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Reichman and Hershfield's
Tuberculosis
A Comprehensive, International Approach
Third Edition
Part A
Edited by
Mario C. Raviglione
World Health Organization
Geneva, Switzerland
New York London
This volume is not an official publication of the World Health Organization, and the opinions expressed
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Introduction
Theyear2006isanimportantyearinthehistoryoftuberculosisandinthe
fight to control it. As was declared during World TB Day in March 2006,
the world showed a new resolve by announcing a ‘‘Global Plan to Stop
TB, 2006–2015.’’
The goal of this worldwide effort, or global strategy, is to begin to
reversethe incidence of tuberculosis by 2015. The TB Fact Sheet (1), pub-
lishedbytheWorldHealthOrganizationontheoccasionofthe2006World
TB Day, provides staggering data from 2004 on the incidence, prevalence,
and mortality from tuberculosis, indicating that there were as many as 1.7
million deaths.
Asweseesuchnumbers,itbecomeseasytoalsoseetherationalefor
the Global Plan to Stop TB, 2006–2015. For this strategy to be successful,
however,itwillbenecessarytohaveasolidfoundationforthedevelopment
of newactions, be theytherapeutic or in the publichealth arena. However,
just as well, it will require a strong and continuous international commit-
ment to support and implement the program.
Verylikely,thecynicswillsaythatthisnewprogramhasabitof‘‘de´ja`
vu.’’Indeed,tuberculosisisnotanewdisease,andmuchworkhasbeendone
over the years to combat it, but it is the first time that a strategic plan has
iii
iv Introduction
been formulated with the endorsement of health, business, and financial
world leaders, not at the World Health Organization, but during the 2006
Economic Forum in Davos, Switzerland.
The publication in 2006 of the third edition of Reichman and
Hershfield’s Tuberculosis: A Comprehensive, International Approach, pre-
sented by the series of monographs Lung Biology in Health and Disease,
may be a coincidence, but it is very opportune as it gives the reader not
onlyastatusreportofwherethefieldoftuberculosisistoday,butalso pro-
videsapanoramicreviewofthemanynewresearchavenuesthatareinneed
of investigation.
The purpose of this volume, as stated by its editor, Dr. Mario C.
Raviglione, is to show ‘‘what needs to be integrated in practice through
effectivecollaborationbetweenresearchscientists,physicians,public-health
officials, epidemiologists, and policy makers’’ if indeed the Global Plan
to Stop TB is to succeed. Truly, this volume gives us a road map to reach
this goal!
Dr. Raviglione, the chief officer of the World Health Organization
tuberculosis program, has shown a remarkable vision in the preparation
and development of thisvolume.Suffice it toreviewthe list ofcontributors
to see that they represent the ‘‘Who’s Who’’ of the tuberculosis field and
that they have paved the way to reaching the Stop TB goal.
As the editor of this series of monographs, Lung Biology in Health
and Disease, I am immensely grateful to Dr. Raviglione and to all the
expertswhoparticipatedinthepreparationofthisvolumefor theopportu-
nitytopresentthisneweditionofReichmanandHershfield’sTuberculosis:A
Comprehensive, International Approach.
Claude Lenfant, MD
Gaithersburg, Maryland, U.S.A.
Reference
1. WorldHealthOrganizationTuberculosisFactSheet#104.RevisedMarch2006.
Historical Background
Sixteenyears ago, the first edition of Tuberculosis: A Comprehensive, Inter-
nationalApproachwaspublished;itwasthefirsttextbookontuberculosisin
several years. At that time, although very prevalent, tuberculosis was a
forgotten disease. There had been no new drugs or diagnostic initiatives
inseveraldecades,theDOTSstrategyhadnotbeennamed,andtheWorld
Health Organization tuberculosis program was a small office with one
professional and one support person. Advocacy and concerned groups of
patients and caregivers relating to tuberculosis were not even a figment
of one’s imagination. The relationship between tuberculosis and HIV was
recognized but routinely ignored. Multidrug-resistant tuberculosis was
scarybutacceptedwithoutinterveningoreventreatingpatientssoafflicted.
Becauseofrapidadvancesinthefield,asecondeditionwaspublished
in 2000. There was increasing interest and progress. Consequently, other
textbooks devoted to this subject and its ramifications were published by
many different publishers.
Now we are pleased to see that the continuing vast progress and
improvementsinthefieldrequireathirdeditionofthistext.Thereisnoth-
ing more fitting for us, then, to pass the editorship to an individual who is
widely recognized for his tuberculosis expertise as well as his influence in
v
vi Historical Background
policymatters,Dr.MarioC.Raviglione.Hehasputtogetheratableofcon-
tents that is a ‘‘Who’s Who’’ of the unquestionable world leaders in the
field. He has also made provisions to distribute the book at a reduced cost
to developing nations where the global burden of tuberculosis is most
strongly reflected.
It is with humility and pride that we hand over the editorship of this
volume to our successor, and our gratitude goes to him and the publisher,
InformaHealthcare,forextendingandenhancingthefranchiseofReichman
and Hershfield’s Tuberculosis: A Comprehensive, International Approach.
Lee B. Reichman, MD, MPH
Newark, New Jersey, U.S.A.
Earl S. Hershfield, MD
Winnipeg, Manitoba, Canada
Preface
Tuberculosis, an ancient scourge of humanity known for several thousands
of years, is still a major public health challenge in many countries today.
Global targets for tuberculosis control by the year 2005 were set by the
World Health Assembly to encourage a concerted worldwide effort to
end this situation. It is therefore timely and appropriate for the interna-
tionaltuberculosiscontrolandresearchcommunitytoassesswhathasbeen
achieved in the past decade since the launch and promotion in 1995 of a
modern tuberculosis control strategy, branded under the name of
‘‘DOTS’’a. It is also time to consider what more needs to be done to elim-
inate tuberculosis as a significant disease threat.
Looking back, there have been remarkable achievements in recent
years. They include: the rapid adoption of the DOTS strategy, which is
now being applied in most countries; the high rate of cure demonstrated
aTheDOTSstrategyhasfiveessentialcomponents:governmentcommitmenttotubercu-
losis control; diagnosis via bacteriology through an effective laboratory network;
standardized short-course chemotherapy with supervision and full patient support
throughout treatment; uninterrupted supply of quality-assured anti-tuberculosis drugs;
andrecordingandreportingtomeasurepatientandprogramoutcomes.
vii
viii Preface
amongmillionsofinfectioustuberculosispatientsthroughouttheworld;the
efforts to tackle multi-drug resistant tuberculosis and human immunodefi-
ciency virus–associated tuberculosis; the launch of successful initiatives,
suchastheGlobalDrugFacilityandtheGreenLightCommittee,toprovide
accesstoanti-tuberculosisdrugsinresource-poorcountries;theinclusionof
tuberculosis among the targeted diseases for support by new international
financial mechanisms, which are mobilizing unprecedented resources; and
major public–private research initiatives to develop new tools to improve
thediagnosis,treatment,andpreventionoftuberculosis.Thisisundoubtedly
animpressivetrackrecordthathasbeenwidelysupportedandfacilitatedby
the establishment in 2001 of the global coalition to fight tuberculosis: the
Stop TB Partnership.
However,despitesubstantialprogressinmanycountries,tuberculosis
still kills 1.7 million people and affects 8.9 million new patients every year.
Clearly,moredetailedknowledgeisnecessarytostrengthenresearchefforts
toward development of new diagnostics, new anti-tuberculosis drugs, and
an effective vaccine. Better understanding of pathogenesis, for instance, is
crucial. At the same time, whileawaiting the tools of the future, we cannot
afford to relax our efforts to control tuberculosis using the current tools
more effectively in the (often weak) health systems existing today in
the world. On the contrary, the threat of resistance to anti-tuberculosis
drugs, especially in the former USSR, and the overlap of the tuberculosis
and human immunodeficiency virus/acquired immunodeficiency virus
epidemics,especiallyinAfrica,obligeustoreinforceDOTSprogramsevery-
wherebypromotingpublic–privateapproachesandengagingcommunitiesto
reachmorepatients,establishcollaborationbetweentuberculosisandhuman
immunodeficiency virus/acquired immunodeficiency virus programs, and
contributetohealthsystemstrengtheningtoaddress,forinstance,thescar-
city of human resources capable of delivering high quality tuberculosis
services. With this in mind, the new Stop TB Strategy recently announced
by the World Health Organization was formulated to widen the focus of
DOTS and address all modern challenges. All these issues, whether they
are in the field of research or that of program implementation, deserve
our full attention.
Therefore, in preparing the third edition of this widely respected
book,Isoughttolinktheclinical‘‘stateoftheart’’totheprinciplesof pro-
grammatic tuberculosis control and to current and upcoming research
initiatives,therebyintegratingonpaperwhatneedstobeintegratedinprac-
ticethrougheffectivecollaborationbetweenresearchscientists,physicians,
public health officials, epidemiologists, and policy makers. The book’s 50
chapters bring together our current knowledge of tuberculosis, its control,
andrelatedscientificdiscoveries.Itisaddressedtoallwhoworkinthefield
oftuberculosiscontrol,whetherinlow-income,high-prevalenceareasorin
low-prevalence industrialized countries. As a compendium of information
on all aspects of tuberculosis, it enables up-to-date knowledge to reach
Preface ix
all parts of the world, especially those settings where access to modern
scientific ideas may still be difficult.
I am immensely grateful to Lee B. Reichman and Earl S. Hershfield
for inviting me to continue the successful tradition of their book. Aspiring
tomatchtheir previousstandards,Ihaveaskedmanyoftheworld’sleading
authorities on tuberculosis to contribute chapters to this book and I thank
themfortheirgenerousandexpertcollaboration.Finally,Ithankmyfamily
for patiently tolerating my enthusiasm for this important endeavour to
share knowledge on the global fight against tuberculosis.
Mario C. Raviglione
