LETTER TO THE EDITOR

Supporting health systems for tuberculosis through research

When drug treatment for HIV was rst trialled in sub-Saharan
Africa, there was an outcry that these expensive drugs would
then be used in the most developed countries but not benet the
population which had supported the drug trials. In the same way,
research in tuberculosis (TB) is often conducted by richer countries
in those with less resources and poorer health systems. Is there not
the same responsibility to benet the populations with the higher
incidence of TB where research is being undertaken?
TB differs from HIV in that a cure is possible with simple antibi-
otics. The reasons why there are still almost 9 million new cases
each year and 1.1 million deaths, excluding the 0.35 million with
HIV co-infection,
1
are many but most relate to health care delivery.
2
Diagnosis is delayed because the symptoms are not recognised as
signicant until after the infectious period has begun. Access to
health care is limited. The physician does not consider TB as
a possible diagnosis. Only after TB is suspected can the new diag-
nostic tests be implemented. Delivery of antibiotics, including
second-line treatment for those with drug-resistant infections,
has much improved through the Global Plan to Stop TB.
3
Active
case-nding (contact tracing), using the index case to identify those
with whomthey spend most time, is important in identifying those
with TB who have not yet sought medical care and who may not yet
be infectious.
A recent issue of Tuberculosis reported on a study
4
to identify
areas where multidrug-resistant (MDR) TB is being transmitted.
The paper uses an interesting mathematical model and the heat
maps indicate the geospatial distribution of MDRTB in an infor-
mative manner. The question remains whether this study
beneted the local population. The research group could have
supported contact tracing for those identied to determine
whether their analysis was better than the standard approach.
Drug sensitivity testing was sporadic, so should the funder have
supported a more universal approach to testing in order to
conrm that the data are reliable? Should strain typing of the
isolates have been included to conrm transmission rather than
multiple different strains indicating a pattern of poor TB control?
Is transmission the only problem, or should a follow-up study be
planned to determine the effectiveness of the local TB programs
in case MDRTB is being generated through a lack of resources
for directly observed therapy (DOT), lack of supply of treatment,
poor protocols to deal with treatment failure and lack of struc-
tures to deliver second-line treatment?
Scientic validity should encourage this broader perspective.
Supporting local health structures can avoid the bias towards those
study subjects or samples which are entered on the basis of oppor-
tunityrather thaninclusiveness. This inclusiveness has reapedbene-
ts in understanding the molecular pathogenesis of TB by analysing
vast amounts of information in studies of genomes,
5
transcrip-
tomes,
6
proteomes,
7
metabolomes
8
and even exhaled volatomes,
9
as reported in these pages, without prior selection or bias to those
molecules easy to identify or accorded special status by a particular
researchgroup. The challenge is nowtoapplythesesametechniques
to the human host, human behaviour and the environment as much
as to the pathogen Mycobacterium tuberculosis itself.
References
1. World Health Organization. Global tuberculosis control: WHO report 2011. WHO/
HTM/TB/2011.16. Geneva, Switzerland; 2011.
2. World Health Organziation. The World Health Report health systems nancing
the path to universal coverage. Geneva: WHO; 2010.
3. Stop TB Partnership and WHO. The global plan to stop TB 20112015. Geneva,
Switzerland: World Health Organization; 2011.
4. Manjourides J, Lin HH, Shin S, et al. Identifying multidrug resistant
tuberculosis transmission hotspots using routinely collected data. Tuberculosis
2012;92:2739.
5. Ford C, Yusim K, Ioerger T, et al. Mycobacterium tuberculosis heterogeneity
revealed through whole genome sequencing. Tuberculosis 2012;92:194201.
6. Kesavan AK, Brooks M, Tufariello J, Chan J, Manabe YC. Tuberculosis genes
expressed during persistence and reactivation in the resistant rabbit model.
Tuberculosis 2009;89:1721.
7. Liu S, Han W, Sun C, et al. Subtractive screening with Mycobacterium tuberculosis
surface protein phage display library. Tuberculosis 2011;91:57986.
8. Chandra N, Kumar D, Rao K. Systems biology of tuberculosis. Tuberculosis 2011;
91:48796.
9. Phillips M, Basa-Daley V, Bothamley G, et al. Breath biomarkers of active pulmo-
nary tuberculosis. Tuberculosis 2010;90:14551.
Graham Bothamley*
Department of Respiratory Medicine,
Homerton University Hospital,
London E9 6SR, UK
* Tel.: 44 2085107814; fax: 44 2085107731.
E-mail address: graham.bothamley@homerton.nhs.uk
17 February 2012
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Tuberculosis
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Tuberculosis 92 (2012) 289
1472-9792/$ see front matter 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tube.2012.03.003