Kids, the silent victims of TB
Not adequately considering children in assessments has enabled a hidden epidemic
NATIONS of the world came together in 2000 to make a solemn commitment to humanity to combat TB, HIV/Aids and other devastating diseases. This pushed governments to set up aggressive public health measures towards eradicating TB, but they have achieved only limited success.
The moderate achievements have been plagued by the paucity and poor quality of health data from lower-income countries.
But more importantly, while its global TB programme marches on, the World Health Organisation (WHO) recognises a critical unmet need. In 2012, the director of WHO’s Stop TB Department said: “Unfortunately, to a large extent, children have been left behind, and childhood TB remains a hidden epidemic in most countries. It is time to act and address it everywhere.”
The full scope and extent of childhood TB is not known. This is because TB detection for that age group has often been neglected by those who collect health data, since children (defined as under the age of 15) were not considered to contribute to the spread of the disease or pose a high risk to others.
Global plans to eradicate TB, drawn up by international bodies like WHO and the Stop TB Partnership, often omit any childhood TB-specific goals.
Diagnosing childhood TB is subject to many procedural and socio-economic challenges.
The numbers, when reported, are muddied by deaths caused by other reasons, such as HIV, malnutrition, pneumonia or meningitis, resulting in severe underestimates.
The 2010 TB data from WHO reported new disease cases segregated by age group, affecting 49 000 children all over the world. This considered only one measure of positive cases, and was probably an underestimate.
The 2012 Global TB Report represented the first concerted attempt by WHO to assess the childhood-TB burden, estimating 490 000 new cases and 64 000 deaths in children who had no HIV. The 2013 Global TB report puts these numbers at more than half a million new cases, and death of about 74 000 children.
A recent study published in the Lancet Global Health employed extensive mathematical modelling, and put together 2011 TB and population data from WHO and other agencies, 2010 case notification data, with exposure predictions and natural history of paediatric TB. According to the study, 53 million children were infected via exposure by 2010, with 7.5 million in 2010 alone, of which 650 000 developed active TB disease, in the 22 high-burden countries.
This model yielded larger numbers compared to the WHO statistics. However, regardless of the calculation methods, these figures highlight the immense burden of TB disease borne by children across the world.
Of all the infectious diseases plaguing humans, the disease caused by rod-shaped Mycobacterium TB has contributed significantly to the global burden of disease throughout history.
TB is contagious. When a diseased patient coughs, sneezes or speaks, the exhaled air carries microscopic, bug-laden droplets, which enter the lungs of others nearby. This exposure risk is especially high in regions of high TB prevalence, such as sub-Saharan Africa, parts of Asia, Central and South America.
Simply being exposed to the bug doesn’t cause disease. Immune defence cells can kill the bug. Only if one’s immune system is weakened – as in Aids patients – or if the immunity is not robust enough – as in small children – does the TB bug becomes active and starts multiplying inside the body. This is what makes TB the leading killer of people living with HIV/Aids.
But because the TB bacteria has been around for a long time, it has learnt a few tricks of its own. These allow it to hide within the immune cells, and, when the environment is favourable, to escape the confinement and spread to neighbouring cells by subverting the immune cell functions. This means healthy individuals may become unsuspecting carriers of TB. This condition is called “latent TB”. It can become active TB years later, if one’s immunity is compromised.
Doctors diagnose active TB by evaluating a combination of clinical symptoms via a skin or blood test, a chest X-ray and tests to find the presence of the TB bug. Recently it has become often necessary to test the bug for resistance to TB drugs.
Drug-resistant TB is an escalating public health challenge. The WHO recommends DNAbased tests for rapid diagnosis of such patients.
The diagnosis of latent TB is of great importance but it is challenging. The disease is unrecognisable in individuals who have no tell-tale symptoms. This leaves specialised blood tests as the only indicators.
These difficulties have made it hard to accurately estimate how many people have latent TB. Estimates could be as high as 2.3 billion, with one in every 10 such individuals likely to have active TB during their lifetime.
Once diagnosed, TB is treated by using a combination of several anti-tubercular drugs, usually for six to nine months. To ensure all the bugs in the body are dead, it is essential to complete the entire course of drugs. Treatment of latent TB requires fewer drugs, but for the same time span.
Not adequately considering the children while assessing the disease burden has so long enabled the “hidden epidemic”. This can, and must, be addressed.
In 2013, taking stock of the successes of its Global TB programme, the WHO has acknowledged that the target of 50% reduction in active TB disease worldwide may not be achievable by 2015, the time set by the 2000 UN Millennium Development Goals. When the international community sets up a new deadline, they should accord childhood TB a higher priority. Datta is a Post-doctoral Fellow, Johns Hopkins Medicine. TUBERCULOSIS ranks alongside HIV/Aids as a leading cause of death worldwide. According to the World Health Organisation, 1.5 million people died from TB in 2014. The challenges in tackling the disease include the fact that people are tested too late and that the turnaround for most tests is long. To remedy this, a point-of-care rapid diagnostic test for TB has been developed by a multinational team of scientists led by researchers at Stellenbosch University. One of its co-inventors, Professor Gerhard Walzl, spoke to The Conversation Africa’s health and medicine editor Candice Bailey:
How have TB tests been done up until now and what are the challenges? There are three main tests that are in use. A culture test – the most sensitive – requires people to produce a sputum sample that is sent to a centralised laboratory where a culture test is done. A positive result shows up after 10 days. A confirmed negative result takes up to 42 days.
The problem with this test is that it is only available in centralised laboratories, so patients must make several trips to a hospital or health facility to get their results. And it is very expensive.
Then there is the sputum microscopy test. This is widely used in Africa. It requires the sputum slides of each patient to be individually checked.
The test is inexpensive. But it is labour-intensive, which means that only a limited number of smear tests can be assessed a day. Also, it only has a 60% sensitivity rate.
On top of this, the test poses particular challenges for children and for people living with HIV.
In the case of young children, samples need to be taken from their stomachs as they cannot follow instructions to produce a good quality sputum sample. This requires the use of a nasal tube, which is not pleasant.
The test also isn’t effective for people living with HIV, as their sputum often has low levels of the bacteria.
There is also a molecular test that detects bacterial DNA in the sputum sample. This test only takes two hours to produce a result and although it speeds up the detection of TB, it is not widely available to people in rural areas. How will your test change this? If our test is accepted after clinical trials are completed, it will be able to provide almost immediate results. People will be able to be diagnosed and start treatment in a single visit to a health-care facility.
The test is done with blood obtained from a finger prick and can make a TB diagnosis in less than an hour. The diagnostic test is a hand-held, battery-operated instrument that will measure chemicals in the blood of people with possible TB. This test will not have to be done in a laboratory and healthcare workers will be able to perform it with minimal training. At what stage is the test? The test is still in development. We have patented the biosignature, which identifies the levels of chemicals in the blood of a patient. A biosignature consists of a combination of chemicals and indicates a disease state. This signature was discovered by African scientists. The inventors included South African, Cameroonian and Ethiopian scientists.
The test’s accuracy and efficacy will be tested in five African countries over the next three years. We will recruit 800 people who have TB symptoms from Namibia, the Gambia, Uganda, Ethiopia and South Africa.
Why is the test important for South Africa?
South Africa has the highest TB rates in the world. Each year, between 450 000 and 500 000 people develop TB. This gives the country an incidence rate of 834 infections for every 100 000 people.
On the rest of the continent, the incidence rate is between 300 and 600 infections for every 100 000 people. In China the incidence is 68 for every 100 000 people and in most European countries it is less than 10 for every 100 000 people.
One of the challenges in South Africa is that people in remote areas with high TB incidence still do not benefit from newer developments in TB testing. As a result, they face long diagnostic delays and often need to come back before they are diagnosed.
This test will mean that health care workers with minimal training can use the test at grassroots level and get immediate access to screening test results.
It would also reduce the cost of testing for TB. Our test would initially cost $2.50 (R31) a test. With commercialisation, that price could drop significantly. Currently, the culture test costs $45 a test, while the DNA sample test costs $12 a test.
How does this test fit into the bigger picture of dealing with TB?
The test would be used best as a screening test. So far we have been able to identify 70% of patients who do not need further testing.
The World Health Organisation has identified a screening test as important for these areas.
Walzl runs the Immunology Research Group at the Division of Molecular Biology & Human Genetics, in the Department of Biomedical Sciences, Faculty of Medicine & Health Sciences, Stellenbosch University.