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Learning Objectives

This module will focus on the approaches used to prevent TB in children and adolescents including vaccination, TB preventive treatment, and TB infection control. Detection of new cases of childhood and adolescent TB among close contacts (contact screening) will also be covered

At the end of this module, participants will be able to:

Describe the approaches used to prevent TB in children
Describe the guidance on administration of BCG
Identify groups for which TB preventive treatment (TPT) is recommended and which TPT regimens are recommended
Identify methods used to prevent the spread of TB
Detect new cases of childhood and adolescent TB in households of TB patients.

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Introduction

TB prevention is one of the priority strategies in TB control

Increasing attention is being given to prevention within the End TB Strategy

Recommended approaches for TB prevention include:-

BCG vaccination
Contact screening and management

Improved active TB case finding and management
TB Preventive Treatment (TPT) – also known as treatment of TB infection – for eligible contacts and PLHIV

TB Infection control

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Discussion: Setting specific practices for TB prevention

	Is BCG vaccination included among the TB prevention strategies in your setting? At what age is the BCG vaccine usually given?
	What is the BCG vaccine coverage in your setting? What are some of the challenges hindering access to BCG vaccination?
	What is the BCG vaccination policy in the context of HIV in your setting?

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Bacille Calmette-Guérin (BCG) vaccination (1)

One way to protect someone from an infectious disease (such as TB) is by giving a vaccine
In high burden TB settings, newborns should routinely receive the BCG vaccination
BCG is a live vaccine which stimulates the immune system so it is ‘prepared’ and can react when confronted with TB bacteria

BCG contains a mycobacteria (Mycobacterium bovis) from the same family as Mycobacterium tuberculosis, which have been modified (attenuated) so as not to cause disease

BCG efficacy is variable between populations, including age

When given to newborns, BCG mainly protects infants and young children from getting severe forms of disseminated TB such as TB meningitis or miliary TB

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Bacille Calmette-Guérin (BCG) vaccination (2)

Most people develop a small scar that you can look for if you want to know if a child has been vaccinated with BCG.

Ideally it is recorded in the child health card if BCG given.

Disseminated BCG disease may occur in up to 1% of HIV-infected infants, but risk of BCG disease in baby of HIV-infected mother is much lower in context of PMTCT program
It is advised that BCG is given soon after birth and before the newborn is discharged home.

If the vaccine cannot be administered at birth, it should be given at the earliest opportunity thereafter.
BCG vaccination may be delayed in the context of a neonate born to a mother with TB - will be covered in module 7.

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WHO guidance on BCG vaccination in the context of HIV

Newborns of mothers of unknown HIV status should receive BCG vaccination as the benefits outweigh the risks.
Neonates of unknown HIV status born to HIV-infected mothers should be vaccinated if they have no clinical evidence suggestive of HIV infection, regardless of whether the mother is receiving ART.
A HIV-infected child who did not receive BCG at birth should not receive BCG unless (s)he is on ART, clinically well and immunologically stable.
In settings where early virological testing can be done to confirm HIV infection, BCG vaccination should be delayed in HIV-infected infants until ART has been started and the infant is confirmed to be immunologically stable (CD4 >25%).

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Discussion: Setting specific practices for prevention

	How are close contacts of TB patients currently being identified in your setting – are you using an active or a passive contact tracing model? Are contacts identified at the household level, or only through questions to the TB case? And how do you currently ensure that all contacts are informed and screened for TB?
	Are there clear guidelines in your setting to explain roles and responsibilities related to tracing, screening and follow up of child TB contacts? Is there dedicated staff available at your facility to conduct community based household contact investigation?
	What definition of a household contact is used in your setting? How common is it that multiple unrelated families might share a house or a plot? And if it is common, are questions asked to identify children outside of the immediate family of the TB case who might be in close contact with the case?

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Discussion: Setting specific practices for prevention

	Which contacts are eligible to receive TB preventive treatment? What are the TB preventive treatment regimens that are being used in your setting?
	How is contact management and TB preventive treatment documented in your setting? Do you have any structured tools in place to record number of child contacts identified and screened for TB? Do you have registers to record and monitor preventive treatment delivered to child contacts, including TPT completion?
	How is this process of contact management and TB preventive treatment monitored and reported? Are there programmatic indicators for implementation?
	If there is a high burden of MDR-TB in adults or adolescents your setting? Are there any guidelines on how to manage children exposed to MDR TB?

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TB Contact screening and management

Screening of close contacts of recently diagnosed (usually bacteriologically confirmed) TB patients is widely and strongly recommended by NTPs, but is rarely implemented
Contact screening serves two main functions: –

Active case detection: to identify and treat contacts that have undiagnosed TB disease
Prevention: to identify and treat at-risk contacts that require TB preventive treatment

Contacts may be within the household or outside the household (e.g. school, workplace, neighborhood)
Contact screening can be initiated at the primary health or community care level

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TB contact screening and management

Categories of TB patients prioritized for contact tracing include:-

Bacteriologically confirmed pulmonary TB cases
Children
PLHIV
MDR TB

Any contact with symptoms should be carefully assessed for TB disease and promptly treated if TB is detected

Any contact without symptoms or active disease should be evaluated for TB preventive treatment

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TB contact screening and management

If the index TB patient is the child’s parent and is HIV–infected, test all children for HIV

Align to the national HIV testing algorithm

Follow–up visits for contact screening should be guided by national recommendations

Integrate the approach to screening, follow-up and treatment support for index case and contacts

Use the same opportunity to reach the index case and contacts e.g. TB contact screening for contacts and TB medicine refill for the index TB case as well as TB preventive treatment initiation or refill for the eligible contacts

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Approaches to TB contact management �TB symptom screen

Rationale : to detect contacts of any age with presumptive TB
High sensitivity and a high negative predictive value * Sensitivity is the ability of a test to correctly identify individuals with the disease α Negative predictive value of a test is the probability that individuals who screen negative truly do not have the disease Can be performed by health workers at all levels of care including household Also important to identify contacts who may be eligible for TPT Additional tests such as CXR can improve case detection of active TB or “rule out” for TPT, especially in adolescent contacts

Risk group	Sensitivity*	Negative predictive value^α
Infants and children living with HIV	90%	99%
PLHIV ≧ 10 years	79%	97%
HIV negative contacts ≧ 5 years and other clinical risk groups	73%	99%

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Approaches to TB contact management �chest radiography

Rationale: CXR is commonly used to evaluate symptomatic contacts, often those who are sputum negative or not done. CXR can also be used to detect or rule out TB disease in older child and adolescent contacts (5 years and older) who are negative on symptom screen
CXR has high sensitivity so, in addition to symptom screen, can further increase yield for case detection of TB disease (refer to module 2) Therefore, among older contacts (≥5 years), use of CXR together with TB symptom screening will increase the likelihood and confidence of health providers that disease has been ruled out before commencing TPT CXR has poor specificity in asymptomatic young child contacts There is no need to obtain CXR for asymptomatic young child contacts (< 5 years) who should receive TB preventive treatment as soon as possible

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Approaches to TB contact management �test for infection

Rationale: TB preventive treatment is most effective in contacts without active TB who also have evidence of infection
“Latent” TB infection = a positive test for infection AND no evidence of active TB Either TST or IGRA can be used to indicate previous infection Neither TST or IGRA determines active TB disease and neither test is preferred over the other in terms of predicting progression from infection to disease Both tests have limitations with sensitivity and TST has limited specificity Major practical challenges include cost, not being “point-of-care” and lack of availability, especially for community-based or decentralized care Therefore, WHO recommends that: High-risk contacts such as young children (<5 years) and PLHIV do not require LTBI testing prior to TPT initiation Other HIV-uninfected contacts can be considered for TPT when test is unavailable

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TB preventive treatment (TPT)

Contacts of TB cases are at high risk of infection, and TPT reduces the risk of those with infection from developing TB disease
Approximately 5–10% of people infected with TB will develop disease, most within five years after initial infection
Young child contacts have very high risk of disease (around 20%) if infected and most of these will develop disease within 6 months
TPT is prioritized for individuals at highest risk for progression to TB disease following exposure and infection

Under five contacts
PLHIV

TPT greatly reduces disease risk in infected young children, by 90%
TPT should not be given to someone with active TB

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Suggested Algorithm for TB screening and TPT, WHO, 2020

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Example: TB contact tracing register

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Example: TB contact tracing register & TPT register

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TB preventive treatment options and care

The options for TPT have recently been expanded to include:-

6H 6 months of daily isoniazid i.e. IPT
3RH 3 months of daily isoniazid + rifampicin
3HP 3 months of weekly isoniazid + rifapentine

Other shorter regimens include 1 month of daily rifapentine or 4 months of daily rifampicin
Compared to isoniazid, shorter regimens are equally effective with fewer severe adverse events and better adherence/completion rates
Regular follow-up remains an important part of treatment support to review side-effects, assess for TB disease, check weight and correct dosage, provide sufficient medicine and to strengthen adherence
Children and adolescents generally tolerate TPT very well, especially young children, and serious adverse events are rare

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TB preventive treatment options and care

It can be challenging to counsel and convince a family that their child needs to take medicine every day for months, when the child is well. For this reason, caregiver education and sensitization is critical.
Pyridoxine can be considered for co-administration with TPT that contains isoniazid to reduce risk of isoniazid-related neuropathy. However, this risk is extremely low in child contacts who are otherwise well

The majority of contacts require only a single course of TPT, and there is no evidence to support or define the role of repeated courses of TPT.
However, this can be considered on a case-by-case basis such as among contacts who have an additional (separate) close or household TB exposure after completing TPT.
Consideration will include careful assessment of infection risk, disease risk and potential benefits versus risk of TPT.

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Considerations for TPT initiation and follow-up

Consideration	Rationale
Exclusion of active TB disease	Do not give TPT to a person with active TB as not effective and risks development of drug-resistance
TB characteristics of index case	Contacts of known or presumptive DR TB are not eligible for TPT using isoniazid, rifampicin or rifapentine
Characteristics of contact	Age, pregnancy*, comorbidities and weight for dosage considerations
Comorbidities and concurrent medications	Possible drug-drug interactions (such as ART); integration of care packages. Rifamycin based TPT regimen are not recommended for PLHIV on PIs or NVP based ART due to reduction in plasma levels of ART medicines
Regimen selection	Appropriate regimen – age, availability
Appropriate dosage	Dosage is by weight (not age) and recheck at follow-up

* Prefer child-friendly formulations in young children.

* Rifapentine not recommended for <2 years; ** or for pregnant women

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Considerations for TPT initiation and follow-up

Consideration	Rationale
Availability of regimen option	Ensure sufficient supply for regimen completion
Pyridoxine	INH can cause peripheral and central neuropathy due to vit B6 deficiency, though this is extremely rare in well children. Pyridoxine should be given with isoniazid-containing regimens to at-risk populations: including those with co-morbidities such as PLHIV, malnourished, renal failure and diabetes, as well as to pregnant and breastfeeding women
Education and counseling	Ensure understanding of justification for preventive treatment for well child and adolescent contacts and PLHIV
Follow–up; monitoring and evaluation	Monitor weight and for signs & symptoms of TB disease Assess adherence and side-effects to TPT NTP register and reporting requirements

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Considerations for TPT regimen selection

Population	Preferred TPT regimen	Alternative TPT regimen
Children < 25 kg	3RH (Pediatric FDC RH 75:50 formulation)	6H* 3HP**(if ≧ 2 years)
Children ≧ 25kg	3RH or 3HP (Adult formulations)	6H (Adult formulations)
Children living with HIV	6H*	For children on Efavirenz 3HP** (among ≧ 2 years) or 3RH
Adolescents living with HIV	3HP	6H (Adult formulations)

*Dispersible formulations for Isoniazid are preferred

** Currently there is no pediatric formulation for the 3HP regimen

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Examples of dosage charts using 6H and 3RH

Weight band	Isoniazid daily dose	H 100 mg* tablet	H 300 mg tablet	RH 75/50 mg FDC
4-7 kgs	50 mg	0.5	-	1
8-11 kgs	100 mg	1	-	2
12-15 kgs	150 mg	1.5	-	3
16-24 kgs	200 mg	2	-	4
≧ 25 kgs	300 mg	3	1	Use adult formulations

Dosages for in children: H 10 mg/kg (range 7-15 mg/kg); R 15 mg/kg (10-20 mg/kg)

Dosage in adolescents and adults: H 5 mg/kg, max 300 mg; R 10 mg/kg, max 600 mg

*Dispersible formulations for Isoniazid are preferred

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Examples of dosage charts: 3HP using fixed dose combination tablet options

Weight band	Isoniazid (H) weekly dose	Rifapentine (P) weekly dose	HP 300/300 tablet
10-14 kgs	300 mg	300 mg	1
15-24 kgs	450 mg	450 mg	1.5
25-29 kgs	600 mg	600 mg	2
30 kgs or more	900 mg	900 mg	3

Currently, rifapentine is not recommended for use in infants and children of less than 2 years: await safety and PK data.

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Considerations for monitoring children and adolescents on TPT

Follow–up visits	Conduct regular follow–up visits as per national guidelines Align follow-up visits for the index TB case and contacts on TPT to strengthen adherence, including PLHIV receiving ART
Weight monitoring	Check weight on every follow–up visit and adjust dosages accordingly
Adherence	Review adherence to TPT Implement a family-centered approach to strengthen adherence
TB symptoms	Assess for TB symptoms at each follow–up visit
Side effects	Assess for side effects at each follow–up visit and manage as per the national guidelines

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How to manage TPT interruptions

TPT regimen	Duration of interruption	Management
3RH or 6H	< 2 weeks OR > 2 weeks and > 80% of doses taken	Extend TPT duration by number of days of missed doses to complete as per original plan
	> 2 weeks and < 80% of doses taken and treatment can be completed within expected time of completion*	Continue and complete the remaining doses as per original plan
	> 2 weeks and < 80% of doses taken and treatment cannot be completed within expected time of completion*	Consider restarting the full TPT course
3HP	1 weekly dose missed and missed dose is remembered within 2 days	Advise client to take missed dose and continue TPT as per original plan following same schedule
	1 weekly dose missed and missed dose is remembered after 2 days	Advise client to take the missed dose and change the schedule for weekly intake to the day the missed dose was taken until completion.
	1 – 3 weekly doses missed	Continue treatment until 12 doses are taken (to maximum of 16 weeks)
	≥ 4 weekly doses missed	Consider restarting full TPT course

*Expected time of completion = Treatment duration + 33% additional time

Always remember to address barriers to adherence

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How to manage TPT related side effects

Side effect	What to do
Hepatitis (anorexia, malaise, vomiting or jaundice)	Potentially the most serious side effect Stop TPT and refer the patient
Gastrointestinal symptoms	Continue TPT: Usually mild – reassure the patient Suggest administer with food
Lethargy	Continue TPT and re-assure the patient
Itching with or without rash	Mild: continue TPT and administer antihistamines Moderate/severe: stop TPT and give steroids
Flu-like syndrome	Likely rifamycin-related (R or P) Mild: Continue treatment and observe Moderate – severe: Stop TPT and consider 6H
Drug-associated fever	Stop TPT and re-introduce if fever settles below 39⁰c. Stop permanently if fever recurs
Neurological (neuropathy, psychosis, seizures)	Likely INH-related; Stop TPT, continue pyridoxine and consider 4R

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Example: TPT treatment card (front side)

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Example: TPT treatment card (backside)

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TB preventive treatment and NTP

All individuals initiated on TPT should be registered with NTP in order to ensure adequate supply, monitoring of uptake, adherence and outcome of TPT.

Many NTPs have developed contact screening registers and TPT (or IPT) registers

The WHO now requests and reports data of TPT implementation
Key programmatic performance indicators include:

Coverage: numbers (%) of eligible contacts screened
Uptake: numbers (%) of eligible contacts who initiate TPT
Completion: numbers (%) with full adherence of those who initiated TPT

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Checklist: key steps in considering TPT

Perform symptom screen and weight at every visit: initial and follow-up
Detect - and rule out- active disease in contacts with :

Collect a sample for rapid diagnostics (such as Xpert MTB/RIF) whenever possible
Chest X ray: if symptomatic but unable to provide diagnostic sample or negative on rapid diagnostic

Assess for TPT eligibility if TB is excluded
For child contacts < 5 years

Consider if TPT contraindicated

Active or chronic hepatitis; concurrent medication with risk of hepatotoxicity (e.g. nevirapine); previous intolerance to TPT drugs

If TPT is not contraindicated, initiate TPT

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Checklist: key steps in considering TPT

Counsel individual and family

Rationale; education; safety; adherence; follow-up; school/work

Update the relevant tools

For child contacts ≥ 5 years

Test for infection (if available) for HIV-uninfected contacts ≧ 5 years
Initiate those eligible for TPT without contraindications to TPT
Counsel individual and family

Rationale; education; safety; adherence; follow-up; school/work

Update the relevant tools

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Considerations for TPT in DR TB contacts�WHO 2020

WHO does not currently recommend a specific TPT regimen for contacts of MDR-TB
The decision for treatment of infection (i.e. TPT) in contacts of MDR-TB contacts should be taken on an individual basis

Active disease in contacts must first be detected or ruled out
Considerations for TPT include:

Characteristics of contact - high-risk such as young children, PLHIV or people receiving immunosuppressive therapy
Drug susceptibility of the index case, such as established sensitivity to fluoroquinolone (by LPA or DST)

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Considerations for TPT in DR TB contacts�WHO 2020

TPT should be considered only after TB disease is ruled out by an appropriate clinical evaluation or according to national guidelines and after a careful risk assessment

Confirmation of infection by TST or IGRA is desirable prior to TPT initiation.

Reduces the likelihood of TPT being given unnecessarily for MDR-TB

Strict clinical observation for signs of TB disease for at least two years after exposure should be ensured, regardless of whether TPT for MDR-TB is given or not

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Case study 4: Missed opportunity for TB (and HIV) prevention

Case study 4	Saka is an 8-month-old boy who was taken to the hospital severely ill with a decreased level of consciousness, convulsions, and fever. He had started on a course of antimalarial treatment before the onset of convulsions. Saka has a mild cough as well and has lost weight. His mother is on TB treatment and reports that he has not missed any doses. On examination, Saka responds to painful stimulation. His temperature is 38.10c. His head and neck are arched back. His fontanelle is full. No palpable lymph nodes. He has normal breath sounds with shallow and fast breaths (50/min) HIV test is positive. Urine LF-LAM test is positive and Xpert MTB/RIF on gastric aspirate is positive (MTB detected/ RIF sensitive) He is diagnosed with TBM and TB treatment is commenced. Identify possible missed opportunities for TB prevention Identify possible missed opportunities to prevent HIV

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Case study 7: Conducting contact screening

Case Study 7	Paul is a 15 year-old boy who presented to the community clinic with cough and evening fevers for 3 weeks; associated profuse sweating and weight loss. He is HIV negative and has bacteriologically confirmed TB - sputum smear positive; Xpert MTB/RIF test: MTB detected/RIF sensitive. He lives with 7 other people at home, attends a nearby secondary school and helps out at the family shop after school. 1. Select the group of contacts that should be your first priority for contact screening . Neighborhood Household members (4yr, 54yr, 45yr, 10yr, 2yr, 12yr, 9yr) Grandmother who visited 5 months ago Community School mates 2. Identify priority groups for TPT among the household members who have been traced in the community as indicated in the table that follows. 3. Complete the TB Contact tracing and TPT registers

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Case study 7: Evaluation for TPT

Contact information	Symptom screen in the community	Eligible for TPT (Yes/No/ Additional evaluation required)	Explain your response	If eligible for TPT, list regimen options
4 years – sibling	Asymptomatic
54 years - mother	Cough for 2wks
45 years – aunt living with HIV	Asymptomatic
10 years – sibling	Asymptomatic
2 years – sibling	Poor weight gain
12 years – aunt’s son, HIV negative	Asymptomatic
9 years – sibling	Cough for 5 days

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Case study 7: Conducting contact screening in a school setting

Case Study 7	As mentioned, Paul attends a nearby secondary school 1.Select the group of contacts that should be your first priority for contact screening in the school setting. Teachers Classmates Support staff Other children in the school 2.Describe the contact screening approach you would use in this setting 3. Paul has now been receiving treatment at home for more than 2 weeks and is already feeling much better. What discussion with teacher about Paul’s return to school?

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Case study 9: Conducting contact screening

Case Study 9	Ojore is a five year -old boy on ART (ABC/3TC/LPVr). He was diagnosed with bacteriologically confirmed PTB (Xpert MTB positive / RIF sensitive). He and his two siblings are being cared for by his father. During the day, his father leaves Ojore and his siblings with a neighbour who has a chronic cough. The neighbour has 2 children (3yrs and 6yrs). 1. Select the group of contacts that should be your first priority for contact screening . Neighbor /day caretaker Household members (father, 10yr, 7yr) Siblings’ school mates Neighbor’s children (3yr, 6yr) 2. Identify priority groups for TPT among the close contacts who have been traced in the community as indicated in the table that follows. 3. Complete the contact tracing and TPT registers

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Case study 10: Identifying priority groups for TPT

Contact information	Symptom screen in the community	Eligible for TPT (Yes/ No/ Additional evaluation required)	Explain your response	If eligible for TPT, list regimen options
40 years – Father living with HIV	Asymptomatic
10 years – Sibling living with HIV	Cough
7 years – Sibling living with HIV	Asymptomatic
Neighbor/day carer – HIV negative	Cough for 2 months
Neighbor’s child – 3yrs	Cough
Neighbor’s child –6yrs	Asymptomatic

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Discussion: Setting specific practices for infection control

	Are basic infection control measures implemented in healthcare facilities in your setting and if so, what are they? What facilities or clinical settings are regarded as settings where children might have a high risk of exposure to TB? Discuss firstly how patients and their children are protected, and then how healthcare workers are protected.
	Which children with TB that require hospitalisation are at particular risk of transmitting TB to other children in the hospital ward? What do you do to reduce this risk?
	A mother with TB has a sick new born who requires inpatient care. How do you reduce the risk of that mother transmitting TB to other sick infants while caring for her baby?
	Are TB patients informed about basic infection control principles that they could implement at home? Is there any opportunity (for example, home visits) where the messages about infection control could be reinforced, and the entire household could be educated?

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TB Infection Control

Infection control is a key strategy to prevent further spread of TB
Interventions may be implemented at the health facility or community level
Health facility level interventions and administrative measures aimed at reducing exposure and transmission may include:-

Early identification of patients who have presumptive TB (e.g. cough triage and separation of coughing patients)
Prompt diagnosis and linkage to treatment
Keeping windows and doors open to allow adequate air circulation
Respiratory hygiene (including cough etiquette) among people with presumptive or diagnosed TB
Use of masks for patients

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