Overview of the disease
This disease is defined as tuberculosis with an active basis and associated symptoms, signs and imaging manifestations of cough, sputum, blood in sputum, hemoptysis, fever, night sweats, lethargy, fatigue, etc. This disease is caused by infection with Mycobacterium tuberculosis and is treated mainly with chemotherapy, supplemented by symptomatic therapy and surgery.
Definition
Active pulmonary tuberculosis (APTB) is a type of tuberculosis that has been confirmed by Mycobacterium tuberculosis pathogenesis, imaging, and pathology to have a basis for activity, and to have clinical symptoms and signs related to tuberculosis.
Active tuberculosis, especially Mycobacterium tuberculosis-positive patients, is highly infectious, so screening for active tuberculosis is the key to tuberculosis prevention and treatment.
Typing
Classification according to the location of the lesion and imaging manifestations
Primary tuberculosis
Including primary syndrome and intrathoracic lymph node tuberculosis.
The main imaging manifestations are primary lesions in the lungs, lymphangitis and enlarged hilar lymph nodes.
Hematologically disseminated tuberculosis
Includes acute, subacute and chronic hematogenous disseminated tuberculosis.
Acute hemorrhagic disseminated tuberculosis can be seen on imaging as evenly distributed, uniformly sized, and densely packed granulomatous nodules in both lungs.
Imaging of subacute and chronic hematogenous disseminated tuberculosis reveals nodules of variable size and density in the upper and middle portions of both lungs.
Secondary tuberculosis
It is the most common type of TB in adults.
Including infiltrative tuberculosis, tuberculosis ball, caseous pneumonia, chronic fibro-cavitary tuberculosis.
Imaging manifestations are varied and may include plaques, nodules, striated shadows, caseous exudates, and cavities.
Tracheobronchial tuberculosis
It is a special clinical type of tuberculosis.
Tracheoscopy shows ulceration, erosion, congestion, thickening, lumen narrowing or obstruction.
Imaging may have irregular thickening of trachea or bronchial wall, lumen narrowing or obstruction and pulmonary atelectasis.
Tuberculous pleurisy
Including dry pleuritis, exudative pleuritis and tuberculous pyothorax.
Dry pleurisy has no significant imaging abnormality or a little pleural thickening.
Exudative pleurisy imaging may show pleural effusion and pleural thickening and adhesions.
Tuberculous pyothorax may have a purulent pneumothorax.
Classification by drug resistance status
Sensitive tuberculosis
In vitro drug susceptibility testing does not reveal resistance to the antituberculosis drugs used.
Drug-resistant tuberculosis
Monoresistant TB: In vitro drug susceptibility testing shows that Mycobacterium tuberculosis is resistant to one of the first-line antituberculosis drugs.
Multidrug-resistant TB: In vitro drug susceptibility testing shows that Mycobacterium tuberculosis is resistant to more than one first-line antituberculosis drug, excluding isoniazid and rifampicin, which are both resistant.
Multidrug-resistant TB: In vitro drug susceptibility testing shows that Mycobacterium tuberculosis is resistant to at least two or more first-line antituberculosis drugs that are resistant to both isoniazid and rifampicin.
Extensively drug-resistant TB: In vitro drug susceptibility testing shows that Mycobacterium tuberculosis is resistant to at least one of the second-line fluoroquinolone antibiotics, and at least one of bedaquiline and linezolid, in addition to resistance to isoniazid and rifampicin, which are both first-line antituberculosis drugs.
Rifampicin-resistant tuberculosis: in vitro drug susceptibility testing shows that Mycobacterium tuberculosis is resistant to rifampicin, whether or not it is resistant to other antituberculosis drugs.
Classification according to treatment history
Primary tuberculosis: one of the following conditions is met.
Those who have never been treated with anti-tuberculosis drugs for tuberculosis.
Those who are on a standard chemotherapy regimen with less than a full course of regular medication.
Those who have been on irregular chemotherapy for less than 1 month.
Resumption of tuberculosis treatment: one of the following conditions.
Those who have been unreasonably or irregularly treated with anti-tuberculosis drugs for ≥ 1 month for tuberculosis.
Those who failed the initial treatment and relapsed.
Incidence
Globally, there will be approximately 9.9 million new cases of TB in 2020, with an incidence rate of 127/100,000 people [6].
The estimated number of new TB patients in China in 2020 is 842,000 (833,000 in 2019), and the estimated TB incidence rate is 59/100,000 (58/100,000 in 2019).
Causes of the disease
Causes of the disease
The disease is primarily caused by infection with Mycobacterium tuberculosis, and there are three basic conditions that lead to epidemics.
Sources of infection
The main infectious source of the disease is the patient with expelled tuberculosis (sputum direct smear positive), especially untreated patients with expelled bacilli.
The degree of infectivity is related to the number and virulence of Mycobacterium tuberculosis in the sputum.
Routes of transmission
The main mode of transmission of the disease is respiratory droplet transmission, while other forms of transmission can also be seen in the digestive tract and skin.
Infectious tuberculosis patients can cough, sneeze, speak, etc. to discharge droplets containing Mycobacterium tuberculosis.
Susceptible people
People are generally susceptible, but whether or not a person becomes ill after being infected with Mycobacterium tuberculosis depends on two things.
The number and virulence of infected Mycobacterium tuberculosis.
The specific and non-specific immunity of the human body to Mycobacterium tuberculosis, and the susceptibility to the disease when immunity is low.
Risk factors
The following factors increase the risk of developing active TB, as listed below.
Close contacts with patients with active TB.
Elderly people, infants and young children, and pregnant women who are close to giving birth.
People with human immunodeficiency virus (HIV) infection, silicosis, chronic diseases, chemotherapy, immunosuppressive drugs, and malnutrition.
People who live in crowded places with poor sanitary conditions.
Residents or travelers in areas where tuberculosis is endemic.
Symptoms
Main Symptoms
Cough and sputum may persist for more than 2 weeks; cough is mild, may be dry or cough a little mucus sputum; in combination with other bacterial infections, may cough up purulent sputum.
Hemoptysis may be present, mostly in small amounts.
Fever may be present, which is the most common symptom, mostly afternoon hot flashes, i.e., the temperature starts to rise in the afternoon and returns to normal in the next morning.
Chest pain may be present when the lesion involves the pleura, and may be aggravated by deep breathing and coughing.
Dyspnea and shortness of breath may occur when the lesion involves several lobes of the lungs or when there is a large amount of pleural effusion.
Other symptoms
Weakness, night sweats, loss of appetite and weight loss may occur.
Women of childbearing age may have symptoms such as irregular menstruation and amenorrhea.
Consultation
Department of Medicine
Department of Infectious Diseases
If tuberculosis is highly suspected on physical examination, or if symptoms such as cough, sputum, hemoptysis, low-grade fever in the afternoon and night sweating appear after contact with a patient with tuberculosis, it is recommended to consult the Department of Infectious Diseases in a timely manner, or consult the Tuberculosis Hospital.
Respiratory medicine
Low-grade fever, cough, sputum, blood in sputum, hemoptysis, etc., can also be consulted in the Department of Respiratory Medicine, and then transferred to the Department of Infectious Diseases or the Tuberculosis Hospital for further treatment after confirmation of the diagnosis.
Emergency Department
For symptoms such as massive hemoptysis, high fever and respiratory distress, immediate medical attention is recommended.
Preparation for medical treatment
Preparing for medical treatment: registration, preparation of documents, and common problems.
Tips for seeking medical treatment
For patients with high fever, physical cooling can be done first, such as applying cold compresses to the forehead and wiping the hands, feet and armpits with lukewarm water.
Wear a mask and avoid going to places where people gather.
Wear clothes that are easy to put on and take off for examination.
Preparation Checklist
Symptom checklist
Pay particular attention to the time of onset of symptoms, special manifestations, etc.
Is there cough, sputum, blood in sputum or hemoptysis?
Is there fever? What is the highest temperature?
Is there any loss of appetite, night sweating, or fatigue?
When did the above symptoms appear?
List of medical history
Is there any history of close contact with TB patients?
Have you ever had tuberculosis in the past?
Have you received BCG vaccination?
Any history of diabetes, pneumoconiosis, AIDS, malnutrition, etc.?
Any application of glucocorticoids, immunosuppressants, etc.?
Checklist
Test results in the last six months, which can be brought to the doctor’s office.
Laboratory tests: blood test, blood sedimentation, tuberculin test, sputum smear, culture of Mycobacterium tuberculosis, etc.
Imaging examination: chest X-ray, chest CT, etc.
Others: bronchoscopy
Medication list
Medications used in the last 3 months, if available in boxes or packages, bring them to the doctor’s office
Antipyretic and analgesic drugs: ibuprofen, acetaminophen, etc.
Anti-tuberculosis drugs: isoniazid, rifampicin, pyrazinamide, ethambutol, streptomycin, etc.
Anti-infective drugs: levofloxacin, moxifloxacin, etc.
Diagnosis
Diagnosis is based on
Medical history
A patient with active tuberculosis may have the following medical history.
Past history of tuberculosis.
History of close contact with sputum positive TB patients.
Clinical manifestations
Symptoms
Coughing, coughing up sputum, blood in sputum, hemoptysis, fever, night sweats, malaise, and loss of appetite may be present.
Physical signs
Physical examination of the lungs by a doctor may reveal increased palpation of the lungs, tremor, turbidity on percussion, and bronchial breath sounds and fine wet rales on auscultation.
Laboratory Tests
Blood tests
The white blood cell count and neutrophil ratio may be elevated in the presence of secondary bacterial infection.
Blood Sedimentation
Blood sedimentation is often elevated in patients with active tuberculosis.
Tuberculin test (PPD test)
Used to determine the presence or absence of Mycobacterium tuberculosis infection, but can be affected by BCG vaccination.
Intradermal injection of 5 IU of a pure protein derivative of Mycobacterium tuberculosis, 48-72 hours to observe the diameter of the hard skin nodule, ≥5 mm is considered positive.
Tuberculin test results tend to be negative or weakly positive in malnutrition, HIV infection, measles, chickenpox, cancer, and severe bacterial infections including severe tuberculosis (e.g., blood-borne tuberculosis and tuberculous meningitis).
Gamma-interferon release test
The gamma-interferon release test is not affected by BCG vaccination or non-tuberculous mycobacteria. A positive result may be latent TB infection or active TB disease.
The T-cell spot test for tuberculosis infection (T-SPOT) test is commonly used in China.
Sputum smear
Antacid staining of sputum smear is a major means of screening for active TB. The direct smear method is affected by the amount of bacilli carried in the sputum and the location of the sampling point, while centrifugal precipitation of bacilli collection smear can increase the positive rate compared with direct smear.
A positive sputum smear only indicates the presence of antacid bacilli in the sputum, but does not distinguish between Mycobacterium tuberculosis and non-Mycobacterium tuberculosis, and is usually tested at least three times.
A negative sputum smear test only indicates that no bacilli have been detected in the patient’s current sputum, but it does not completely rule out the diagnosis of tuberculosis.
Mycobacterium tuberculosis culture
Culturing Mycobacterium tuberculosis is the gold standard for confirming the diagnosis of tuberculosis and is more sensitive than smear.
The culture period is long and usually takes 2 to 8 weeks.
The excretion of bacilli in TB patients is intermittent and uneven, so sputum should be taken at different time periods (e.g. early morning sputum, night sputum and immediate sputum) and sputum should be checked several times.
Mycobacterium tuberculosis nucleic acid test
Molecular biology tests are more sensitive than smear and culture.
Newer molecular biology testing methods, such as gene amplification testing, have advantages in speed and accuracy over traditional PCR.
Imaging
Chest X-ray and chest CT are the main reference indexes for diagnosing active tuberculosis, and chest CT is more sensitive than chest X-ray for diagnosing tuberculosis, and some studies have shown that the sensitivity of chest CT in detecting tuberculosis is 96%, and the sensitivity of chest X-ray is 48% [4].
Chest X-ray
Routine preferred method of diagnosing tuberculosis, active tuberculosis in chest X-ray can be manifested as patchy shadows with blurred edges, nodular shadows, fibrous cord shadows, dissolution of the center of the lesion or the formation of cavities as well as the visible dissemination of the lesion.
Chest CT
It can detect hidden small chest lesions and endobronchial lesions, and can show the characteristics and nature of tuberculosis.
Multi-slice CT chest
Signs of active tuberculosis may include gross glass shadow, patchy shadow, bud sign, nodular shadow in the center of lobules with segmental distribution, thick-walled cavities, etc.
Bronchoscopy
Bronchoscopy can be used to understand the condition of the trachea and bronchi.
Pathologic examination of lesion tissue can be taken through bronchoscopy, and alveolar lavage fluid and lower respiratory secretion can be smeared, cultured and examined by molecular biology.
Differential Diagnosis
Pneumonia
Similarities: both may present with fever, cough and sputum.
Differences:
Pneumonia may have high fever, and flaky or patchy shadows can be seen on imaging. After active anti-infective treatment, the body temperature may return to normal, and the lung shadows may improve or be absorbed.
Active tuberculosis is usually a low-grade fever in the afternoon, and may also have night sweats, and is effectively treated with standardized anti-tuberculosis therapy. It can be differentiated by chest imaging and bacteriology.
Bronchiectasis
Similarities: Both may present with cough, sputum, hemoptysis and other symptoms.
Differences:
Bronchiectasis can have chronic cough, cough up sputum, cough up large amount of purulent sputum, repeated hemoptysis, and bronchiectasis can be seen in high-resolution lung CT.
Active tuberculosis, cough is milder, may have dry cough or cough a little mucus sputum, hemoptysis is less. It can be differentiated by chest imaging, tuberculin test or gamma-interferon release test.
Old tuberculosis
Similarity: Both may present with lung cavities.
Differences:
Patients with old tuberculosis usually have no obvious symptoms, and relatively stable tuberculosis-related imaging changes, such as calcification, fibrosis, pleural thickening or adhesion, etc., can be seen on imaging, and the results of antacid staining of sputum smears and culture are usually negative.
Patients with active tuberculosis may have symptoms such as cough, sputum, fever, night sweats, loss of appetite, etc. Signs of activity can be seen on chest X-ray, such as patchy shadows with blurred edges, lysis or cavities in the center, and disseminated foci, and bacilli can be found by sputum smear antacid staining and culture.
Treatment
Aim of treatment: to control the development of the disease, improve the symptoms of patients, eliminate Mycobacterium tuberculosis, cure the disease, prevent the production of drug-resistant bacteria, and reduce the recurrence of the disease.
Principle of treatment: Chemotherapy centered on “early, regular, whole course, appropriate amount and combination”, combined with symptomatic treatment and surgical treatment.
Chemotherapy
Chemotherapy is the core of active tuberculosis treatment.
TB chemotherapy drugs
Anti-tuberculosis drugs are categorized into two groups according to their effectiveness and adverse effects, i.e. first-line anti-tuberculosis drugs and second-line anti-tuberculosis drugs.
First-line anti-tuberculosis drugs
are effective and have few adverse effects, including the following drugs.
Isoniazid (H): with strong bactericidal effect, it is one of the basic drugs for the treatment of tuberculosis. Adverse reactions include peripheral neuritis, central nervous system toxicity, and elevated ghrelin.
Rifampicin (R): with bactericidal effect, adverse reactions include gastrointestinal discomfort, elevated glutamic transaminase, jaundice.
Pyrazinamide (Z): bactericidal effect, adverse reactions are drug hepatitis, hyperuricemia and so on.
Ethambutol (E): has bacteriostatic effect, adverse reactions are retrobulbar optic neuritis, allergic reactions, etc.
Streptomycin (S): bactericidal effect, adverse reactions are hearing loss, tinnitus, etc..
Second-line antituberculosis drugs
The efficacy or safety is not as good as the first-line antituberculosis drugs, and can be used when the first-line antituberculosis drugs are resistant or have adverse reactions that cannot be tolerated, including the following kinds of drugs.
Group A: fluoroquinolones, including levofloxacin (LFX, L), moxifloxacin (MFX, M), gatifloxacin.
Group B: second-line injectable drugs, including amikacin (Am), kanamycin (Km), colistin (Cm), streptomycin.
Group C: other core second-line drugs, including cycloserine (CS), propylthioisonicotinic acid hydrazide (Pto)/ethylthioisonicotinic acid hydrazide (Eto), linezolid (LZD).
Additional drugs in group D: Divided into 3 subgroups, group D1 includes pyrazinamide, ethambutol, high-dose isoniazid; group D2 includes bedaquiline (BDQ), delamanid (DLM); and group D3 includes para-aminosalicylic acid (PAS), imipenem/cilastatin, meropenem, amoxicillin/clavulanic acid, and aminothiuronium.
Standard chemotherapy regimen
Primary active TB
2HRZE/4HR regimen is often chosen.
Intensive phase is treated with isoniazid, rifampicin, pyrazinamide, and ethambutol once daily for 2 months.
Consolidation phase is treated with isoniazid and rifampicin once daily for 4 months.
Retreatment of active tuberculosis
2HRZSE/6HRE, 3HRZE/6HR, and 2HRZSE/1HRZE/5HRE regimens are often used.
Resuscitated TB should be tested for drug sensitivity, and if treatment with the above regimens is ineffective, drug-resistant TB should be treated as such.
Treatment of drug-resistant TB
The intensive phase of drug-resistant TB treatment should include at least five effective antituberculosis drugs, including short-course regimens and long-course regimens.
The total duration of treatment for short-course regimen is 9-12 months, and the total duration of treatment for long-course regimen is 18-24 months, but the specific medication and duration of treatment need to be clarified under the guidance of doctors.
Sputum culture should be used to monitor the effect of treatment.
Symptomatic treatment
Fever
For patients with fever, antipyretic and analgesic drugs such as ibuprofen can be given.
Glucocorticosteroids can be given to improve symptoms in patients with persistent high fever.
Hemoptysis
For small amount of hemoptysis, bed rest can be given, and drugs such as thrombin and aminocaproic acid can be used to stop bleeding.
When a large amount of hemoptysis, it is necessary to avoid asphyxia, open the airway, and can be given posterior pituitary hormone treatment.
If hemoptysis medication is ineffective, emergency surgery or bronchial artery embolization can be given.
Surgery
Surgery is an option for patients with unilateral tuberculosis who have failed drug therapy or who have a life-threatening condition.
Prognosis
Cure
With timely and standardized treatment, most active tuberculosis can be cured, while a few may die due to the progression of the disease.
There is a possibility of recurrence and regular review is required as prescribed by the doctor.
Hazards
Patients with active TB may die due to disease progression or complications such as hemoptysis, spontaneous pneumothorax, pulmonary heart disease, or extrapulmonary tuberculosis.
Patients with active TB are prone to develop drug-resistant TB if they are not treated in a standardized manner, and once drug-resistant, the cure rate will be reduced.
It is contagious and may be transmitted to others.
Daily
Daily Management
Dietary management
Take in more high quality protein as appropriate to improve the immunity of the body, such as milk, white meat, seafood and soy products.
Consume more fresh vegetables and fruits as appropriate, such as spinach, cabbage, pumpkin, colored peppers, carrots, yellow peaches, tomatoes, grapefruit and watermelon.
Avoid or eat less fried food such as doughnuts and potato sticks and indigestible food such as rice cakes and dumplings.
Life management
Cover your mouth and nose with your upper arm or tissue paper when coughing or sneezing.
For home treatment, try to live in separate rooms with others, keep the room ventilated and wear a mask to avoid family members being infected.
Do not spit on the floor. Spit sputum into a covered spittoon with disinfectant solution or disinfected wet tissue or sealed sputum bag.
Keep a regular schedule, do not stay up late and stay in a good mood.
Disease monitoring
If symptoms such as coughing, sputum, fever and night sweats worsen, the patient needs to consult a doctor promptly.
If the patient applies the anti-tuberculosis drugs to have adverse reactions, such as peripheral neuritis, liver function damage, central nervous system poisoning, drug rash, etc., need to consult the doctor in time.
Prevention
Stay away from infectious sources
Avoid contact with TB patients and wear a mask when going to crowded places.
BCG Vaccination
For children, an effective measure to prevent tuberculosis is BCG vaccination, but the preventive effect on adults is not very effective. The BCG vaccine is effective in preventing tuberculous meningitis and granulomatous tuberculosis, which often occur in children.
After BCG vaccination of newborns, care must still be taken to isolate them from patients with tuberculosis.
Preventive Chemotherapy
Applicable people
Mainly used for high-risk groups of tuberculosis, including HIV-infected patients, close contacts of smear-positive tuberculosis patients, untreated pulmonary sclerosing fibrotic foci (inactive), silicosis, diabetes mellitus, long-term use of glucocorticoids or immunosuppressants, drug addicts, malnourished, children and adolescents with tuberculin test sclerosis ≥ 15 mm in diameter.
Usage
Commonly used isoniazid, once daily for 6 to 9 months, children according to body weight; or rifampicin and isoniazid, once daily for 3 months; or rifapentine and isoniazid, 3 times a week for 3 months.