RESEARCH ON TB

DIAGNOSING DRUG RESITANT TB


How does a child get TB? A child gets TB in basically the same way as an adult, which is by inhaling TB bacteria which are in the air as a result of being released into the air by someone with active TB. The source of infection for children is usually an adult in their household who has active TB, is coughing and is infectious, although there have also been instances of children being infected in a communal setting such as a school. Children with TB in South Africa Children with TB in South Africa ©WHO/TBP/Gary Hampton Once the TB bacteria have been inhaled they may reach the lungs, where they can multiply and then spread through the lymph vessels to nearby lymph nodes. The child's immune response then develops a few weeks after this primary infection. In most children their immune response stops the TB bacteria from multiplying further although there may continue to be a few dormant bacteria.5 However in some cases the child's immune response is not strong enough to stop the multiplication of the bacteria, and TB disease then develops. The risk of progression to TB disease is greatest when the child is less than four years old, and to a lesser extent when they are less than ten years old. There is also a greater risk of progression in children who have a compromised immune system, for example because they are HIV positive. Children who develop TB disease usually do so within two years of first being infected. A small number of older children develop TB later, either due to reactivation following a period when the TB bacteria have been dormant, or as a result of reinfection. Some children are at greater risk of getting TB than others and these include: A child that lives in the same household as a person who has been recently diagnosed with smear positive TB A child less than 5 years old A child with HIV infection A child with severe malnutrition. How do you diagnose TB in children? Diagnosing TB in children is difficult as children are less likely to have obvious symptoms of TB, and samples such as sputum are more difficult to collect from young children. Even when sputum can be collected, it may have very few TB bacteria in it (paucibacillary smear-negative disease). It is recommended that evidence in the following categories is collected and carefully considered before a diagnostic decision is made.6 Collecting diagnostic evidence of TB in children Type of evidence Evidence to be collected Clinical Careful history (including TB contacts; symptoms consistent with TB), Physical examination (including growth assessment), HIV testing (in high HIV prevalence areas) Non-microbiological Tuberculin skin testing (TST), Other investigations relevant for pulmonary or extra pulmonary TB (e.g. X-rays) Microbiological Bacteriological confirmation whenever possible What are the symptoms of TB in children? As with adults the symptoms of TB depend on the type of TB that the child has. Children usually have pulmonary TB but they develop extra pulmonary TB (disseminated TB) more often than adults. Disseminated TB such as TB meningitis particularly occurs in young children less than 3 years old. Miliary TB is another name for disseminated TB. In children with pulmonary TB the commonest chronic symptoms are a chronic cough that has been present for more than 21 days, a fever, and weight loss or failure to thrive. TBFacts.org has more about the symptoms of different types of TB. TB diagnosis in practice It can often be helpful to consult with a colleague when making a diagnosis.7 For example: “It is really difficult for one person to make a diagnosis where the case is not straightforward. So you always consult each other. You can go to the next room, present the case, show the person the x-ray. Then you can have a small discussion in relation to the x-ray and the previous history. Then you can take a collective decision.” HussainKerrow, MSF Clinical Officer, Kenya Although on some occasions there are no facilitates such as x-ray, and nobody else to consult. “So most of the time you make a decision based on your clinical observation. Should I or should I not treat this child for TB. And making that decision you're talking about the life of a child, so it is not something to to be taken lightly.” Dr Bern-Thomas Nyang'wa, MSF TB Implementer Sometimes it is necessarily to use the test results from the adult who is believed to have passed TB on to the child, to ensure that the child is properly diagnosed and treated. How do you treat TB in children? In the same way as TB treatment is provided for adults, TB treatment for children involves a child taking a number of different drugs at the same time for several months. What dosage of the drugs should be used to treat TB in children? In 2006 the World Health Organisation (WHO) carried out a review of TB drug treatment for children and produced a set of recommendations about the amount of different TB drugs that should be provided per kg of a child's body weight.8 In 2010 the recommendations were changed with the amount of each TB drug in general being increased.9 Are there special formulations of the TB drugs for children? There are no special formulations of the TB drugs for children, although there are some Fixed Dose Combinations (FDCs) that can be used. A FDC is when specific dosages of several drugs are combined in one tablet. Unfortunately when in 2010 the WHO changed the recommendations for the dosages of the TB drugs in children, it meant that using the currently available FDCs became much more difficult.10 Recommendations have now been made for new FDCs for children, but they are not yet available.11 “This leads to a situation where, attempting to arrive at a suitable dose of a TB drug for a young child, the clinic staff [in a peripheral clinic] may take a kitchen knife to halve an adult tablet and then perhaps, will have to halve it again. This must lead to inaccuracies and the possibility of under dosing affecting efficacy and over-dosing that could precipitate toxicity. In the early twenty first century this is no longer an acceptable situation” Professor Peter Donald, University of Stellenbosch and Tygerberg Children's Hospital, South Africa12 TBFacts.org has more about TB treatment for children. How do you prevent TB in children? The main way that TB is prevented in children is by the use of the BCG vaccine. TB can also be prevented in children by diagnosing and treating cases of active TB amongst adults, as it is usually adults, particularly adults in the same household, who pass TB on to children. Children with TB are usually not infectious, and so will usually not pass on TB to either other children or adults.13 Challenges for National Tuberculosis Programs (NTPs) In relation to childhood TB NTPs face a number of ongoing challenges which include:14 Insufficient training on diagnosis and treatment of childhood TB Decentralizing and making available new diagnostic technologies Engagement of the private sector in childhood TB diagnosis and reporting Availability of TB drugs in compliance with updated WHO guidance (and inclusion in NTP guidelines) Adequate TB dosing among children due to weight gain

How do you get TB?

TB is spread through the air from one person to another. A person can get TB by inhaling TB bacteria that have been released into the air by a person with active TB. When a person with active TB disease of the lungs or throat coughs, sneezes, or talks, droplets containing the TB bacteria are released into the air.

People with active TB disease are not equally infectious. Generally it is only people with TB of the throat or lungs who are infectious.6 Also, the most important factor for people who can be infectious is whether someone is on effective TB treatment, as effective treatment dramatically reduces the number of infectious droplets released by a person with active TB disease. The strength of a person's cough can also affect the number of droplets released. Children with TB are generally not infectious.

TB bacteria can sometimes stay alive in the air for a few hours, especially in small places with no fresh air. Fresh air and sunlight make it harder for TB bacteria to stay alive. The fresh air scatters the bacteria and the sunlight kills them. It is not known why some people who are exposed to TB bacteria become infected when other people don’t. The probability of becoming infected if exposed to TB bacteria, depends primarily on the concentration of infectious droplets in the air, and the duration of exposure to a person with infectious TB disease. The closer the proximity and the longer the duration of exposure, the higher the risk is of being infected.

TB is not transmitted:
  • food and water
  • or by kissing
  • or by skin contact such as shaking hands
  • or by touching a toilet seat
  • or by sharing a toothbrush.
What are the symptoms of TB disease?

The symptoms of TB disease depend on which area of the body has been infected. If someone has pulmonary TB disease, which is TB in the lungs, then they may have a bad cough that lasts longer than two weeks, they may have pain in their chest and they may cough up blood or phlegm from deep inside their lungs. Other symptoms of TB disease include weakness or fatigue, weight loss, lack of appetite, chills, fever and night sweats

It is though very difficult to diagnose TB disease via symptoms alone, because the symptoms are not exclusive to TB. Diagnosing TB disease and latent TB infectionMycobacterium tuberculosis, the bacteria that cause TB, copyright NIAID Electron micrograph of Mycobacterium tuberculosis bacteria, the bacteria that cause TB disease. © CDC/Dr Ray Butler Whether the person has symptoms or not, TB is often difficult to diagnose. A diagnosis of active TB disease is usually only certain when there is definite evidence of TB bacteria. Some of the diagnostic tools look directly for the bacteria, although others such as the chest X-ray look for the effect of the bacteria on the person suspected of having TB disease.

TB tests include the TB skin test, the IGRA tests, sputum microscopy, culture as well as the new Xpert MTB/RIF test. Major problems with TB tests are the lack of accuracy as well as the time they take, and with newer tests the cost. Treatment of TB disease

Active TB disease can usually be cured. The treatment consists of a combination of TB drugs that must usually be taken over at least six months. But the TB treatment will only be successful if the drugs are taken exactly as required for the entire length of time.

Drug resistant TB

Drug resistance is one of the major problems affecting the worldwide control of TB. A person can have drug resistant TB either because they have become infected with a drug resistant strain, or because resistance developed during the time that they were taking drug treatment for TB.

There is more about drug resistant TB generally, as well as more specifically XDR TB and totally drug resistant TB.

TB disease worldwide

TB is estimated to have killed 1.42 million people in 2011. There were an estimated 990,000 deaths from TB disease in HIV negative people, and then a further 430,000 deaths from HIV and TB co-infection. In addition an estimated 8.7 million people developed active TB disease.11 A third of the world's population, nearly two billion people, are estimated to have latent TB infection. Major efforts are being made in global TB control but with varying degrees of success