From the Special Topic of
In our Special Topics analysis of tuberculosis (TB)
research over the past decade, the work of Dr. Christopher
Dye is ranked at #5 by total cites, based on 48 papers
cited a total of 3,751 times. According to
Science IndicatorsSM from
Reuters, Dr. Dye's full citation record for the period
of January 1, 1998 and August 31, 2008 includes 92 papers,
largely classified in the field of Clinical Medicine, cited
a total of 4,660 times. This latter figure also includes
papers on TB that weren't picked up in our analysis.
Dr. Dye is the Director of Health Information in the Office of
Malaria & Neglected Tropical Diseases at the
World Health Organization in Switzerland.
In the interview below,
he talks with ScienceWatch.com about his highly
cited research on TB.
Would you tell us a bit about your
educational background and research experiences?
My first love was ecology and I trained as a biologist at the University of
York in the UK, specializing in population biology, with plenty of ecology,
genetics, mathematics, and computing. After a get-away-from-it-all year
working as a desert ecologist in New Mexico, I came back to Oxford
University in the UK to do postgraduate research.
"...in sub-Saharan Africa...HIV
coinfection is the most powerful known risk
factor for developing active
I wanted to combine theory, experiments, and fieldwork, so I picked a
project on mosquitoes. Mosquitoes have short generation times (compared to
the three-year DPhil course) so I could do experiments on population
dynamics. And mosquitoes live in every country of the world, so I had a
wide choice of field sites. I first went to Kenya and Cameroon, and I have
been going back to Africa regularly ever since, interspersed with visits to
Asia, South America, and Eastern Europe. Of course mosquitoes also transmit
pathogens, which is how I got interested in infectious diseases.
Epidemiology is essentially disease ecology.
What first interested you in TB research?
I'd been on the faculty of the London School of Hygiene and Tropical
Medicine for 12 years and I was due for a sabbatical. Although I'd done
plenty of research on infectious and parasitic diseases, I knew practically
nothing about TB, and embarrassingly little about the World Health
During the mid 1990s, WHO was launching and expanding its "DOTS Strategy"
for TB control (based on combination drug therapy), and they were looking
for an epidemiologist to help. I went to WHO in Geneva for one year and, 12
years later, I'm still there. I had not anticipated that the world's TB
data had such rich possibilities, or that working at the boundary of
science and policy would be so stimulating.
Two of your most-cited papers (Dye
C, et al., "Global burden of tuberculosis - estimated
incidence, prevalence, and mortality by country," JAMA-J. Am. Med.
Assn. 282: 677-86, 18 August 1999 and Corbett
EL, et al., "The growing burden of tuberculosis—global
trends and interactions with the HIV epidemic," Arch. Intern.
Med. 163: 1009-21, 12 May 2003) deal with global trends in
tuberculosis. What did the 2003 paper report that was
different—for better or for worse—than the 1999
The 1999 paper was the first major synthesis of data that defined the scale
of the global TB problem, in terms of infection and disease and as a
cause of death. By 2003 we needed to update our assessment, but we also
used that second paper to look more closely at the major cause of TB's
resurgence during the 1990s, namely coinfection with HIV, especially in
Africa. Those two papers were really offshoots of the work we publish every
year in our WHO report on "Global Tuberculosis Control." We distribute
about 10,000 copies of that report around the world, and it has a far wider
audience than the journal publications.
Your 2001 NEJM paper (Espinal MA, et
al., "Global trends in resistance to antituberculosis drugs,"
344: 1294-1303, 26 April 2001), among others, discusses the growth
of resistance to anti-tuberculosis drugs – how big of a problem
is drug resistance, and what can be done about it?
We know that around 1 in 10 new TB cases in former Soviet countries is
multidrug resistant (MDR-TB); that is, resistant to (at least) the two main
first-line drugs used in combination therapy, isoniazid and rifampicin. The
numbers of multidrug-resistant cases are also high in India and China.
Within the last year, patients have been found with extensively
drug-resistant TB (XDR-TB) in more than 50 countries; these strains are
refractory to second-line as well as first-line drugs. Globally, the number
of resistant cases is probably increasing year on year, though we do not
yet have the data to be sure. It is a good bet, too, that the number of
strains resistant to both first- and second-line drugs is increasing, and
we need to closely monitor the distribution of these strains from now on.
But there is some good news about drug resistant TB: countries that have
taken the problem seriously—including Estonia, Hong Kong, and the
United States—have shown that MDR cases can be reduced even more
quickly than drug-sensitive cases.
The interaction of tuberculosis and HIV seems to be
a growing concern – can you walk our readers through the reasons
"Epidemiology is essentially disease
We estimated in 1999 that, while there are 8 to 9 million new cases of TB
each year, as many as 2 billion people carry dormant TB infections. These
dormant infections stay dormant for life in the majority of people, unless
their immunity is somehow compromised. HIV coinfection, if left untreated
with antiretroviral drugs, destroys immunity, allowing the dormant or
latent mycobacteria to progress to active disease. This has happened on a
devastating scale in sub-Saharan Africa, and HIV coinfection is the most
powerful known risk factor for developing active TB.
There is, however, some good news, too, about the interaction between TB
and HIV: new HIV infections are now falling in most parts of the world, and
we have some effective methods to prevent TB among HIV-positive
people—antiretroviral drugs to clear HIV virus and maintain immunity,
and isoniazid to prevent active TB. WHO and other organizations are working
to encourage much wider use of these treatments, in addition to promoting
methods for preventing HIV and TB infection.
What are the biggest obstacles in establishing and
maintaining prevention and control programs for tuberculosis?
A decade or more of evidence suggests to me that, while good DOTS programs
can cure almost all TB patients, they do not diagnose and begin treatment
soon enough to have a major impact on transmission. The problem lies in the
interaction between the biology of TB and the organization of health care.
Where health services are not easily accessible, as in some of the most
affected countries of Asia and Africa, TB patients do not go to a clinic or
hospital care until they are quite sick, or until they realize that a
persistent cough is not going to get better without treatment, after which
they have transmitted infection to other members of their families and
What would you like the "take-away lesson" about
your research to be?
That the world is full of under-exploited information. Much of my work has
been done with the data that are routinely collected by health ministries.
In WHO we have relatively good access to those data but, even so, we can
only work with a fraction of it. The fullest possible analysis of these
data, ideally done by national TB programs, would put us in a far stronger
position to combat entrenched endemic disease like
Christopher Dye, DPhil, FMedSci
Office of HIV/AIDS, Tuberculosis, Malaria & Neglected Tropical
World Health Organization
Keywords: tuberculosis, TB, epidemiology, infectious
diseases, WHO, HIV, global tuberculosis control reports, multidrug
resistance, dormant infections, prevention, control.