Investigate recent evidence regarding the rise in multi drug resistant TB in the UK and outline the methods of detection and prevention that the UK should follow to stop this rise.Tuberculosis (TB) is one of the top three diseases that has the most death rates worldwide. Although TB was almost wiped out in the UK by 1970, it is starting to spread again because of foreigners who come to the UK from areas with high TB rates and also due to the increased number of people travelling abroad. Although the number of cases reported in the UK reduced from 8276 in 2011 to 6520 in 2014, it is still quite high (Public Health England, 2015), which is becoming a major concern and has to be dealt with as soon as possible because it is becoming extremely difficult to treat TB. This is due to the bacteria becoming resistant to the most effective drugs, such as isoniazid and rifampin (Nachega and Chaisson, 2003).Symptoms of TB itself are not very extreme and it is easy to cure if the right treatment is given on time and at the earliest stages. TB usually affects the lungs but can spread to other parts of the body, such as the glands and bones if not treated quickly. It is a disease caused by the bacteria called mycobacterium tuberculosis, which is spread through air droplets when the infected person coughs, sneezes or talks and others inhale these droplets. Some of the most common symptoms of TB include, coughing, swelling, fever, tiredness and fatigue (British Lung Foundation, 2016). Having experienced any of these symptoms, it is essential for patients to be diagnosed as soon as possible in order to receive the right treatment. There are a plethora of methods for diagnosing patients with TB including: chest X-rays, urine and blood tests, computerised tomography (CT) scan, Magnetic resonance imaging (MRI) scan, Ultrasound or mantoux test (skin test). Once the diagnosis is complete, the doctor should prescribe the right treatment. Multiple antibiotics are used, usually for 6 months, because some forms of TB have evolved to become resistant to certain antibiotics, making it hard to treat the resistant TB (NHS, 2016).Those who fail to take their TB medication as advised by their doctor or do not complete their full course of treatment are at a greater risk of developing resistance to TB drugs (British Lung Foundation, 2016) . People who are diagnosed with TB for the second time are also at a risk of having bacteria that is resistant to the drugs used to cure TB. There are two types of drug resistant TB that can be developed: Multi drug resistant TB (MDR TB) and extensively drug resistant TB (XDR TB). MDR TB is when the bacteria of a TB patient is unable to respond to the first line of treatment, isoniazid and rifampin, because they are resistant to those drugs. Therefore, a second line of treatment must be used to treat the patient. On the other hand, XDR TB is a type of MDR TB that is even harder to cure because patients infected with it are not only resistant to isoniazid and rifampin but also some of the second line of drugs, which means that the last option of drugs are ineffective (Zager and McNerney, 2008). In spite of the fact that only 9.7%, of approximately 480,000 patients diagnosed with MDR TB in 2014 worldwide, had XDR TB (World Health Organisation, 2015), it is a serious concern for people infected with the human immunodeficiency virus (HIV) or weak immune systems. This makes it even harder to treat, increasing their chances of death.Whilst it can be hard to treat MDR and XDR TB, there are enough drugs available which can be used. The most common cure for isoniazid resistance is to use the standard 4-drug treatment for two months and then isoniazid and rifampin for 4 months. Alternatively, rifampin, pyrazinamide, and ethambutol can be taken for 6–9 months. Unfortunately, those who are also resistant to rifampin can have MDR TB, so only the second line of drugs, such as fluoroquinolones, ethionamide, the aminoglycosides kanamycin and amikacin, can be effective. This means that it is even more complicated to treat XDR TB as patients are unable to respond to some of the second line of drugs too (Nachega and Chaisson, 2003) . On top of that, it can be impossible to cure HIV patients with drug resistant TB as they have weak immune systems and so new drugs have to be invented. HIV affects the way TB patients are treated, therefore a Universal HIV test is offered to individuals at TB clinics in the UK. One in four people infected with HIV in the UK are unaware about their infection, so it is important for them to get this Universal HIV test done as soon as possible (Public Health England, 2013). An early diagnosis would lead to a better treatment for both HIV and TB, and if patients refuse to the HIV test then their condition could worsen, which could eventually lead to death. Consequently, it would be better to prevent the spread of TB and protect individuals from contracting TB by using a BCG vaccine (British Lung Foundation, 2016) . However, the risk of being infected with TB is less in the UK compared to other countries, so a BCG is only recommended for people who are at a higher risk of developing it. This includes health care workers, children living in areas with high TB rates and people from countries where the TB rates are high. In the past enough people were injected with a BCG in the UK causing a herd effect. This meant that the majority of the population was immune to TB so it was harder to spread it onto others who are at risk, hence the need for the BCG decreased drastically (NHS, 2016). However, the 4700 affected people out of the total 6520 cases reported in England in 2014 were those not born in the UK (Public Health England, 2015). This suggests that TB is quickly spreading because of immigration, which is why it is important to vaccinate those who are more at risk of contracting TB, so that it can be controlled in the UK again. This rise due to immigration is further controlled by the pre-entry TB screening that is required for individuals coming to the UK from areas of high TB rates. In fact, 233,251 applicants for UK visas were screened in 2014 alone (Public Health England, 2014).Preventing TB is easier than preventing the rise in drug resistant TB, which occurs due to random mutations in the chromosomes of mycobacterium tuberculosis. Resistance to isoniazid occurs due to mutations in multiple genes such as katG, ahpC, inhA, kasA and ndh. However, deletions in KatG contributes to 40-50% of the resistance because it codes for catalase peroxide, which activates isoniazid in the cell. This means that katG is unable to code for catalase peroxide thus isoniazid remains inactive in the cell and is unable to function. In contrast to this, resistance to rifampin develops because of the mutations in the 81—base pair region of the rpoB gene, which is a gene that codes for the B-subunit of RNA polymerase. This means that rifampin is no longer able to target this region, therefore it is no longer effective (Nachega and Chaisson, 2003). Although the chances of drug resistance increase because of many careless reasons – for example when a patient does not take all the medications; the doctor prescribes the wrong drugs/dosage, or when there are not enough good quality drugs available in a country – mutations are random and out of our control, therefore it is better to prevent TB from spreading (NHS, 2016). This is because bacteria multiplies very fast, which means the rate of these mutations and hence the resistance to these drugs is very high.Although multi drug resistant TB is uncommon in the UK at the moment, it is easier to pass this resistance on meaning it can rise in the future, making it difficult to treat. One way that bacteria becomes resistant is due to random mutations so when the bacteria is exposed to these drugs, the susceptible bacteria will die and the resistant bacteria will survive. Therefore, only the resistant bacteria will be able to reproduce and pass on their advantageous alleles on to the next generation. As a result, the new generation of bacteria will be completely resistant to the drugs, so the antibiotic will no longer work and a different treatment may be required (Lowrie, 2015, ch.11). Another way that bacteria can become resistant is through the process of conjugation, which is also called the horizontal gene transmission. This is when the alleles for antibiotic resistance is passed from one bacterial cell to another. Finally, a virus can spread antibiotic resistance by attacking bacteria as it carries it from one bacterium and injects it into another (APUA, 2014). Due to these multiple ways that resistance can pass on so easily to others, it is very important to diagnose the patients with TB at early stages to see if they have a drug resistant TB, in order to treat it on time and stop them from passing it on to others. In many countries, they detect for drug-resistant strains of bacteria by giving the initial treatment to patients with TB and checking if their health improves. This allows them to see whether the drugs have worked and if not then they will suspect that the patient has MDR TB. It is after this that they will attempt to detect the resistant TB, which can be too late (Iseman and Heifets, 2006). This is a very ineffective method as the person with drug resistant TB will be receiving the wrong treatment, and can therefore die if their condition is serious as well as spreading it to other people around them. A more efficient way to detect the drug resistant TB is the implementation of culture isolation at the initial stages of detecting TB, so that they can check the susceptibility of the culture to isoniazid and rifampin. This would be very effective if it is easy and cheap to implement because it would mean that everyone will be able to have access to it. Also the testing time in the lab should be short. This will help to recognise whether the patient has drug resistant TB fast enough for the doctor to prescribe the right drugs on time. Rifampin resistant strains are easier to identify because the mutations in the rpoB gene can be directly detected, so patients can be diagnosed with it earlier (Iseman and Heifets, 2006). Since this is a better method of diagnosing TB, it would be great if people were diagnosed with TB using this method in the UK, in order to ensure that the patients are receiving the correct treatment and to prevent it from spreading.To conclude, the number of TB cases have increased in the UK over the past few decades and as a consequence, there has also been a rise in the number of cases of drug resistant TB. Despite the fact that there are plenty of drugs available to treat the resistant TB at the moment, the bacteria can become resistant to more drugs in the future. As a result, more treatment options should be available in the future to make sure the UK is prepared for it, but more importantly they should focus on the prevention right now. In order to do this, they must ensure that they vaccinate those who are at risk of developing TB and also monitor the health of the TB patients’ families. Prevention would mean that there is no more rise in drug resistant TB cases, suggesting that not many new drugs are required to treat it. Additionally, it is better to detect the multi drug resistant TB at the early stages in order to to treat it before it becomes severe and spreads onto others.