Childhood TB
Investigation and management of children suspected to have tuberculosis (TB) or who are close contacts of a TB case (sputum smear positive or negative)
Recommended approach to diagnosing TB in children includes:
a) Careful history including history of TB contact and symptoms consistent with TB b) Clinical examination including growth assessment
c) Mantoux test if available (a Mantoux test is a Tuberculin skin test [TST])
d) Sputum microscopy and culture when possible (especially in children>8 years of age) e) HIV testing – Provider Initiated Testing and Counselling (PITC)
See clinical algorithm Diagnosis of TB in children
Any child with symptoms suggestive of TB should be investigated. Children can present with TB at any age but it is most common in the under-‐5 age group and during adolescence.
Symptoms suggestive of TB meningitis TBM) especially in a young child with documented TB exposure
Decreased appetite often with weight loss Lethargy
Vomiting without diarrhoea, early morning headache, irritability Drowsiness/lethargy and convulsions, especially focal seizures Older children may present with behavioural changes
Key facts
Children who are close contacts of an infectious (usually adult) TB case are at high risk of becoming infected with M. tuberculosis and developing active TB. Clinicians should, therefore, have a low threshold for investigating TB and commencing young children on TB treatment. Once an adult contact is confirmed, the main clinical decision is whether the child needs full 4-‐drug treatment or isoniazid (INH) chemoprophylaxis.
Key facts
The presence of two or more of the following should strongly suggest a diagnosis of TB
• Current cough of any duration – productive/non-‐productive,
• Unexplained weight loss not responding to standard treatment/food supplement
• Failure to thrive and/or malnutrition • Fever and /or night sweats
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Physical signs highly suggestive of TB include• Chest examination with stony dull percussion in a child that is not acutely ill is a rare but fairly specific symptom complex of TB pleural effusion.
• A painless, enlarged mass of matted lymph nodes (>2x2 cm) in the neck, without a visible local cause on the scalp or response to a course of antibiotics, is highly suggestive of TB cervical adenitis
Investigations and Management
CXR, Mantoux test (if available) PITC, sputum/early morning gastric washings/induced sputum for AFB (and culture if available)
Tuberculin skin testing (TST) – the Mantoux test
The Mantoux test measures the delayed type hypersensitivity response to purified protein derivative (PPD), also known as tuberculin.
A positive Mantoux does not indicate active disease (TB) it only indicates infection with TBM.
tuberculosis.
The Mantoux skin test is "positive" when the diameter of skin induration (swelling, not redness) is ≥10mm (≥5mm in an HIV-‐infected or malnourished child).
A negative TST does not exclude TB infection or disease The tuberculin test may be falsely negative in a child with: Severe malnutrition
HIV infection
Disseminated (miliary) TB and/or TB meningitis (TBM) Immunosuppressive drugs e.g. high dose steroids Very recent TB exposure (in the past 2-‐3 months) Very young children (≤ 12 months)
Sample collection for AFB microscopy and culture a) Sputum Collection
Gastric aspirates are safe and easy to perform, although best performed in hospitalised patients after a 3 hour fast or early in the morning after an overnight fast.
b) Fine Needle Aspiration (FNA)
In children with large, palpable cervical lymph nodes collection of a FNA offers a convenient way of collecting samples for microscopy and culture if available. The aspirate can be smeared onto a slide and sent for AFB microscopy where culture is not available or if insufficient for culture.
c) Lumbar puncture (LP)
Should be performed on any child in whom TBM is suspected and repeated on a child failing to respond to standard treatment for bacterial meningitis. Suspect TBM if there is a lymphocyte predominance, high protein level and low glucose. Absence of acid fast bacilli on microscopy does not exclude a diagnosis of TBM.
TB culture is of particular value in complicated cases or when there is a concern regarding drug resistance. The probability of obtaining a positive TB culture improves when more than one sample is taken.
Chest x-‐ray
Key facts
TB in children is usually sputum smear-‐negative: • lung cavities are rare
• disease is paucibaciliary
• collection of adequate sputum samples is difficult since young children usually swallow their sputum.
However, this is not true for older children (>8 years of age). The sputum smear (and TB culture where available) remains a valuable test to perform in any child who is able to produce a sputum specimen. In children who are unable to expectorate spontaneously, gastric aspirates and/or sputum induction offer alternatives.
Key facts
X-‐rays need to be of good quality and interpretation depends on the expertise of the person reading them.
Chest x-‐ray changes are often non-‐specific and in the HIV infected or malnourished child may be completely normal.
TB disease should not be diagnosed from the chest x-‐ray alone but the whole clinical picture should be taken into account.
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The most common radiological signs of TB in children are:
• Enlarged hilar lymph nodes and/or a broad mediastinum due to enlarged mediastinal lymph nodes (this is the most common presentation in children).
• Lobar disease may also be seen and, following dissemination, miliary disease • Isolated pleural effusions usually occur in children older than 5 years of age.
• Compression of the airways due to diseased lymph nodes; partial occlusion may cause a ball-‐valve effect with segmental or lobar hyperinflation, complete airway occlusion may cause collapse of a lung segment or lobe.
The CXR is useful in HIV-‐infected children but the presentation may overlap with other HIV-‐ related lung diseases e.g. Lymphoid Interstitial Pneumonitis (LIP).
Treatment of paediatric TB – first line TB regimen
New paediatric drug dosages are as follows:
• Isoniazid (H): 10 mg/kg (range 10 – 15 mg/kg); max. dose 300 mg/day • Rifampicin (R): 15 mg/kg (range 10 – 20 mg/kg); max. dose 600 mg/d • Pyrazinamide (Z): 35 mg/kg (range 30 – 40 mg/kg)
• Ethambutol (E): 20 mg/kg (range 15 – 25 mg/kg)
See Appendix in final NTB guidelines for the number of FDC tablets required in each weight band to give adequate treatment doses
It is important to monitor the child’s weight at each clinic visit and adjust drug doses accordingly. Many children rapidly gain weight after initiation of TB treatment.
The revised treatment guidelines for TB recommend two different regimens for defined situations:
SITE OF TB DISEASE HRZE HR TOTAL LENGTH OF TREATMENT TB MENINGITIS
MILIARY TB
BONE TB (SPINE, JOINTS)
2 MONTHS 10 MONTHS 12 MONTHS PULMONARY TB
TB LYMPHADENITIS ALL OTHER FORMS OF TB
2 MONTHS 4 MONTHS 6 MONTHS
Note: Streptomycin is no longer used in first line TB regimens.
Prednisolone:
In TB meningitis and pericardial effusion, steroids have a supportive therapeutic effect. They have been shown to improve survival in TB meningitis and decrease the risk of developing constrictive pericarditis in patients with pericardial effusions.
• Dose: 2mg/kg/day (maximum dose of 40 mg) for four weeks, followed by a reduction regimen over two weeks.
Pyridoxine:
Pyridoxine, or vitamin B6, helps protect against Isoniazid-‐induced peripheral neuropathy • Recommended for all children on TB treatment and IPT
• Dose: 25mg/day until treatment is completed
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Proven or suspected multi-‐drug resistant TB (MDR-‐TB)Children with proven or suspected TB caused by multi-‐drug resistant bacilli should be treated with an appropriate MDR-‐TB regimen according the recommended Malawi NTP guidelines, using paediatric doses. The decision to treat should be taken by a clinician experienced in managing paediatric TB or through consultation with the national TB Programme manager.
Initial assessment before commencing treatment includes: • baseline renal and liver function
• baseline hearing test • CXR
Daily drug intake under DOTS is a crucial part of the programme. Careful assessment by a specialist has to take place before the decision is made to stop treatment after the full course of treatment is completed.
Refer all children for nutritional assessment and support and reassess growth at each clinic visit. Monitor the child’s weight and adjust drug doses accordingly.
At follow-‐up renal function and hearing should, where possible, be checked every three months because of the risk of ototoxicity and renal toxicity associated with injectable drugs.
Key fact
Suspect MDR-‐TB in any child:
• who is a contact of an adult MDR-‐TB case and has symptoms and signs suggestive of TB disease.
• who remains symptomatic after completion of first-‐line TB treatment (with good medication adherence).
Neonates exposed to a mother with TB
If a mother is diagnosed with TB before the third trimester of pregnancy, is taking TB medications with good adherence and is clinically well:
• Examine her baby for signs of disease. If the baby is well, no action is required.
• Refer all other household children <5years of age to the TB clinic for clinical assessment.
If the mother is diagnosed with TB in the third trimester of pregnancy or shortly after delivery: • Examine her baby for signs of disease and consider investigations if available:
o CXR, gastric aspirates • Do not give BCG*
• If the baby is well commence isoniazid (INH) prophylaxis at 10mg/kg/day and continue for 6 months.
• If the baby is not well and has signs/symptoms suggestive of TB disease, collect gastric aspirates where possible and commence full TB treatment.
Weight Isoniazid dose
Under 2.5 kg 25 mg (1/4 tablet) 24-‐hourly
2.5-‐5 kg 50 mg (1/2 tablet) 24-‐hourly
5-‐10 kg 100 mg (1 tablet) 24-‐hourly
• Infants need to be reviewed at 1, 3 and 6 months after commencing INH and their weight checked regularly and the dosage increased as they grow.
• Refer all other household children to the TB clinic for clinical assessment and screening. • If INH is commenced within 12 weeks of receiving BCG vaccine, the infant will need
repeat BCG vaccination at the end of treatment.
• If no BCG vaccine given, then vaccinate two weeks after completing INH*
*Note: As BCG is a live vaccine INH will kill the vaccine and prevent an effective immune response from developing.
Key Facts
A significant number of mothers reactivate latent TB infection in the third trimester of pregnancy or around the time of delivery/immediate post-‐partum period.
Any mother in whom TB is suspected should be sent for a CXR and two sputum samples collected for AFB microscopy.
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INSERT IN CHAPTER 3 SECTION 3.1.1BCG disease
The presence of right-‐sided axillary or regional lymph nodes in a young child or infant indicates possible BCG disease and immunocompromise. This most commonly presents in the two years of life after BCG vaccination. It requires further evaluation:
1. Are they known to be HIV infected?
• Have they recently commenced ART? If so, then this is likely to be BCG IRIS. Management:
• If thriving and with no other signs of disseminated disease (other lympadenopathy, fevers) then no drug treatment is required, although repeated needle aspiration of a large,
fluctuant lymph node may be needed until it spontaneously resolves.
• If it fails to resolve within six weeks or there is extensive disease, patients may then require surgical excision or treatment for TB to prevent severe scarring.
2. HIV status unknown? • Send for PITC. Management:
• HIV uninfected or exposed and thriving and with no other signs of disseminated disease -‐ no drug treatment required, although repeated needle aspiration of a large, fluctuant lymph node may be needed until it spontaneously resolves.
• HIV infected and otherwise well, refer the patient to the ART clinic and commence on ART if <2 years of age.
Needle aspiration of a large, fluctuant lymph node may be required.
• HIV infected and unwell – febrile, failure to thrive, and / or respiratory signs and symptoms – admit for further investigation and management of possible disseminated BCG disease. These children always require TB treatment since co-‐infection with
M. tuberculosis may occur. Key facts
Bacille Calmette-‐Guerin (BCG) is a live, attenuated vaccine and is routinely given to neonates in Malawi, in the right deltoid, in the first week of life.
BCG vaccination may be associated with injection-‐site abscesses, (suppurative) adenitis, and (very rarely) with disseminated disease.
HIV-‐infected infants and other immunocompromised infants are at particular risk of BCG-‐related complications.
Key Facts
BCG adenitis should not routinely be referred to the surgeons for incision and drainage as a chronically draining sinus may result.
Fluctuant abscesses should be managed with observation and needle aspiration if necessary– as detailed above.
Rarely, if there is no improvement or there is deterioration after 6 weeks of RHZE, consider excision biopsy.
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TB and HIV Infection
Diagnosis of TB in HIV-‐infected children
The current approach to clinical diagnosis of TB in HIV-‐infected children is similar to that recommended for HIV-‐uninfected children
*See Diagnosis section for special notes on Mantoux and CXR as diagnostic tools in HIV-‐infected children.
Treatment of TB in HIV-‐infected children
It is currently recommended that HIV-‐infected children are treated with the same TB treatment regimens and for the same duration as HIV-‐uninfected children in the same treatment category. Children with TB/HIV must be followed up regularly and have dosages adjusted for weight gained.
HIV-‐infected children being treated for TB must be started on cotrimoxazole preventive therapy (CPT) and should also be started on ART within 2 weeks of commencing TB treatment, or on the same day if stable.
Antiretroviral therapy in children with TB/HIV co-‐infection
ART is indicated for all HIV-‐infected children and infants with any form of TB.
Children must be followed regularly and drug doses for ART and anti-‐TB treatment adjusted for changes in weight. See the table below for details of treatment regimen according to the new Malawi National HIV guidelines (2011).
ART status at time of
starting TB therapy
< 3 years of age
> 3 years of age
Already taking 1
stline ART
AZT/3TC/Nevirapine
AZT/3TC/Nevirapine
Not yet started ART
AZT/3TC/Nevirapine
AZT/3TC/Efavirenz
On 2
ndline ART
Refer to specialist centre
(Note: major drug interactions between LPV/r and
Rifampicin)
Key facts
TB is common in HIV-‐infected children and HIV infection is common in children with TB in regions endemic for TB/HIV
HIV-‐infected children are more likely to be exposed and infected with M. tuberculosis than HIV-‐uninfected children
HIV-‐infected children are at increased risk of TB disease if infected with TB and this risk is related to the degree of immune suppression
Note: TB IRIS is more common in severely immuno-‐suppressed children and usually occurs within 3 months of starting ART.
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Isoniazid Preventive Therapy (IPT)Contact definition:
A history of a close contact with an adult patient with pulmonary TB (sputum positive or negative)
Eligibility for IPT
See algorithm for IPT prophylaxis in HIV infected and uninfected children
General rules:
• All children need active TB ruled out before starting IPT.
• For any children with a documented contact history, a minimum of 6 months IPT is indicated, even if they are on ART.
• For HIV-‐infected children not on ART, IPT is to be given for the entire time period until ART is initiated, regardless of contact history.
• A CXR is recommended, but not required, to rule-‐out active TB in HIV-‐infected and exposed children with a positive contact history.
Dosing of isoniazid
• For all paediatric age groups, the recommended dosing of IPT is 10mg/kg once daily for 6 months. Patients should not be given a 6 months supply to take home. A minimum of two monthly monitoring is required to check for medication toxicity or development of active TB. Children less than a year of age should be weighed monthly and the dose of isoniazid adjusted with weight gain.
• If a child develops signs and symptoms of active TB while on IPT, then isoniazid
monotherapy should be stopped and the patient should be re-‐assessed and started on full TB treatment.
• All HIV infected children must receive pyridoxine 25mg/day for the duration of IPT
Note: If children have none of the following symptoms or signs -‐ poor weight gain, current cough, or fever -‐ then active TB can be ruled-‐out without TST or CXR.
Key Facts
IPT is intended to prevent recent infection progressing to active TB disease and to prevent latent TB infection (LTBI) from reactivating.
IPT is given for six months after a contact.
If a patient is diagnosed with active TB they need full TB treatment and not isoniazid. mono-‐therapy.
Key fact
Current medical evidence suggests that IPT will not lead to the development of drug-‐ resistant TB provided that children are screened for signs and symptoms of TB before initiating IPT, and periodically during the 6-‐month course of treatment.
