were calculated, and odds ratios
(OR) along with their 95% confidence intervals (CI) were determined to elucidate the correlation between
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variables. The independent sample T test was employed to assess differences in the distribution of demographic
characteristics between the two groups. The chi-square test was used for comparing categorical variables, and
univariate and multivariable binary logistic regression (reverse stepwise logistic regression) were employed to
identify important variables affecting the incidence and infectivity of tuberculosis. All statistical analyses were
performed using SPSS 26 software, with a P-value threshold set at 0.05.
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Results
Baseline feature comparison
The study reviewed data from 2514 hospitalized patients suspected of pulmonary tuberculosis. A total of 1612
patients with pulmonary tuberculosis were included, with 1180 in the “sputum smear negative but GeneXpert
positive” group and 432 in the “sputum smear positive” group. Table 1 and Fig. 2 summarize the clinical char-
acteristics of the two groups of patients.
There was no significant difference between the two groups in terms of gender, ethnicity, smoking his-
tory, alcohol consumption history, blood lipids, etc. (P > 0.05). However, a statistically significant difference was
observed in age stratification (p < 0.001) and BMI stratification (P < 0.01). The sputum smear positive group
exhibited symptoms such as cough, sputum (72.5% vs. 56.4%, P < 0.001), hemoptysis (13.2% vs. 9.5%, P < 0.05),
shortness of breath, difficulty breathing (26.2% vs. 21.4%, P < 0.05), and weight loss (37.5% vs. 32.6%, P < 0.05).
The proportion of tuberculosis meningitis (3.7% vs. 1.3%, P < 0.05), tuberculous pleurisy (8.1% vs. 2.7%,
P < 0.001), and tuberculous peritonitis (4.4% vs. 0.9%, P < 0.001) was higher in the sputum smear positive group.
Extrapulmonary tuberculosis was diagnosed according to the Health Industry Standards of the People’s Republic
of China—Guidelines for the Classification of Tuberculosis issued by the National Health and Family Planning
Commission of the People’s Republic of China. There was no significant difference (p > 0.05) between the two
groups of patients in terms of other clinical symptoms, other pulmonary tuberculosis, and other diseases, except
for those mentioned above.
Discussion
In our study, elderly patients aged 75 to 89, when compared with patients in other age groups (multivariate analy-
sis: OR 2.199; 95% CI 1.087–4.446; p < 0.05), were found to be more likely to excrete bacteria and develop infectiv-
ity. This association may be attributed to factors such as decreased lung function, immune aging, inflammation,
lack of appropriate diagnostic/intervention measures, and age-related comorbidities. In most elderly cases, the
reactivation of latent pulmonary tuberculosis is prevalent, primarily caused by declining immunity associated
with aging. Age-related complications often mask the disease, extending the time to diagnosis. The symptoms
of pulmonary tuberculosis in the elderly are generally atypical, making early identification c hallenging14. By the
time of diagnosis, the disease may have advanced, leading to a significant increase in sputum bacteria and higher
likelihood of infectivity. Moreover, as the only approved tuberculosis vaccine, the BCG vaccine, its effectiveness
tends to decrease with age15, which could be another contributing factor to the elevated risk of infectivity in the
75 to 89 year-old group. Therefore, in clinical practice, it is essential to pay attention to pulmonary tuberculosis
patients aged 75 to 89 with atypical clinical symptoms to avoid delays in diagnosis and treatment, ultimately
preventing high infectivity.
Our study reveals that the sputum smear positive group exhibits a lower average BMI, is more susceptible to
symptoms of weight loss, and has a higher prevalence of individuals classified as underweight (BMI < 18.5 kg/m)2).
Compared to the high sensitivity of GeneXpert detection, the positive rate of sputum smear detection for Myco-
bacterium tuberculosis is lower16. Generally, patients who test positive on sputum smear are highly infectious,
and their condition is often severe. Mild cases may have a lower bacterial count, resulting in negative sputum
smear results. As tuberculosis is a chronic wasting disease, severe patients commonly experience weight loss
and emaciation. Additionally, various diseases associated with low weight (malnutrition, late HIV) are also more
susceptible for tuberculosis17–19. Our research indicates that being underweight (BMI < 18.5 kg/m)2 is helpful for
identifying highly infectious pulmonary tuberculosis patients early, enabling timely and rapid isolation measures
and the interruption of transmission routes.
However, the correlation between BMI and the prognosis of pulmonary tuberculosis patients is currently
unclear, and our future research will delve into these aspects. In clinical practice, when dealing with symptomatic
pulmonary tuberculosis patients and awaiting final bacteriological test results, doctors often initiate empirical
treatment. Therefore, when clinicians need to make empirical treatment decisions for high-risk tuberculosis
patients, considering routine BMI assessment initially, awaiting bacteriological test results, and implementing
isolation measures could be a prudent approach.
In our study, individuals with positive sputum smears exhibited a higher likelihood of coughing, cough-
ing (p < 0.001), shortness of breath, difficulty breathing (p < 0.05), and hemoptysis (p < 0.05). Coughing and
expectoration are early prominent symptoms of respiratory tract infections, physiologically aiding in clearing
and protecting the respiratory tract. However, in patients with tuberculosis, coughing can expel TB bacilli from
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Table 1. Clinical features of GeneXpert-positive and sputum smear-positive PTB patients. *:P value < 0.05;**:P
value < 0.01;***:P value < 0.001.
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Fig.2. Box plots of age and BMI in GeneXpert-positive and sputum smear-positive PTB patients The boxplot
showed that, overall, the sputum smear-positive group had a higher age and a lower BMI.
Table 2. Unilogical and multilogistic regression to assess related factors for tuberculosis contagiousness. *:P
value < 0.05;**:P value < 0.01;***:P value < 0.001.
cavities, consolidation areas and airway mucus, making it easier to detect TB bacilli in sputum s mears20. Some
studies have reported that compared with smear-negative TB, the proportion of patients with cough is higher
among smear-positive patients, and the frequency of sputum cough is also h igher21–23. Studies have shown that
smear-negative patients may have no respiratory symptoms or mild respiratory symptoms24.
When pulmonary tuberculosis patients experience difficulty in breathing, it often indicates that their tuber-
culosis infection is severe or that corresponding complications have occurred, such as caseous necrosis, scar
repair, chronic pulmonary heart disease, etc. Additionally, if concurrent with tuberculous pleurisy, it can cause
a large amount of pleural effusion to compress lung tissue, leading to atelectasis and respiratory distress25. At
this time, the condition is severe, with a significant increase in tuberculosis bacteria in the body and noticeable
respiratory symptoms. A large quantity of bacteria is excreted from the respiratory tract, increasing infectivity.
In tuberculosis patients, hemoptysis happens mainly because severe inflammation caused by active disease and
bacterial growth. This can damage blood vessels and lead to bleeding24. A recent study shows that the best pre-
dictors of high PTB infectivity (AFB +) are hemoptysis (OR = 4.33), cough (OR = 3.00), dyspnea (OR = 2.89)26.
Consistent with this, our study also demonstrates that cough, expectoration, tightness of breath, dyspnea, and
hemoptysis are factors predicting the high infectivity of tuberculosis.
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Our study reveals that individuals with positive sputum smears are more likely to develop tuberculous men-
ingitis (p < 0.01), tuberculous pleurisy (p < 0.001), and tuberculous peritonitis (p < 0.001) compared to the Gen-
eXpert positive group. A large-scale multicenter observational study on the epidemiology of extrapulmonary
tuberculosis demonstrated that the most common type of extrapulmonary tuberculosis is tuberculous pleurisy,
and the most common complication of extrapulmonary tuberculosis is tuberculous pleurisy combined with
tuberculous peritonitis2. Tuberculous meningitis (TBM) is the most severe manifestation of extrapulmonary
tuberculosis, with a high patient mortality rate and a high incidence of survivor sequelae27.
In most cases, tuberculosis originates in the lungs and spreads through the respiratory tract. When the body’s
immunity is weakened, Mycobacterium tuberculosis can disseminate in lymph or blood, invading organs other
than the lungs (except teeth, hair, and nails), leading to extrapulmonary tuberculosis. Mycobacterium tuber-
culosis may spread outside the lungs through three transmission mechanisms: (1) Mycobacterium tuberculo-
sis initially infects a large number of alveolar macrophages, which are transported and disseminated as these
macrophages enter and exit the lymphatic and circulatory systems. (2) Mycobacterium tuberculosis directly
infects the epithelial cells that make up the lung barrier, translocating between these cells without damaging the
epithelium, or inducing cell death to cause barrier rupture. Dendritic cells that sample antigens in alveoli can
transport Mycobacterium tuberculosis to lymph n odes28. Therefore, patients with weakened physical resistance
are usually accompanied by extrapulmonary tuberculosis, which is more severe, carries more bacteria, and is
easier to excrete bacteria, resulting in high infectivity.
This study has several limitations. Firstly, being a cross-sectional study, while sputum smears have assisted in
diagnosing infectious pulmonary tuberculosis compared to Gene X-pert, we cannot establish a causal relationship
between age, BMI, and TB contagiousness. Secondly, it is a small sample size, single-center study, emphasizing
the need for larger samples and multicenter studies in the future. Additionally, being an observational study,
potential selection bias in the research queue may be unavoidable. Thirdly, as the study focuses on tuberculosis
patients in southwest China, the generalizability of our results beyond this region may be limited. Last but not
the least, although findings demonstrated association between smear/Xpert status and symptoms, the symptoms
may be due to comorbidities of TB or increased age.
Conclusions
Our study underscores the heightened susceptibility of elderly individuals with pulmonary tuberculosis aged 75
to 89 to bacterial discharge and contagion, attributable to aging-related factors. A pivotal focus on this demo-
graphic in clinical practice is imperative to curb disease progression and enhance contagion control measures.
Early identification of underweight individuals (BMI < 18.5 kg/m2) proves crucial for promptly recognizing highly
infectious pulmonary tuberculosis patients, facilitating swift isolation measures, interrupting transmission routes,
and initiating early empirical treatment to curtail disease advancement. Clinical factors like cough, expectora-
tion, hemoptysis, and dyspnea emerge as reliable indicators of heightened tuberculosis infectivity. Furthermore,
individuals with compromised physical resistance exhibit a greater propensity for developing extrapulmonary
tuberculosis, encompassing tuberculous meningitis, tuberculous pleurisy, and tuberculous peritonitis. In these
instances, the condition manifests with increased severity, higher bacterial loads, and a proclivity for bacterial
elimination, collectively contributing to elevated infectivity levels.
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Data availability
The datasets generated and/or analyzed during the current study are not publicly available concerning students’
privacy and their own or guardian’s willingness but are available from the corresponding author Lan Shang
(shanglan8282@163.com) on reasonable request.
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Acknowledgements
The authors would like to thank teachers and parents for their support, as well as all of the students who par-
ticipated in the project.
Author contributions
(1) Conception and design:Lan Shang and Weifang Kong (2) Provision of study materials or patients: Yan Gao
and Junzhu Lu, (3) Collection and assembly of data: Junzhu Lu and Shiqing Yu, (4) Data analysis and interpre-
tation: Rongping Zhang, Guojin Zhang and Weifang Kong and Xinyue Chen, (5) Manuscript writing: Shiqing
Yu and Yan Gao, (6) Final approval of manuscript: Lan Shang and Weifang Kong. All authors reviewed the
manuscript.
Funding
The Sichuan Provincial Cadre Health Research Project, Grant No. 2021 − 230. The National Natural ScienceFoun-
dation of China, No.82202147. Sichuan Science and Technology Program, Grant No.2022YFS0075. Liangshan
Science and Technology Bureau, Grant No. 21ZDY0069.
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Competing interests
The authors declare no competing interests.
Additional information
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