Childhood TB Handbook Somalia

Version 5

March 2015

2

Table of Contents

Acknowledgements 3

Abbreviations 3

Chapter One

Epidemiology of Childhood TB

4

Chapter Two

Diagnosis of Childhood TB

5

2.1 Approach to diagnosis 5

2.2 Extrapulmonary TB 6

2.3 Indications for hospitalisation 6

2.4 MDR TB risk assessment 7

Figure 1: Guidance for the diagnosis of TB in children 8

Figure 2: Guidance for the assessment of MDR TB in children 9

Chapter Three

Treatment and Management of Childhood TB

10

3.1 Case definition and reporting 10

3.2 Drug regimens and monitoring of drug sensitive TB 10

3.3 Drug regimens and monitoring of MDR TB 12

3.4 Treatment failure 14

3.5 Adverse effects 15

3.6 Criteria for hospitalization and referral 15

3.7 Management of co-morbidities 15

3.8 Social support 17

3.9 Treatment interruption 17

Chapter Four

Prevention of Childhood TB

18

4.1 BCG vaccination 18

4.2 Contact screening 18

4.3 Isoniazid Preventive Therapy 18

Figure 3: Guidance for the screening of contacts 19

4.4 Infection control 19

Appendix A: Specimen collection 20

Appendix B: CXR examples 22

Appendix C: Images of Extrapulmonary TB 23

Appendix D: MDR TB dosing chart for children 24

Appendix E: Useful resources on Childhood TB 25

Appendix F: Child TB referral sites in Somalia 25

3

Acknowledgements This field guide was developed by the Somalia childhood TB working group (names) with support from The International Union Against Tuberculosis and Lung Disease (Marianne Gale, Anne Detjen, Steve Graham). FOR REVIEW (CONTENT AND LOGOs) The Global Health Bureau, Office of Health, Infectious Disease and Nutrition (HIDN), US Agency for International Development, financially supports the development of this field guide through TB CARE I under the terms of Agreement No. AID-OAA-A-10-00020. This field guide is made possible by the generous support of the American people through the United States Agency for International Development (USAID). The contents are the responsibility of TB CARE I and do not necessarily reflect the views of USAID or the United States Government.

Abbreviations

TB Tuberculosis

PTB Pulmonary Tuberculosis

EPTB Extrapulmonary Tuberculosis

MDR TB Multi Drug Resistant Tuberculosis

CXR Chest X-ray

IPT Isoniazid Preventive Therapy

ART Anti-Retroviral Therapy

CPT Cotrimoxazole Preventive Therapy

MUAC Mid Upper Arm Circumference

Chapter One Epidemiology of Childhood Tuberculosis

Tuberculosis (TB) is a significant cause of morbidity and mortality in children under 15 years old in settings of high TB prevalence like Somalia. Social conditions associated with poverty such as overcrowding and under nutrition contribute to ongoing TB transmission. TB often remains undiagnosed in children who present with pneumonia and malnutrition. In 2013, an estimated 550 000 TB cases in children under 15 years of age occurred globally. This represents approximately 6% of all TB cases. The World Health Organization (WHO) recognizes that the true global burden of childhood TB is underestimated. In Somalia in 2013, children represented only 4% of all new TB cases.

1 Experience from other high TB burden

countries indicates that children may account for up to 30% of all TB cases.2 It is likely that

many children with TB in Somalia are not being diagnosed and treated. Most child TB cases occur in children less than 5 years of age. TB disease can be more severe and of rapid onset in infants and young children. Children are likely to be exposed to TB in their household or community (eg schools or koranic schools), and TB often develops within a year following exposure. The younger the child, the more likely that a close contact can be identified. Child contacts of patients with MDR TB are at risk of MDR TB as well. Not all children infected with TB will develop TB disease, but children with weak immune systems have a greater risk for TB morbidity and mortality. This includes:

infants and young children under 3 years of age children who are malnourished children with recent measles children with HIV

Most cases of TB in children are pulmonary TB (PTB) cases, but smear positivity is rare. This is because:

children have a low bacillary load compared to adolescents and adults and diagnostic tests such as smear microscopy are often negative

it is often difficult to obtain sputum specimens from children Extrapulmonary TB (EPTB) is also common in children and occurs in about 20-30%

3 of

cases. The site of EP disease varies with age, the most common form of EPTB is peripheral lymph node TB. The BCG vaccine, given post-natally, is not fully protective against TB disease in children. However neonatal BCG vaccination is important in providing protection against disseminated TB such as TB meningitis in infants and young children. A history of BCG vaccination does not exclude the possibility of a child having TB. Multi Drug Resistant (MDR) TB in Somalia is a significant problem. An estimated 5.2% of new TB cases and 41% of previously treated cases have MDR TB. In Somalia, around 52% of people with TB have known HIV status. Of these, 3% are co-infected with HIV.

1 Offering early

HIV testing and treatment to all adults and children with TB is important to reduce mortality. Understanding the epidemiology of MDR TB and TB/HIV in your setting will help you to assess a child’s risk. In order to have accurate data on TB in Somalia, all cases of TB, whether treated in public or private facilities, need to be reported to the National TB Program (NTP).

1 Global tuberculosis Report 2014. Geneva, World Health Organization, 2014 2 Desk-guide for diagnosis and management of TB in children. Paris, International Union Against Tuberculosis and Lung Disease,

2010 3 Roadmap for childhood tuberculosis: towards zero deaths. Geneva, World Health Organization, 2013

5

Chapter Two Diagnosis of Childhood TB

Key principles 1. The diagnosis of TB can be made with confidence in the majority of children using clinical assessment that includes:

careful history including contact history clinical examination follow up to exclude other conditions

2. Bacteriology (microscopy, Xpert MTB/RIF, culture) should be done wherever possible 3. X-ray and Tuberculin Skin Testing can be useful, but are not essential in most cases 4. Serological tests for the diagnosis of TB are NOT recommended

4

5. The characteristics of TB disease and the approach to diagnosis in children > 10 years of age is similar to that for adults 6. All children in nutrition programs in Somalia should be routinely assessed for TB signs and symptoms on admission using Figure 1. A careful TB contact history is particularly important in these children. 7. The risk of MDR TB should be assessed for each child with TB

2.1 Approach to diagnosis

Table 1. Key diagnostic elements in child TB

Careful History Contact with a known or suspected TB case 1. Timing of the exposure

↑ risk if exposure occurred within the last 2 years 2. Closeness of the contact

↑ risk if female (eg mother or caregiver), same household or sleeping in the same room

3. Type of TB disease of the contact

↑ risk if contact was smear positive or had cavities on CXR MDR TB contact history is very important

Symptoms suggestive of TB

Typical symptoms, often in combination: Cough especially if persistent and not improving Weight loss or failure to gain weight Fever and/or night sweats Fatigue, reduced playfulness, less active Especially if symptoms persist (>2 weeks) and/or do not respond to other appropriate therapies such as broad-spectrum antibiotics for pneumonia or nutritional support.

Atypical presentations to be aware of:

Acute severe pneumonia: Especially in infants and HIV-infected children

Wheezing: Often unilateral, not responding to bronchodilators. Due to compression of the airways by TB lymph nodes

Clinical examination including HIV testing

Vital signs: fever and increased respiratory rate may be present.

Growth: measure weight, height and MUAC, and record on a growth chart.

Weight loss or flattening of the growth curve can signal a chronic disease like TB, especially in infants and young children < 3 years.

4 Guidance for national tuberculosis programmes on the management of tuberculosis in children 2nd

edition. Geneva, World Health Organization, 2014

6

Respiratory examination: often normal, but abnormal auscultation (e.g. crackles,

wheezing) or percussion (dullness as sign of pleural effusion) may be present. May have signs of respiratory distress, but respiratory rate is often normal even in children with extensive pulmonary TB. This is unlike bacterial pneumonia.

Physical signs of EPTB: (see table 2)

HIV testing: all children with presumptive TB should have an HIV test as part of

the diagnostic process.

Follow up and re-assessment

The diagnosis of TB in children can often not be made at the first consultation

Follow up is critical to assess if signs and symptoms persist or progress despite treatment for other conditions like pneumonia, malaria or malnutrition

Persistent respiratory symptoms, fever, weight loss or fatigue for more than 2 weeks are highly suggestive of TB

Other investigations if available

Special Investigations:

Bacteriology - wherever possible

Try to confirm a diagnosis of TB with Xpert MTB/RIF, smear microscopy and/or culture if available. Xpert MTB/RIF is the preferred first test in children as it has the highest yield. Confirmation of TB should not delay treatment. A negative bacteriologic test (including Xpert) does not exclude TB in children.

Older children can often produce sputum. Appendix A provides guidance on specimen collection and testing in younger children.

X-Ray - if available and clinically relevant

Chest X-ray can be helpful in the diagnosis of pulmonary TB in children. Hilar lymphadenopathy is the most common finding (see Appendix B for example images). X-ray may also be useful in the diagnosis of other forms of TB (see table 2)

Tuberculin Skin Test (TST) - if available and clinically relevant

In a TB endemic country like Somalia, TST is not a very helpful tool in diagnosing active TB. It is also often not available. A positive test can support a TB diagnosis in a symptomatic child, especially

in the absence of a TB contact. TST cannot differentiate between TB infection and disease.

A negative test does not exclude TB Causes of false positive TST: BCG, Mycobacteria other than tuberculosis Causes of false negative TST: HIV, malnutrition

2.2 Extrapulmonary TB EPTB accounts for approximately 20-30% of cases of TB disease among children

5. The most

common form is peripheral lymph node TB (TB adenitis). See Table 2 for a summary of diagnosis and management of EPTB A child with suspected EPTB may need to be referred to a high level of care or a hospital for diagnosis and/or initial management.

2.3 Indications for hospitalization Signs of severe pneumonia (i.e. chest in-drawing) or respiratory distress Severe malnutrition for nutritional rehabilitation Other life threatening medical conditions eg severe anaemia or meningitis

5 Roadmap for childhood tuberculosis: towards zero deaths. Geneva, World Health Organization, 2013

7

Table 2 Clinical features and management of extra pulmonary TB disease in children

Site of EPTB

Typical clinical presentation Special diagnostic investigations

Comment

TB adenitis Visible asymmetrical, painless, non-tender lymph node enlargement for more than one month (usually > 3 cm)

May have discharging sinus

Most commonly in neck area

Fine needle aspiration when possible for Xpert MTB/RIF especially if MDR risk and/or culture and histology if available

Treat

If axillary node enlargement on same side as BCG, consider BCG disease and refer for further management

Pleural TB Dullness on percussion and reduced breath sounds

May have chest pain

CXR

Pleural tap#

Treat

Refer if clinically indicated

§

Usually young (< 5 years) with disseminated disease and severely ill

TB meningitis

Headache, irritability/abnormal behaviour, vomiting (without diarrhoea), lethargic/reduced level of consciousness, convulsions, neck stiffness, bulging fontanelle, cranial nerve palsies

Lumbar puncture to obtain CSF*

CXR

Refer for hospitalization

§

Initiate treatment immediately

Usually 5 years and older

Abdominal TB

Abdominal swelling with ascites or abdominal masses or pain

Ascitic tap#

Ultrasound if available

Refer§

Spinal TB Deformity of spine May have lower limb weakness/paralysis/unable to walk

X-ray spine Treat

Refer for hospitalization if clinically indicated

§

Pericardial TB

Cardiac failure Distant heart sounds Apex beat difficult to palpate

CXR

Cardiac ultrasound

Refer for hospitalisation

§

TB bone and joint

Painless swelling at the end of long bones Limitation of movement Unilateral joint effusion-usually knee or hip

X-ray bone/joint

Joint tap#

Refer for hospitalization if clinically indicated

§

# typical findings: straw colored fluid, exudate with high protein, white blood cells predominantly lymphocytes on microscopy *typical findings: high protein (100 – 500 mg/dL), low glucose (<45mg/dL), high lymphocytes (100 – 500 cells/microL) § Referral may be necessary for investigation procedure and laboratory support as well as clinical care. If all options for referral have been explored and referral is not possible, start anti-TB treatment.

2.4 MDR TB risk assessment Once a diagnosis of TB has been made, the risk of drug-resistant TB should be assessed in every child before starting TB treatment. The following 3 questions should be asked for every child: 1. Has the child been treated for TB in the past? 2. Has the child had close contact with any person known to have MDR-TB? 3. Has the child had close contact with any person who died from TB despite treatment; or who failed TB treatment; or who is non-adherent to TB treatment? If any of the questions is answered with YES, a diagnosis of MDR should be attempted by collecting specimens for bacteriologic testing (Xpert MTB/RIF and culture). Children should be referred to a specialized center for MDR TB treatment initiation.

8

Figure 1: GUIDANCE for the diagnosis of TB in children

#INDICATIONS FOR IMMEDIATE HOSPITALIZATION

Signs of severe pneumonia (i.e. chest in-drawing) or respiratory distress

Severe malnutrition for nutritional rehabilitation

Other life threatening medical conditions eg severe anaemia, meningitis

*’Managing the symptom’ may involve antibiotics, nutritional support or other treatment depending on clinical findings.

^Children who are HIV infected may have a range of medical problems. Refer to an HIV experienced clinician. TB is very common in children with HIV. Have a low threshold for treating TB even if the diagnosis is uncertain. ~Perform a CXR if it is available. If not, assess physical signs only.

*BEFORE STARTING TB TREATMENT, DO THIS MDR-TB RISK ASSESSMENT FOR EVERY CHILD:

YES

NO

Are there 2 or more of: • Cough/wheeze for > 2 weeks not responding to treatment

• Loss of weight or failure to thrive not responding to nutritional

rehabilitation or severe malnutrition

• Fatigue or reduced playfulness

• Persistent fever > 2 weeks

Documented TB contact in the preceding 2 years and/or HIV

positive^?

Regular follow-up If poor response to therapy

after 2 months, suspect MDR TB and refer

NO

Consider other diagnoses Follow up after 1-2 weeks until symptom resolution

Refer if symptoms persist

YES

Symptoms suggestive of TB#

Any cough, weight loss, unexplained fever or fatigue

Manage existing symptom* and review child in 1-2 weeks

Persistent symptoms?

TREAT FOR TB* Physical signs or CXR

~

supportive of TB diagnosis?

YES NO

Smear or Xpert

positive

Smear/Xpert-negative or not done

1. Has the child been treated for TB in the past? 2. Has the child had close contact with any person known to have MDR-TB? 3. Has the child had close contact with any person who died from TB despite treatment; or who failed TB treatment; or who is non-adherent to TB treatment? If the answer is YES to any of these questions, suspect MDR-TB. Refer to Figure 2

9

Figure 2: GUIDANCE for the assessment of MDR-TB in children

* MDR-TB RISK ASSESSMENT - to be done for every child before starting treatment:

Child with TB disease

Risk of MDR TB?*

1. Has the child been treated for TB in the past? 2. Has the child had close contact with any person known to have MDR-TB? 3. Has the child had close contact with any person who died from TB despite treatment; or who failed TB treatment; or who is non-adherent to TB treatment? If the answer is YES to any of these questions, suspect MDR-TB

YES NO

Use standard first line regimen

Attempt to get a specimen for Xpert MTB/RIF and Culture/DST.

Refer if necessary for gastric aspiration, biopsy

or other relevant test

Specimen collection not possible or results do not

confirm TB

Specimen collection possible but results

delayed

Specimen collection possible and results

confirm TB

Results confirm

drug sensitive

TB

Use standard first line regimen

Results confirm

multi-drug resistant

TB

Start MDR treatment regimen

(see Table 7)

Child’s clinical

condition is stable without signs of severity

Await results and monitor

closely

Child’s clinical

condition is severe or

deteriorating

Consider starting

MDR-TB treatment regimen

(see Table 7)

Consider obtaining another specimen for

testing if possible and if child is clinically stable

Otherwise, consider

starting MDR-TB treatment regimen (see Table 7)

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Chapter 3 Treatment and Management of Childhood TB

Key principles

Once TB treatment starts it must be completed; a “trial of TB treatment” should not be used as a diagnostic tool

Adherence to the full course of treatment should be emphasized and reinforced

In general, TB drugs are better tolerated in children than in adults. Most adverse reactions can be managed without stopping treatment, except hepatitis and severe drug reactions

Children with a body weight ≥ 25 kg can be treated according to adult dosages

Ensure that children followed up in the TB clinic do not miss out on other routine childhood interventions especially vaccination. Children on TB treatment, including MDR TB treatment can safely receive all routine childhood vaccines.

3.1 Case definition and reporting Register all children receiving anti-TB treatment in the TB register

Record case definition, treatment regimen and date of commencement in road-to-health book, TB treatment card and TB register

Each TB case should be defined as either o ‘Bacteriologically confirmed’: positive microscopy, culture or Xpert MTB/RIF

or o ‘Clinically diagnosed’: diagnosed by a clinician without positive bacteriology

In addition, cases are classified according to the anatomical site of disease as either Pulmonary TB (PTB): a case of TB involving the lung parenchyma or

tracheobronchial tree. This includes miliary TB. Extrapulmonary TB (EPTB): a case of TB involving organs other than the

lung parenchyma, e.g. peripheral and intra-thoracic lymph nodes, pleura, abdomen, genitourinary tract, skin, joints and bones, meninges, brain.

A case with both pulmonary and extrapulmonaryTB should be classified as pulmonary TB.

Cases should also be classified according to o History of previous TB treatment: new, previously treated or unknown o HIV status: positive, negative, unknown

o Drug resistant status: monoresistant, polydrug resistant, rifampicin resistant6,

multidrug resistant (MDR), extensively drug resistant (XDR)

The same outcome definitions apply for children as for adults

3.2 Drug regimens and monitoring of drug sensitive TB Table 3 displays the recommended first line TB treatment regimens for children according to WHO 2014 guidelines. An intermittent TB treatment regimen (3 times per week) is not recommended in Somalia. Streptomycin should no longer be used in any TB treatment regimen for children. In children classified as previously treated cases, use Figure 2 (guidance for the diagnosis of MDR TB in children) to assess the risk of MDR TB.

6 This category is not mutually exclusive. Cases of MDR and XDR will also be rifampicin resistant

11

Table 3. Recommended first line treatment regimens for children in Somalia

H=isoniazid. R=rifampicin. Z=pyrazinamide. E=ethambutol Numeral refers to number of months of the regimen e.g. 2 HRZE refers to two months of daily isoniazid, rifampicin, pyrazinamide and ethambutol

*Children with TB meningitis should receive corticosteroids in addition to TB treatment. Suggested treatment for children is prednisone 2mg/kg daily increased to 4mg/kg daily in the case of seriously ill children (max 60mg/day). This should be given for 4 weeks then tapered over 2 weeks before stopping. Corticosteroids may also be considered in children with TB pericarditis or airway obstruction resulting from lymphadenopathy.

Table 4. Recommended dosages according to weight (WHO, 2014)

Drug Daily dosage in mg/kg Range (maximum)

Isoniazid (H) 7-15 (300 mg)

Rifampicin (R) 10-20 (600 mg)

Pyrazinamide (Z) 30-40 (2000 mg)

Ethambutol (E) 15-25 (1200 mg)

Table 5. Numbers of tablets by weight band for FDC (RHZ: 60/30/150)*

Weight bands

Numbers of tablets

Intensive Phase Continuation Phase

RHZ E RH

60/30/150 100 60/30

<4 kg** ½ ½ ½

4-6kg 1 1 1

7-10kg 2 2 2

11-14kg 3 2 3

15-19 kg 4 3 4

20-24kg# 5 4 5

*Children gain weight while receiving anti-TB treatment. Care must be taken to adjust dosages as needed. **There are no specific WHO recommendations for dosing children less than 4kg. Where possible, give half tablets. #At 25 kg, children can adopt adult dosage recommendations and use adult preparations.

TB disease category

Recommended regimen

Intensive phase

Continuation phase

All forms of TB in children (except TB meningitis and osteoarticular TB)

2 HRZE

4 HR

TB meningitis osteoarticular TB

2 HRZE

10 HR

12

Table 6. Minimum follow-up schedule for children on first-line TB treatment

Follow up activities

Month

Baseline 1 2$ 3 4 5 6

@

Clinic visit* • • • • • • •

Measure height, weight and MUAC Plot on growth chart Check drug doses are correct for weight

• • • • • • •

Smear microscopy# • •

% • •

CXR^ •

Discussion of adherence • • • • • • •

$Switch to continuation phase at the end of month 2

@Record treatment outcome at the end of month 6

*Children with HIV, malnutrition or other co-morbidities should be seen every 2-4 weeks depending on their clinical condition #Smear microscopy during follow up is needed only for children who were smear positive at baseline, or

any child with clinical deterioration. If smear positive at month 3 or later do Xpert MTB/RIF and/or culture to look for drug resistance %

if positive repeat the following month ^CXRs do not need to be repeated unless there is failure to improve or clinical deterioration

3.3 Drug regimens and monitoring of MDR TB Children in Somalia with presumed MDR TB should be referred and managed through specialized centres (Appendix F). The basic principles of an MDR treatment regimen are the same in children as in adults. These include:

Key differences in children to

consider are: Treatment regimens for children are usually empiric as bacteriologic confirmation is

often hard to obtain. Regimens should be based on the drug susceptibility pattern of the source case if known

Second line drug formulations are not child friendly. Care must be taken in splitting tablets and capsules to prepare correct dosages

Table 7 displays the recommended treatment of MDR TB for children in Somalia. Treatment regimens will be decided by the hospital MDR committee. Some cases of TB that are resistant to one or more first line drugs, but are not MDR may be identified from drug sensitivity testing. In such cases, contact a drug resistant TB specialist for advice on a treatment regimen. Table 8 displays the recommended drug dosages for MDR treatment. Further details on dosing of second line drugs for children can be found in Appendix D. Table 9 summarises the minimum follow up schedule for children on MDR TB treatment. Table 7. Recommended MDR treatment regimens for children in Somalia

Use of any first line drug to which susceptibility is known or likely Use of at least 4 drugs in the intensive phase that are likely to be

effective. One of these agents should be an injectable agent and one a fluoroquinolone. Also include pyrazinamide (Z).

Use high-end dosing when possible Never add a single drug to a failing regimen Medication should be given daily by DOT

13

Likely MDR TB source case is identified

Treat child according to the DST pattern of the source case The intensive phase should be at least 8 months or 6 months post culture conversion, whichever is longer The continuation phase should be between 12 – 16 months

NO likely MDR TB source case is identified

Laboratory confirmation of MDR TB is not possible

Intensive phase (8 months*)

Am – Lfx – Eto – Cs – Z + B6

Continuation phase (12 - 16 months*)

Lfx – Eto – Cs – Z + B6

Laboratory confirmation of MDR TB and No prior use of second line drugs

Intensive phase (8 months*)

Am – Lfx – Eto – Cs – Z + B6

Continuation phase (12 - 16 months*)

Lfx – Eto – Cs – Z + B6

Laboratory confirmation of MDR TB and Patient received Amikacin previously

Intensive phase (8 months*)

Cm -Lfx - Eto – Cs – Z + B6

Continuation phase (12 - 16 months*)

Lfx- Eto – Cs - Z + B6

Laboratory confirmation of MDR TB and Patient received Fluoroquinolones previously

Intensive phase (8 months*)

Am -Lfx - Eto – Cs – PAS - Z + B6

Continuation phase (12 - 16 months*)

Lfx- Eto – Cs – PAS - Z + B6

Key: Am = Amikacin, Cm= Capreomycin, Lfx= Levofloxacin, Eto=Ethionamide, Cs=Cycloserine, PAS=Para-amino Salicylic Acid, Z=Pyrazinamide, B6= vitamin B6 (pyridoxine)

*The optimal duration of MDR TB treatment for children is not known. Existing guidelines suggest an intensive phase of at least 8 months (and 6 months post culture conversion, whichever is longer); and total treatment duration of between 18-24 months

Note that all children on MDR TB treatment should be given daily pyridoxine (B6) at a dose of 10mg/kg

The hospital MDR TB committee may adjust these standard regimens based on further details of the treatment history and DST pattern on children with MDR TB.

Table 8: Recommended dosages of drugs used for MDR TB treatment in Somalia

Drug Daily dose recommended

Amikacin 15-20 mg/kg once daily

Capreomycin 15-20mg/kg once daily

Levofloxacin* 5 years of age and under: 15-20mg/kg per day in 2 divided doses Over 5 years of age: 15-20mg/kg once daily

Ethionamide 15-20 mg/kg once daily

Cycloserine 15-20 mg/kg once daily

PAS (4g sachets) 150-200 mg/kg per day in 2 divided doses

Pyrazinamide 30-40 mg/kg once daily

*Levofloxacin should be dosed twice daily in children under 5 years of age as they metabolise the drug

faster than older children.

Table 9. Follow-up schedule for children on MDR TB treatment

14

1 Repeat only if new risk exposure

2 If on Ethambutol

3 If pulmonary involvement at baseline. Do as required if clinical deterioration

4 If smear positive at baseline, otherwise do only if clinical deterioration. Many children will be unable to produce

specimens during follow up. In such cases, rely on clinical findings 5 If on Ethionamide and/or PAS

Note that children co-infected with HIV will additionally require monitoring of CD4 counts. Some antiretroviral drugs may cause abnormal liver function and anaemia therefore monitoring of LFTs and Hb may be required.

3.4 Treatment failure Most children with TB will start to show signs of improvement after 2 to 4 weeks of anti-TB treatment. Children with MDR TB may take longer to show improvement. Suspect failure in any child who has been on first or second line treatment for at least 2 months and has:

No symptom resolution or worsening symptoms or Continued weight loss or A positive sputum smear or culture after >3 months of treatment or A worsening CXR compared to baseline. Note that CXRs can show initial worsening

during the first 4-6 weeks after treatment initiation before resolving. To manage cases of suspected treatment failure:

Baseline

Intensive Phase Continuation Phase

Every month Every 3 months

Every 2 months

Every 3 months

HIV status1 •

Symptoms and signs of toxicity

• • •

Measure height, weight and MUAC Record on a growth chart

Check drug doses are correct for weight

• • •

Discussion of adherence

• • •

Hearing assessment • •

Colour vision testing2 • • •

CXR3 • • •

TB smear, culture and DST

4

• • •

Creatinine and potassium

• • •

TSH, T45 • • • •

Liver function tests •

Investigate poor adherence as a possible cause and reinforce if necessary Check the drug regimen is appropriate and dosing is correct for weight Rule out drug interactions Obtain specimens to look for TB and assess drug resistance* Refer patient or seek specialist advice

15

*Note that Xpert is only useful to detect the emergence of rifampicin resistance and is therefore the test of choice for suspected failure of first line treatment. Suspected failures of a second line treatment regimen should have a sample sent for culture and first and second line drug sensitivity testing

3.5 Adverse effects Anti-TB drugs are usually better tolerated in children than in adults. Second line drugs used to treat MDR TB are more likely to cause adverse reactions than first line drugs. Most adverse reactions can be managed without stopping treatment, except in the case of hepatitis or Stevens Johnson Syndrome (SJS). Table 10 summarises the management of adverse effects.

3.6 Criteria for hospitalization and referral Hospitalization

Severe forms of PTB and EPTB for further investigation and initial management Severe malnutrition for nutritional rehabilitation Signs of severe pneumonia (i.e. chest in-drawing) Other co-morbidities such as severe anaemia, meningitis Social or logistic reasons to ensure adherence Severe adverse reactions such as hepatotoxicity Cases of MDR TB usually require hospitalization or accommodation close to the

MDR TB centre at the start of second line treatment Referral to a specialist (not necessarily for hospitalization);

Advice on HIV-related care is needed e.g. to commence ART There is failure to respond to treatment despite good adherence to anti-TB treatment

3.7 Management of co-morbidities

HIV in a child with drug sensitive or MDR TB Seek specialist advice on the management of HIV if necessary Commence cotrimoxazole preventive therapy (CPT) as soon as possible Commence antiretroviral therapy (ART) within 2 - 8 weeks after starting TB treatment Conduct family-based HIV screening and care Give Pyridoxine (10 mg/kg) for the duration of TB treatment Due to increased risk of toxicity, avoid the following drugs or drug combinations if

possible:

Efavirenz and Cycloserine

Tenofovir and injectable agents

Malnutrition in a child with drug sensitive or MDR TB All children should have height, weight and MUAC measured at each clinic visit.

Results should be plotted on a growth chart. If failure to gain weight, rule out other medical conditions and consider causes of TB treatment failure

Start any child with severe acute malnutrition on therapeutic feeding as per local protocols. These children should routinely receive Pyridoxine (10mg/kg/day)

Children not severely malnourished should receive nutritional supplementation for at least the first 2 months of treatment wherever possible. This may involve a standard food package for the family or ready-to-use food

Breastfeeding infants and children should continue to breastfeed while receiving anti-TB treatment

16

Table 10. Adverse effects from anti-TB treatment Type of adverse event

Likely drug responsible

Identification Initial management

Management by TB specialist

Hepatotoxicity H; Z; R; Eto; PAS;

Tender liver, visible jaundice

Stop all drugs Refer to nearest TB centre for further management

Wait for liver function to return to normal Re-introduce drugs one-by-one every two days. Monitor liver function if possible

Visual problems E Regular testing with Ishihara Chart

Stop E Refer to nearest TB centre for further management

Stop E or substitute for alternative drug

Hearing problems Am; Cm Ask about any observed problems; Test child’s response to sound; Audiometry if available

Urgently refer to nearest MDR TB specialist

Consider stopping the injectable drug and substitute for an alternative drug or Increase the dose interval or Reduce the dose (keeping within dosing range)

Thyroid dysfunction Eto; PAS Regular blood testing, clinical hypothyroidism or goitre

Refer to nearest MDR TB specialist

Give thyroxine supplementation (0.05mg daily) if clinical hypothyroidism or raised TSH and low fT4

Renal impairment Am; Cm Regular blood testing, symptoms of high potassium

Stop injectable Urgently refer to nearest MDR TB specialist

Substitute for alternative drug or Dose three times a week or

Reduce dose (keeping within dosing range)

Severe rash (SJS)

Any drug Severe rash, peeling mucus membranes, child unwell

Stop all drugs Wait until clinical condition has improved Re-introduce drugs one-by-one sequentially, every two days, monitoring clinically

Nausea and vomiting Eto; E; PAS Clinically Refer to nearest TB centre

Consider giving Eto at night Consider splitting the dose Give anti emetics

Diarrhoea PAS Clinically Refer to nearest TB centre

Split dose of granules to give small doses throughout day. Reduce dose (keeping within dosing range) Consider loperamide

Peripheral neuropathy

H; Eto Clinically Refer to nearest TB centre

Give or increase pyridoxine If persistent or severe, stop the causative drug

Neuropsychiatric problems

Cs; H; Lfx; Seizures, headache, behaviour changes, sleep disturbances

Refer to nearest MDR TB specialist

Verify correct dosing Reduce the dose or stop the likely responsible drug

Joint problems Z; Lfx; Clinically Refer to nearest TB centre

Verify correct dosing Trial anti-inflammatory medications If severe, consider reducing dose or stopping likely responsible drug

Painful injection sites Am; Cm Clinically Refer to nearest TB centre

Add local anaesthetic to injectable drug in equal volumes; Vary site of injection on a daily basis If severe, consider splitting dose and giving half into two different sites

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3.8 Social support Adherence to TB treatment, especially for MDR can be a challenge. Risk factors for poor adherence include: distance/transport; being an orphan or vulnerable child (especially if mother has died); having a primary caregiver who is unwell; and being an adolescent.

Tips for improving adherence in children

3.9 Treatment interruption Interruption of first line anti-TB treatment

Type of interruption

Management

> 2 weeks in the intensive phase

or >2 months in the continuation phase

Assess risk of drug resistance. Consider obtaining specimen for testing

If low risk, restart first line anti-TB treatment from the beginning

< 2 weeks in the intensive phase or < 2 months in the continuation phase

Continue first line anti-TB treatment from the point it was stopped

Interruption of second line (MDR TB) treatment

Type of interruption

Management

< 2 months at any point in treatment

Obtain specimen for culture and DST if possible

Continue MDR TB regimen at the point it was stopped

> 2 months at any point in treatment

Obtain specimen for culture and DST if possible Restart MDR TB treatment from the beginning

Give age appropriate patient education for child and care giver. Adolescents should be addressed directly and feel responsible for their treatment.

Explain why they must take the full course of treatment even if they are feeling better

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

Deliver treatment by community based DOT via treatment supporters.

Try to offer incentives (eg food baskets) or enablers (transport money) to promote adherence

For MDR TB treatment, if the pill burden is causing problems, consider splitting into morning and evening doses

Manage side effects early

Offer simple, fun incentives for children on a daily or at least weekly basis (especially for children on MDR TB treatment). These may include making a positive mark on wall chart, singing a song or eating a special food.

Chapter 4 Prevention of Childhood TB

Key Principles Preventing TB disease in children relies on early diagnosis and treatment of TB in adults, BCG vaccination, comprehensive contact screening with isoniazid preventive therapy (IPT) for children at high-risk, as well as good infection control practices.

4.1 BCG vaccination The BCG vaccine, given post-natally, is not fully protective against TB disease in children. However neonatal BCG vaccination is important in providing protection against disseminated TB such as TB meningitis in infants and young children. A history of BCG vaccination does not exclude the possibility of a child having TB.

4.2 Contact screening All children who are close contacts of a smear-positive TB case should be screened for TB. A close contact is defined as a child living in the same household or in frequent contact with the case (for example a caregiver or grandparent). Contact screening should be initiated by the facility diagnosing a smear positive TB case. Contacts can be asked to come to the clinic but it is more effective if someone visits the household, for example a community-based health care worker or treatment supporter. Symptoms alone are used to screen child contacts for possible TB disease: any cough, weight loss, unexplained fever or fatigue. If the child has symptoms, refer to the clinic and use the TB diagnostic algorithm (Figure 1) If the child has no symptoms suggestive of TB, use the contact algorithm (Figure 3) If the TB source case is the child’s parent and is HIV-infected, test all children in the family for HIV. For every child diagnosed with TB, ‘reverse contact tracing’ should be done. That is, to look for possibly undiagnosed source cases within the close network of the child.

4.2 Isoniazid preventive therapy IPT greatly reduces the risk of an infant, young child or HIV-positive person with TB infection from developing disease. Indications for IPT

*Close contact is defined as living in the same household as, or in frequent contact with a source case **If MDR TB is known or suspected, do not give IPT. Refer to Figure 3.

IPT must be given for a full 6 months to be effective. Dosage of 10 (7-15) mg/kg is same as for treatment of TB disease. Follow up for children on IPT is critical: Review every 2 months and continuously re-enforce message of adherence Investigate for TB if typical symptoms develop i.e. cough, fever, fatigue, poor weight gain If TB is diagnosed, start TB treatment

Key messages to the parents/caregiver Even though the child appears healthy, he/she is at increased risk of developing TB and

this can be prevented Children usually tolerate the medicine very well It is important to give the medicine for the whole 6 months to protect the child from

developing TB disease

Close contacts* of a sputum smear positive case** who are asymptomatic and: - Less than 5 years old or

- HIV-infected regardless of age

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Figure 3. GUIDANCE for the screening of children in close contact* with an adolescent or adult with newly diagnosed sputum smear positive TB

*Close contact is defined as living in the same household as, or in frequent contact with a case

4.3 Infection control Infection control is important both at health facilities as well as the households of smear

positive TB patients to reduce transmission Infection control messages such as cough hygiene, ventilation and mask wearing should

be given to newly diagnosed TB patients, their parents/caregivers and to other household members

Older children/adolescents with adult-type TB with cavities can be infectious For the first 2 weeks after initiation of anti TB treatment children should:

o Not attend school; o Avoid sleeping in the same bedroom as other family members, especially young

children and HIV-positive people; o Avoid crowded settings such as buses

Documented TB exposure

Symptoms suggestive of TB? Any cough, weight loss, unexplained fever or fatigue

NO

Index case with known or suspected

MDR TB

YES

≥5yrs AND HIV-uninfected

No further action

Suspect TB Use TB diagnostic

algorithm (Figure 1)

Follow up only for 2 years (no IPT) Review every 3-6 months: Measure weight Monitor for TB symptoms Refer to TB diagnostic algorithm if TB is suspected

Give IPT for 6 months

Review every month: Measure weight Monitor for TB symptoms Refer to TB diagnostic algorithm if TB is suspected

Index case with drug sensitive TB

< 5yrs or HIV infected

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Appendix A: Specimen collection This annex reviews basic procedures for the main methods of obtaining clinical samples from children for smear microscopy that will be used in Somalia: expectoration and gastric aspiration. Sputum induction will not be developed as a specimen collection method in Somalia at this time. This section is adapted from the WHO Guidance for national tuberculosis programmes on the management of tuberculosis in children 2

nd Edition

Expectoration Children who can produce a sputum specimen may be infectious, so, as with adults, they should be asked to do this outside and not in enclosed spaces. Two sputum specimens should be obtained: an on-the-spot specimen (at first evaluation) and an early morning specimen (collected at home by the patient). Procedure 1. Give the child confidence by explaining to him or her (and any family members) the

reason for sputum collection. 2. Instruct the child to rinse his or her mouth with water before producing the specimen. 3. Instruct the child to take two deep breaths, holding the breath for a few seconds

after each inhalation and then exhaling slowly. Ask him or her to breathe in a third time and then forcefully blow the air out. Ask him or her to breathe in again and then cough. This should produce sputum from deep in the lungs. Ask the child to hold the sputum container close to the lips and to spit into it gently after a productive cough.

4. If the amount of sputum is insufficient, encourage the patient to cough again until a satisfactory specimen is obtained. Many patients cannot produce sputum from deep in the respiratory track in only a few minutes. Give the child sufficient time to produce an expectoration that he or she feels is produced by a deep cough.

5. If there is no expectoration, treat the container as used and dispose of it in the appropriate manner.

Gastric aspiration Children with TB may swallow mucus that contains M. tuberculosis. Gastric aspiration is a technique used to collect gastric contents to try to confirm the diagnosis of TB when expectoration is not possible. Because of the distress caused to the child, and the generally low yield of smear-positivity on microscopy, this procedure should be used only where Xpert MTB/RIF and/or culture is available. Gastric aspiration on each of two consecutive mornings should be performed for each patient. This is the number that seems to maximize the yield of smear-positivity. Gastric aspirations can be performed on an outpatient basis. The first gastric aspirate generally has the highest yield. Performing the test properly usually requires two people (one doing the test and an assistant). The child should have been fasting for at least 4 hours (3 hours for infant) before the procedure. Children with a low platelet count or bleeding should not undergo the procedure. Gastric aspiration is generally not an aerosol-generating procedure. As young children are also at low risk of transmitting infection, gastric aspiration can be considered a low risk procedure for TB transmission.

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The following equipment is needed: - gloves - nasogastric tube (usually 10 French or larger) - syringe of capacity 5, 10, 20 or 30 ml, with appropriate connector for the nasogastric tube - litmus paper - specimen container - pen (to label specimens) - laboratory requisition forms - sterile water or normal saline (0.9% NaCl) - sodium bicarbonate solution (8%) - alcohol/chlorhexidine. Procedure 1. Find an assistant to help. 2. Prepare all equipment before starting the procedure. 3. Position the child on his or her back or side. The assistant should help to hold the

child. 4. Measure the distance between the nose and stomach, to estimate how far the tube

will need to be inserted to reach the stomach. 5. Attach a syringe to the nasogastric tube. 6. Gently insert the nasogastric tube through the nose and advance it into the stomach. 7. Withdraw (aspirate) gastric contents (2–5 ml) using the syringe attached to the

nasogastric tube. 8. To check that the position of the tube is correct, test the gastric contents with litmus

paper: blue litmus turns red in response to the acidic stomach contents. (This can also be checked by pushing some air (e.g. 3–5 ml) from the syringe into the stomach and listening with a stethoscope over the stomach.)

9. If no fluid is aspirated, insert 5–10 ml sterile water or normal saline and attempt to aspirate again. If still unsuccessful, repeat the procedure. (Even if the nasogastric tube is in an incorrect position and water or normal saline is inserted into the airways, the risk of adverse events is still very small). Do not repeat more than three times.

10. Withdraw the gastric contents (ideally at least 5–10 ml). 11. Transfer gastric fluid from the syringe into a sterile container (sputum collection cup). 12. Add an equal volume of sodium bicarbonate solution to the specimen (in order to

neutralize the acidic gastric contents and so prevent destruction of tubercle bacilli). After the procedure 1. Wipe the specimen container with alcohol/chlorhexidine to prevent cross-infection

and label the container. 2. Fill out the laboratory requisition forms. 3. Transport the specimen (in a cool box) to the laboratory for processing as soon as

possible (within 4 hours). 4. If it is likely to take more than 4 hours for the specimens to be transported, place

them in the refrigerator (4–8 degrees) and store until transported. 5. Give the child his or her usual food.

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Appendix B: CXR examples

Taken from the Desk-guide for diagnosis and management of TB in children. Paris, International Union Against Tuberculosis and Lung Disease, 2010

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

empyema

Miliary TB: typical bilateral diffuse

micronodular pattern.

Spinal TB: collapse of thoracic vertebra

causing angulation

Pericardial TB: enlarged cardiac shadow. Ultrasound to differentiate from other causes of cardiac failure

CXR suggestive of PTB: right perihilar lymph node enlargement

with opacity in the right mid zone

CXR suggestive of PTB: left upper lobe opacification with narrowing and

shift of left main bronchus

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Appendix C: Images of Extra Pulmonary TB

Taken from the WHO/IUATLD Management of Childhood TB training Desk-guide, Module 2 – Diagnosis. 2014

TB adenitis Abdominal TB

Spinal TB (Potts disease) TB bone and joint

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Appendix D

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Appendix E: Other resources on Childhood TB

Somalia TB guidelines (year), chapter xxx: Childhood TB. Available at xxxx

Somalia MDR guidelines, chapter xxx. Available at xxx

WHO guidance for national tuberculosis programmes on the management of tuberculosis in children. Second edition (2014). Available at http://apps.who.int/iris/bitstream/10665/112360/1/9789241548748_eng.pdf The Sentinel project: Second Edition of Management of Multidrug Resistant Tuberculosis in Children: A Field Guide (2014). Available at: https://sentinelproject.files.wordpress.com/2014/11/field_handbook_2nd_ed-112014.pdf The Union’s Diagnostic Atlas of Intrathoracic Tuberculosis in Children: A guide for low-income countries (2003). Available at http://www.theunion.org/what-we-do/publications/technical/english/pub_diagnostic-atlas_eng.pdf Online training: Childhood TB for healthcare workers (The Union/WHO). A self-taught 6 module certified course for healthcare workers. Access at: www.childhoodTB.theunion.org

Appendix F: Child TB referral sites in Somalia Zone Referral Centre Contact person South Central

Puntland

Somaliland