Difference between revisions of "Team:Peking/Practices/Background"

In the recent 20 years, tuberculosis (TB) has become a serious infectious disease all over the world. How’s the current epidemic situation of TB like in the world, especially in China? Is this kind of disease curable or fatal? Is early detection very important to the prognosis of TB patients? And how can our project be applied to the diagnosis of pulmonary TB? To find out the answers to all the questions above, we proceeded literature reviews and wrote a comprehensive report on the white plague, generally referred to as the pulmonary tuberculosis.

“Pale complexion, gaunt trunk, and a fit of acute coughing…” There are no lack of descriptions like these in the novels and dramas of the 19th century. What caused these clinical signs in those years was the pulmonary tuberculosis (TB), also called “the white plague”. In the 19th century, there were millions of people died of this fulminating infectious disease. It became curable and preventable since the applying of antibiotics and BCG in the 20th century. Nevertheless, WHO has warned the whole world that the white plague is staging a comeback; we should never get slack at the prevention and control of tuberculosis.

Chest X-ray of a pulmonary TB patient (left) ^[1] and a healthy person (right) ^[2].
(a)Diffusion and random distribution of numerous miliary nodules and fibrous-cavities with thick walls in a pulmonary TB patient. M= miliary pattern. Arrow indicates cavities at the right upper lobe.(b)Normal structures in chest. L= left collarbone.

In 1882, a German scientist named Robert Koch announced his discovery of Mycobacterium tuberculosis. Pulmonary tuberculosis is exactly a kind of chronic wasting disease with high contagiosity, which is caused by the invasion of Mycobacterium tuberculosis into the lungs. As the bacteria grow in the lung tissue, the patients may develop chronic fibro-cavitary pulmonary tuberculosis or miliary tuberculosis. If the former, you can find huge cavities with thick wall in the patients’ lungs (Figure 1a, Figure 2). The latter means that the bacteria have destroyed the lung tissue and result in the diffuse and random distribution of numerous miliary nodules in both lungs (Figure 1a, Figure 2). As for the mode of transmission, over 90% of pulmonary tuberculosis cases are spread from person to person through the air. When people with lung TB cough, sneeze or spit, they propel the TB germs into the air. A person needs to inhale only a few of these germs to become infected.

Figure 2. Cavitating pulmonary TB - gross pathology image [3].
There is prominent scarring and cavitation, predominantly affecting the apical aspect of the right lung(A), along with nodules of calcification at the left upper lobe(B)

The appearance of chemotherapeutic drugs and BCG vaccine can be marked as the milestone in the antituberculous history, which has saved millions of lives. However, this kind of stubborn communicable disease has launched a new round of assault on human beings. According to the report from WHO, there is a trend that TB has become a more and more threatening disease all over the world. In 1995, 3 million people died of TB, much more than the death toll in 1900, making it a horrible year with the largest number of deaths. The ignorance of TB gives rise to the above situation in many areas of the world, leading to the deficiency of TB prevention and control system. Moreover, the probability of developing TB is much higher among people infected with HIV. As the spread of HIV, the number of pulmonary tuberculosis patients is increasing rapidly. Additionally, diverse TB strains of multiple drug resistance make it harder for us to cure it.

Figure 3. Top six countries with the largest number of new TB cases in 2013.

TB now is considered as a severe communicable disease in the world, ranking as the 2nd leading cause of death among various infectious diseases, just after the human immunodeficiency virus (HIV). According to the Global Tuberculosis Report 2014, it was estimated that there were 9 million people infected with Mycobacterium tuberculosis, more than a half in the area of Southeast Asia and Western Pacific. In details, 56% of the new cases occurred in Asia, and 29% in the African region. The six countries that stand out as having the largest number of incident cases in 2013 are India, China, Nigeria, Pakistan, Indonesia and South Africa (Figure 3). India and China alone accounted for 24% and 11% of the global cases respectively [4]. With most TB cases occurring in Asia and Africa, the regional imbalance of TB control is increasingly serious (Figure 4). The lowest rates are found predominantly in high-income countries including most countries in Western Europe, Canada, the United States of America. Poverty in low-income countries indicate that most common people in the society cannot afford the high medical fees of TB diagnosis. This current situation urges the whole world to develop a cheaper detection method for Mycobacterium tuberculosis.

Figure 4. Estimated TB incidence rates in 2013 [4].
The number of incident TB cases relative to the population size (the incidence rate) varies significantly among countries.

On the other hand, though pulmonary TB is curable and the recovery rate is over 85%, there were 1.5 million TB deaths (1.1 million among HIV-negative people and 0.4 million among HIV-positive people) in 2013. Approximately 78% of total TB deaths and 73% of TB deaths among HIV-negative people occurred in the African and South-East Asia in 2013. India and Nigeria accounted for about one-third of global TB deaths. As the spread of HIV and the appearance of strains with multi-drug resistance, the mortality rate is no longer easy to have great decline in recent years, unless new diagnosis and treatment techniques of high efficiency are applied in clinical practice as soon as possible.

Of the 9.0 million incident cases, an estimated 550 000 were children and 3.3 million occurred among women. 510 000 women and 80 000 children died of this disease in 2013 [4]. These figures are indicative of high burden of TB among women and children. On the other hand, TB is more common among men than women, and affects mainly the most economically productive age groups, making the disease not only a killer posing a health risk on human beings, but also a public problem threatening social stability. What’s more, the absolute number of incident cases is falling slowly, at a rate of 0.6% between 2012 and 2013. The current decline rate needs to accelerate to reach the Stop TB Partnership target of a 50% reduction by 2015.

It was measured by WHO that near 1 million new TB cases were Chinese in 2013, accounting for 11% of the total number. In recent years, as the implementation of DOTS (Directly-Observed Treatment Strategy), the epidemic situation of TB has been controlled in China. However, it has been estimated that the amount of patients over 15 with active pulmonary TB is still huge, about 4.99 million. The morbidity is 45.9 per 1 million based on the 5th National Tuberculosis Epidemiological Survey in 2010 [5]. The good news was that the prevalence rate had decreased, but it just has a slower descending tendency in recent years (Figure 5). What’s worse, the absolute number of patients with active pulmonary TB estimated in 2010 had increased due to a great increase in the population size.

Figure 5. The trend of incidence population in China from 2008 to 2012.

As a high burden country, the epidemic situation of tuberculosis in China is severe and complicated, especially with the largest population in the world. The fact that 1/3 of the people are infected with Mycobacterium tuberculosis warns us that near 500 million people in China might be infected. Such an enormous population infected doubtlessly makes it difficult to fight against the disease. In addition, the regional development imbalance is another problem existing in our country. The prevalence in rural area is higher than in cities, while the western part is also significantly higher than the middle and eastern parts. Low educational level, poverty, remoteness and poor medical conditions make more people suffer from TB in the areas with higher morbidity.

To ensure TB patients receive standard treatment, Chinese government requires all levels of medical organizations to transfer patients suspicious of or defined as TB to local tuberculosis dispensaries for proceeding unified examinations, treatments and managements. The government provides free primary examination items and antitubercular agents for infectious pulmonary tuberculosis patients. These items include [6]:

Pulmonary tuberculosis is not a kind of fatal illness any more thanks to the chemotherapeutics such as Rifampicin, Isoniazid and Ethambutol. If the therapeutic regimen for TB, which is a long course of taking medicine without any interruption, is strictly followed, pulmonary TB is curable with a high recovery rate of over 85%. Thus, early detection is core for TB control since the disease has a high recovery rate. Studies have demonstrated that there is a significant difference between the delayed treatment group and the early therapy group both in the severity and prognosis of the disease [7].

Delayed treatment has various degrees of impact on the prognosis of TB patients. Pulmonary tuberculosis cases, accompanied by tuberculous pleuritic, are more common among patients with delayed treatment. The chest radiography has prompted that there is more chance to attain multi-lobar lesions and extra pulmonary tuberculosis for patients with delayed treatment. Mycobacterium tuberculosis in active state will proliferate in patients’ lung tissue to form a nidus before the patients receive any treatment. Congestion, exudation, edema and phagocytosis can be seen in the injured tissues. It will keep on developing hyperplastic nodules in lungs composed of collective lymphocytes, or caseous necrosis with the bacteria and necrotic tissues. Both conditions will stimulate the body to produce fibroblasts, and proceed to the next step of fibrosis, which make the antitubercular agents difficult to infiltrate into the injured tissues. Thus the possibility of failure on chemotherapeutics in short course greatly increases in these cases. On the other hand, if the bacteria in the caseous necrosis multiply rapidly, tissues would often form thick cavities with liquefactive necrosis. Once fibrosis of the cavity wall occurs, the number of blood vessels will greatly decrease, therefore leading to a low concentration of the antitubercular agents in the affected tissues if drugs are administered orally or by intravenous injection.

Figure 6. Tubercular nodule in the lung tissue in the microscopic view.
(A) Caseous necrosis in the center of the tubercle contains a huge number of Mycobacterium tuberculosis.
(B) Mononuclear phagocytes and lymphocytes surrounding the caseous necrosis.

The most serious condition is that a small portion of patients will not be sensitive to antitubercular agents due to delayed treatment, and it may develop chronic fibro-cavitary pulmonary tuberculosis, which may never be cured. Chronic fibro-cavitary pulmonary tuberculosis will destroy normal tissues in lungs. Even if the bacteria are sensitive to the agents, the lung tissue can never return to normal state with a permanent deficiency of the pulmonary functions.

As earlier detection means better prognosis, it is more urgent for the whole world to develop a rapid and convenient diagnostic method with high specificity and sensitivity.