Although this disease is not a tumor, it is closely related to cancer.

The 2021 Global Tuberculosis Report released by WHO shows that in 2020, there were 9.87 million new cases of tuberculosis worldwide, with an incidence rate of 127/100,000. In China, there were approximately 842,000 new tuberculosis patients in 2020, with an incidence rate of 59/100,000. The number of cases in my country ranked second among the 30 countries with a high burden of tuberculosis, accounting for about 8.5%, second only to India (2.59 million). Tuberculosis remains one of the main causes affecting people's health.

March 24th of every year is World Tuberculosis Day. Tuberculosis, also known as "consumption", is associated with the story of the blood-soaked steamed bun written by Mr. Lu Xun and the frail Lin Daiyu in "Dream of Red Mansions". On March 24, 1882, German microbiologist Robert Koch discovered the tuberculosis pathogen, and March 24 was designated as World Tuberculosis Day. People also began to have a deeper understanding of tuberculosis. Tuberculosis is a chronic infectious disease caused by Mycobacterium tuberculosis that can seriously affect human health. It can be traced back to ancient times. More than 80% of tuberculosis occurs in the lungs, and it can also invade other organs of the human body except nails, hair, and teeth. Pulmonary tuberculosis can be transmitted to healthy people through droplets when patients cough, sneeze or spit.

How do I know if I have tuberculosis?

If you experience cough (or accompanied by sputum or blood), hemoptysis, chest pain, low-grade fever in the afternoon (37.5-38°C), night sweats (sweating during sleep), fatigue, weight loss, etc., and the symptoms persist for more than two weeks, you need to pay attention and go to a local hospital for a systematic examination as soon as possible.

When you go to the hospital, you will usually undergo chest X-ray or CT scans, sputum smears, sputum cultures, etc. Sputum culture is the gold standard for diagnosing tuberculosis, and the culture process takes about 2-8 weeks. WHO recommends the use of rapid molecular diagnostic techniques, such as Xpert MTB/RIF and Xpert MTB/RIF Ultra.

However, nearly 1/3 of tuberculosis patients in the world are still not diagnosed or reported. In difficult-to-diagnose tuberculosis (young children, HIV carriers and extrapulmonary tuberculosis), underdiagnosis or underreporting is particularly prominent. The reasons for this include the low amount of bacteria in sputum, the difficulty in specimen collection, and the low positive detection rate of etiology. The difficulty in diagnosis has also made people realize that more effective non-sputum tuberculosis diagnostic methods are needed for these populations.

This test can quickly diagnose tuberculosis within two hours

Recently, Professor Tony Hu's team developed an ultra-sensitive CRISPR/Cas12a fluorescence detection system (CRISPR-TB) to sensitively diagnose TB by detecting Mtb-cfDNA (Mycobacterium tuberculosis-pathogen free DNA) in blood samples. The results were published in The Lancet.

The study tested blood samples from non-HIV-infected children and adults (Eswatini cohort) and longitudinal samples of HIV-coinfected children in severe immunosuppression (PUSH cohort), showing that CRISPR-TB-mediated ultrasensitive blood Mtb-cfDNA detection is expected to improve the diagnosis rate of childhood tuberculosis and HIV-associated tuberculosis, and has the potential to diagnose tuberculosis early, assess tuberculosis progression, and rapidly monitor tuberculosis treatment.

This study shows that CRISPR-TB is expected to help clinicians quickly and accurately identify tuberculosis, including difficult-to-diagnose tuberculosis, and provide results within two hours. In addition, the technology also has the potential to predict the progression of tuberculosis and monitor treatment.

CRISPR-TB diagnoses tuberculosis by analyzing blood Mtb-cfDNA (Image source: Lancet Microbe)

Although tuberculosis is not a tumor, it is closely related to cancer. Tuberculosis has always been considered a "contagious cancer", which is just to illustrate its terribleness. Tuberculosis itself is not cancer, but just an infectious disease. But in fact, tuberculosis and cancer do have a close relationship.

Studies have shown that tuberculosis is an independent risk factor for cancer, and past tuberculosis may increase the risk of lung cancer and some extrapulmonary cancers, including hematological malignancies, esophageal cancer, head and neck cancer, breast cancer, genitourinary cancer, etc. In particular, the risk of cancer is greatest in the first two years after tuberculosis is diagnosed, and remains high for a long time.

Some cohort studies have shown that the incidence of cancer in tuberculosis patients ranges from 7.2% to 11.6%, and in highly endemic areas of China, approximately 5% of cancer patients have a history of tuberculosis.

The coexistence of tuberculosis and lung cancer requires more attention

At present, the incidence and mortality of lung cancer in China are increasing year by year, ranking first among malignant tumors. Generally, it is already in the advanced stage when seeking medical treatment. In clinic, many patients are found to have lung cancer during the treatment of tuberculosis every year, and some patients are diagnosed with tuberculosis after being diagnosed with lung cancer. This is because tuberculosis and lung cancer have similar clinical manifestations and imaging, so they are easy to misdiagnose and miss the diagnosis, thus delaying treatment.
There are three possible explanations for the coexistence of pulmonary tuberculosis and lung cancer: tuberculosis increases the risk of lung cancer, lung cancer leads to reactivation of tuberculosis, or the two diseases coexist fortuitously.

1. Tuberculosis increases the risk of cancer: This may be due to the chronic inflammatory state caused by tuberculosis, which impairs T cell-mediated immunity and promotes the development of cancer. Studies have found that patients with pulmonary tuberculosis are 10.9 times more likely to develop lung cancer than healthy people.

2. Lung cancer causes tuberculosis reactivation: Since most cancer patients are elderly, their immune function is relatively low, and surgery, radiotherapy, chemotherapy, and drug use can also damage the body's immunity, so the possibility of pulmonary tuberculosis is greatly increased. Invasive lung cancer can also cause tuberculosis recurrence when it invades adjacent old tuberculosis lesions.

3. Accidental coexistence: In areas where tuberculosis and lung cancer are both prevalent, their coexistence may also be coincidental.

4. In clinical practice, doctors should be alert to the relationship between cancer and tuberculosis, and promptly and accurately determine whether tuberculosis and lung cancer coexist. This plays a very important role in choosing treatment plans, reducing economic burden and improving prognosis.

How to detect tuberculosis and lung cancer early?

The clinical diagnosis of combined pulmonary tuberculosis and lung cancer depends on infection symptoms, typical imaging manifestations and pathogen examination. It is very difficult to distinguish when the two coexist, which is a challenge for clinicians. We have mentioned the symptoms and diagnostic methods of pulmonary tuberculosis above, so we will not go into details here.

As for lung cancer, if there are symptoms such as persistent cough, shortness of breath, blood in sputum or hemoptysis, chest pain, sudden weight loss, and some manifestations of extrapulmonary metastasis, especially for elderly patients who smoke for a long time, more attention should be paid and go to the hospital for examination as soon as possible to achieve early detection, early diagnosis, and early treatment. Patients with chronic pulmonary tuberculosis should have regular checkups every year to be alert to the occurrence of lung cancer. In addition, patients who do not respond well to anti-tuberculosis treatment should be highly suspected of having lung cancer.

What should I do if I have tuberculosis and lung cancer at the same time? How should I treat them?

The treatment of pulmonary tuberculosis and lung cancer should be individualized, with the main goal of saving lives. If it is inactive tuberculosis, lung cancer should be treated as the main goal, but pulmonary tuberculosis should be monitored at the same time, because immunosuppression caused by surgery and chemotherapy may lead to the reactivation of Mycobacterium tuberculosis. If it is active tuberculosis, anti-tuberculosis treatment is generally carried out first, so as to facilitate the subsequent treatment of lung cancer. Anti-tuberculosis treatment does not affect the effect of chemotherapy, nor does it increase the adverse reactions of chemotherapy.

Patients with lung cancer and active tuberculosis who have surgical indications can choose surgical treatment after the sputum smear is negative. Perioperative anti-tuberculosis treatment will not increase additional postoperative risks. Doctors should decide on the use of personalized treatment plans based on the patient's body tolerance and drug interactions, and persuade patients to quit smoking to improve their quality of life and relieve their pain.

How to prevent tuberculosis?

Tuberculosis is indeed terrible, but with the development of modern medicine, it is completely preventable and curable. So how can we prevent tuberculosis? Measures include:

1. Vaccinate newborns with BCG vaccine.

2. Open windows frequently for ventilation and try to reduce activities in public places.

3. Maintain personal hygiene, wash hands frequently, do not share personal items, change clothes frequently, and disinfect regularly. Cover your mouth and nose when coughing or sneezing, and do not spit anywhere.

4. Exercise actively, eat a balanced diet, maintain a good lifestyle, and be in a good mood.

Once unfortunately infected with Mycobacterium tuberculosis, most tuberculosis patients can be cured as long as they receive standardized antibiotic treatment in an "early, combined, appropriate, regular and full-time" manner.

About the Author:

Deputy Director of the Laboratory Department of the Affiliated Cancer Hospital of University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Doctor of Medicine from Germany, Postdoctoral Fellow in Nanomedicine from the United States, Academic Supervisor of Clinical Laboratory Diagnostics, engaged in clinical, teaching and scientific research work in laboratory medicine. His main research direction is the development and application of new disease biomarkers and in vitro diagnostic technologies.

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