Tuberculosis Management in Children

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Tuberculosis Management

in Children

Ministry of Public Health and Sanitation

Division of Leprosy, Tuberculosis and Lung Disease

November, 2011

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Treatment of tuberculosis has over the years focused more on adults leaving children unattended appropriately as medical practitioners considered children of little epidemiologic significance. Available data indicate that more than 11% of TB cases notified in Kenya are children below 15 years. This is thought to be an under estimate considering the challenges faced in diagnosing TB in children. With the emergence of MDR TB, children are victims of contacts and poor case control of adult TB cases. This pool of cases will defeat the ultimate aim of eliminating TB.

Kenya has pioneered interest in TB control amongst children by defining the epidemiologic parameters for children in age groups 0 – 4, 5 – 9 and 10 – 14 years.

Since children are born without TB and they are an important segment of the society for they signify the future, these guidelines seek to provide guidance to the management of TB in children. It seeks to demystify TB diagnosis in children especially with the coming of new diagnostic methods expected to revolutionalize TB diagnosis and management.

The guideline is specifically designed for general health care workers’ readership and is therefore expected to stimulate interest in pediatric TB treatment and how to protect the children from getting infected. This guideline will also act as a reference material for medical students, researchers and the community.

Dr. S. K. Sharif, MBS, MBChB, M. Med. DLSHTM, MSc. Director of Public health and Sanitation

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Acknowledgement

The Division of Leprosy, Tuberculosis and Lung Disease is indebted to support received from the Ministries of Public Health and Sanitation and Ministry of Medical Services including health care workers in both Ministries of health in the implementation of TB control activities in the country.

The Division specifically, acknowledges the support received from the following officers who worked tirelessly and sometimes worked late into the night in developing this guideline:

Dr. Joel Kangangi WHO

Mr. Hillary Kipruto WHO

Dr. Joseph Odhiambo CDC

Dr. Nicholas Wambua CDC

Dr Maurice Maina USAID-Kenya

Dr. Joseph Sitienei DLTLD

Dr. Tsegaye Sentayehu TBCARE1

Dr. Herman Weyenga DLTLD

Dr. Bernard Langat DLTLD

Dr. Kamene Kimenye DLTLD

Dr. Hajara El Busaidy PTLC Coast

Dr. Immaculate Kathure PTLC Nairobi

Dr. Shobha Vakil NASCOP

Prof. Elizabeth Maleche Obimbo University of Nairobi

Dr. Evans Amukoye KEMRI

Dr. Agnes Langat CDC

Dr. Francis Ogaro MTRH

The Divison registers appreciation to the International Union against TB and Lung Diseases and specifically Prof Steve Graham and Penny Enarson for sharing and allowing the use of the WHO/IUATLD Paediatric TB Deskguide as a template in the development of our own Kenyan Paediatric TB Guideline.

The division is indebted to USAID for providing funds for printing of this guideline.

Dr. Joseph Sitienei Head, DLTLD

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List of Abbreviations

 AFB Acid Fast Bacilli

 ART Antiretroviral therapy  BCG Bacille Calmette Guerin  CXR Chest X-ray

 DLTLD Division of Leprosy Tuberculosis and Lung Disease  DOT Directly observed therapy

 DST Drug Susceptibility Testing  HIV Human Immunodeficiency Virus  IPT Isoniazid Preventive Therapy  MDR –TB Multi-drug resistant

 NNRTI NonNucleoside Reverse Transcriptase Inhibitor  NRTI Nucleoside Reverse Transcriptase Inhibitor  PPD Purified protein derivative

 PTB Pulmonary Tuberculosis  TB Tuberculosis

 TST Tuberculin Skin Test  WHO World Health Organization  XDR-TB Extensively Resistant Tuberculosis

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Chapter 1: Introduction and Definitions

1.1Introduction

It is estimated that one third of the world’s population is infected with

Mycobacterium tuberculosis (the bacterium that causes tuberculosis (TB)), and that each year, about 9 million people develop TB, of whom about 2 million die. Of the 9 million annual TB cases, about 15% occur in children (under 15 years of age). Kenya is among the 22 TB high burden countries in the world and is among the top 5 from sub Saharan Africa. 75% of these childhood cases occur annually in these 22 high-burden countries that together account for 80% of the world’s estimated incident cases.

In 2009 Kenya reported a total of 110,065 cases of all forms of TB (case notification rate of 326/100,000). Paediatric age group of less than 15 years constituted 11% of all cases notified which is a significant proportion requiring special attention. In the last 5 years, Kenya has reported annual decline in the number of reported TB cases at a rate of 1% possibly due to effective control interventions coupled with the declining HIV prevalence in the population. Infection with M. tuberculosis usually results from inhalation of infected droplets produced by a patient who has pulmonary TB. The source of infection for most children is an infectious adult in their close environment (usually the household). This exposure leads to the development of a primary parenchymal lesion (Ghon focus) in the lung with spread to the regional lymph nodes.

The immune response (delayed hypersensitivity and cellular immunity) develops about 4–6 weeks after the primary infection. In most cases, the immune response stops the multiplication of M. tuberculosis bacilli at this stage. However, a few dormant bacilli may persist. A positive tuberculin skin test (TST) where available would be the only evidence of infection.

In some cases, the immune response is not strong enough to contain the infection and disease occurs within a few months. Risk of progression to disease and development of disseminated TB is increased in the very young (0-4 years), immuno-compromized and malnourished. In vast majority of children who

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develop disease usually do so within 2 years following exposure and infection. Children can present with TB at any age, but the most common age is between 1 and 4 years. HIV infected children have a lifelong risk of developing TB.

TB in young children and in the HIV infected is often disseminated and rapidly progressive

1.2Definitions and Distinctions

Infection with Mycobacterium tuberculosis usually results from inhalation of infected droplets produced by someone who has PTB and who is coughing. The most infectious source cases are those with sputum smear-positive disease. The closer the contact is to the source case, the greater the exposure and the greater the risk of getting infected with tuberculosis.

TB infection is when a person carries the Mycobacterium tuberculosis bacteria inside the body. Many people have TB infection and are well. A positive TST indicates infection - but a negative TST does not exclude the possibility of infection.

TB disease occurs in someone with TB infection when the bacteria inside the body start to multiply and become numerous enough to damage one or more organs of the body. This damage causes clinical symptoms and signs and is referred to as “tuberculosis” or active disease.

Pulmonary TB sputum smear positive

The criteria are.

 Two or more initial sputum smear examinations positive for AFBs or  One sputum smear positive for AFB plus CXR abnormalities consistent

with active PTB, as determined by the clinician or

 One sputum smear examination positive for AFB plus sputum culture positive for M. Tuberculosis.

Adolescents or children of any age with complicated intrathoracic disease are more likely to have smear positive PTB.

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Pulmonary TB sputum smear negative.

A case of PTB that does not meet the above criteria for smear positive PTB: The Criteria are;

 At three sputum specimens negative for AFB, and  Radiological abnormality consistent with active PTB, and  No response to a course of broad spectrum antibiotics and

 Decision by clinician to treat with a full course of anti- TB chemotherapy. Such cases include cases without smear results, which is a common phenomenon in children.

Extra pulmonary TB

Children with EPTB should be classified under the same definition. Those with both PTB and EPTB should be classified as PTB

Drug Resistant TB

This is a laboratory diagnosis, however Drug resistant TB should be suspected if.

1. Features in the source case that are suggestive of drug resistant TB,  Contact with known case of drug resistant TB.

 Remains sputum smear positive after 3 months of treatment,  History of previously treated TB,

 History of treatment interruption.

2. Features of a child suspected of having drug resistant TB.

 Contact with a known case of drug resistant TB,  Not responding to the anti- TB treatment regimen.  Recurrence of TB after adherence to treatment

The diagnosis and treatment of drug resistant TB in children is complex and should be carried out at referral centre,

Source Case: Usually an adult with smear positive pulmonary TB.

Close contact is defined as living in the same household as, or in frequent contact with (e.g. child minder, school staff), a source case with PTB.

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Children refer to the 0 to 14 year age group

Infant is a child of less than 1 year of age (0-12 month age group)

1.3Rationale for Pediatric TB guideline

The TB control program has in the past paid less attention on pediatric TB mainly due to the fact that children with TB rarely transmit the infection. However children contribute a significant proportion of the disease burden and suffer severe tuberculosis related morbidity and mortality, particularly in the endemic areas. The diagnosis of TB in children is particularly difficulty, more so in resource constrained settings like in Kenya with poor laboratory and X-ray services and high TB/HIV co infection rates. Hence there is need for pediatric TB management guidelines that will enhance early and accurate case identification and treatment as well as contact screening and management.

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Chapter 2: Diagnosis of Tuberculosis in Children

The diagnosis of TB in children relies on a careful and thorough history and physical examination as well as any relevant investigations e.g. TST, CXR and sputum smear microscopy. Even though microbiological diagnosis is not always feasible, all efforts should be made to do sputum microscopy where possible in children with suspected pulmonary tuberculosis. A trial treatment with anti- TB drugs is not recommended as a method of diagnosing TB in children. There are no clinical features that are diagnostic of TB in children as such.

2.1Careful History

a. Contact.

Close contact is defined as living in the same household as or in frequent contact with smear positive PTB case. Smear negative but culture positive source cases are also infectious, but to a much lesser degree.

 All children who are symptomatic must be screened for TB.

 When any child is diagnosed with TB all efforts should be made to detect the source case.

 Children with smear positive TB or cavitary TB on CXR are infectious, their child contacts must be sought and screened for TB.

If no source case is identified, always ask about anyone in the household with chronic cough- if present request assessment of that person for possible TB. Most children will develop TB within two years of exposure

b. Symptoms.

The commonest symptoms associated with TB. Include the following.  Progressive and non-remitting cough for more than 2 weeks.

 Fever for more than 2 weeks, (usually low grade fever 38c) after common causes such as pneumonia, Malaria and Typhoid have been excluded.  Fatigue, reduced playfulness, less active

 Failure to thrive. Weight loss, no or poor weight gain following nutritional rehabilitation.

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The diagnosis of TB in children relies on a careful and thorough history and physical examination

2.2 Clinical Presentation of Pulmonary TB (PTB) Respiratory system

 May have increased respiratory rate  May have signs of respiratory distress

 Auscultation and percussion: usually normal but may have abnormal sounds (e.g. crackles, bronchial breathing) or pleural effusion (dullness and reduced breath sounds)

Atypical clinical presentations of PTB

 Acute severe pneumonia

o Presents with fast breathing and chest in-drawing o Occurs especially in infants and HIV-infected children o Suspect PTB if response to antibiotic therapy is poor –

o If HIV infected also suspect other HIV-related lung disease e.g. PCP  Wheeze

o Asymmetrical and persistent wheeze can be caused by airway compression due to enlarged tuberculous hilar lymph nodes o Suspect PTB when wheeze is asymmetrical, persistent and non

responsive to bronchodilator therapy

PTB can also present acutely as bronchopneumonia in children with tachypnoea, respiratory distress and crackles.

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2.3 Investigations

After history and physical examination, if investigations are available in the facility or nearby, attempt should be made to investigate every child suspected to have TB as follows:

1 Tuberculin Skin Test (Mantoux test)

A positive TST is evidence that one is infected with M. Tuberculosis, but doesn’t necessarily indicate disease. Mantoux test is the recommended test. Correct technique of administering the TST reagent, reading and interpretation of mantoux text is very important. Appendix 1

TST is regarded as positive if the induration is.

 More than 10 mm in all other children, whether they received BCG vaccine or not.

 More than 5mm in HIV infected, immunocompromised, or severely malnourished.

Sometimes it is useful to repeat TST test once the nutritional status has improved.

A positive mantoux test in the absence of symptoms or signs does not necessarily indicate active disease. Causes of false positive and false negative Mantoux test are listed in table 1

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Table 1: Causes of false-negative and false- positive tuberculin skin tests (TST)

Causes of false negative TST Causes of false positive TST

 Incorrect administration or interpretation of test

 HIV infection

 Improper storage of tuberculin

 Viral infections (e.g. measles, varicella)

 Vaccinated with live viral vaccines (within 6 weeks)

 Malnutrition

 Bacterial infections (e.g. typhoid, leprosy, pertussis)

 Immunosuppressive medications (e.g. corticosteroids)

 Neonatal patient

 Primary immunodeficiencies

 Diseases of lymphoid tissue (e.g. Hodgkin disease,

 lymphoma, leukemia, sarcoidosis)

 Low protein states

 Severe TB

 Incorrect interpretation of tests

 BCG vaccination

 Infection with non-tuberculous

mycobacterium

A negative mantoux test does not rule out TB 2. Bacteriological diagnosis

Bacteriological confirmation is particularly important for children with  Suspected drug resistant TB,

 Severe and complicated disease,  HIV infected

 Diagnostic uncertainties.

As much as possible appropriate specimen (sputum, CSF, gastric aspirate, lymph node biopsy etc) should be obtained for

 Microscopy for mycobacterium

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9  Histopathology depending on specimen

 Xpert MTB/RIF (to be used only with sputum and sputum sediments)  Line Probe Assays (LIPA)`

Expectoration, gastric aspirate or sputum induction can been used to obtain sputum depending on the age of the child. Sputum induction should be conducted in outdoor or in specially designed rooms with negative pressure and UV light for purposes of infection control. Appendix 2 and 3

3. Chest X-Ray

This is particularly important in children with suspected PTB. Radiological features suggestive of PTB will include,

 Persistent lung opacification especially if focal  Enlarged hilar or subcarinal lymph nodes,

 Diffuse micronodular infiltrates (miliary pattern)

 Pleural effusions with apical infiltrates and cavities especially in adolescents.

 The finding of marked abnormality on CXR in a child with no signs of respiratory distress (no fast breathing or chest in-drawing) is highly supportive of TB

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CXR Pictures suggestive of Pulmonary TB

Right perihilar lymph node enlargement with opacity in the

right mid zone

Left upper lobe opacification with narrowing and shift of left main bronchus

Miliary TB - Typical bilateral diffuse micronodular pattern. Note differences to LIP X-ray above

Lateral CXR showing enlarged hilar lymph nodes (“doughnut sign”)

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Lymphoid interstitial pneumonitis: typical features are bilateral, diffuse

reticulonodular infiltration with bilateral perihilar lymph node enlargement

Bronchiectasis: focal opacification in right lower zone with thickening of bronchial walls and honeycomb appearance

TB pleural effusion: large right-sided effusion. Pleural tap to differentiate

from emphysema _{Spinal TB: collapse of thoracic vertebra} causing angulation

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4. Other Tests.

A number of other tests have been used in the diagnosis of TB. Examples include  Serological tests,

 Nucleic acid amplification tests,  Gamma interferon assays  PCR Gene Xpert

Most of these tests have not been adequately studied and evaluated for use in children and especially in TB endemic set ups.

CT scan and bronchoscope are useful but not recommended for routine diagnosis of TB in children, except in special situations.

5. HIV test

All children with suspected TB should be tested for HIV

2.4 Differential Diagnosis for child with Chronic Cough /Respiratory Symptoms

Other conditions to consider, in a child with chronic cough /chronic respiratory symptoms who does not fulfil the classical clinical picture of PTB includes: (Table 2)

Pericardial TB: enlarged cardiac shadow. Ultrasound to differentiate

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TABLE 2: Common causes of chronic cough/ respiratory symptoms in children Possible diagnosis Clinical Presentation

Asthma Recurrent wheeze/cough – responds to

bronchodilators. Usually associated with other allergies such as eczema, rhinitis

Upper airway conditions  Allergic rhinitis  Adenoid

hypertrophy

Recurrent/persistent runny nose and/or nasal blockage and snoring

Seasonal pattern Triggers

Foreign Body Inhalation Usually sudden onset in previously well child May have history of choking

Persistent cough

One sided respiratory signs – inspiratory stridor, wheeze

Gastro-esophageal Reflux Disease

Recurrent cough/wheeze Onset in early infancy +/- hoarse voice

Bronchiectasis Severe persistent cough, much sputum (often infected green or yellow in colour).

Finger clubbing

CXR shows reticular or honey-comb pattern Congenital Heart Disease Easily fatigueability, breathlessness,

Onset early infancy

Acquired heart disease Older children, palpitations, easy fatigueability, dyspnoea on exertion.

+/- oedema Congenital respiratory

disorders

Onset early infancy

Commonly premature baby

Noisy breathing during inspiration not responding to bronchodilators

2.5Extra Pulmonary Tuberculosis (EPTB)

Extra pulmonary TB is common in children and presentation varies with age. Table lists typical clinical features for various forms of EPTB and suggested investigations for each category. Symptoms are usually persistent and progressive. The most common form of EPTB is TB lymphadenitis

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Table 3 Extra Pulmonary Tuberculosis in Children

Site of EPTB Typical clinical presentation Investigation Comment TB lymphadenitis - Asymmetrical, painless, non-tender lymph node enlargement for more than one month +/- discharging sinus - Most commonly in neck area Fine needle aspiration when possible Mantoux Treat if axillary node enlargement on same side as BCG in HIV-positive infant, consider BCG disease and refer

Pleural TB

Dullness on percussion and reduced breath sounds +/-chest pain CXR Pleural tap1 Treat if pus in pleural tap, consider empyema and refer TB meningitis Headache, irritability/abnormal behaviour, lethargic/reduced level of consciousness, convulsions, neck stiffness, bulging fontanelle, cranial nerve palsies Lumbar puncture obtain CSF1 CXR CT scan Hospitalise for TB treatment 2

Miliary TB Non-specific, lethargic, fever, wasted

CXR Treat and refer

where appropriate

Abdominal TB

Painless abdominal swelling with ascites

Ascitic tap Ultra-sound Mantoux test Refer where appropriate Spinal TB Painless deformity of spine

May have lower limb weakness/paralysis

X-ray spine Refer where appropriate 2

Pericardial TB

Cardiac failure Distant heart sounds Apex beat difficult to palpate CXR Cardiac ultrasound Pericardial tap Refer where appropriate TB bone and joint Painless, non-tender swelling end of long bones with limitation of movement

Painless, non-tender unilateral effusion of usually knee or hip

X-ray of affected bone and/or joint Joint tap Refer where appropriate

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15 1. Require 5ml of CSF.

2. Typical findings: straw coloured fluid, exudates with high protein, white blood cells especially lymphocytes

3. Referral may be necessary for investigation procedure and laboratory support as well as clinical care. If referral is difficult or not readily available, start anti-TB treatment.

The above table highlights the more common forms of EPTB; however TB may infect other organs.

4. Abdominal ultra-sound shows complex ascites +/- septation

All specimens (FNA, CSF, aspirates etc) should be sent for AFB microscopy and TB culture where visible

Clinical assessment in all cases of EPTB should consider:

 Time lapse from exposure to disease presentation can be quite variable – shorter for young children with disseminated disease, longer for other forms that present in school-aged children

 Common symptoms present in most cases of EPTB include fever, weight loss/poor weight gain, and lethargy/reduced play lasting > 2weeks. Symptoms and signs specific to the site of EPTB as shown in the table below  Investigations for TB as appropriate according to site of infection (see table

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2.6Score Charts/ Diagnostic Criteria

Due to the numerous challenges associated with the diagnosis of TB in children a number of scoring criteria have been suggested and used for TB diagnosis in children, best example is Keith Jones Criteria. Unfortunately most of them have not been evaluated and validated against “a gold standard”. They perform poorly in suspected PTB in children and even worse in TB/HIV co infected. Currently they are at best used as screening tools and not as a means of making a firm diagnosis. For the purposes of our National TB program the clinical diagnosis of PTB in children shall be based on the following.

The approach to a child with suspected PTB is Shawn in the algorithm/ flow chart below

Presence of 2 or more of the following symptoms

 Cough > 2weeks

 Weight loss or poor weight gain

 Persistent fever and/or night sweats > 2 weeks

 Fatigue, reduced playfulness, less active PLUS

Presence of 2 or more of the following:

 Positive contact history

 Respiratory signs

 CXR suggestive of PTB (where available)

 Positive Mantoux test (where available

Then PTB is likely, and treatment is justified

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Figure 1: Approach to Pulmonary TB diagnosis in Children

Notes:

1. All children should be tested for HIV

2. Mantoux test should be regarded as positive as follows:

 >5 mm diameter of induration in high-risk children (includes HIV-infected children and severely malnourished children

 >10 mm diameter of induration in all other children (whether they have received a BCG vaccination or not)

3. Please note that a mantoux may be negative despite the child having TB, especially in severe disseminated TB, malnutrition and HIV disease.

If child not very sick, give 7 days antibiotics then review after 1-2 weeks

 Positive contact history

 Respiratory signs

 CXR suggestive of PTB (where available)

 Positive Mantoux test (where available)

TREAT FOR TB

If only one or none of the features are present

Make a diagnosis of TB if two or more of these features are present

If child sick, admit to hospital for further management

No Sputum or Negative for AFB Smear-positive

If child improves, complete the treatment and discharge and

continue routine follow up

If child improves, complete the treatment and continue routine follow up

If no improvement, re-evaluate for TB (may need CXR, Mantoux test etc) If suspected, start TB treatment, continue regular follow up and complete the treatment

TB suspected based on two or more typical symptoms (Cough, fever, poor weight gain, fatigue > 2 weeks)

Sputum

Clinical Diagnosis

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Chapter 3: Treatment of Tuberculosis

The main objectives of anti- TB treatment in children are to.

1. Cure the child of TB by rapidly eliminating most of the bacilli. 2. Prevent death from active TB or its late effects

3. Prevent TB relapse by eliminating the dormant bacilli

4. Prevent the development of drug resistance by using a combination of drugs 5. Decrease TB transmission to others.

Some of the important points to note about TB treatment in children are.

 Children usually have pauci- bacillary (low organism numbers) pulmonary disease, cavitating disease is rare and EPTB is common.

 Severe and disseminated TB occurs especially in young children (less than 4years) and in HIV infected.

 Both the bacillary load and type of disease may influence the treatment regimens.

 Treatment outcomes in children are generally good even in the HIV infected provided treatment is started promptly.

 Children generally tolerate the anti- TB drugs better than adults.

3.1Classification of TB in Children Table 4: TB Classification in children

1. Non Severe TB

 Pulmonary TB without extensive parenchymal lung disease  TB lymphadenitis

 TB pleural effusion

2. Severe TB

 PTB with extensive parenchymal lung disease  Miliary TB

 All other forms of extra-pulmonary TB including: o TB bone or joint o TB meningitis o Pericardial TB o Abdominal TB etc. 3. Retreatment 4. Multi-drug resistant TB

TB is also classified as either pulmonary tuberculosis (PTB) or extra- pulmonary tuberculosis (EPTB)

Standard Operating Procedures for Treatment

 Classify the case of child TB before starting treatment into non-severe or severe, pulmonary or extra-pulmonary, or retreatment. For extra-pulmonary forms, specify the site.

 Treatment regimens by disease category are listed in treatment table below  Record the TB diagnostic category, treatment regimen and date anti-TB

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18  A caregiver should be identified as the DOT provider for all ages including older

children – educate them on anti-TB regimen and adherence  Record weight at each visit.

 Calculate drug dosages at every visit according to the child’s current weight (note that children gain weight while receiving anti-TB treatment)

 Once treatment is started it must be completed; “trial of TB treatment” should never be used as a diagnostic tool

3.2Recommended Treatment Regimens

Table 5 below shows the treatment regimens currently in use in 2011 as recommended by the National TB program in 2011. Note that treatment is according to classification of severity and site of TB infection (pulmonary versus extra-pulmonary), and if patient is a newly diagnosed case, or for re-treatment.

Table 5A: Kenya Paediatric TB Treatment Regimen (in use until 2012)

Diagnostic Category TB Cases Regimen* Intensive Phase Continuation Phase

III _{NON SEVERE TB}

-Pulmonary TB without extensive parenchymal lung disease

-TB lymphadenitis -TB pleural effusion

2HRZ HR

I a

SEVERE TB (excluding TB meningitis)

- Pulmonary TB with extensive parenchymal Involvement

- New smear positive PTB

- Extra-pulmonary TB (miliary TB, spinal TB, abdominal TB, bone and joint TB, etc) - Severe concurrent HIV disease

2HRZE 4HR

I b SEVERE TB: TB Meningitis 2RHZS* 4HR

II

RETREATMENT

- relapse

- treatment after interruption/default - treatment failure

2HRZES/ 1HRZE

5HR

IV Multi-drug resistant (MDR) TB Refer to TB specialist centre

*Numeral refers to number of months of the regimen. H= Isoniazid

R= Rifampicin Z= Pyrazinamide E= Ethambutol

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19 Table 5B below shows the NEW WHO recommended TB treatment regimens which shall be implemented in Kenya during 2012 when new four drug paediatric formulations of RHZE become available. The following changes are recommended:

 Use of four drugs during intensive phase for all children living in HIV endemic areas such as Kenya, adding ethambutol as a fourth drug for children of all ages.  Treatment of TB meningitis and TB bone to be extended to a total of 12 months

(2 months intensive phase, and 10 months continuation phase)

 In TB meningitis, ethambutol to replace streptomycin during intensive phase (RHZE) due to poor penetration of streptomycin across the blood brain barrier as well as toxicity.

Table 5B: New WHO Recommended Treatment Regimen (for implementation 2012 when paediatric RHZE formulations become available)

*Numeral refers to number of months of the regimen. H= Isoniazid

R= Rifampicin Z= Pyrazinamide E= Ethambutol

2 HRZE refers to two months of Isoniazid, Rifampicin, Pyrazinamide and Ethambutol

Table 6; Dosage of Individual anti-TB drugs according to body weight

Other important observations to note include

 Treatment regimens are the same for HIV-infected and HIV-uninfected children  Response to treatment in HIV infected may be slower.

 Register all children receiving anti-TB treatment with the National TB Program  TB drugs are very well tolerated in almost all children.

 Side-effects are unusual and the most important is hepatotoxicity.

 Ethambutol can be safely used in all ages of children at recommended dosages of 20 mg/kg or as per the drug dosage chart.

TB disease category

Recommended regimen*

Intensive phase Continuation phase

All forms of PTB and EPTB except TB

meningitis and osteoarticular TB 2 HRZE 4 HR

TB meningitis Osteoarticular TB 2 HRZE 10 HR Drug Recommendations Average dose in mg/kg Range in mg/kg Maximum Dose Isoniazid 10 10 – 15 300 mg Rifampicin 15 10 – 20 600 mg Pyrazinamide 35 30 – 40 1.5 g Ethambutol 20 15 – 25 1.6 g

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3.3Additional Management Decisions

 Hospitalization: The following categories of children with TB should be treated as in-patients

o Severe forms of PTB and EPTB (e.g. Spinal TB) for further investigation and initial management.

o TB meningitis

o Severe malnutrition for nutritional rehabilitation o Signs of severe pneumonia (i.e. chest in-drawing) o Other co-morbidities e.g. severe anaemia

o Social or logistic reasons to ensure adherence o Severe adverse reactions such as hepatotoxicity

 Steroid therapy: This should be given in the following situations: o TB meningitis,

o PTB with respiratory distress,

o PTB with airway obstruction by hilar lymph nodes. o Severe Miliary TB,

o pericardial effusion,

Give prednisone at 2mg/kg once daily for 4 weeks, and then taper down over 2 weeks (1mg/kg for 7 days, then 0.5mg/kg for 7 days)

 For all HIV-infected children

o Commence Cotrimoxazole prophylaxis (25 – 30mg/kg of CTX once daily, or see appendix for dose in weight bands)

o Commence antiretroviral therapy within 2 – 8 weeks of starting anti-TB therapy

o Conduct family-based care/screening

 Immune re-constitution inflammatory syndrome (IRIS) - This is a paradoxical deterioration after initial improvement following treatment initiation.

o Seen during the initial weeks of TB treatment with initial worsening of symptoms due to immune re-constitution.

o IRIS is commonly seen in the severely immuno-compromised TB/HIV co-infected child after initiating ARV treatment

o Management: Continue TB therapy; give non steroidal anti-inflammatory drugs or/and prednisone until severe symptoms subside.  Referral of children with TB should be considered if

o Diagnosis is uncertain

o Necessity for HIV-related care e.g. to commence ART o Failure to respond to treatment despite good adherence  Pyridoxine 5 – 10 mg once daily should be given to.

o All malnourished children throughout the anti-TB therapy. o HIV infected children

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21 o Pregnant Adolescents

3.4Follow-up of a Child on anti-TB Therapy

Patients visit the health facility 2 weekly during intensive phase and monthly during continuation phase and should be assessed for.

o Drug adherence. o Drug toxicity. o Weight gain.

o Symptom assessment.

o Sputum for AFBs at two months for those who were smear positive at the beginning of treatment.

This is a critical part of effective TB treatment requiring a clear management plan.

The following should be done at each visit

 Weigh the child at each visit, document and adjust dosage if necessary  Address Adherence issues

o Explain and emphasize to care-giver and child why they must take the full course of treatment even if they are feeling better

o Note risk factors for poor adherence such as distance/transport; orphan (especially if mother has died) or primary care-giver unwell; adolescents o Education and adherence support especially TB/HIV

 Explain that anti-TB drugs in children are well tolerated and safe.

 CXR is not required in follow-up if the child is responding well to anti-TB treatment  At end of treatment, all children who had abnormal X-rays at baseline should have a

repeat x-ray.

3.5Poor Response to Treatment

Most children with TB will start to show signs of improvement within 4 – 8 weeks of anti-TB treatment. Weight gain is a sensitive indicator of good response to treatment Potential causes of poor response to treatment include:

 Poor adherence; this should be evaluated and problems addressed.  HIV infection

 Wrong diagnosis

 Other concurrent chronic lung diseases  Under dosage of drugs

 Resistant form of TB  Unusual Complications

Consider treatment failure if child is receiving anti-TB treatment and: The most important side-effect is hepatitis which usually presents with nausea, vomiting. Presence of abdominal pain, jaundice and tender enlarged liver suggest severe hepatotoxicity. Stop the anti-TB drugs immediately and refer to hospital

(28)

22  No symptom resolution or symptoms getting worse

 Continued weight loss

 If smear positive at baseline and remains smear positive at 5 months

Refer children with suspected treatment failure for further assessment 3.6Treatment Interruptions

 If a child interrupts anti-TB treatment for a period less than 1 month, then restart them on first-line anti-TB therapy.

 If the child interrupts anti-TB therapy for a period longer than 1 month, then put them on a re-treatment regimen (Table 5).

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23

Chapter 4: TB and HIV Co-infection

Human Immunodeficiency Virus (HIV) infection is one of the risk factors associated with development of Tuberculosis in children. HIV influences TB in several ways, some of which include:

 Reactivation of Latent TB infection.

 Rapid progression of new TB infection to TB disease.  Recurrence of TB after successful treatment.

 Increased risk of adverse reactions to anti-TB drugs  Increased risk of death

 Increased risk of other infectious diseases including invasive pneumococcal disease.

HIV infected children may have multiple and concurrent opportunistic lung infections that clinically present like TB, thus making the diagnosis of TB in an HIV infected child more difficulty. The ARVs and anti-TB drugs have potentially significant drug-drug interactions as well as overlapping toxicities that pose additional challenges

Therefore comprehensive approach to management of both TB and HIV is critical.

4.1Diagnosis

 Approach to diagnosis of TB in HIV infected children is similar as for HIV uninfected children,

 History of contact with TB is extremely important in pointing to possibility of TB disease in the HIV infected child

 The clinical presentation of TB is similar in those in early stages of HIV disease, however for those with advanced HIV disease they may not have the typical TB clinical features, and chronic respiratory symptoms may be due to other causes (differential diagnosis see table below)

 HIV test is indicated in all children with suspected TB

 TST reaction of ≥ 5mm is interpreted as positive in HIV. The TST (Mantoux Test) may be negative due to depressed immune response, this does not rule out TB  CXR may be not show typical changes, and therefore may be difficult to

interpret.

4.2Treatment

 TB in HIV infected children should be treated with a 6 month regimen as in HIV-uninfected children.

 Response to TB treatment may be slow

 All children with TB/HIV should receive co-trimoxazole prophylaxis  All children with TB/HIV should receive antiretroviral therapy.  Nutritional support is often needed for children with TB/HIV

 The management of children with TB/HIV should be integrated so that all family members are counselled and tested for HIV and screened for TB

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4.3Prevention

 All HIV-infected children need to be screened for TB

 All HIV infected children exposed to sputum smear positive TB case should be evaluated for TB disease and treated if active disease present. If no active TB disease they should be offered isoniazid preventive therapy (IPT) at 10mg/kg for 6 months

 All TB infected children should be offered counselling and testing for HIV infection

 Known HIV infected children should minimize their exposure to other patients with chronic cough (e.g. separate waiting area, or fast track).

 The specific needs of each family need to be determined and a plan of action developed to ensure that the family receives comprehensive care using all available services

 Deliberate efforts be made to expand the prevention of mother to child transmission of HIV

 BCG vaccine to be given to all new born babies except those with symptoms of HIV infection or those on IPT

4.4Differential Diagnosis in HIV infected Child with Chronic Respiratory Symptoms

The diagnosis of PTB can be particularly challenging in the HIV-infected child because of clinical and radiological overlap with other HIV-related lung disease.

The respiratory system is a common site for many opportunistic infections in HIV infected children. Often there is co-infection with other microbes as well, which further complicates the diagnosis. Other possible causes of chronic lung disease in HIV infected children are shown in the table 7.

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Table 7: Causes of chronic respiratory symptoms in HIV infected children Differential

Diagnosis

Clinical features

Recurrent pneumonia

Recurrent episodes of cough, fever and fast breathing that usually respond to antibiotics

Lymphoid interstitial pneumonia (LIP)

Slow onset cough associated with generalised symmetrical lymphadenopathy, finger clubbing, parotid enlargement, sometimes with breathlessness, andmild hypoxia

CXR: diffuse reticulonodular pattern and bilateral perihilar adenopathy

Tuberculosis Persistent respiratory symptoms not responding to antibiotics. Often poor nutritional status; positive TB contact especially in younger children

CXR: Perihilar adenopathy, miliary, lobar consolidations or effusions (older child)

Bronchiectasis Cough productive of purulent sputum, halitosis (foul breath), finger clubbing, seen in older children.

CXR: honeycombing usually of lower lobes

Complicates recurrent bacterial pneumonia, LIP or TB Pneumocystic

jirovecci pneumia (PCP)

Common cause of acute severe pneumonia, severe hypoxia especially in infants. Unusual after 1 year.

CXR: diffuse interstitial infiltrates, hyperinflation Mixed infection Common problem: LIP, bacterial pneumonia, TB

Consider when poor response to first-line empiric management

Kaposi sarcoma Uncommon

Characteristic lesions on skin or palate

4.5 Antiretroviral Therapy in HIV Infected Children with Tuberculosis

Tuberculosis is an increasingly common opportunistic infection in HIV-infected children. HIV infection increases a child’s risk of progressive primary tuberculosis and reactivation of latent TB in the older child.

The pill burden in treating TB/HIV co-infection is large. Intensive adherence support and monitoring should be offered. The risk of adverse drug reactions is increased during concomitant therapy. Perform a full clinical evaluation at every clinic visit and if there are symptoms suggestive of adverse drug reactions, particularly liver toxicity, do the appropriate laboratory tests.

If significant problems are experienced, either severe drug intolerance, or erratic

adherence, continue the anti-TB, but consider interrupting anti-retroviral therapy (ART).

Resume after the problem has been adequately addressed (may occasionally have to wait until completion of anti-TB therapy).

(32)

26 The principles of treatment of tuberculosis in HIV-infected children are similar to those in HIV-negative children, and the same regimens should be used as those used in HIV negative children. Recent data suggest that early initiation of ART early in TB treatment reduces TB morbidity and mortality, without excess adverse events.

Any child with active tuberculosis should begin TB treatment immediately; and begin ART as soon as the TB treatment is tolerated; i.e. no nausea or vomiting and no on-going or evolving adverse drug events, usually 2 to 8 weeks into TB therapy

The HIV/TB co-infected child has not only diagnostic but also drug management

challenges due to potential for drug-drug interactions and overlapping toxicity between the ARVs and anti-TB medications, and a high pill burden. However children generally appear to tolerate these drugs well, and experience side effects less frequently than adults.

Rifampicin interacts with both PIs and NNRTIs, reducing their blood levels, therefore reducing their effectiveness, therefore when treating TB and giving concurrent ART the ART regimen may require adjustment.

ART options with rifampicin are recommended as follows in Kenyan paediatric ART guidelines.

 Two nucleoside reverse transcriptase inhibitors (NRTIs) plus efavirenz (EFV) e.g. ABC or AZT + 3TC + EFV (children above 3 years only).

 Two NRTIs plus super boosted LPV/r (add ritonavir to standard LPV/r dose to achieve lopinavir:ritonavir at ratio 1:1) during TB treatment and revert to the normal LPV/r dosing after completion of TB treatment.

 Triple NRTI (e.g. ABC + AZT + 3TC). This is a weak ART combination and should be used only when other options are not possibleor not tolerated. After completion of anti-TB with triple NRTI regimen, it is ideal to do a viral load and ensure viral suppression before reverting to the standard first line ART regimen.



Scenario A: Child develops TB before Initiating ART

Start TB treatment as soon as possible and ART within 2 – 8 weeks of starting anti-TB therapy.

o a child who is severely ill needs to be started on ART sooner (within 2 weeks) o a child who is less severely ill may be started on ART within 2 - 8 weeks. o The ART options are as shown below:

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27

Table 8: Initiation of ART in a Child 2 – 8 weeks after starting anti-TB Therapy Nevirapine exposed NOT Nevirapine exposed

Irrespective of age and

weight < 3years and <10kg > 3 years and >10 kg

Preferred option:

ABC/AZT + 3TC + LPV/r + RTV

(add extra dose of RTV to make the LPV/RTV ratio 1:1 - super boosted LPV)

Preferred option:

ABC/AZT + 3TC + LPV/r + RTV (add extra dose of RTV to make the LPV/RTV ratio 1:1 - super boosted LPV) ABC/AZT+3TC+EFV Alternative Option: ABC+3TC+AZT Alternative Option: ABC + 3TC + AZT

(If RTV formulation not available, or cannot tolerate LPV/r + R)

Alternative option: ABC + 3TC + AZT

(if cannot tolerate EFV)

Scenario B: Child develops TB during the first 6 months of first-line ART

Start TB treatment immediately and also change ART regimen IF indicated below. Table 9: Recommended ART regimens in a Child who Develops TB while already on First Line ART

NVP exposed NVP non- exposed

Irrespective of age and

weight < 3years and <10kg > 3 years and >10 kg

Preferred option:

ABC/AZT + 3TC + LPV/r + RTV(add extra dose of RTV to make the LPV/RTV ratio 1:1-super boosted LPV)

Preferred option:

ABC/AZT + 3TC + LPV/r + RTV (add extra dose of RTV to make the LPV/RTV ratio 1:1-super boosted LPV)

After completion of the TB treatment, child can be restarted on original 1st line i.e.

ABC/AZT+3TC+NVP

Preferred Option:

ABC/AZT+3TC+EFV

Alternative Option: ABC+3TC+AZT

Change ART to AZT +3TC+ LPV/r after completion of TB treatment

Alternative Option: ABC+3TC+AZT

(If RTV formulation not available, or cannot tolerate LPV/r + R)

Alternative Option:

ABC + 3TC + AZT (if cannot tolerate EFV)

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28

Scenario C: Child developsTB while on 1st line ART for more than 6 months

There is the possibility that this new episode of TB is an indication of poor response to ART due to non-adherence or of ARV treatment failure or both. Manage as follows:

1. Initiate anti-TB treatment immediately. 2. Evaluate for treatment failure for all.

3. Evaluate adherence to ART and ensure that any problems in adherence have been addressed before embarking on any change in ART regimen.

4. If there is good adherence, and viral load is suppressed, they should continue on first line ART regimen, using the guidelines in table 9 above.

5. If there is poor adherence and/or evidence of treatment failure (high viral load), adherence must first be addressed before modifying the ART regimen. This child’s further ART should be managed in consultation with a paediatrician experienced in HIV treatment. REFER OR CONSULT!

Scenario D. Child develops TB while on 2nd line ART regimen 1. Anti-TB therapy should be started immediately.

2. Evaluate for failure of 2nd line ART (do viral load and CD4 count). There is the possibility that this new episode of TB is an indication of poor response to ART due to non-adherence, or of ARV treatment failure, or both.

3. REFER! If treatment failure is confirmed, do not discontinue ART, continue with their existing regimen, and refer to a consultant with expertise in the

management of HIV infection and the National HIV Therapeutics Committee.

4.6 Co-trimoxazole Preventive Therapy (CPT)

Cotrixamozole has been shown to reduce mortality among TB children infected with HIV. All HIV/TB co-infected children should be offered CPT and it should be started as soon as possible. The duration of treatment is usually indefinite with a once daily dosing.

The children should be monitored for side effects which include skin rashes and GI disturbances. Severe adverse reactions are uncommon and usually include extensive exfoliative rash, Steven Johnson syndrome or severe anemia / pancytopenia. CPT should be discontinued if a child develops severe adverse reactions.

Table 10:Recommended doses for cotrimoxazole Weight in Kg Suspension 5mlsyrup of (200mg/40m g) Child Tablet (100mg/20mg) Single strength adult tablet (400mg/80mg) Double strength adult tablet (800mg/160mg)

<5 2.5 ml One Tablet ¼ tablet -

5-15 5 ml Two tablets ½ tablet -

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29

(36)

30

4.7 Isoniazid Prophylactic Therapy (IPT) in Children

 Children living with HIV who are more than 12 months of age and who are unlikely to have active TB on symptom-based screening, and have no contact with a TB case should receive six months of IPT (10 mg/kg/ day) as part of a comprehensive package of HIV prevention and care services.

 In children living with HIV who are less than 12 months of age, only those who have contact with a TB case and who are evaluated for TB (using investigations) should receive six months of IPT if the evaluation shows no TB disease

Dose and duration of INH for IPT in children

INH 10 mg/kg/day for 6 months (maximum 300 mg/day).PLUS Pyridoxine 25 mg/day

Table 11 Dose of isoniazid for Prophylaxis (IPT)

Weight Dose in mg/day Number of 100

mg, INH tablets Number of 300 mg (Adult) tablets <5 50 _½ - 5.1 – 9.9 100 1 - 10-13.9 150 ₁_½ _½ 14-19.9 200 2 - 20-24.9 250 ₂_½ - >25 and adults 300 3 1

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31

Chapter 5: Tuberculosis in special circumstances

3.7Tuberculous Meningitis (TBM)

TB meningitis is common in young children and is associated with high morbidity and mortality particularly if the diagnosis is delayed. It is therefore important to consider a diagnosis of TBM in young children as early as possible, especially in children who have a history of contact with an adult with infectious TB.

Miliary or haematogenously disseminated TB has a high risk (60–70%) of meningeal involvement and should therefore be managed same way as TB meningitis. For this reason, all children with miliary TB (or suspected of having miliary TB) should undergo a lumbar puncture to exclude TB meningitis.

Clinical presentation of TBM is usually insidious (subtle) and one must have a high index of suspicion (refer to chapter 2, table 3 for clinical features and investigation of TBM).

Treatment

Children with TB meningitis or miliary TB should be hospitalized, preferably for at least the first 2 months or until they have clinically stabilized. TB meningitis is one of the severe forms of TB and therefore four anti-TB drugs are recommended for the intensive phase. Ethambutol has poor CNS penetration and Streptomycin is currently used as the fourth drug. Isoniazid and Rifampicin are used for the continuation phase.

Corticosteroids (usually prednisone) are recommended for all children with TB meningitis in a dose of 2 mg/kg daily for 4 weeks. The dose should then be gradually reduced (tapered) over 1–2 weeks before stopping.

3.8Management of a Newborn born to a Mother with PTB

Once a pregnant woman has been on anti- TB treatment for at least 4 weeks before delivery she is generally no longer infectious and is therefore unlikely that her baby will become infected. A newborn infant has a high risk of infection/ disease from a mother with smear-positive pulmonary TB if the mother is diagnosed at delivery or soon thereafter.

If the mother is diagnosed with TB shortly before delivery, then the baby and possibly the placenta should be investigated for evidence of congenital TB

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32

infection. The neonate should be screened for TB. Signs and symptoms of neonatal TB disease are usually non specific and may include, fever, feed intolerance, poor weight gain, hepato-splenomegally and, irritability (symptoms of neonatal sepsis).

 Those that are symptomatic should be treated for TB.

 Those without active TB disease should be on IPT for 6 months.

If child had not received BCG by the time of instituting IPT, BCG should be withheld until 2 weeks after completion of IPT. Breast feeding can be safely continued during this period.

If mother has MDR-TB, then IPT is not useful due to resistant bacilli, and in this scenario, BCG should be given at birth, and neonate is handled as MDR contact.

3.9Drug Resistant TB

Mono- and poly-resistance

Resistance to Isoniazid and/or Rifampicin is the most important, as these two drugs form the backbone of the current chemotherapy. In the case where mono-resistance to Isoniazid is known or suspected addition of Ethambutol to Isoniazid, Rifampicin and Pyrazinamide in the intensive phase is recommended.

For patients with more extensive disease, consideration should be given to the addition of a Fluoroquinolone and to prolonging treatment to a minimum of 9months.Mono-resistance to Rifampicin should be treated with Isoniazid, Ethambutol and a Fluoroquinolone for at least 12–18 months, with the addition of Pyrazinamide for at least the first 2months).

Multidrug-resistant TB

MDR-TB is resistant to both Isoniazid and Rifampicin, with or without resistance to other anti-TB drugs. MDR-TB in children is mainly the result of transmission of a strain of M. tuberculosis that is MDR from an adult source case, and therefore often not suspected unless a history of contact with an adult pulmonary MDR-TB case is known. The diagnosis of MDR needs culture and drug susceptibility testing (DST) and its treatment is difficult. Referral to a specialist is always advised

(39)

33  Do not add a drug to a failing regimen.

 Treat the child according to the drug susceptibility pattern and use the treatment history of the source case’s M. tuberculosis strain if an isolate from the child is not available.

 Use at least four drugs certain to be effective.

 Use daily treatment only; directly observed therapy is essential.

 Counsel the child’s caregiver at every visit, to provide support, advice about adverse events and the importance of compliance and completion of treatment.

 Follow-up is essential: clinical, radiological and bacteriological (mycobacterial culture for any child who had bacteriologically confirmed disease at diagnosis).

 Treatment duration depends on the extent of the disease, but in most cases will be 12 months or more (or at least 12 months after the last positive culture).

 With correct dosing, few long-term adverse events are seen even with the more toxic second line drugs in children, including Ethionamide and the Fluoroquinolone.

Children with MDR-TB should be treated with the first-line drugs to which their

M. tuberculosis strain (or that of their source case) is susceptible to, including streptomycin, Ethambutol and Pyrazinamide. Ethambutol is bactericidal at higher doses, so daily doses up to 25 mg/kg should be used in children being treated for MDR-TB.

Extremely Drug Resistant (XDR) TB.

By definition XDR is MDR TB that is also resistant to a second line injectable anti-TB drug and any fluoroquinolone. Compared to MDR it is even more difficult to treat and mortality is very high.

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34

Chapter 6: TB Prevention

6.1 Screening for Child Contacts of Known TB Cases

Young children living in close contact with a source case of smear positive pulmonary TB are at a high risk of TB infection and disease. The risk of infection is greatest if the contact is close and prolonged. The risk of developing disease after infection is much greater for malnourished children, children under 5 years and HIV infected children than it is for HIV un-infected children and those over 5 years. If the disease develops it usually does so within 2 years of infection, but in infants the time lag can be as short as a few weeks.

Isoniazid preventive therapy (IPT) for young children with infection who have not yet developed disease will greatly reduce the likelihood of developing TB during childhood.

Contact screening refers to the screening or evaluation for TB infection or disease of all close contacts of smear positive source PTB case

The main purposes of child contact screening are to:

1. Identify symptomatic children (i.e. children of any age with undiagnosed TB disease), and treat them for TB.

2. Provide Isoniazid preventive therapy (IPT) for the high risk children who have no signs or symptoms of TB disease i.e

o All children aged under 5 o All HIV infected children

The best way to detect TB infection is the TST, and CXR is the best method to screen for TB disease in symptomatic children contacts. Where these two tests are unavailable contact screening and management can be conducted on the basis of simple clinical assessment.

Generally clinical assessment is sufficient to decide whether the contact is well or symptomatic

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Symptoms for Child Contact Screening

1. Non remitting cough of more than 2 weeks 2. Persistent fever of more than 2 weeks 3. Loss of weight/poor weight gain 4. Lethargy/malaise/reduced play 5. Enlarged cervical LN

IPT should be given at a dose of 10mg/kg for duration of 6 months. IPT Follow-up:

 Review monthly and continuously reinforce message of adherence  Screen for TB disease i.e. persistent cough, fever, fatigue, poor weight

gain

 Monitor INH adverse effects.  Maintain a contact register

6.2Management of Child exposed to PTB

The algorithm below outlines the approach to management of a child contact

Child in close contact with source case with PTB

Under 5 yrs of age Aged 5 years or over

Well Symptomatic Symptomatic Well

6H Evaluate for TB No treatment

If becomes symptomatic If becomes symptomatic

The symptomatic contacts should be evaluated for TB disease and managed in the usual manner once found to have TB.

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Child contact known to be HIV-infected

If the child contact is HIV-infected and asymptomatic, then IPT should be considered for all ages, including those 5 years and older. As with other contacts, active disease should be ruled out before providing HIV-infected children with IPT. HIV infected children who have symptoms should be carefully evaluated for TB, and if found to have TB should be started on TB treatment

Suspected HIV infection of contact

If the source case is a parent and is HIV infected, their children may be at risk of both TB and HIV infection. It is important to counsel and test for HIV as we screen for TB infection in all the contacts. (Consider joint TB/HIV contact investigations)

Child contacts of infectious MDR-TB cases

By definition MDR-TB is resistant to both Isoniazid and Rifampicin, it is unlikely that use of these drugs to treat latent infection caused by an MDR-M. Tuberculosis strain will prevent the development of active TB disease. Close contacts of MDR-TB patients should receive careful clinical follow-up for a period of at least 2 years. If active disease develops, prompt initiation of treatment of the child with a regimen designed to treat MDR-TB is recommended. The use of second-line drugs for chemoprophylaxis in MDR-TB contacts is currently not recommended.

6.3Tracing of TB Source

Where the child is the first person in the household diagnosed to have TB, the household members and other close contacts of the child should be evaluated in order to identify the source case of TB.

Evaluation should include screening for classic TB symptoms: cough, fever, weight loss and lethargy.

Note: The source case may have transmitted TB to the child several months earlier, and may not currently be living in the household.

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37

6.4BCG Vaccination in Children

BCG is a live attenuated vaccine derived from M. bovis, the vaccine offers protection against the more severe types of TB such as Miliary TB and TB meningitis, which are common in young children.

All children should be vaccinated against BCG vaccine as soon as possible after birth EXCEPT those with suspected TB infection at birth. The BCG vaccination should then be differed till 2 weeks after IPT/ TB treatment.

A child who has not had routine neonatal BCG immunization and has symptoms of HIV disease/ congenital immunodeficiency syndrome should also not be given BCG because of the risk of disseminated BCG disease.

A small number of children (1–2%) may develop complications following BCG vaccination. These commonly include:

 Local abscesses at the injection site  Secondary bacterial infections

 Suppurative adenitis in the regional axillary lymph node  Local keloid formation.

 Disseminated BCG disease

Most reactions will resolve spontaneously over a few months and do not require specific treatment. Children who develop disseminated BCG disease should be investigated for immunodeficiencies and treated for TB using a 4-drug first-line regimen: 2RHZE then 4RH (The BCG bacillus has poor susceptibility to Pyrazinamide).

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6.5TB Infection Control

Prevention of TB transmission and infection in the household and health facilities are important components of control and management of TB in children.

The following simple procedures are effective in TB infection control at home and clinics

 Early diagnosis and management of adult TB cases in the household

 At the clinic promptly identify potential and known infectious cases of TB; separate and treat them with minimal delay by conducting triage and screening

 Provide health education about TB transmission without stigmatizing TB patients

 Encourage proper cough hygiene both at home and at health facilities  Natural ventilation and sunlight:

o Keep doors and windows open on opposite sides of the TB clinic and other clinics where children and adults stay together open to bring in air from the outside.

o Advise TB patients to do the same at home

o Advise patients and household members to allow sunlight into their house (rooms) by opening the doors and windows

Tuberculosis Management in Children