Introduction

Japan used to be a high-burden pulmonary tuberculosis country. Tuberculosis had once been feared as a deadly disease with the highest mortality rate in the country in 1950, 146.4 deaths per 100,000 inhabitants. After more than 60 years later, in 2013, this mortality rate fell to 1.7, or 26th in the mortality rankings. The discovery and development of antituberculosis drugs and the establishment of standardized treatment played key roles in this decrease.

Nevertheless, group infections of tuberculosis still break out in schools or hospitals from time to time and grab the headlines.

The origins of tuberculosis

Analysis of the full-genome sequence of the tuberculosis bacteria shows that its ancestors go back about 2.5 million years, but the first appearance of a bacteria adapted to the inside of the human body is thought to have been around 35,000 years ago, making it a relative newcomer among the numerous other kinds of bacteria. The oldest tuberculosis currently confirmed on a genetic level is in a human bone about 9,000 years old, at which time there were probably only sporadic intrafamilial infections, but then the Mesopotamian civilization appeared and population density rose as cities began to take shape, which probably led to a sharp increase in infection. Urban civilization also developed somewhat later in Egypt, where reports estimate that tuberculosis reached epidemic proportions. The prevalence of tuberculosis is thought to be closely related to population growth, and it is assumed to have spread worldwide partly because of increased infectiousness due to variations in the tuberculosis bacteria accompanying the dramatic rise in the populations of Europe and East Asia over the last thousand years.

Pulmonary tuberculosis in Japan

Looking at the changes in numbers of tuberculosis cases, we can see a continuing significant decrease after World War II until around 1980, so much so that tuberculosis was no longer considered prevalent. But then the rate of decrease slowed down, and in around 1996 the prevalence rate began to rise and kept rising for another three years. In 1997, about 42,000 new patients were diagnosed with tuberculosis, around 2,700 of whom died of the disease. The number of new cases had increased for the first time in 38 years and the prevalence rate for the first time in 43 years, which the Ministry of Health and Welfare (as it was called then) took very seriously, declaring a state of tuberculosis emergency in 1999 and bringing in national measures for the renewed recognition of the disease. The results have shown another decreasing trend in the prevalence rate that continues to this day.

Japan, a medium-burden tuberculosis country

In spite of this decreasing trend in the prevalence rate of tuberculosis, the prevalence rate of newly registered patients per 100,000 inhabitants in 2013 was 16.1, the number of people newly afflicted with the disease, that is to say, the number of newly registered tuberculosis patients, having exceeded 20,000. By comparison, the rate is 3.1 in the USA, 4.7 in Canada, 5.5 in the Netherlands, and 5.9 in Sweden (all figures for 2012), positioning Japan still as a medium-burden tuberculosis country. Meanwhile, other East Asian and African countries are still high-burden, with rates of 89 in South Korea, 65 in China, 224 in the Philippines, 89 in Thailand, 307 in Botswana, 289 in Zambia, and 120 in Tanzania.

Worldwide, according to 2012 WHO statistics, tuberculosis is still a major infectious disease to this day, with 8.6 million new cases and 1.3 million deaths annually. This is thought to be related to AIDS-linked tuberculosis and multi-drug resistant tuberculosis.

Age distribution of tuberculosis patients

In Japan, more than 70 percent of newly registered tuberculosis patients are aged 60 or more, with patients aged 70 or more accounting for 57.4 percent. Notably, tuberculosis patients aged 80 or more account for over a third of all tuberculosis cases. In the majority of these elderly cases, tuberculosis develops when bacteria that were transmitted during youth and lay dormant within the body for decades are reactivated due to the immune system being suppressed by diabetes or cancer, treatment with immunosuppressive drugs, or old age. At present, the proportion of sufferers who are elderly is expected to increase further, although this rise will not necessarily continue because of the significant decrease in the prevalence rate of tuberculosis following post-war improvements in living conditions and advances in medical treatment.

Meanwhile, the younger generation is characterized by a high rate of newly registered tuberculosis patients who were born overseas. According to 2013 statistics, foreign-born tuberculosis patients made up 5.2 percent of the total number of patients, but 41.3 percent of patients in their 20s. This figure was 25.1 percent in 2009, indicating a sharp rise in the last few years. Caution is required as globalization advances into various areas of our modern society.

Infection and onset of pulmonary tuberculosis

Tuberculosis bacteria passing out of an infected person’s body by coughing is called germ discharge. The possibility of infection arises when tuberculosis bacteria inside the body of an already infected person are dispersed into the air by coughing and then inhaled by someone else. In most cases, however, infection does not occur because the tuberculosis bacteria are trapped by the mucus membrane of the nose or throat and expelled before they can multiply. If the quantity or frequency of inhalation is high, some bacteria can avoid the mucus membrane and reach the alveoli deep inside the lungs, which is the state that constitutes an infection. But even the occurrence of such an infection does not necessarily lead to a tuberculosis attack. Tuberculosis bacteria can be contained within the alveoli and remain dormant, if the immune system does its job, and 90 percent of infected people live the rest of their lives without showing symptoms. In 6 or 7 percent of infected people, the tuberculosis bacteria overcome the body’s immune system in a few months to two years and a tuberculosis attack occurs. The remaining 3 or 4 percent of infected people are the type who will get ill when they are old, as mentioned above.

Diagnosis and treatment of pulmonary tuberculosis

Someone who experiences continuous coughing, phlegm and fever for two weeks or more will visit a medical institution and if necessary be given a chest X-ray examination or chest CT scan to check for lesions. If a microscopic examination reveals tuberculosis bacteria in the sputum, it means tuberculosis bacteria are being discharged so there is a risk of spreading the infection to surrounding people. A definitive diagnosis is also made using the PCR method of amplifying and detecting the nucleic acids in the tuberculosis bacteria.

It also helps diagnosis if there has been an immune response to the tuberculosis bacteria. Previously this was done by tuberculin reactivity, but more recently developed interferon gamma release assays (QFT or T-SPOT) have become popular because they enable testing from a blood sample. They utilize the fact that immunocytes specific to tuberculosis bacteria appear in the blood of people with tuberculosis disease and produce interferon gamma. These tests are also used when there is a risk of group infection, in order to screen people who have come into contact with a patient already found to have tuberculosis disease.

A patient discharging tuberculosis bacteria needs immediate hospital treatment, but this can be changed to outpatient treatment once the discharge has become unnoticeable and the patient is in good overall shape. A six-month course of medication is required using a number of antituberculosis drugs simultaneously in consideration of the existence, and prevention, of drug-tolerant tuberculosis bacteria.

Preventing infection and onset

Tuberculosis infection occurs by the airborne transmission of droplet nuclei from person to person. As a consequence, group infections can occur when people share the same air for a long time in a confined space. Forty percent of group infections occur in workplaces such as offices or factories, 30 percent in hospitals and other medical institutions, and 10 percent in ordinary schools or cram schools. Cases have been reported of teachers developing tuberculosis disease and causing group infections among pupils, and hospital staff developing and spreading it among their patients. Keeping oneself in good shape on a routine basis, seeing a doctor if one has a lingering cough, and having regular annual medical checkups are vital for the prevention of infection and onset of tuberculosis.

References

Ministry of Health. Labour and Welfare. “Annual Report on Survey of Registered Tuberculosis Incidents in 2013.”
The Tuberculosis Surveillance Center, Research Institute of Tuberculosis. “Report on Tuberculosis Preliminary Report [2013 Nen Kekkaku Nenpo Sokuho].” July 2014.
Iwai et al. “The Archaeology of the Tuberculosis Bacterium and Tuberculosis” [Kekkakukin to Kekkakusho no Kokogaku]. Kekkaku. 85(5) (2010): 465-475.