Tuberculosis (TB)

Table 10.6 gives the main features of this disease. TB

is caused by either of two bacteria, Mycobacterium

tuberculosis (Figure 10.12) and Mycobacterium bovis.

These are pathogens that live inside human cells,

particularly in the lungs. This is the first site of infection,

but the bacteria can spread throughout the whole body

and even infect bone tissue.

Some people become infected and develop TB quite

quickly, while in others the bacteria remain inactive for

many years. It is estimated that about 30% of the world’s

population is infected with TB without showing any

symptoms of the infection; people with this inactive,

or latent, infection do not spread the disease to others.

However, the bacteria can later become active, and this is

most likely to happen when people are weakened by other

diseases, suffer from malnutrition, smoke, have diabetes,

consume large quantities of alcohol or become infected with HIV. Those who have the active form of TB
often

suffer from debilitating illness for a long time. They have a

persistent cough and, as part of their defense, cells release

hormone-like compounds, which cause fever and suppress

the appetite. As a result, people with TB lose weight and

often look emaciated (Figure 10.13). TB is often the first opportunistic infection to strike

HIV+ people. HIV infection may reactivate dormant

infections of M. tuberculosis which may have been

present from childhood or, if people are uninfected,

make them susceptible to infection. TB is the leading

causes of death among people living with HIV. The

TB pandemic. Transmission of TB

TB is spread when infected people with the active form

of the illness cough or sneeze and the bacteria are carried

in the air in tiny droplets of liquid. The transmission

cycle is complete when people who are uninfected inhale

the droplets. TB spreads most rapidly among people

living in overcrowded conditions. People who sleep

close together in large numbers are particularly at risk.

The disease primarily attacks the homeless and people

who live in poor, substandard housing; those with

low immunity, because of malnutrition or being HIVpositive, are also particularly vulnerable.

The form of TB caused by M. bovis also occurs in

cattle and is spread to humans in meat and milk. It

is estimated that there were about 800 000 deaths in

the UK between 1850 and 1950 as a result of TB

transmitted from cattle. Very few now acquire TB in

this way in developed countries for reasons explained

later, although meat and milk still remain a source of

infection in some developing countries.

The incidence of TB in the UK decreased steeply well

before the introduction of a vaccine in the 1950s, because

of improvements in housing conditions and diet. The

antibiotic streptomycin was introduced in the 1940s, and

this hastened the decrease in the incidence of TB. This

pattern was repeated throughout the developed world.

Once thought to be practically eradicated, TB is increasing.

There are high rates of incidence all across the developing

world and in Russia and surrounding countries. High rates

countries where TB is more common. Parts of London,

for example, have rates of TB much higher than the rest of the UK. The incidence in such areas is as high
as in less

economically developed countries. This increase is due in

part to the following factors:

• some strains of TB bacteria are resistant to drugs

• the HIV/AIDS pandemic

• poor housing in inner cities and homelessness

• the breakdown of TB control programmes; partial

treatment for TB increases the chance of drug

resistance in Mycobacterium.

Treating TB

When a doctor first sees a person with the likely

symptoms of TB, samples of the sputum (mucus and

pus) from their lungs are collected for analysis. The

identification of the TB bacteria can be done very

quickly by microscopy. If TB is confirmed, then patients should be isolated while they are in the most
infectious

stage (which is at two to four weeks). This is particularly

if they are infected with a drug-resistant strain of the

bacterium. The treatment involves using several drugs to

ensure that all the bacteria are killed. If not killed, drug resistant forms remain to continue the infection.
The

treatment is a long one (six to nine months, or longer),

because it takes a long time to kill the bacteria, which

are slow growing and are not very sensitive to the drugs

used. Unfortunately, many people do not complete their

course of drugs, because they think that they are cured

when they feel better. People who do not complete their

may spread these to others if the bacteria become active.

The WHO promotes a scheme to ensure that patients

complete their course of drugs. DOTS (direct

observation treatment, short course) involves health

workers or responsible family members making sure

that patients take their medicine regularly for six to

eight months (Figure 10.14). The drugs widely used are

isoniazid and rifampicin, often in combination with

others. This drug therapy cures 95% of all patients, and

is twice as effective as other strategies.

Figure 10.14: The WHO DOTS scheme in action: TB

patients take their drugs under supervision in a hospital

clinic in Tomsk, Russia. DOTS is helping to reduce the

spread of MDR strains of TB.

Drug-resistant TB

Strains of drug-resistant M. tuberculosis were identified

when treatment with antibiotics began in the 1950s.

Antibiotics act as selective agents, killing drug-sensitive

strains and leaving resistant ones behind (Chapter 17,

Section 17.2, Natural selection). Drug resistance occurs

as a result of mutation in the bacterial DNA. Mutationis a random event and occurs with a frequency of
about

one in every thousand bacteria. If three drugs are used

in treatment, then the chance of resistance arising to

all three of them by mutation is reduced to one in a

thousand million. If four drugs are used, the chance is

reduced to one in a billion.

If TB is not treated, or the person stops the treatment

bacteria spread throughout the body, increasing the

likelihood that mutations will arise, as the bacteria

survive for a long time and multiply. Stopping treatment

early can mean that M. tuberculosis develops resistance

to all the drugs being used. People who do not complete

a course of treatment are highly likely to infect others

with drug-resistant forms of TB. It is estimated that one

person may transmit the disease to 10 to 15 other people,

especially if the person lives in overcrowded conditions.

Multiple-drug-resistant forms of TB (MDR-TB)

now exist. MDR-TB strains of TB are resistant to at

least the two main drugs used to treat TB – isoniazid

and rifampicin – which are known as first-line drugs.

Extensively (or extremely) drug-resistant TB (XDRTB) has also emerged as a very serious threat to health,

especially for those people who are HIV+. XDR-TB

strains are resistant to first-line drugs and to the drugs

used to treat MDR-TB. These resistant strains of TB do

not respond to the standard six-month treatment with

first-line anti-TB drugs and can take two years or more

to treat with drugs that are less potent and much more

expensive. Treatment for MDR-TB takes longer, uses

more toxic drugs and is more expensive. A new drug

called bedaquiline is now available to treat MDR-TB.

Drug-resistant TB continues to be a public health crisis.

The best estimate is that, worldwide in 2017, 558 000

people developed TB that was resistant to rifampicin,

the most effective drug, and of these, 82% had MDRTB. Among cases of MDR-TB in 2017, 8.5% were

estimated to have XDR-TB.

TB is a global problem. Worldwide, TB is one of the

top ten causes of death, yet the majority of people who

fall ill with TB live in one of eight countries. Of those

that fell ill with MDR-TB, almost half lived in just three

countries. Contact tracing and the subsequent testing

of contacts for the bacterium are essential parts of

controlling TB. Contacts are screened for symptoms of

TB infection, but the diagnosis can take up to two weeks. The only vaccine currently available for TB is
the BCG

vaccine, which is derived from M. bovis and protects up

to 70–80% of people who receive it. The effectiveness of

the vaccine decreases with age unless there is exposure

to TB. Many countries with high numbers of people

with TB use the BCG vaccine to protect children from

getting the disease. Countries such as the UK and USA

do not include BCG vaccination in their immunisation

programmes. Instead, it may be given only to people

who are at high risk of becoming infected because, for

example, they live with an adult who is being treated

for the disease. There are no vaccines that can be

administered to protect adults. In 2019, there were 12

vaccines for TB being trialled.

TB can be transmitted between cattle and humans.

To prevent people catching TB in this way, cattle are

routinely tested for TB and any found to be infected

are destroyed. TB bacteria are killed when milk is

pasteurised. These control methods are very effective

and have reduced the incidence of human TB caused by

countries where these controls operate.