Childhood TB: Management of childhood tuberculosis

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Childhood TB was written to enable healthcare workers to learn about the primary care of children with tuberculosis. It covers: introduction to TB infection, the clinical presentation, diagnosis, …

Childhood TB was written to enable healthcare workers to learn about the primary care of children with tuberculosis. It covers: introduction to TB infection, the clinical presentation, diagnosis, management and prevention of tuberculosis in children

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  • 1. 4 Management of childhood tuberculosisBefore you begin this unit, please take the PLANNING THEcorresponding test at the end of the book toassess your knowledge of the subject matter. MANAGEMENT OF A CHILDYou should redo the test after you’ve worked WITH TUBERCULOSISthrough the unit, to evaluate what you havelearned. 4-1 What are the principles of managing children with tuberculosis? Objectives • Correct treatment • Good adherence When you have completed this unit you • Careful follow up should be able to: • Improved nutrition • Screening for HIV • Give the principles of managing a child with tuberculosis. 4-2 Should all children with • Identify which children can be managed tuberculosis be treated in hospital? at home. Most children with uncomplicated pulmonary • Describe first-line treatment. tuberculosis or tuberculous lymphadenopathy • Explain the importance of good do not need admission to hospital. They can adherence. be treated at home and managed from a local • Monitor a child on treatment. clinic. Usually bed rest is not required. • Clinically recognise drug resistance. Children with complicated tuberculosis • Understand the role of improved (severe pulmonary or miliary tuberculosis or nutrition. tuberculous meningitis) should be admitted • List the problems of treating to hospital. tuberculosis and HIV co-infection.
  • 2. MANAGEMENT OF CHILDHOOD TUBERCULOSIS 43TREATING TUBERCULOSIS adverse events from drugs should be reported to the local authority.4-3 Can tuberculosis in children be cured? 4-8 What drugs are used for first-line treatment?Most cases of uncomplicated tuberculosis(more than 90%) can be cured with multiple The three commonly used first-line anti-drug treatment. tuberculous drugs in uncomplicated childhood tuberculosis are: Most patients with tuberculosis can be cured. • Isoniazid (INH) • Rifampicin • Pyrazinamide (PZA)4-4 What are the aims oftreating tuberculosis? Other first-line drugs (ethambutol and streptomycin) have also been used. However• To cure the tuberculosis they are less effective and have more serious• To make the patient not infectious to others adverse events. Streptomycin is no longer used• To prevent relapse of tuberculosis in children.• To prevent the development of drug resistance Commonly used first-line drugs to treat4-5 How many drugs are used in tuberculosis are isoniazid, rifampicin andthe treatment of tuberculosis? pyrazinamide.Two or more drugs are always used. NOTE Streptomycin was used in 1946Tuberculosis is never treated with one drug as the first anti-tuberculous drug.alone. Usually three or four drugs are usedtogether. One drug (usually INH) may be used 4-9 How long is a course ofin prophylaxis. first-line treatment?4-6 Why is more than one drug needed? For uncomplicated tuberculosis, the course of treatment usually lasts six months. This isMultiple drugs (two or more) are used as they divided into two phases.are more effective than one drug only. Thismakes sure that tuberculosis is cured. 1. The intensive phase of two months 2. The continuation phase of four monthsThere is also less chance of drug resistancedeveloping if multiple drugs are used. TB All three drugs (isoniazid, rifampicin andbacilli rapidly become resistant if only a single pyrazinamide) are used for the intensive phasedrug is used. while only two drugs (isoniazid and rifampicin) are used during the continuation phase. NOTE Some drugs kill rapidly growing bacilli (bacteriocidal drugs) while others kill slow growing bacteria (sterilising drugs). Drug treatment for many months is needed to cure tuberculosis.4-7 What is first-line treatment?These are the drugs usually used to treat 4-10 What is the aim of thechildren who present with tuberculosis. They intensive phase of treatment?are the first choice as they are cheap, effective To rapidly kill as many TB bacilli as possible. Toand have few side effects (adverse events). All achieve this intensive treatment is needed with a number of drugs that have a high ability to
  • 3. 44 CHILDHOOD TBkill TB bacilli. Rapidly reducing the number of 4-15 How is rifampicin given?TB bacilli stops the progression of the disease, Rifampicin is also very good at killing TBmakes patients less infectious and helps to bacilli and is used throughout the six-monthprevent the development of drug resistance. course. It is given by mouth and has adverse events in children. Rifampicin colours the4-11 What is the aim of the urine orange but this is harmless.continuation phase of treatment? The dose of rifampicin is 15 mg/kg/day.This longer phase of treatment is necessary tomake sure that the remaining TB bacilli do not NOTE Range in 10 to 20 mg/kg/day.start to multiply once again. Fewer drugs areneeded to achieve this. 4-16 How is pyrazinamide given? Pyrizinamide is used during the intensive4-12 What is short-course treatment? phase to help kill dormant TB bacilli which areThis is the modern way of treating tuberculosis not multiplying. It is also taken by mouth.where a six-month course of drug treatment The dose of pyrizinamide is 35 mg/kg/day.is used. Before rifampicin was developed, NOTE Ethambutol (20 mg/kg/day) is sometimescourses of 12 to 18 months were used. added to first-line treatment to help preventHowever compliance was often poor with the development of resistance to the otherthese longer courses as many patients did anti-tuberculous drugs in more extensivenot take their medication regularly or disease in children. The dosing range ofstopped treatment too soon. The cure rate of ethambutol is 15 to 25 mg/kg/day.tuberculosis has improved with shorter, well-monitored courses of anti-tuberculous drugs. 4-17 How often are first-line drugs taken?Short-course treatment is more cost effectivebut must be well managed. In South Africa INH, rifampicin and pyrazinamide are taken by mouth at the same time once a day, usually in the morning before4-13 How are drug doses breakfast.calculated in children? NOTE In some countries treatment isUsually body weight is used to calculate drug given in larger doses two or three timesdoses in children (i.e. mg/kg). When children a week. Treatment twice a week is notrespond to treatment and gain weight, the recommended by WHO as one missed dosedose may need to be increased even though is a large part of the weekly treatment.the dose per kg body weight remains the same. 4-18 What are the adverse4-14 How is isoniazid given? effects of first line drugs?Isoniazid (INH) is an excellent drug which Usually there are few serious adverse effectsis taken by mouth. It is cheap, has few side (side effects) with children. Adverse effectseffects in children, and is particularly good at are more common in adults. The organ mostkilling TB bacilli during the intensive phase. commonly affected by first-line anti-TB drugsINH is given throughout the six-month is the liver. All commonly used first-linecourse of treatment. drugs can cause hepatitis. There is no need to routinely measure liver enzymes. HoweverThe dose of INH is 10 mg/kg/day. It is liver enzymes must be measured in patientsimportant not to use a smaller dose. who are jaundiced and all anti-TB drugs NOTE Range is 10 to 15 mg/kg/day. should be stopped and patients referred for investigation and change of anti-TB treatment.
  • 4. MANAGEMENT OF CHILDHOOD TUBERCULOSIS 45If a child develops hepatitis on TB treatment • Syringes and needles are expensive.other common causes of hepatitis must be • It can cause permanent nerve damagelooked for e.g. viral hepatitis A. Nausea and leading to deafness and difficulty withskin rashes may occur. balance. NOTE INH may cause peripheral neuropathy, • Dirty needles can spread HIV. but this is very uncommon in children and routine pyridoxine supplementation 4-22 How does the treatment of is not needed. Hepatitis recovers once the children and adults differ? drug causing the problem is stopped. Four drugs are used in adults during the initial phase of two months. Ethambutol is added Drugs used to treat tuberculosis can cause to INH, rifampicin and pyrazinamide. This hepatitis. is because there are far more TB bacilli in tuberculosis with cavities which commonly4-19 What are the advantages of occurs in adults. As children rarely havefixed-dose combination drugs? cavities, only three drugs are used in the initial phase. Just like in children, adults are usuallyFirst-line drugs are often given as fixed-dose treated with INH and rifampicin for the four-combination drugs especially in older children. month continuation phase.All three drugs are given as a single tablet(fixed-dose combination). This reduces the 4-23 When should treatment be started?number of tablets that have to be taken andprevents children leaving out the drugs they do When the diagnosis of tuberculosis isnot like. As a result adherence is improved and confirmed by identifying TB bacilli, usually inthe development of drug resistance reduced. the sputum. When the history, examination, skin test and4-20 What is the management of chest X-ray strongly suggests tuberculosiscomplicated tuberculosis? even if the diagnosis cannot be confirmed byChildren with severe pulmonary or miliary identifying TB bacilli. Some of these childrentuberculosis must be treated in hospital. Usually are diagnosed after failing to respond totreatment is given for six to nine months and treatment for acute pneumonia. Therefore,ethambutol is added as an extra drug to prevent some children are treated for tuberculosisthe development of drug resistance. without confirming the diagnosis on sputum examination.In South Africa the treatment of tuberculousmeningitis is for six months and ethionamideis used instead of ethambutol as it crosses well Drug treatment should be started if tuberculosisinto the CSF (cerebrospinal fluid). is proven or if there is a high clinical suspicion of disease.Children with complicated tuberculosis mustbe managed in hospital by doctors who havethe required training and experience. GOOD ADHERENCE4-21 Why is streptomycin nolonger used in children? 4-24 What is good adherence?Streptomycin is not used in treating Excellent adherence (compliance) means thattuberculosis in children because: every dose of medication is taken each day• It has to be given by injection which is at the correct time. If more than 80% of the painful.
  • 5. 46 CHILDHOOD TBdoses are taken correctly, adherence is said to trained treatment supporter) does not havebe good. to be a health professional and is usually not a family member. However the DOT support4-25 Why is good adherence important? person must be reliable and trained for the task. They should be encouraging and make• It greatly increases the chance for a cure. sure that the correct dose of each drug is taken.• It greatly reduces the risk of drug resistance Unfortunately DOT is often not correctly developing. implemented.• It prevents the relapse (recurrence) of tuberculosis. With DOT a responsible person must see the childThe most important aspect of treating a takes the tablets.child with tuberculosis is to ensure that themedicine is taken correctly and regularly. This NOTE In contrast to DOT, DOTS (Directly Observedis often difficult as medication has to be taken Therapy-Short course) is a strategy which hasfor many months. five elements: political commitment, sputum smear or culture diagnosis, regular supply of drugs, treatment supervision, and recording and Good adherence is essential to cure the patient reporting. DOT is only the supervision part. and prevent drug resistance. 4-28 What are the advantages of DOT?4-26 How can adherence be improved? DOT ensures good adherence without the• By the healthcare worker clearly explaining child having to go to the clinic for every dose. what tuberculosis is, and why treatment If DOT is correctly used, the failure rate of must be given for such a long time even if treatment is greatly reduced and over 90% of the child is clinically improving children should be cured. The general public• By the healthcare worker giving clear can play an important role in the control of instructions on when and how to take the TB by supporting DOT. DOT is a key factor in medication obtaining high cure rates and reducing the risk• By a good understanding of these of drug resistance. instructions by the child and parents• It is essential that the clinic staff establish a The success of treatment depends on good good relationship with mother and child. support.• With a written treatment plan• By supporting the family NOTE The cure rate for TB without DOT in• By good follow up to check adherence poor countries may be as low as 40%.• With a treatment diary to record medication taken• Using a daily pill box MONITORING TREATMENT• Using ‘DOT’4-27 What is DOT? 4-29 How is treatment monitored?‘DOT’ stands for Directly Observed Therapy. The child should be carefully followed up atWith DOT some responsible person in the the treatment clinic (ideally a clinic close tocommunity observes the child swallowing every the family home). Each child must have adose of the anti-tuberculous drugs. In practice, treatment sheet where each visit is recorded.this is usually done from Monday to Friday with The child’s clinical condition, weight, drugsthe family making sure that the drugs are taken taken and any identified problems must beover weekends. The DOT worker (community noted. A careful record of the date of the next
  • 6. MANAGEMENT OF CHILDHOOD TUBERCULOSIS 47appointment must be made. If the child fails poor countries it is common for patientsto attend on that date, the family must be with tuberculosis not to complete theircontacted by phone or by a community health full course of treatment. Once they feelworker. It is important to be aware when a well again they stop their medication. As achild misses a clinic appointment. result, relapse of TB occurs, drug resistance develops and many people die of TB.4-30 How is the response to • The child is HIV infected and is nottreatment monitored? receiving antiretroviral treatment. Response to anti-TB treatment is usuallyOnce the child has been on triple drug good in children with HIV infection.treatment for a few weeks the signs and • Tuberculosis caused by multi-drug-symptoms should gradually improve and the resistant TB.child should start to feel well and gain weight.The most reliable feature of a good response totreatment is the disappearance of symptoms Treatment of tuberculosis is difficult as it isand weight gain. lengthy and requires good adherence.After starting treatment the child should beseen every two weeks for the first month andthen monthly for the rest of the treatment. DRUG-RESISTANTThe child should be weighed at every visit. Asthe child gains weight the drug dosages must TUBERCULOSISbe adjusted.In older children with sputum smear-positive 4-32 What is drug-resistant tuberculosis?tuberculosis, a sputum sample for smear This is tuberculosis where the TB bacilli areexamination is collected at the end of the resistant to one or more of the first-line drugs.initial phase at two months. This should benegative for TB bacilli. Sputum samples are Resistance to both INH and rifampicincollected again after five months of treatment. is called multi-drug-resistant (MDR)If sputum smears or culture remain positive, tuberculosis. In multi-drug resistance, the TBdrug susceptibility testing must be done to bacilli continue to multiply and are not killedexclude drug resistance. by the usual combination of first-line drugs.A definite improvement in the chest X-ray Multi-drug-resistant tuberculosis may developmay be seen in early infections after a month. because of incorrect treatment or poorHowever, the X-ray changes may take months adherence (acquired resistance). Multi-drug-to improve. Therefore X-rays are not routinely resistant tuberculosis can then be transmittedused to determine if a child is responding to to close contacts (primary resistance). Bothtreatment. forms of multi-drug resistance are becoming a major problem in South Africa. Primary drug4-31 What are the commonest causes resistance is far more common than acquiredof failure to cure tuberculosis? resistance in children.• Failure to take the medication correctly With extensively drug-resistant (XDR) as prescribed (non-adherence). If doses tuberculosis, the TB bacilli are resistant to a of the drugs are missed repeatedly the wide range of anti-TB drugs including INH tuberculosis will not be cured and drug and rifampicin. This is extremely dangerous resistance may develop. as most of these patients die. Like multi-drug• If the treatment is stopped too soon the resistance, extensively drug resistance may be tuberculosis can return (relapse). In many primary or acquired.
  • 7. 48 CHILDHOOD TBPatients with multi-drug-resistant or Drug-resistant tuberculosis should be suspectedextensively drug-resistant tuberculosis must when children with good adherence fail tobe admitted to hospital for management withother expensive anti-TB drugs which often improve clinically or have been in contact with ahave more side effects. multi-drug-resistant patient. Drug resistance is becoming a major problem in 4-34 What are the causes of acquired drug resistance? South Africa. These patients do not have drug resistance NOTE Patients with XDR TB are resistant when antituberculous treatment is started. to rifampicin and INH plus injectable It develops during the course of treatment second-line drugs (kanamycin, amikacin or because of failure of good adherence due to: capreomycin) as well as the fluoroquinolones (e.g. ofloxacin or moxifloxacin). • Inadequate patient education on the importance of good adherence • Failure to understand the importance of4-33 How is drug resistance diagnosed? completing the full course of treatmentThese patients fail to respond clinically even if the patient is feeling much betterto correct treatment with first-line drugs. • Poor support (failed DOT)This should always suggest drug resistance • Inadequate supply of drugs (no drugsespecially if there has been good adherence. It available at the clinic)is very important to recognise drug resistance • Side effects leading to poor adherence oras soon as possible. stopping one drugIn children, drug-resistant tuberculosis should • Poor follow up of patients on treatmentbe suspected if they are in contact with an These factors are all related to the inadequateadult suffering from drug-resistant pulmonary care of patients with tuberculosis. Therefore,tuberculosis. poor management of tuberculosis in theDrug resistance can be diagnosed by one of community is the main cause of drug resistance.two methods.1. In the first method TB bacilli are cultured Drug resistance is caused by poor tuberculosis and then tested against the anti-TB drugs management. (INH and rifampicin). Using this method takes weeks to months to get a result. 4-35 How are patients with2. In the second method drug resistance can drug resistance managed? be proved by rapid tests which identify the abnormalities in the DNA of TB They must be managed by special TB units bacilli which are know to be associated with doctors who are experienced in caring for with drug resistance. Resistance to INH these patients. and rifampicin are usually determined. These new rapid tests can be done on a sputum sample or culture and the results are available in a few days. This method is being introduced in South Africa.
  • 8. MANAGEMENT OF CHILDHOOD TUBERCULOSIS 49GOOD NUTRITION 4-38 How can nutrition be improved? By improving the child’s diet. Sugar or vegetable oil will add energy to a meal while4-36 Why is good nutrition important milk powder or beans will add protein.in children with tuberculosis? All children with tuberculosis should receive• Because malnutrition and tuberculosis 200 000 units of vitamin A once by mouth as go ‘hand in hand’, most children with well as a daily multivitamin supplement. tuberculosis are underweight.• Malnourished children with an inadequate Once the appetite returns the amount of food diet have a weakened immune system and eaten each day will need to be increased. are at high risk of developing tuberculosis. Financial assistance (e.g. child support grants)• Tuberculosis leads to poor appetite, failure or food parcels may be needed. to thrive and weight loss which results in malnutrition.• Poverty and overcrowding are common TREATING TUBERCULOSIS factors in both malnutrition and tuberculosis. AND HIV CO-INFECTIONIt is therefore important to improve thenutrition of all children to help protect them 4-39 What is the relation betweenagainst tuberculosis, and improve the nutrition tuberculosis and HIV infection?in children with tuberculosis. Often both TB and HIV infections occur together. The risk of getting tuberculosis Malnutrition and tuberculosis are often found is many times higher in children who are together. HIV infected, especially if they are not on antiretroviral treatment.4-37 How can the nutrition of Tuberculosis is more severe in childrenchildren be assessed? with an immune system weakened by HIV infection. Children with HIV infection areWeighing is the best method of screening also more likely to develop tuberculosis if theychildren for malnutrition. All children with a are infected with TB bacilli.weight below the normal range for their ageare at high risk of malnutrition. In turn, tuberculosis speeds up the progress from asymptomatic HIV infection to severeThe weight of children with tuberculosis clinical disease.must be regularly recorded and plotted ona weight-for-age chart. The Road-to-Health Therefore, all children presenting withcard should be used in children under five tuberculosis must have provider-initiatedyears of age. Gaining weight is an important HIV screening.sign that the child is responding to anti-tuberculous treatment. 4-40 How may HIV infection interfere with the drug treatment of tuberculosis? Plotting weight is an important way of assessing There may be an interaction between the drugs a child’s response to treatment. used to treat tuberculosis and the drugs used to treat HIV infection. Adherence may also be poor as a greater number of drugs have to be taken while the risk of side effects to some of the anti-TB and antiretroviral drugs increases.
  • 9. 50 CHILDHOOD TBRifampicin lowers the blood levels of some 2. What drugs should beantiretroviral drugs especially nevirapine and used to treat this boy?the protease inhibitors. He should receive first-line treatment ofWhen children with tuberculosis also have rifampicin, INH and pyrazinamide for twoHIV infection, both infections must be treated. months followed by rifampicin and INH onlyThis should be managed at a clinic with the for another four months. This is known asexperience and expertise to treat children with short-course treatment. The first two monthsTB/HIV co-infection. of treatment is called the intensive phase while the last four months are called the4-41 What is immune reconstitution continuation phase.inflammatory syndrome (IRIS)? 3. Why is he not treated withThis is the unexpected clinical deterioration in rifampicin alone?a patient who was improving on anti-TB andanti-retroviral treatment. IRIS presents a few Because TB bacilli become resistant toweeks after antiretroviral treatment is started. treatment if only a single drug is used. That isAs the immune system starts to recover the why either two or three drugs are always usedbody may have an inflammatory reaction to together as multiple-drug treatment.the TB bacilli resulting in IRIS.The two most common symptoms of IRIS 4. How often should the drugs be taken?are unexplained fever and enlarging lymph It is best if the drugs are taken once every daynodes. These children need to be referred to of the week, usually at breakfast.facilities with experience in managing TB/HIVco-infected children as the diagnosis can be 5. Are side effects to the drugs common?difficult and other causes of deterioration suchas drug resistance need to be excluded. Children usually have no, or only mild, side effects to the first-line drugs used to treatIRIS due to previous BCG immunisation may tuberculosis.also occur once antiretroviral treatment isstarted in infants. 6. How are the doses of the drugs calculated?CASE STUDY 1 The child’s body weight is used to calculate the daily dose. As the child improves and gainsA boy of six years old is diagnosed with weight, the daily dose may have to be increased.uncomplicated pulmonary tuberculosis and isfollowed up at a district hospital. His parentsare told he will need to take medication every CASE STUDY 2day for six months. They are worried thattuberculosis cannot be cured. A seven-month-old child is admitted to hospital with tuberculous meningitis. One of1. Can uncomplicated pulmonary the older children in the family is also foundtuberculosis be cured? to have tuberculosis. The mother asks whether the infant can be treated at home as it is a longThere is an excellent chance that he will be way to the hospital.cured provided that adherence to treatmentis good.
  • 10. MANAGEMENT OF CHILDHOOD TUBERCULOSIS 511. What drugs are used to treat family is always fighting and is not interestedtuberculous meningitis? in helping her with her treatment.The standard first-line drugs plus ethionamide.This drug is chosen as it crosses the blood 1. Why is she failing tobrain barrier well. Treatment is given for six to respond to treatment?nine months. Poor adherence. Not taking medication regularly every day is a common cause of2. What other anti-TB drug is added for treatment failure. Lack of family support issevere pulmonary or miliary tuberculosis? a serious problem when treating childhood illnesses such as tuberculosis.Ethambutol. 2. How can this problem be corrected?3. Is streptomycin also used in childrenwith complicated tuberculosis? By using DOT (Directly Observed Therapy). A treatment supporter must support her takingNo, as it is a painful injection which has to be her medication each day while the importancegiven daily and has serious side effects. The of good adherence must be explained to her.needles and syringes are expensive and can Trained members from the community canspread HIV if they are reused. become DOT supporters.4. Should treatment be started if a definite 4. What other steps can be takendiagnosis of tuberculosis cannot be made? to improve adherence?If there is a strong clinical suspicion of A written treatment plan, treatment diary andtuberculosis but TB bacilli cannot be pill box should help to improve adherence.identified, for example in the sputum, Support from the clinic staff is also verytreatment should be started. important.5. Can this infant with tuberculous 5. What other problem maymeningitis be treated at home? result from poor adherence?While the child remains clinically ill treatment Drug resistance to the medication used formust be given in hospital. If discharged first-line treatment.home, it is essential that treatment is strictlysupervised as a break in treatment may resultin death or serious neurological damage. 6. What is multi-drug resistance? Resistance to both rifampicin and INH. This is6. What other infection must always be becoming a major problem in South Africa.screened for in children with tuberculosis?HIV. THE SIX MOST IMPORTANT ‘TAKE-HOME’ MESSAGESCASE STUDY 3 1. Uncomplicated tuberculosis in children isAn adolescent with pulmonary tuberculosis treated with three first-line drugs.is referred to hospital because she has not 2. Good adherence is essential to cureimproved after six weeks of treatment. The tuberculosis.home conditions are poor and she admits that 3. Good appetite and weight gain are earlyshe often does not take her medication. Her indicators of response to treatment
  • 11. 52 CHILDHOOD TB4. Good nutrition is an important part of managing children with tuberculosis.5. Poor response to treatment in spite of good adherence suggests multi-drug resistance.6. Suspect drug resistance if the child has been in contact with an adult suffering from drug-resistant pulmonary tuberculosis.