children with tb:

A FAMILY DISEASE, A FORMIDABLE BURDEN
TB is among the top 10 causes of illness and death among children. TB
is commonly passed from adults to children within the same family
and household. Current estimates indicate 550,000 new cases each year
and more than 80,000 deaths. However, many children with TB go
undiagnosed, so experts suspect the number of children suffering from
TB is even larger. In some particularly hard-hit countries, children
represent 20-40% of the TB caseload.
children with tb:
Neglect Them No Longer
new pediatric tb treatments are urgently needed
Tuberculosis (TB) is a neglected disease, killing nearly
1.4 million each year in part due to the inadequacy
of the tools available to tackle this global pandemic. But
perhaps no group of TB patients is more neglected
than the estimated more than half a million children or
more who suffer from the disease each year. Today, there
are no appropriate TB medicines for children, hindering
effective treatment and fueling the development of
drug-resistance. Creating child-friendly formulations and
speeding the development of new childhood TB
treatments is a moral and global health imperative.
For more information, visit www.tballiance.org/children
APPROPRIATE TREATMENTS URGENTLY NEEDED
No pediatric TB treatments currently exist in the correct formulation
and dosage. In 2010, the World Health Organization released revised
guidelines for pediatric TB drug doses, however no such treatments have
reached the marketplace. Currently, those treating children with TB must
grind up or cut adult treatments to approximate an appropriate dose for
a child. This leads to improper or incomplete treatment, institutionalizing
poor health outcomes and the development of drug resistance.
REPAIRING THE MARKET
The need for pediatrics TB drug has been ignored for far too long, resulting
in a complete lack of appropriate medicines. Clear information on
the TB burden and regulatory processes can help catalyze manufacturers and
others to invest in the field of pediatric TB drugs.
CLOSING THE GAP FOR TOMORROW’S TREATMENTS
It is critical to reduce the time between the introduction of new TB drugs
in the pipeline and the corresponding pediatric formulations. We can’t
allow the current reality—where childhood formulations come to market
decades after adult therapies—to be perpetuated.
TIME FOR ACTION IS NOW
The neglect of children with TB must end today. Appropriate treatment
for children with TB simply does not currently exist. Increased focus
and attention on the unique treatment needs of children with TB is a moral
and practical imperative. Only by embracing a comprehensive approach
that includes the development of new tools can we protect the world’s children
from this enduring pandemic.
TB Alliance operates with the support of the Bill & Melinda Gates Foundation, AIDS Clinical Trial Group, UK aid, Irish Aid, UNITAID,
the United States Agency for International Development (USAID), Australia Department of Foreign Affairs and Trade (DFAT),
European Commission, Global Health Innovative Technology (GHIT) Fund, National Institute Of Allergy And Infectious Diseases (NIAID), and the United
States Food and Drug Administration (FDA). For more information on TB drug development and TB Alliance, please visit www.tballiance.org.

© Giulio
Donini / UNI-
TAID
SPEEDING TREATMENTS
TO END PEDIATRIC TB:
Repairing
the market,
improving
child survival
For more information, visit
www.tballiance.org/children
Tuberculosis (TB) is one of the leading killers of children. Despite the extent of the problem – and the
fact that young children are very vulnerable to illness and death from TB – appropriate TB treatments
for children simply do not exist.
TB Alliance, in partnership with the World Health Organization (WHO), UNITAID, and others, is
working to lower market barriers that currently prevent appropriate and affordable TB treatments from
reaching children. We hope to facilitate the availability, access, and use of improved pediatric TB medicines—for
today’s treatments, and tomorrow’s—and make a sustainable global health impact.
Childhood TB has long been a neglected crisis. To jumpstart the field and create ongoing access for new
and improved drugs for children, interventions are needed throughout the lifecycle of product development
and delivery. Our work is designed to deliver new, correctly formulated, child-friendly drugs of
existing TB treatments, while enhancing the market understanding needed to accelerate the time in
which new and better treatments will be available and taken up by countries. This global effort can be
best understood by focusing on a number of strategic goals.
DEFINE THE MARKET
The burden of childhood TB has not been adequately studied or quantified. Gaps in information exist
at many levels, including incidence and treatment rates, which obscure the true size of the market. The
lack of information acts as a disincentive to manufacturers.
TB Alliance operates with the support of the Bill & Melinda Gates Foundation, AIDS Clinical Trial Group, UK aid, Irish Aid, UNITAID,
the United States Agency for International Development (USAID), Australia Department of Foreign Affairs and Trade (DFAT),
European Commission, Global Health Innovative Technology (GHIT) Fund, National Institute Of Allergy And Infectious Diseases (NIAID), and the
United States Food and Drug Administration (FDA). For more information on TB drug development and TB Alliance, please visit www.tballiance.org.

TB MEDICINES FOR CHILDREN ARE NEEDED: No pediatric TB treatments currently exist in the correct formulation
and dosage. In 2010, the WHO released revised guidelines for childhood TB drug doses; however, no such treatments have reached the
marketplace. In the absence of proper drugs, those treating children with TB must grind or cut adult drugs to approximate an appropriate
dose for a child. This leads to improper treatment, contributing to poor health outcomes and the development of drug-resistant TB.
PHOTOGRAPHY: DARBY FILMS (FIRST PAGE AND LEFT); DESMOND TUTU, TB CENTRE, DEPARTMENT OF PAEDIATRICS AND CHILD HEALTH, STELLENBOSCH UNIVERSITY (RIGHT)
»»
TB Alliance and the WHO are working to obtain an accurate understanding
of the childhood TB burden, and in so doing, understand the real demand
for pediatric TB treatment. Equally important is to understand the
market dynamics that influence uptake and appropriate use of products.
CLARIFY REGULATORY REQUIREMENTS
A key challenge to development of child-friendly formulations for TB
has been the lack of clarity on regulatory requirements for developers and
manufacturers. Additionally, there are no data available on the correct dosages
for TB medicines for newborns and infants weighing 5 kg or less. With
these data, manufacturers will be able to make formulations available to
treat all children, rather than leaving clinicians to take their best guess on
appropriate treatments for babies.
»»
We are building consensus among industry, clinicians, researchers, and
regulators to determine the clinical trial standards and data required for
submission of new childhood TB treatments. Clear regulatory requirements
are an incentive for developers and could help speed new treatments
through clinical testing. This should decrease the current time gap between
availability of adult and pediatric formulations so vulnerable children can
benefit from TB innovations.
COLLABORATE TO DEVELOP NEW
DRUGS AND FACILITATE UPTAKE
Development of new policy and treatment guidelines at a global level is
not sufficient to ensure uptake of new medicines within countries. Manufacturers
are understandably reluctant to embark on the development of
new formulations.
»»
The aim is to catalyze change that prioritizes care and treatment of children
and ends the neglect of this highly vulnerable group. TB Alliance,
in partnership with WHO, will survey current treatment guidelines and
practices in countries to understand the obstacles to uptake. Additionally,
TB Alliance will prepare a case for donors and governments to sustain and
expand investment in procurement of childhood TB medicines, particularly
for low-income countries, so that changes in guidelines can be paired
with availability of product.
»»
Our initial goal is to encourage the development, manufacture and stable
supply of high quality, affordable pediatric formulations of today’s existing
first-line TB drugs meeting the updated WHO guidelines. For future
treatments, TB Alliance will work to shorten the regulatory pathway to
accelerate the approval of pediatric formulations of new drugs.
RESHAPE THE INFORMATION LANDSCAPE
Information surrounding the market for pediatric TB treatments, the
process of developing and manufacturing them, and the case for their
procurement and distribution is woefully lacking.
»»
By organizing existing information and disseminating critical new data revealed
through our efforts, a clearinghouse for data and intelligence necessary
to advance pediatric TB product development and use can be created.
Providing this information will transform the current chaos of pediatric
TB treatment into a clearly defined marketplace that addresses manufacturers’
barriers and meets the needs of children.
Working with our partners, our goal is an ambitious one—to stop the neglect
and create a sustainable supply of new and improved treatments for
children with TB. To find out more, visit tballiance.org/children.

Women, Children & TB:
New
Treatments
to Save
Families
The impact of tuberculosis (TB) on women and children must be
told as two parts of one terrible story. Mothers with TB can easily
spread the disease to their children, jeopardizing both their
near-term survival and long-term security. TB often infects children
in its deadliest form. If children are to survive, the effects of the
disease could still be devastating. TB negatively impacts parents’
ability to work, further entrenching families in the cycle of poverty.
In 2010, according to the World Health Organization, about 10
million children were orphaned after their parents died of TB.
For more information, visit www.tballiance.org/children
TB Alliance operates with the support of the Bill & Melinda Gates Foundation, AIDS Clinical Trial Group, UK aid, Irish Aid, UNITAID,
the United States Agency for International Development (USAID), Australia Department of Foreign Affairs and Trade (DFAT),
European Commission, Global Health Innovative Technology (GHIT) Fund, National Institute Of Allergy And Infectious Diseases (NIAID), and the
United States Food and Drug Administration (FDA). For more information on TB drug development and TB Alliance, please visit www.tballiance.org.

TB OFTEN INFECTS
CHILDREN IN ITS
DEADLIEST FORM
Ripple Effect
TB causes a ripple effect through families, often starting with a mother.
Worldwide, some 900 million women of reproductive age are infected
with TB, and at least 2.5 million every year develop active TB. In settings
in which HIV is prevalent, a woman’s risk of developing TB is
substantially increased, and further so during pregnancy. Poor women
are also less likely to receive diagnostic and treatment services.
Women with TB pose a threat to their children, even before that child is
born. Infants born to women with TB face a number of complications
including higher rates of premature birth and low birth weight.
After birth, children have a high risk of being infected with TB by their
family members. As an air-borne disease, the natural closeness that is
between mother and child can actually be a death sentence, increasing
the risk of child mortality. The risk is even greater among those living in
poverty, who very often live in small, crowded conditions with poor ventilation,
which is conducive to the spread of the disease. Often, mothers
infected with TB are ostracized from their own household in an attempt
to protect their children from the disease.
The transmission of the disease further entrenches a cycle of poverty
in which the sick are made poor, and the poor are at increased risk of
sickness. As the disease passes from adult to child, the poverty cycle
tightens its inter-generational grip.
Repairing Families through Research
TB is among the top 10 causes of illness and death among children. It
is also a major cause of death in infants infected with HIV, even those
being treated with anti-retrovirals. Importantly, it is often noted that TB
in children is a barometer for TB in a community.
The WHO reports that 550,000 children became ill with TB and
80,000 children died from the disease in 2013. Some experts believe
that due to challenges in diagnosing pediatric TB, the true burden of
the disease in children is considerably higher. Still, little has been
done to ensure children get the treatment they need.
New technologies are critically needed to reduce the burden of TB on
men, women and children, and to create healthy families that can break
the poverty cycle.
Today, there are no appropriate tuberculosis drugs that are made for
children. However, amid a renaissance in TB drug development, TB
Alliance is working to ensure that children are not left out and proper
child-friendly TB drugs are developed as quickly as possible. At the same
time, improved treatment for adults will help to shrink the reservoir of
adult TB patients who can infect children. Further, a better functioning
marketplace and better informed regulatory community will help reduce
the lag between the development of new drugs for adults and their adaptation
for use in children.

© Giulio
Donini / UNI-
TAID
TWICE NEGLECTED:
Children
and TB
Treatment
Tuberculosis is one of the leading killers of children, attacking them
so severely that it is often fatal. Despite the extent of the problem,
appropriate TB treatments for children simply do not exist.
TB is a neglected disease, with treatments that are old and inadequate.
The regimen of drugs, and in some cases injectables, must
be taken from 6 months to two years and very often has side effects.
Unfortunately, children are twice neglected. Not only must they
suffer through the long treatment, but there are no regimens available
in the right doses and in child-friendly formulations. For the
smallest children, there’s little understanding of what the dose even
should be. Clinicians, and in turn parents who are caring for their
children, are forced to concoct their own treatments by splitting or
crushing pills, which can lead to inaccurate dosing—institutionalizing
poor health outcomes and the development of drug resistance.
For more information, visit www.tballiance.org/children PHOTOGRAPH © GIULIO DONINI / UNITAID
TB Alliance operates with the support of the Bill & Melinda Gates Foundation, AIDS Clinical Trial Group, UK aid, Irish Aid, UNITAID,
the United States Agency for International Development (USAID), Australia Department of Foreign Affairs and Trade (DFAT),
European Commission, Global Health Innovative Technology (GHIT) Fund, National Institute Of Allergy And Infectious Diseases (NIAID), and the
United States Food and Drug Administration (FDA). For more information on TB drug development and TB Alliance, please visit www.tballiance.org.

“
THERE CONTINUES TO BE A HUGE GAP OF SEVEN YEARS
OR LONGER BETWEEN WHEN NEW TREATMENTS ARE
INTRODUCED AND WHEN CHILD FORMULATIONS ARE
PROJECTED TO REACH THE MARKET.
“
SPOTLIGHT: REALITIES OF TREATMENT
A
yanda was diagnosed with TB shortly after birth and
spent five months in hospital on daily treatment. Since
he could not swallow pills, Ayanda needed intravenous TB
drugs in the beginning. But even if he could take pills, there
is still no optimal treatment. Today, there are no correctly
formulated TB drugs designed for children. Further, for the
youngest children like Ayanda, there is often uncertainty
even about what the dose should be. “We have to split adult
formulations and getting the right dose for children is challenging,”
says Dr. Anneke Hessling, from the Desmond Tutu
TB Centre, who is on the frontlines of the battle against pediatric
TB. “For babies, not only is it difficult to get the drugs
into them, but we don’t actually know if the recommended
dose is safe. We urgently need appropriate formulations.”
The stakes of imprecise measures of TB treatment are
high. Infants and young children are at increased risk of suffering
from severe forms of TB that can leave them blind,
deaf, paralyzed or mentally disabled, and 80,000 children
die of TB each year. Further, giving treatment to children in
improper doses increases the likelihood of the development
of deadlier forms of the disease, such as MDR-TB or XDR-TB.
URGENTLY NEEDED:
»»
Fixed-dose combinations specifically developed for children in the right doses and child-friendly formulations
» » New, faster-acting and less toxic drugs that are specially formulated to treat children with TB and drugresistant
TB, and that can be co-administered with HIV therapy
SUSTAINABLE, SCALABLE SOLUTIONS
Until recently, there was little hope of improving TB treatment for
children. How ever, today TB Alliance and partners are working to
develop ur gently needed new TB drugs for children.
TB Alliance is catalyzing the development of an appropriate childfriendly
fixed- dose combination (FDC) of the first-line TB treatment.
This project has near-term impact, with a new FDC
expected to be available by 2016. The project also focuses on
facilitating the availability, uptake, and use of improved pediatric
TB medicines, in-cluding partnering with manufacturers to ensure
they produce these important new medicines and reach the
children who need them.
However, much more needs to be done. There continues to be a
huge gap of seven years or longer between when new treatments
are introduced and when child formulations are projected to reach
the market. That means too many precious moments in the life of a
child will be defined by illness and disease.
Through our work, TB Alliance will help lay the groundwork needed
to accelerate the development of pediatric-appropriate forms of the
new TB treatments in development today. Only by scaling up efforts
to de velop new, better tools to help stop TB, can we end and the
neglect of so many vulnerable children.