Kids, the silent vic­tims of TB

Not ad­e­quately con­sid­er­ing chil­dren in as­sess­ments has en­abled a hid­den epi­demic

Saturday Star - - INSIGHT - KAUSIK DATTA

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.

The ex­tent of child­hood TB is not known be­cause 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, says the writer.

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