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Key acts about children andtuberculosis (TB)

TB exposure

Any child living or spending time in a setting where there are people with inectiousTB may be exposed to Mycobacterium tuberculosis.

TB inection

Inection with M. tuberculosis usually ollows exposure to a person with TB who iscoughing; inection occurs when TB bacilli are inhaled into the respiratory system.

The likelihood o becoming inected ollowing exposure is greatest when there hasbeen close contact with an inected person (or example, in a household) and i theinected person has sputum smear-positive pulmonary TB. However, transmission

can also occur rom persons with smear-negative, culture-positive pulmonarydisease.

When inection occurs, the TB bacilli multiply and drain to regional lymph nodeswhere cell-mediated immunity is activated to contain the inection. The tuberculinskin test is an indicator o this immune response to inection, and will usually becomepositive within 812 weeks o inection. Around 90% o children inected withM. tuberculosis will contain the inection and remain well.

Progressing rom inection to disease

Any child inected with M. tuberculosis may develop TB. Most children develop TB disease within one year o becoming inected. This is why

taking a contact history is relevant, and why the burden o TB in children reectscontinuing transmission within a population.

Risk actors or developing disease ollowing inection include young age (that is,being less than three years old) and immunodefciency (such as that caused by HIVinection, measles or severe malnutrition). Adolescence is another period duringwhich there is an increased risk o developing disease.

Progression rom inection to disease is indicated by the onset o symptoms.

TB disease

The most common type o TB disease in children is pulmonary TB, o which sputumsmear-negative disease is most requent. Cases in which sputum cannot be

obtained or smear microscopy are also considered to be and reported as sputumsmear-negative. Extrapulmonary TB occurs in approximately 2030% o all cases in children; TB

adenitis and TB pleural eusion are the most common orms. The presentation o TB disease in children is age-related and dependent on immune

response. Inants and young children are at particular risk o developing severe,disseminated and oten lethal disease, which may present as TB meningitis or miliaryTB. Adolescents are at particular risk o developing adult-type disease (that is, theyare oten sputum smear-positive and highly inectious).

Diagnosing TB in HIV-positive children is similar to diagnosing HIV-negative childreno a similar age.


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WHO Library Cataloguing-in-Publication Data

Roadmap or childhood tuberculosis: towards zero deaths.

1. Tuberculosis, Pulmonary prevention and control. 2. Tuberculosis. 3. Child. 4. National healthprograms. 5. Health policy. I. World Health Organization. II. UNICEF. III. Center or Disease Control (U.S.).IV. International Union Against TB and Lung Disease. V. Stop TB Partnership. VI. USAID.

ISBN 978 92 4 150613 7 (NLM classifcation: WF 300)

World Health Organization 2013

All rights reserved. Publications o the World Health Organization are available on the WHO web site(www.who.int) or can be purchased rom WHO Press, World Health Organization, 20 Avenue Appia, 1211Geneva 27, Switzerland (tel.: +41 22 791 3264; ax: +41 22 791 4857; e-mail: [email protected]).

Requests or permission to reproduce or translate WHO publications whether or sale or or non-commercial distribution should be addressed to WHO Press through the WHO web site (www.who.int/about/licensing/copyright_orm/en/index.html).The designations employed and the presentation othe material in this publication do not imply the expression o any opinion whatsoever on the part o theWorld Health Organization or contributing agencies concerning the legal status o any country, territory,city or area or o its authorities, or concerning the delimitation o its rontiers or boundaries. Dotted lineson maps represent approximate border lines or which there may not yet be ull agreement.

The mention o specifc companies or o certain manuacturers products does not imply that they areendorsed or recommended by the World Health Organization or contributing agencies, in preerenceto others o a similar nature that are not mentioned. Errors and omissions excepted, the names oproprietary products are distinguished by initial capital letters.

All reasonable precautions have been taken by the World Health Organization to veriy the inormationcontained in this publication. However, the published material is being distributed without warranty o anykind, either expressed or implied. The responsibility or the interpretation and use o the material lies withthe reader. In no event shall the World Health Organization or contributing agencies be liable or damagesarising rom its use.

Printed by the WHO Document Production Services, Geneva, Switzerland.

WHO/HTM/TB/2013.12

Design by Ins Communication www.iniscommunication.com

Cover photo credits: Top right: WHO/Damien Schumann

Caption: For Zanele and Lilathi, the fght is not over. They will have to stick to their clinicappointments and keep taking their medication. But thanks to the integrated TB and HIV servicesprovided in Nyanga they both have the chance to lead ulflling lives. Without these services,Zaneles TB could have been ignored in the shadow o HIV.

Top let: WHO/HM.Dias

Caption: Jerome has multidrug-resistant TB, he has been undergoing treatment or over a month atthe East Avenue Medical Center, Philippines.

Bottom right: ECDC/Tobias Hosss


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Acknowledgements

The writing and overall coordination o this document was led by members o theChildhood TB Subgroup o the Stop TB Partnership. Feedback was sought rom all

members o the subgroup and rom partners within the broader feld o internationalchild health. WHO is grateul to all who contributed to the document, especially toHannah Monica Yesudian Dias who coordinated the fnal editing and publication o thedocument.

Core writing team

Anne Detjen, Marianne Gale, Ines Garcia Baena, Steve Graham, Malgorzata Grzemska,Coco Jervis, Heather Menzies (leader), Charalambos Sismanidis, Jerey Starke,Soumya Swaminathan.

Contributors

Lisa Adams, Farhana Amanullah, Annemieke Brands, Dick Chamla, Dennis Cherian,Colleen Daniels, Danielle Doughman, Gunta Dravniece, Vijay Edward, Anthony Enimil,Robert Gie, Walter Haas, Barbara Hauer, Anneke Hesseling, Anna Mandalakas, DavidMcNeeley, Gloria E. Oramasionwu, Alonso Rosales, Clemax SantAnna, Alan Talens,Renee Van de Weerdt, Clara van Gulik, Christine Whalen, and all who participated in theannual meeting o the Childhood TB Subgroup held in Kuala Lumpur, Malaysia in 2012.


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Contents

WHO/S. Labelle

Acknowledgements 1

Abbreviations 4

Preace 6

Executive summary 8

Childhood TB: identiying the challenges 11

Tackling childhood TB: a progress update 16

The roadmap towards a TB-ree uture or children and adolescents 21

1. Include the needs o children and adolescents in research,

policy development and clinical practices 21

2. Collect and report better data, including data on prevention 21


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3. Develop policy guidance, training and reerence materials or

health care workers 23

4. Foster local expertise and leadership 24

5. Do not miss critical opportunities or intervention 25

6. Engage key stakeholders 27

7. Develop integrated amily-centred and community-centred strategies 298. Address research gaps 30

9. Meet unding needs or childhood TB 32

10. Form coalitions and partnerships to improve tools or diagnosis and treatment 33

Achieving zero deaths 35

Resources 37



Abbreviations

AIDS acquired immunodefciency syndrome

BCG bacille CalmetteGurinDOTS basic package o interventions or TB control that underpins

the Stop TB strategy

GDP gross domestic product

HIV human immunodefciency virus

iCCM integrated community case management

IMCI integrated management o childhood illness

IMPAACT International Maternal Pediatric Adolescent AIDS Clinical Trials Group

MDR-TB multidrug-resistant tuberculosis

TB tuberculosis

WHO World Health Organization



WHO/Karin Bergstrom



Preace

Ater decades o being relegated to the shadows, the childhood tuberculosis (TB)epidemic is now in the global spotlight. The goal o a world with zero TB deaths in

children has been endorsed by the international TB community and has melded keystakeholders to make this goal a reality. This is a signifcant breakthrough or partnersand advocates who have worked tirelessly to draw attention to the misunderstoodepidemic o TB in children.

The urgency o the problem o TB in children, whose ull scope is still not ully known,cannot be underestimated. World Health Organization (WHO) estimates in 20121revealed that up to 74 000 children die rom TB each year and children account oraround hal a million new cases annually. It should be noted that the estimated deathsonly include those in human immunodefciency virus (HIV)-negative children. In act,the actual burden o TB in children is likely higher, especially given the challengein diagnosing childhood TB. Compounding this difculty with diagnosis is the act

that children with TB oten come rom amilies that are poor, lack knowledge aboutthe disease and live in communities with limited access to health services. Anothercompelling reason is that TB is important in the context o childrens overall survival. Wedo not know the extent to which TB is a cause o childhood deaths that are reportedin global statistics as deaths due to HIV, pneumonia, malnutrition or meningitis, but thenumber is likely to be substantial.

The strategy or global TB control expanded beyond DOTS in 2006 with the Stop TBstrategy. This emphasizes prioritization o actions or vulnerable populations suchas children, including intensifed case- and community-based care.2 A post-2015 TBstrategy is currently being developed and the proposed ramework includes increasedocus on TB care or children integrated with child health and HIV services as wellas other preventive services. Building on the global strategies, as well as the globalchild survival movement A Promise Renewed this roadmap developed by WHOand partners under the aegis o the Childhood TB Subgroup lays out the strategicramework or combating childhood TB. This provides an important opportunity toaddress TB in children and needs to be backed with enhanced resource commitmentsboth globally and nationally. Global estimates indicate that at least US$ 80 million peryear will be required to address TB in children. An additional US$ 40 million per year willbe needed or antiretroviral therapy and co-trimoxazole preventive therapy or childrencoinected with TB and HIV. Filling this resource gap would save tens o thousands ochildrens lives rom this preventable and curable disease.

Furthermore, success in ending the TB epidemic in children cannot be achieved withoutadvances in research and development. There is urgent need or improved diagnosticand treatment options or children with TB. The research community needs to comeorward and take action to address these challenges.

At the country level there is good news. A signifcant transormation o political will andcommitment to intensiy eorts to address TB among children has taken place. NationalTB programmes are increasingly striving to address the challenges o caring orchildren with TB, including those inected with both HIV and TB, and children who areclose contacts o people with TB. National priorities are being identifed, and countries

1 Global tuberculosis report 2013. Geneva, World Health Organization, 2013 (in press).

2 DOTS is the basic package o interventions or TB control that underpins the Stop TB strate. For more inormation, see:The Stop TB strategy: building on and enhancing DOTS to meet the TB-related Millennium Development Goals. Geneva,

World Health Organization, 2006 (WHO/HTM/TB/2006.368). (Available rom http://whqlibdoc.who.int/hq/2006/WHO_HTM_

STB_2006.368_eng.pd).



have had more input into international activities that address TB in children. A growingnumber o national TB programmes are orming working groups and dedicating stato coordinating activities aimed at addressing childhood TB. National policies andguidelines are being developed or updated, but there is still a wide gap between policyand practice that must be bridged.

While eorts by TB programmes contribute to combating the childhood TB epidemic,the root o this problem can only be addressed with the engagement and accountabilityat all levels o the health care system and community. Children with TB present tohealth services in the same context as children with common childhood illnesses,which is generally at primary and secondary care settings. This includes those thatprovide maternal and child health care, HIV care, or nutritional rehabilitation support,as well as outpatient and inpatient acilities that care or sick children or adults withTB. In act, the most obvious point o entry into the health system or many childrenwith TB (or those who are contacts o someone with TB) is at the community level,where the childs parent, guardian or other household contacts have been diagnosedwith TB or where their care is being managed. In order to oer a more comprehensiveand eective service at the community level or children and their amilies aectedby TB, increased eorts are being launched to improve integration, coordination andcommunication among dierent care providers. Decentralizing TB care or children isalso likely to be highly cost eective because it will improve access to diagnosis andthe early initiation o treatment, and will not require a large increase in resources.

This is a pivotal moment in the fght against childhood TB. We need determinedleadership, political commitment at all levels and research all backed by sustainableresources to achieve the goal o zero TB deaths in children. We also need to movebeyond the traditional approach to TB care and control by working synergisticallyacross the entire health system and partnering with communities, making the most ocritical opportunities to get to zero deaths among children with TB.

Any child that dies rom TB is one child too many, so there should be no question owhy to act. This roadmap shits us toward how we can chart a course to accelerateprogress against this deadly disease in children.

Dr Nicholas Kojo Alipui

Director o Programmes

United Nations Childrens Fund

Dr Steve Graham

Chair, Childhood TB Subgroupo the Stop TB Partnership

Centre or International Child Health,University o Melbourne, AustraliaConsultant in Child Lung Health,The Union

Dr Mario Raviglione

Director, Global TB Programme

World Health Organization



Executive summary

The goal o reaching zero tuberculosis (TB) deaths among children worldwide iswithin our grasp. Achieving this requires sustained advocacy, greater commitment,

mobilization o increased resources and a joint eort by all stakeholders involved inproviding health care or children and in TB control. This roadmap indicates key actionsand the enhanced investment urgently needed to tackle childhood TB.

Key messages

Childhood TB needs to be lited out o the shadows

Every day, up to 200 children3 lose their lives to tuberculosis a preventable andcurable disease.

Over hal a million children all ill with TB each year and struggle with treatment thatis not child riendly.

TB in children is oten missed or overlooked due to non-specifc symptoms anddifculties in diagnosis. This has made it difcult to assess the actual magnitude othe childhood TB epidemic, which may be higher than currently estimated.

There is an urgent need or public attention, prioritization, commitment and undingor this disease that today should never take the lie o a child.

Research is urgently needed to address TB in children

Currently there is a lack o eective diagnostic tests that can detect TB in children,child-riendly drug ormulations or treatment and care or children with TB and/orthose in contact o someone diagnosed with TB.

Research should include children in clinical trials or testing o new diagnostics anddrugs. There is a need to strengthen the evidence base that supports the integration o care

or childhood TB into other child care services, and also about the impact that theseeorts have on TB case-fnding and child survival.

Childhood TB can only be eectively addressed with collaboration acrossthe health system and community

Childhood TB should move rom being the sole responsibility o national TBprogrammes, as care or sick children is primarily sought in separate paediatricservices at dierent levels o the health system. Prioritization o childhood TB is

critical in national health strategies, plans and budgets. There is an urgent need or greater awareness o, and increased screening or, TB in

children, particularly by services that serve children in settings with high prevalenceo TB and human immunodefciency virus (HIV). Children with TB oten present atprimary- and secondary care settings where there is a lack o guidance on how toaddress the challenges o diagnosing and managing childhood TB.

Child health workers and paediatricians in both the public and private sectors shouldreport to national TB programmes all children diagnosed with TB, so that acceptableollow up can be ensured to allow both better care and an improved understandingo TB burden.

3 children aged less than 15



Enhanced investment is critical to end TB deaths among children

Meeting the goal o zero TB deaths in children requires increased investment andleveraging o resources both globally and at the country level to ensure that theactions highlighted in the roadmap are undertaken.

The World Health Organization (WHO) estimates that globally at least US$ 80 million

per year will be required to address childhood TB. An additional US$ 40 million peryear will be needed or antiretroviral therapy and co-trimoxazole preventive therapyor children coinected with TB and HIV. These fgures probably understate thefnancial eort required due to lack o accurate inormation about the actual burdeno TB among children.

The Stop TB Partnership Global Plan to Stop TB 20112015 estimates that duringthis period US$ 7.7 billion is needed or research and development into TB (thisrepresents the amount needed or all age groups).4 O this, at least US$ 0.2 billionwill be required to complete projects directly aimed at providing new tools orpreventing, diagnosing and treating children who have TB. At present, only 32% othe unding needed or TB research and development is available.

4 Global plan to Stop TB 20112015. Geneva, World Health Organization, 2010 (WHO/HTM/STB/2010.2). (Available rom http://

www.stoptb.org/assets/documents/global/plan/TB_GlobalPlanToStopTB2011-2015.pd).

The Childhood TB Roadmap an overviewThis roadmap or addressing childhood TB outlines 10 key actions to be taken at both theglobal and national levels:

1. Include the needs o children and adolescents in research, policy development and clinicalpractice.

2. Collect and report better data, including on preventive measures.

3. Develop training and reerence materials on childhood TB or health care workers.4. Foster local expertise and leadership among child health workers at all levels o the health

care system.

5. Do not miss critical opportunities or intervention (e.g. use strategies such as intensifedcase-fnding, contact tracing and preventive therapy); implement policies or early diag-nosis; and ensure there is an uninterrupted supply o high-quality anti-TB medicines orchildren).

6. Engage key stakeholders, and establish eective communication and collaboration amongthe health care sector and other sectors that address the social determinants o health andaccess to care.

7. Develop integrated amily- and community-centred strategies to provide comprehensive

and eective services at the community level.8. Address research gaps in the ollowing areas: epidemiology, undamental research, the

development o new tools (such as diagnostics, medicines and vaccines); and addressgaps in operational research, and research looking at health systems and services.

9. Close all unding gaps or childhood TB at the national and global levels.

10. Form coalitions and partnerships to study and evaluate the best strategies or preventingand managing childhood TB, and or improving tools used or diagnosis and treatment.



Derwish



Box 1. Childhood TB: a missed opportunity

to improve child survival

Many children who present with TB diseaserepresent an opportunity missed by the healthsystem to have prevented the disease. Thisis particularly the case or inants and youngchildren: studies consistently show that mostcases o TB in children occur in those with aknown contact who has been diagnosed withTB, which is requently a parent or anotherclose relative o the child. Inants and youngchildren are at particularly high risk or severe,disseminated TB disease and or TB-relatedmortality. And yet it is all too common to

have the child o a parent who has TB topresent with TB meningitis, which is requentlyatal, and i not, oten results in marked andpermanent disability. This could be preventedby screening children who are contacts opeople diagnosed with TB and by providingpreventive therapy or children younger thanfve years o age at the time TB is diagnosed ina parent or amily member.

Childhood TB:

identiying the challenges

Defning the true burden o diseaseWHO estimates that the annual global burden o TB in children5 in 2012 wasapproximately 530 000 cases (or 6% o global TB burden), and that up to 74 000children died rom TB that year. It is important to note that TB-related deaths in childreninected with HIV are not included in these estimates because they are classifed asdeaths caused by HIV (i.e. not TB). These estimates have urther limitations, and theburden o TB in children is likely to be higher. For example, in settings with a highburden o TB, around 1020% o all TB cases are expected to occur in children. Thesecountries also have high rates o mortality in children who are younger than fve years

o age. However, in reality, many national TB programmes report numbers well belowthe expected range. There is no data on the burden o multidrug-resistant (MDR-TB)in children but it is likely to be considerable given that up to hal a million adults all illworldwide with this orm o TB each year. The prevention, diagnosis and managemento MDR-TB in children provides special challenges or TB programmes and is oten onlyaccessible at reerral levels o care.

The lack o an accurate diagnostic test or TB inyoung children is another major challenge, andadds to the potential or both an under-diagnosisand an over-diagnosis o cases. Even whenchildren are diagnosed with TB and treated or

it, many are not registered with or reported to/bynational TB programmes.

The clinical overlap o TB symptoms with commonchildhood diseases results in many TB casesbeing missed, including the more severe and otenatal cases that present as severe pneumonia,malnutrition or meningitis. However, TB is notadequately recognized as important within theoverall child survival ramework. The challengeremains to better understand its contribution tothe common causes o morbidity and mortality inyoung children, such as pneumonia, malnutrition,meningitis and HIV. Increasing evidence suggeststhat TB may be an important primary causeo illness or comorbidity in these contexts. Asmortality in children decreases as a result othe wider implementation o vaccines, and aspneumonia, meningitis and malnutrition becomeless common, Mycobacterium tuberculosis willbecome relatively more important and obviousas a causative pathogen o these diseases, sotreatment will hopeully become more easible

(Box 1).

5 children aged less than 15



Adolescents6 are another important group at risk or TB, and there are additionalmanagement challenges that are particular to that age group, especially i anadolescent is also living with HIV. However, diagnosis is usually less challenging inadolescents with TB than in younger children because adolescents can readily providesputum, and are commonly sputum smear-positive.

Struggling against historical neglect

Childhood TB has historically been neglected by the global TB community and thehealth community in general. There are a number o actors that explain this neglect.

The difculty in confrming a case o childhood TB: the lack o accurate, reliablediagnostic tools led to scepticism about the reliability o diagnosis and aconsequent lack o confdence among health workers about their ability to identiychildren with TB.

The poor recording and reporting practices or childhood TB: only sputumsmear-positive cases have been routinely reported to and by national TB controlprogrammes, and so most cases o TB in children (which are oten sputum smear-negative and extrapulmonary) have not been reported; as a result, the burden o

disease in children has been unrecognized at both national and international levels. The misperception o childhood TB as a low public health priority: children with

TB are usually less inectious than adults. Consequently, they have receivedlittle attention rom national TB control programmes that prioritize interruptingtransmission by detecting and treating cases with sputum smear-positive TB.

The misperception that childhood TB would disappear simply by containing TBin the adult population: modelling studies suggest that improving the detectionand management o childhood TB could have a ar greater impact on the healtho children than improving detection and treatment o adults with TB. Further,identiying children with TB inection is important because they orm a large pool opotential TB cases that can urther propagate the epidemic.

A misplaced aith in the protective efcacy o the bacille CalmetteGurin (BCG)vaccine: although the BCG vaccine has been shown to prevent about 60% to90% o cases o meningeal TB and disseminated TB in young children, it does notprevent a high enough proportion o cases in children or adults to be considered anadequately eective measure o TB control.

A lack o research and investment: the scientifc study o childhood TB is largelyattributable to insufcient unding and inadequate interest rom industry. Thisinattention derives partly rom the difculty with microbiological confrmation othe disease, but also originates in the reticence to conduct studies in children, andthe perception that the market or innovations in the diagnosis or management ochildhood TB would be too small to justiy investment.

A lack o advocacy on behal o children and adolescents with TB rom boththe TB community and the child health community: the widely acknowledgedunderreporting o childhood TB means that its impact on childrens survival has beenunderestimated and under recognized. Within child health programmes there hasbeen a lack o recognition o the importance o TB; these programmes serve someo the children who are at highest risk, including those who are malnourished or haveHIV/AIDS, conditions or which TB screening, treatment and prevention have thepotential to substantially reduce morbidity and mortality.

Although these challenges persist, they can be overcome, and children can bediagnosed, treated and cured.

6 WHO defnes adolescence as between 10 and 19 years o age.



Addressing persisting barriers to scale up

Many o the issues o historical neglect remain barriers that will need to be overcome in

order to scale up activities and services or children with TB.

Prioritization in national TB programme

agenda: Addressing childhood TB is rarelyincluded in strategies and budgets or nationalTB control programmes. TB control sta otenhave limited knowledge o and experiencewith managing childhood TB. Althoughguidelines oten exist, the gap between policyand practice is wide in childhood TB. This isparticularly the case or screening children whoare contacts o someone diagnosed with TBand or managing their care. Screening andtreating children who are contacts o someonewith TB are universally recommen but thesesteps are rarely implemented and i they are,there is oten no record o them.

In addition, national reporting o TB casesoccurring in children needs to be strengthenedas it is oten incomplete, and does not providecritical data disaggregated by age on the typeso disease and treatment outcomes.

Collaboration across health system and

community: Although national TB control

There are many contributions which

the paediatrician can make to the

tuberculosis control program. First

the negativism about tuberculosis

so prevalent in paediatrics must be

overcome. Wherever there aretuberculous adults there are infected

children. No one is immune.

Author: Edith Lincoln, a pioneering paediatricianwho originally observed the natural history oinection and TB disease in children, publishedoriginal research on the protective eect oisoniazid

Source: Lincoln EM. Eradication o tuberculosis in

children.Archives of Environmental Health, 1961,3:444455.

amien Schumann



programmes are oten blamed or neglecting children with TB, the broader child healthcommunity is also responsible, and has a critical role to play in overcoming the barriersto diagnosing and caring or children with TB. This was recognized more than 50 yearsago but there is still oten little connection between TB programmes and child healthsectors.

A child with TB becomes engaged with control programmes only once a diagnosishas been made and the child has been registered. Beore this stage, however, a childwith TB presents simply as a sick child requiring the attention o the child healthsector. When child health workers are trained, curricula oten neglect the signs andsymptoms o TB in children, and there is oten a lack o guidance on how to addressthe challenges o diagnosis and management, especially at the levels o primary andsecondary care, where most children with TB present.

There is a need or greater awareness and increased screening or TB in settings whereservices are oered to high-risk children, such as those inected with HIV and thosewho are malnourished. I someone in a childs amily is living with HIV, then the childhas an increased risk o becoming inected with TB, regardless o whether the child is

HIV-positive. Limitations to the tools available or diagnosing TB, especially in youngchildren, create the misperception that all children suspected o having TB need to bereerred to a higher level o care or a specialist. This creates a urther barrier to childrengaining access care.

Many children who are eventually diagnosed with TB by child health workers, includingby paediatricians in both the private sector and the public sector, are never registeredwith national TB control programmes. This is another barrier that still needs to beovercome by the child health community.

The responsibility to end the neglect and overcome barriers in order to improve theprevention and management o childhood TB thereore lies with a wide range o

individuals and with services at all levels o the health care system; however, theresponsibility starts in the community where the burden o TB exists. The responsibilityextends to all who are engaged in delivering health care to children and adolescents, tonational paediatric leaders, to researchers and advocates as well as to sta working inpublic health and disease control programmes, such as those addressing TB, HIV andmaternal and child health.



WHO/S.Labelle



Tackling childhood TB:

a progress update

Building an evidence basePrior to the early 1950s, most o the published works about childhood TB were clinicaldescriptions o disease and large patient series ocusing on the natural history oinection and disease in children. With the advent o isoniazid in 1952, the emphasisshited to studying the treatment o inection and disease. Several large clinical trials,particularly those conducted by the United States Public Health Service, demonstratedthe eectiveness o isoniazid in preventing the progression rom inection to diseaseboth in adults and children. Between the 1950s and the 1980s, research into childhoodTB was sporadic and sparse, apart rom some studies that demonstrated the

eectiveness and saety o short-course regimens o frst-line anti-TB medicines inchildren.7

The emergence o the HIV epidemicprovided many new challenges. In the1990s, reports o the interaction between TBand HIV inection in children were published,and included descriptions o how TB hadbecome a common cause o morbidity andmortality in children with HIV inection whowere living in areas where TB was endemic.However, research on children living in

settings with a high burden o TB and HIV,that could be used to inorm strategies ordiagnosis and treatment, has been restrictedas a result o limited resources and theinrastructure needed to conduct studiesthat include a large number o children withconfrmed disease.

Key achievements

Increasing international leadership and guidance

The decade o 19952005 saw an unprecedented scaling up o the DOTS strategy incountries with a high burden o TB.8 The creation o the Childhood TB Subgroup (aspart o the DOTS Expansion Working Group o the Stop TB Partnership) in 2003 gavechildren a seat at the table; the subgroup provided signifcant input into many WHOinitiatives, triggering increased advocacy around and attention to childhood TB as wellas contributing to eorts to address childhood TB at the global and country levels. Thesubgroup has supported the development o the evidence-based guidelines listed inFigure 1.

7 The box on the inner ront cover summarizes key points about childhood TB rom knowledge that has been accumulated

primarily rom early observational studies o endemic TB in North America and Western Europe.

8 DOTS is the basic package o interventions or TB control that underpins the Stop TB strategy. For more inormation, see: TheStop TB strategy: building on and enhancing DOTS to meet the TB-related Millennium Development Goals. Geneva, World

Health Organization, 2006 (WHO/HTM/TB/2006.368). (Also available rom http://whqlibdoc.who.int/hq/2006/WHO_HTM_

STB_2006.368_eng.pd.)

amien Schumann



Guidance for national

tuberculosis programmes

on the management of

tuberculosis in children.

Geneva, World HealthOrganization, 2006

(WHO/HTM/TB/2006.371).

(Available from http://

whqlibdoc.who.int/hq/2006/

WHO_HTM_TB_2006.371_

eng.pdf).

Revised TB recording and

reporting forms and

registers version 2006.

Geneva, World HealthOrganization, 2006

(WHO/HTM/TB/2006.373).


www.who.int/tb/

dots/r_and_r_forms/en/).

Figure 1. Guidance and guidelines published with the involvement o the Childhood TB Subgroup

o the DOTS Expansion Working Group o the Stop TB Partnership

A research agenda for

childhood tuberculosis.

Improving the management

of childhood tuberculosis

within national tuberculosisprogrammes: research

priorities based on a

literature review. Geneva,

World Health Organization,

2007

(WHO/HTM/TB/2007.381).


whqlibdoc.who.int/hq/2007/

WHO_HTM_TB_2007.381_

eng.pdf).

Rapid advice: treatment of

tuberculosis in children.

Geneva, World Health

Organization, 2010

(WHO/HTM/TB/2010.13).


whqlibdoc.who.int/

publications/2010/97892

41500449_eng.pdf).


tuberculosis and HIV

programmes on the

management of tuberculosis

in HIV-infected children:

recommendations for apublic health approach. Paris,

International Union Against

Tuberculosis and Lung

Disease, 2010.


www.theunion.org/

index.php/en/resources/

technical-publications/

item/759-guidance-for-

national-tuberculosis-and-

hiv-programmes-on-the-

management-of-tuberculosis-

in-hiv-infected-children-

recommendations-for-a-p-

ublic-health-approach).

Desk-guide for diagnosis

and management of TB in

children.Paris, International

Union Against Tuberculosis and

Lung Disease, 2010.


www.uphs.upenn.edu/

bugdrug/antibiotic_manual/

iautldtbkidsdxrx2010.pdf)


TB programmes on the

management of tuberculosis

in children,

2nd ed. (Forthcoming).

2006 2007 2010 2013



The International Childhood TB Training Course convened by Stellenbosch Universityand The International Union against Tuberculosis and Lung Disease, which has beenheld annually in Cape Town since 2007, has provided training on childhood TB tohealth workers rom many countries who represent national TB control programmes,public health services and nongovernmental organizations, as well as researchers andeducators. These workshops have helped to oster leadership at the national level,

and the implementation o activities related to childhood TB by individuals who haveattended the course. Examples o some o these activities are given below.

Development o national guidelines or themanagement o TB in children.

Situation analyses and identifcation o nationalpriorities or implementation.

Inclusion o childhood TB in reviews and monitoring

missions led by national TB control programmes.

Development o national leadership in addressingchildhood TB and development o working groupsocusing on childhood TB.

Implementation and evaluation o training activitiesrelating to TB in children.

Development o clinical guides or managingchildhood TB.

Box 2. Examples o activities undertaken at the national level by champions o childhood TB

O/M. Grzemska

O/Karin Bergstrom

DC/Tobias Hosss



Growing advocacyGlobal advocacy: Several important activities occurred during 20102013. In 2011,an international meeting was sponsored by the Childhood TB Subgroup and theEuropean Centre or Disease Prevention and Control. This resulted in a Call to action orchildhood TB, which has been signed by more than 1000 individuals and organizations,

and is available on the Stop TB Partnership web site.9 Later that year, the unmet needso women and children were the ocus o the Stop TB symposium organized by WHOas the opening event o the 42nd Union World Conerence on Lung Health in Lille. In2012, or the frst time, childhood TB was the theme or World TB Day, and was theocus o a plenary session at the 43rd Union World Conerence on Lung Health aswell as the ocus o the Stop TB Partnerships Kochon Prize, which recognized thecontributions o the Desmond Tutu TB Centre in Cape Town.

Increasing recognition o the importance oaddressing TB in mothers and children: Insettings with a high burden o TB, womenin their childbearing years have the greatestTB burden. TB poses a considerable riskto pregnant women and their children. TBoccurring in a woman with HIV is a riskactor or transmission o HIV to the inant,and is associated with premature delivery orlow birth weight, and with higher mortalityamong mothers and children. In order toachieve Millennium Development Goals(MDG) 4 and 5, additional eorts must bemade to eectively diagnose and treatmothers and their children.

As a result o advocacy eorts made duringthe past three years, there have been increasing calls to develop well integrated,amily-based approaches to care or people coinected with TB and HIV, so thathealth services can remove barriers to access and reduce delays in the diagnosis andtreatment o TB in women and children.

Increasing attention to including children in research: The combined advocacyo and eorts made by a number o organizations, including the WHOs Global TBProgramme and the Special Programme or Research and Training in Tropical Diseases,Mdecins Sans Frontires and the United States National Institutes o Health, resultedin expert panels developing standardized defnitions to be used in research protocols;

these defnitions are aimed at improving the quality and comparability o diagnosticsresearch. Several new research and advocacy initiatives have been developed, andthese have started to address the needs o children with TB and MDR-TB. In additionto the critical need to improve diagnostic tests, research is also beginning to ocusmore on the TB treatment needs o children, and the care o children who are contactso someone diagnosed with TB or MDR-TB. This increase in attention has coincidedwith growth in the capacity to undertake research about childhood TB in a wider rangeo settings than was previously possible.

9 Call to action or childhood TB. Geneva, Stop TB Partnership, 2011. (Available rom: http://www.stoptb.org/getinvolved/ctb_cta.

asp, accessed 6August2013).

ECDC/Tobias Hosss



WHO/Carlos Cazalis



The roadmap towards a

TB-ree uture or children

and adolescentsThe opportunity now exists to build on past knowledge and embrace recent momentumto move orward and reduce the burden o TB in children and adolescents. Followingwide consultation with the TB and child health communities, this roadmap indicates keypriority actions and the enhanced investment urgently needed to tackle childhood TB.

1. Include the needs o children and adolescents in research, policydevelopment and clinical practices

The needs o children and adolescents must be included in the three pillars o publichealth: scientifc research, policy development and the implementation o appropriateclinical practices. Only when all who are involved in caring or children join orces,will a generation o children be ree rom TB and the move towards elimination bestrengthened. In collaboration with diverse partners, WHO is proposing ambitious goalsor a global strategy and targets or TB prevention, treatment and care ater 2015. Thestrategy is built on three pillars: (1) high-quality integrated TB care and prevention; (2)bold policies and supportive systems; and (3) intensifed research and innovation. Theproposed strategy represents a critical opportunity or addressing childhood TB. Newtargets are being set in recognition o the need to develop country-specifc solutionsthat use a knowing-your-epidemic approach to prioritize activities and targets. Thelack o robust, national baseline data or children makes it impossible to set targets

or childhood TB. However, the broadening o the strategy rom a traditional, verticallydelivered public health approach to a more horizontal one, will provide an importantplatorm rom which to engage the broader child health community. National TBcontrol programmes should develop a ramework to support their activities addressingchildhood TB, as suggested in Box 3.

2. Collect and report better data, including data on prevention

I we are to have a better idea o the actual magnitude o the problem o childhood TB,countries must include children in all TB surveillance activities. It has been previouslyrecommended that every case o childhood TB should be registered with national TBcontrol programmes, and reported by age, disease type, HIV status and treatment

outcome (Figure 4). At a minimum, WHO standard defnitions should be used.10National TB programmes may want to develop the means to provide additional dataor monitoring and evaluation. National programmes need to work with child healthservices to improve the reporting o cases o childhood TB, including those occurringin children who are cared or in the private sector. I these steps are taken, estimates ochildhood TB will improve, and not only will they allow or a better understanding o theepidemic but also they will help improve advocacy and action. Simple strategies, suchas adding inormation about contacts to the TB treatment card o index cases, mayvastly improve case-fnding and contact management.

In addition, the ollowing steps should be undertaken: systematic reviews o theliterature on the burden o TB in children and adolescents; measurement o over- and

10 Defnitions and reporting ramework or tuberculosis 2013 revision. Geneva, World Health Organization, 2013 (WHO/HTM/

TB/2013.2). (Available rom http://apps.who.int/iris/bitstream/10665/79199/1/9789241505345_eng.pd).



Box 3. A ramework or improving childhood TB activities within national TB control programmes

under-reporting o TB in children, and assessment o the misdiagnosis among children;a global consultation to urther develop analytical methods to estimate the burdeno childhood TB, and to defne and prioritize the actions needed to obtain new data;promotion o case-based electronic recording and reporting systems that couldacilitate the compilation and analysis o data disaggregated by age; implementationo nationwide inventory surveys to measure the under-reporting o childhood TB;

implementation o more studies involving contact tracing; implementation o morestudies evaluating the integration o TB activities into health services or mothers,neonates and children, in order to identiy childhood cases that would otherwise remainundiagnosed; and advocacy or the urther development o, and continued investmentin, vital registration systems.

Know your epidemic

Ensure that policies are evidence-based and relevant

Identiy priorities and gaps

Engage in continuing surveillance

Train health workers and implement care strategies or

children with TB

Conduct operational research

Assess unding needs

Assign responsibility and ensure accountability

Take leadership and work in partnership with

all stakeholders

Collaborate and communicate across the entire

health care sector



3. Develop policy guidance, training and reerence materials or health careworkers

National policies and guidelines should include guidance that is specifc to inants,children and adolescents; guidelines should be evidence-based and relevant to eachcountrys specifc priorities and possibilities. Currently, national TB guidelines in many

countries lack sufcient detail about TB control in children. The core elements o TBcontrol, and collaboration between HIV and TB services, that have been recommendedby WHO should be adapted or children, although the methods and procedures usedwill vary by country and according to rates o disease, the resources available and thecare provided by health systems. Each national TB control programme should identiylocal resources and partners, including nongovernmental organizations, which can aidthe eort to develop training and reerence materials.

Training is an important tool that can improve the implementation o care and controlstrategies. Training is required to increase the confdence and competence o healthworkers to recognize the clinical presentation o TB in children, and to diagnose andtreat TB in children or to reer them to a higher level o care when appropriate. Training

should always include the rationale or contact screening, inormation on clinicalmanagement and an approach or implementation. Training about childhood TB should

Box 4. From policy to practice through wider engagement in TB control to ensure that children are

included in DOTS implementation: experiences in the Philippines

A number o steps were taken to achieve a publicprivate mix,rom establishing policies at the national level that will givegreater attention to children, to ensuring that children receiveappropriate services in their communities in terms o TB

diagnosis, treatment and prevention.

1. Policy: On 10 August 2010 a memorandum o understandingwas agreed and signed by the Secretary o the Department oHealth, the national TB control programme and the Presidento the Philippine Pediatric Society to clariy the roles that eachorganization would have in advocating or children with TB.

2. Communication gap: Community representatives wereinvited to the annual convention o the Philippine CoalitionAgainst Tuberculosis, which was held jointly with the PhilippinePediatric Society in 2012. The frst day o the meeting was

devoted to childhood TB and attended by a number opartners including:

a. ofcers rom municipal community health departments,thus ensuring public and government involvement;

b. members o fve paediatric societies led by the PhilippinePediatric Society, as well as other medical personnel,including occupational health workers and physicians working in schools, thus ensuring involvemento the private sector and academia.

3. Guidelines: Updated childhood TB guidelines were disseminated through hospital accreditationmechanisms, reimbursement and health insurance mechanisms, and health maintenance organizations;

the revised guidelines included inormation on paediatric dosing or anti-TB medicines that incorporatednew WHO recommendations.

WHO/HM.Dias

Jerome has multidrug-resistant TB, he has beenundergoing treatment or over a month at the EastAvenue Medical Center, Philippines.

Jerome has multidrug-resistant TB, he has beenundergoing treatment or over a month at the EastAvenue Medical Center, Philippines.



be integrated into the routine training and supervision provided by the national TBcontrol programme or other training related to childrens health, such as that oered tohealth workers in maternal and child health services and/or HIV services.

A major role o the Childhood TB Subgroup and experts in childhood TB will be toassist national TB programmes with training. Tools that could be developed include a

manual or health workers or algorithms that provide clear guidelines about when toreer children, when to treat them or when to ollow up or reassessment. Examples osuch practices are provided in Boxes 47. O course, training and implementation toolsalso need to be consistent with the national programmes guidelines.

4. Foster local expertise and leadership

Additional expertise is needed in settings where TB is endemic, and greater attentionis being given to childhood TB as part o reviews conducted by national TB controlprogrammes. Child health workers at all levels o the health care system, including thoseworking in the private sector, should be involved in diagnosing and treating children withTB. National champions o childhood TB and national paediatric associations should lead

eorts to diagnose and treat children with TB, and work with national programmes toeducate paediatricians and other health workers about childhood TB. Eorts to educatehealth care workers should include providing inormation on the public health aspects ofchildhood TB and guidance on how they can become involved in developing, implementing

and monitoring activities that focus on childhood TB.

Box 5 lists steps that could be taken to improve engagement with activities to addresschildhood TB, as identifed and agreed by representatives o national TB-controlprogrammes rom eastern and southern Arica.

Box 5. Steps to improve the diagnosis and care o children with TB identifed by national TBcontrol programmes rom eastern and southern Arica at a meeting to discuss best practices

in tuberculosis control, Kigali, Rwanda, 2010

Adapt international strategies and develop national guidelines or diagnosing and treatingchildren with TB.

Operationalize the guidelines addressing childhood TB.

Identiy someone to champion the cause o children with TB.

Establish a working group on childhood TB at each national TB programme, and identiy aperson at the programme who will develop links with paediatricians and national paediatricassociations.

Provide training about childhood TB, and incorporate it into continuing education on TB and TB/HIV coinection.

Incorporate activities to address childhood TB into annual plans and fve-year strategic plans.

Ensure that national TB programmes incorporate activities addressing childhood TB into theirbudgets.

Include data on TB in children in routine reporting and in reviews o national TB programmes.

Develop and implement operational research to determine the constraints and barriers todiagnosing and treating children.

Implement research aimed at improving the diagnosis and treatment o children with TB and thecare o children who are contacts o someone with TB.



Susceptible Exposed Inected

Loss to ollow up

Inectious Sick

Accessed careRecognizedDiagnosed

Treated Completed

Relapsed

Cured

Re-treated

The review o the national TB control programme highlighted several importantachievements the programme has made in addressing childhood TB:

The majority o cases are diagnosed through active case-fnding in the primary healthcare setting.

Contact investigations in households with TB cases are conducted routinely. A well-developed network o paediatric TB services exists; this includes

paediatricians available at the central and district levels, and hospitals and sanatoriathat specialize in treating children with TB.

Routine access to bacteriological diagnosis or TB in children (that is, culture anddrug-susceptibility testing) is available.

Paediatric ormulations o anti-TB medicines are available, and children have accessto frst-line and second-line treatments.

Standards are excellent or recording and reporting TB in children and adolescents.

5. Do not miss critical opportunities or intervention

One challenge to TB control is that TB comprises a continuum o health states, rangingrom susceptibility to cure (Figure 2).11

11 Enarson DA, Ait-Khaled N. Tuberculosis. In:Annesi-Maesano I, Gulsvik A, Viegi G, eds. Respiratory Epidemiology in Europe.

European Respiratory Monographs 2000; 15: 6791.

Box 6. What can be achieved: experiences in Kazakhstan

An extensive review o the national TB control programme in the Republic o Kazakhstan wasconducted by a WHO mission in May 2012, which ound that the government is strongly committedto preventing TB in children and to caring or those with TB. Kazakhstan has an extensively

developed inrastructure o paediatric TB services that ocus on active case-fnding among childrenand screening children who are contacts o someone with TB. TB notifcation rates among childrendecreased by about 74% rom 1999 to 2011, rom 57.6/100 000 population to 15.1/100 000population. A decrease in TB notifcation rates was also observed among adolescents, rom161/100 000 in 2002 to 97.6/100 000 in 2011; however, as is the case in most o the WHOEuropean Region, the reported rates o MDR-TB have increased threeold among children,and almost fveold among adolescents.

Figure 2. Transitions in tuberculosis: rom susceptibility to cure

Modifed and reproduced with permission o the European Respiratory Society European Respiratory Society Monograph 2000;15 (Respiratory Epidemiology in Europe): 6791.



Table 1. Transitions in TB and opportunities or intervention

Stage Opportunity or intervention

Susceptible, exposed PREVENT INFECTION

Improve TB control in the community

Improve inection controlInfected PREVENT DISEASE

Implement screening or children who are contacts o someone with TB

Manage the care o children who are contacts o someone with TB

Provide preventive therapy to all children younger than fve years and allHIV-positive children

Record and report delivery o isoniazid preventive therapy (IPT)

Sick, accessed care,

recognized

DIAGNOSE DISEASE

Suspect TB in children who are contacts o someone with TB or who havetypical signs and symptoms

Recognize typical signs and symptoms o TB at all levels o the health caresystem

Ensure that capabilities exist to diagnose TB at least to a secondary levelo care

Recognize danger signs, such as respiratory distress or severemalnutrition, and reer to the appropriate level o care

Ensure that reerral systems are in place or children identifed by healthcare providers as well as to reer complicated cases or very sick children toa higher level o care

Treatment completed,

cured, outcome

SUPPORT CHILDREN AND THEIR FAMILIES

Ensure that treatment ollows national guidelines

Ensure that appropriate medicines are available, including those or drug-resistant TB

Provide care or HIV inection

Develop or implement strategies to improve treatment completion ratesand prevent loss to ollow-up

Record outcomes

Register, record,

report

REPORT ACCURATE DATA, MONITOR AND EVALUATE SERVICES,

ENGAGE IN ADVOCACY AND OPERATIONAL RESEARCH

Ensure that all health care workers know that they are responsible orregistering all children with TB

O course, not all susceptible children will advance through all or even most o thesteps rom susceptibility to cure, but the fgure provides a useul ramework orconsidering an individuals risks and the interventions that may potentially reducethose risks. At each stage lies the possibility o intervening and reducing morbidityand mortality (Table 1). Stakeholders involved in TB play dierent roles along thecontinuum, and have dierent opportunities to intervene. Opportunities to provideeective interventions must not be missed. Prevention is the ultimate goal; hence, everyopportunity must be taken to implement intensifed case-fnding, contact-tracing andpreventive therapy.



The eectiveness o interventions depends on the availability o the tools necessaryor implementation, especially those or diagnosis and treatment. Good quality chestradiography is commonly required or diagnostic assessment. Methods or obtainingspecimens, and laboratory techniques that provide a higher yield than microscopy, areimproving. The global scale-up o the Xpert MTB/RIF diagnostic test oers an importantopportunity or children to have access to rapid bacteriological diagnosis. It is essential

that an uninterrupted supply o quality assured anti-TB medicines or children, includingor preventive therapy, is available. There is a need or fxed-dose combinations ofrst-line anti-TB medicines that conorm to the recommendations made in the 2010revision o Rapid advice: treatment o tuberculosis in children;12 there is also a need orpaediatric ormulations that can be readily used or young children.

6. Engage key stakeholders

Eective communication and collaboration among the health care sector and otherstakeholders is increasingly seen as a key component to ensuring the success ohealth interventions. Table 2 describes the key stakeholders in childhood TB that

should engage with one another, and highlights the main roles that each has thepotential to ulfl.

12 Rapid advice: treatment o tuberculosis in children. Geneva, World Health Organization, 2010 (WHO/HTM/TB/2010.13).

(Available rom http://whqlibdoc.who.int/publications/2010/9789241500449_eng.pd).

Box 7. Increased case-fnding and preventive therapy: experiences in Pakistan

Following the initiation o a programme to deliver isoniazid preventive therapy as part o theIndus Hospital paediatric TB programme, it was noted that the enrolment rate o childrenwas low, despite an average o 350 adults being enrolled in the TB preventive programme oradults each month (o which 54% were emales o reproductive age). Some o the measuresused to increase paediatric enrolment as well as paediatric TB case-detection included:

1. actively involving physicians, treatment supporters and counsellors rom the TBprogramme or adults to encourage them to remind parents with sputum smear-positivepulmonary TB o the need or children aged younger than fve years to be seen at thepaediatric clinic or an evaluation;

2. screening all children younger than fve years attending the Expanded Programme onImmunization or a routine visit; screening includes taking a basic contact history and asymptom screening or possible TB disease; children are reerred to the paediatric TBprogramme i either screening is positive;

3. conducting basic contact screening and symptom screening or all malnourished childrenenrolled in the nutrition clinic; children are reerred to the paediatric TB programme i either

screening is positive;4. implementing an awareness campaign that included posters, billboards and the

involvement o general practitioners.

Notifcations o cases o paediatric pulmonary TB at the hospital increased by a actor oseven using these approaches to childhood TB case-fnding.



Table 2. Key stakeholders and their roles in addressing childhood TB

Stakeholder Main roles

POLICY-MAKERS

Globalpolicy-makers

Collaboratively address childhood TB across disciplines by providingleadership and guidance

Develop policies, strategies and guidelines or the management ochildhood TB that are based on the best evidence

Provide support so that activities aimed at addressing childhood TB canbe adopted at the national level; support may include training, tools, data-collection systems, technical support and the monitoring and evaluationo activities

Help defne research needs or childhood TB and TB/HIV coinection

National

policy-makers

(including national

TB-control

programmes as well

as other relevant

stakeholders)

Provide high-level support throughout a country to assist in the scaling upo childhood TB services

Develop a ramework to address TB in women and children that includescollaboration among national disease control programmes (or example,among those addressing TB, HIV, and maternal and child health) andnational leaders in childrens health care (see Box 5)

Include childhood TB in the strategic plans and budgets o national TBprogrammes

Ensure that guidelines on caring or children with TB or HIV, or both,are adopted and implemented; ensure that data on childhood TB arecollected, reported and recorded, and that sta have appropriate training

Support or perorm operational research to improve activities aimed ataddressing childhood TB (see additional inormation or Researchers

below)

RELEVANT NATIONAL HEALTH-CARE PROGRAMMES

Maternal and child

health services

Ensure that children and pregnant women are screened, diagnosed andtreated or TB; this is especially important or HIV-positive women

Give TB preventive therapy when indicated

Provide appropriate care or neonates exposed to TB

Engage community health services in TB control activities, such ascontact tracing

Record and report TB cases to the national TB programme

HIV services Ensure antenatal screening is implemented or HIV and TB

Ensure all children exposed to or inected with HIV are regularly screenedor TB

Provide preventive therapy to HIV-positive children according to nationalguidelines

Ensure that all children exposed to or inected with HIV are screened orTB, and diagnosed and treated promptly

Health education

institutions

Ensure that childhood TB is adequately discussed in the standardcurricula or all levels o health workers

Incorporate inormation on childhood TB into continuing training, inkeeping with national guidelines



Stakeholder Main roles

SPECIFIC HEALTH ACTORS

Private health-care

sector

Ensure that children with TB are managed according to national guidelines

Report all children with a diagnosis o TB to the national TB programme

Community-based

organizations and

nongovernmental

organizations

Support local programmes according to capacity. This may includesupporting initiatives aimed at increasing community education andawareness, or providing contact tracing, preventive therapy, TB diagnosis,and treatment or reerral

Provide technical assistance and training i appropriate

Community leaders Promote TB education and awareness

Help the community to understand TB and its treatment to decrease thestigma associated with the disease

Support case-fnding eorts and adherence to treatment

Promote the empowerment o children and amilies aected by TB byengaging them to help the community better understand the disease

Researchers Develop child-riendly, point-o-care diagnostics

Develop child-riendly ormulations o anti-TB medicines

Develop improved or novel vaccines, or both

Continue work to fll the many knowledge gaps that exist (see point 7below)

Advocacy groups Promote education and awareness

Help the community understand TB and its treatment to decrease thestigma associated with the disease

Advocate or resource mobilization

Provide input into national and international policy-making.

7. Develop integrated amily-centred and community-centred strategies

Attention is increasingly being ocused on the importance o integrating the diagnosis,treatment and prevention o childhood TB into maternal, neonatal and childrens healthservices when easible or appropriate. In addition, it is important that coordinationand communication are improved among dierent service providers to ensure that

comprehensive services are delivered more eectively in the community. Shitingto a amily-centred or community-centred approach requires eective collaborationand joint planning among TB control programmes, maternal and childrens healthservices, and HIV services. Improving TB services or mothers will be crucial to eortsto improve services or children. As much as possible, TB services or children shouldbe mainstreamed into existing childrens health services, and more responsibility andaccountability should be given to primary care providers.

While the exact mechanisms or incorporating childhood TB services into other healthprogrammes will vary, several widely used programmes present clear opportunities orcoordination and integration (Box 8).



Box 8. Programmes into which TB services can be integrated

Integrated management o pregnancy and childbirth (IMPAC)

Integrated management o childhood illness (IMCI)

Integrated community case management (iCCM)

Child HIV care programmes

Prevention o mother-to-child transmission o HIV (PMTCT)

Nutritional programmes or children

Family planning and ertility services

Implementing TB services into these programmes will be challenging since there is little

operational research that defnes the optimal scope o services that should and can beprovided. For each programme, tools will be needed to prompt health care workers toascertain the necessary inormation, ask ollow-up questions and take the appropriateactions. Nongovernmental organizations, community-based organizations and othercivil-society organizations may be instrumental in improving services or childhood TB.There are several critical areas o TB control that are a natural ft or community-leveleorts, such as increasing case-fnding, oering treatment support, providing advocacyor and supporting patients and their amilies, providing training or and supervision ocommunity health workers and volunteers, and implementing research.

8. Address research gaps

Research has a key role to play in the development, implementation and refnement onew tools, policies and programmatic interventions that aim to eectively prevent andmanage childhood TB. There are undamental dierences between children and adultsin terms o the underlying immunology, diagnosis, treatment and management o TBthat need special attention rom the global research agenda. The International roadmapor TB research was developedby the Stop TB Partnerships Research Movement, andormally launched at the October 2011 conerence o the International Union AgainstTuberculosis and Lung Disease in Lille, France.13 The international roadmap prioritizesresearch in six main areas with the aim o eliminating TB by 2050: epidemiology,undamental research, diagnostics, treatments, vaccines, and operational research.These priorities are described below with a special ocus on children.

i. Epidemiology

Better defne the burden o disease in women, adolescents and children; thisincludes conducting nationwide inventory surveys to measure the underreportingand, i possible, under-diagnosis o childhood TB.

Improve recording and reporting systems to capture all TB cases, and report datadisaggregated by age and sex.

Improve the understanding o variations in the dynamics o TB in dierent settings,and the social, environmental and biological drivers o the transmission o M.tuberculosis in dierent settings.

Conduct evaluations to understand better the epidemiology o TB and TB/HIVcoinection in adolescents.

13An international roadmap or tuberculosis research: towards a world ree o tuberculosis. Geneva, World Health Organization,

2011. (Available rom http://www.stoptb.org/assets/documents/resources/publications/technical/tbresearchroadmap.pd).



ii. Fundamental research

Characterize human TB using modern biochemical, clinical and epidemiologicalapproaches, and address issues specifc to improving the understanding o TB inchildren.

Better understand the hostpathogen interaction; this includes improving

understanding o the immune system in children in relation to its responses tomycobacterial inection at dierent ages. Apply discovery science to identiy biomarkers that better dierentiate the various

stages o the disease spectrum and distinguish between inection and disease inchildren.

iii. Development o new diagnostics

Evaluate new diagnostics, and determine whether they are useul or confrming thediagnosis o TB in children.

Develop diagnostics suitable or use with paediatric samples. Develop point-o-care diagnostics or use in children.

iv. Development o new anti-TB medicines

Identiy the optimal doses or children o new and existing anti-TB medicines andregimens.

Identiy the optimal treatment duration and dosing o riampicin-based treatment orchildren.

Identiy aspects o the design o clinical trials that can be tailored specifcally orstudies in children in regards to end-points, sample size, inclusion criteria, and atwhat point studies should assess the use o new anti-TB medicines in children.

Determine whether new and existing medicines or which data on saety or toxicity inchildren are missing are suitable or use in children.

v. Development o new vaccines

Defne suitable clinical end-points and immunological markers or vaccine trials inchildren.

Improve clinical trials o vaccines in inants and children by conducting pre-vaccine epidemiological studies in order to standardize protocols, assays andmethodological and clinical parameters.

Develop improved vaccines or prime-boost vaccination that are sae and efcaciousin preventing TB in children (including in those living with HIV), and defne optimalconditions or their use in children, including defning the best ages or vaccination.

vi. Operational and public health research

Strengthen the recording and reporting o TB; improve global estimates o childhoodTB (including drug-resistant TB in children); promote case-based electronic recordingand reporting systems that can acilitate the compilation and analysis o datadisaggregated by age.

Advocate or and promote the development and establishment o vital registrationsystems that have national coverage.

Determine the best approaches or identiying children who have been exposedto TB and determine how best to provide preventive therapy or children who arecontacts o someone with TB and or children who are HIV-positive.

Develop an evidence base or preventive therapy or children exposed to drug-resistant TB.



Improve collaboration among TB services and other child-care services to increaseTB case-fnding.

Within the general context o health care services and eorts to expand community-based care address issues specifc to children in terms o case-fnding, screening,access to diagnostics, access to treatment and the delivery o treatment, interactionsbetween TB and HIV programmes, and inection control; answer the ollowing

questions:

How can collaboration between TB services and HIV services in maternal andchild health settings be improved?

How can programmes to prevent mother-to-child transmission o HIV be used toensure that both HIV-positive and HIV-negative women receive appropriate TBscreening during pregnancy?

Identiy the unique needs and concerns o adolescents; pilot test, evaluate andscale up optimal approaches to addressing TB and TB/HIV co-inection amongadolescents.

Investigate how to optimize TB case-fnding in children and adolescents; determinehow to best measure the impact o intensive or enhanced case-fnding on mortality

and other outcomes. Determine the value o TB screening strategies in antenatal care programmes, HIV

programmes, and maternal and child health programmes; determine ways in whichscreening can be operationalized.

Develop and evaluate models o how to implement sustainable collaboration with allprivate and public providers o TB care and control services.

Evaluate how pregnant women and children are being or will be addressed duringthe roll-out and scaling up o the use o new diagnostic tests and new treatment orpreventive regimens.

In addition to the areas outlined in the research roadmap and described above, there

is a need to strengthen the evidence that supports the integration o care or childhoodTB into other child care services, such as those models that address malnutrition,deliver integrated community case management (iCCM) and integrated managemento childhood illness (IMCI). Evidence is also needed about the impact that these eortshave on case-fnding and child survival. Models need to be developed to determinehow to best integrate childhood TB interventions into other child-health services.

9. Meet unding needs or childhood TB

The Stop TB Partnership Global plan to stop TB 20112015 estimates that during20122015, US$ 7.7 billion will be needed or research and development into TB (thisrepresents the amount needed or all age groups).14 O this, at least US$ 0.2 billion will

be required to complete projects directly aimed at providing new tools or preventing,diagnosing and treating TB among children. At present, only 32% o the undingneeded or research and development in TB is available.

In addition to the unding needed or research and development, unds are alsorequired to implement interventions addressing childhood TB, including preventivemeasures. National TB programmes ace signifcant challenges because o the lack ounding.

WHO has been monitoring unding or TB since 2002, and can assess the undingneeds, availability and trends in countries that carry an estimated burden o 94% o theworlds TB cases. However, unding requirements or child-specifc TB interventions

14 Global plan to stop TB 20112015. Geneva, World Health Organization, 2010 (WHO/HTM/STB/2010.2). (Available rom http://

www.stoptb.org/assets/documents/global/plan/TB_GlobalPlanToStopTB2011-2015.pd.)



such as diagnosis using sputum induction, treatment using paediatric fxed-dosecombinations o medicines or the provision o child-specifc training have not beenhighlighted in recent national strategic plans, nor have they been specifcally requestedduring the annual collection o TB data by WHO.15

In a frst attempt to put a global price tag on implementing interventions aimed at

childhood TB or the period 20112015, detailed unding requirements or sevencountries were calculated (Bangladesh, the Democratic Republic o the Congo,Ethiopia, India, Indonesia, Pakistan and South Arica). Together these countriesaccount or an estimated 64% o the burden o childhood TB worldwide. The methodused to calculate the cost o implementing interventions or childhood TB used theingredients approach embedded in the WHO tool or planning and budgeting or TBactivities.16 The unding requirements or the remaining 36% o TB cases occurringin children were extrapolated by adjusting each countrys per capita gross domesticproduct. Preliminary results o the detailed cost estimations show that implementing therecommended TB interventions would mean investing between US$ 84 and US$ 319or each case o childhood TB.

This analysis estimates that US$ 80 million per year will be required to addresschildhood TB. An additional US$ 40 million per year will be needed or antiretroviraltherapy and co-trimoxazole preventive therapy or children coinected with TB and HIV(these treatments are usually unded by HIV programmes). These estimates probablyunderstate the fnancial eort required because the burden o TB disease amongchildren is probably greater than the notifcations o cases younger than 15 years oage. Better assessments o the unding needed or the uture depend on improvingthe monitoring and evaluation o the burden o disease in children, and systematicallyincluding interventions aimed at childhood TB in national strategic plans.

10. Form coalitions and partnerships to improve tools or diagnosis and

treatmentIt is essential to work with industry, academia, major agencies, nongovernmental andother organizations involved in the development and evaluation o diagnostics andtherapeutics. Much o the data on pharmacokinetics that is necessary to determineoptimal treatments or inants and children is gathered only ater a new medicine hasbeen licensed that is, ater Phase III testing. However, it is more appropriate to gatherbasic pharmacokinetic data or inants and children ater Phase II studies have beencompleted, when the medicine has been shown initially to be sae in adults. Gatheringdata ater Phase II studies would also allow or child-appropriate and child-riendlyormulations o the medicine to be developed as progress towards licensing ensues.

Because the burden o TB and MDR-TB varies by country, and the resources availableto address it also vary, collaboration and partnerships are important. For example, evenin countries with a high burden o TB, ew areas recognize and treat enough cases oMDR-TB in children to be able to evaluate the best strategies or prevention and care.However, by pooling data and inormation rom many sources, more robust clinicaland research agendas can be addressed. Similarly, research that evaluates noveldiagnostics, medicines or regimens oten requires a large number o confrmed cases.Thereore, multisite collaborative work is necessary, and this may also contribute tobuilding capacity across a wide range o settings where TB is endemic.

15 Updated data are available each year rom: http://www.who.int/tb/data

16Available at: http://www.who.int/tb/dots/planning_budgeting_tool/en/index.html



deaths

tOWaRds

zeRO

ROadmap fOR

childhOOd

tubeRculOsis

Engage key stakeholders

Include the needs o children and adolescents in

research, policy development and clinical practices

Collect and report better data,including data on prevention

Develop training and reerence

materials or health care workers

Foster local expertise

and leadership

Do not miss criticalopportunities or

intervention

Develop integrated amily-centred

and community-centred strategies

Address research gaps

Form coalitions and partnerships to

improve tools or diagnosis and treatment

Meet unding needs or childhood TB



Achieving zero deaths

The recent and marked increase in attention being paid to TB in children providesan important opportunity to address the existing gap between policies and practice;addressing this gap may increase detection and improve the case management andprevention o TB in children. This roadmap is a response to this opportunity, andhas identifed top challenges and priorities or addressing childhood TB in order toacilitate progress by charting a way orward. Reaching zero TB deaths and eventuallyeliminating TB in children worldwide is possible but requires sustained advocacy,

mobilization o adequate resources, and a joint eort by all stakeholders involved inchildrens health care and TB control.

HO/Damien Schumann



.Powell



Resources

Guidance and guidelines

Recommendations or investigating contacts o persons with inectioustuberculosis in low- and middle-income countries. Geneva, World Health

Organization, 2012 (WHO/HTM/TB/2012.9) (Available rom http://apps.who.int/iris/

bitstream/10665/77741/1/9789241504492_eng.pd).

An international roadmap or tuberculosis research: towards a world ree o tuberculosis.

Geneva, World Health Organization, 2011. (Available rom http://www.stoptb.org/assets/

documents/resources/publications/technical/tbresearchroadmap.pd).

Guidance or national tuberculosis and HIV programmes on the management o

tuberculosis in HIV-inected children: recommendations or a public health approach.

Paris, International Union Against Tuberculosis and Lung Disease, 2010. (Available

rom http://www.theunion.org/index.php/en/resources/technical-publications/item/759-guidance-or-national-tuberculosis-and-hiv-programmes-on-the-management-

o-tuberculosis-in-hiv-inected-children-recommendations-or-a-public-health-approach).

Rapid advice: treatment o tuberculosis in children. Geneva, World Health

Organization, 2010 (WHO/HTM/TB/2010.13). (Available rom http://whqlibdoc.who.int/

publications/2010/9789241500449_eng.pd).

Global plan to stop TB 20112015. Geneva, World Health Organization, 2010 (WHO/HTM/

STB/2010.2). (Available rom http://www.stoptb.org/assets/documents/global/plan/TB_

GlobalPlanToStopTB20112015.pd).

Ethambutol efcacy and toxicity: literature review and recommendations or daily

and intermittent dosage in children. Geneva, World Health Organization, 2006 (WHO/HTM/TB/2006.365). (Available rom http://whqlibdoc.who.int/hq/2006/WHO_HTM_

TB_2006.365_eng.pd).

Guidance or national tuberculosis programmes on the management o tuberculosis in

children. Geneva, World Health Organization, 2006 (WHO/HTM/TB/2006.371). (Available

rom http://whqlibdoc.who.int/hq/2006/WHO_HTM_TB_2006.371_eng.pd).

Revised TB recording and reporting orms and registers version 2006. Geneva, World

Health Organization, 2006 (WHO/HTM/TB/2006.373). (Available rom http://www.who.int/

tb/dots/r_and_r_orms/en/).

Field guides and handbooks

Standards and benchmarks or tuberculosis surveillance: checklist and user guide.

Geneva, World Health Organization, 2013 (in press).

Community-based tuberculosis prevention and care: why and how to get involved.

Washington, DC, CORE group, 2013. (Available rom http://www.coregroup.org/storage/

TB/Community-Based_TB.pd).

Assessing tuberculosis under-reporting through inventory studies. Geneva, World Health

Organization, 2012 (WHO/HTM/TB/2012.12). (Available rom http://apps.who.int/iris/

bitstream/10665/78073/1/9789241504942_eng.pd).

Management o multidrug-resistant tuberculosis in children: a feld guide. Boston,

Sentinel Project on Pediatric Drug-Resistant Tuberculosis, 2012. (Available rom http://

sentinelproject.fles.wordpress.com/2012/11/sentinel_project_feld_guide_2012.pd).



Desk-guide or diagnosis and management o TB in children. Paris, International Union

Against Tuberculosis and Lung Disease, 2010. (Available rom http://www.uphs.upenn.

edu/bugdrug/antibiotic_manual/iautldtbkidsdxrx2010.pd).

Advocacy documents

We can heal. Prevention, diagnosis, treatment, care, and support: addressing

drug-resistant tuberculosis in children. Boston, Treatment Action Group, Sentinel

Project on Pediatric Drug-Resistant Tuberculosis, 2013. (Available rom http://www.

treatmentactiongroup.org/tb/publications/2013/we-can-heal).

Being brave: stories o children with drug-resistant tuberculosis. Boston, Sentinel

Project on Pediatric Drug-Resistant Tuberculosis, 2012. (Available rom http://www.

treatmentactiongroup.org/sites/tagone.drupalgardens.com/fles/SP%20report%20v3.pd).

Children and tuberculosis: rom neglect to action. Washin

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