04 >

DOCTOR:
JOEL ERNST New Insights BY: APOORVA
MANDAVILLI
Joel Ernst,
M.D.,holds

into an Old Foe: TB

up a petri
dish filled with
recombinant
E.coli bacteria.

WHITE PLAGUE. KING’S EVIL. WASTING CXjkp\Xi#;i%<iejkËjk\Xdi\]lk\[

[`j\Xj\%G_k_`j`j%:fejldgk`fe%KlY\iZlcfj`jK9 `jXefc[ `ddlefcf^p[f^dXYpj_fn`e^k_Xk#
although the lungs are the primary site
[`j\Xj\n`k_dXepeXd\jXe[^l`j\j%9lk`knXjeËklek`ccXjk f]K9`e]\Zk`fe#X]lcc`ddle\i\jgfej\
p\Xik_XkjZ`\ek`jkj[`jZfm\i\[_fnfc[k_`jXeZ`\ekjZfli^\ i\hl`i\jk_Xkk_\YXZk\i`XÔijkY\kiXej-
really is. Egyptian mummies, skeletal remains, and gfik\[kfcpdg_ef[\jY\kn\\ek_\cle^j#
^\e\k`ZXeXcpj`j_X[Xccjl^^\jk\[k_XkK9_X[Y\\eXifle[ and that M. tb manages to establish a
chronic infection, in part by interfering
]fiXkc\XjkX]\nk_fljXe[p\Xij%9lk`eXYcfZbf]ifZb n`k_k_`jgifZ\jj%K_XkdXpj\\dc`b\YX-
d`e\[]ifdXhlXiip`en\jk\ieKlib\p#Xek_ifgfcf^`jkj[`j- sic information that should have already
covered the fossil of a young Y\\ebefneXYflkjlZ_X]Xd`c`Xi\e\dp#
male dating back some takes hold, it literally consumes the body YlkK9`jefncXi^\cpc`d`k\[kf[\m\cfg-
,''#'''p\XijXe[`e]\Zk\[# ]ifdn`k_`e#\Xk`e^k_ifl^_cle^k`jjl\j
and the blood vessels that run through
ing countries.
K_\jkXe[Xi[ki\Xkd\ek]fiK9_Xjefk
le\og\Zk\[cp#n`k_klY\i- `k%<m\ipk`d\jfd\fe\n`k_X]lcc$Ycfne Z_Xe^\[j`eZ\k_\(0-'j1j\m\iXckfo`Z
Zlcfj`j%K_\pXeefleZ\[ infection speaks, sings, coughs, or sneezes, [il^jkXb\e\m\ip[Xp]fij`odfek_j%K_\
in December 2007 that the the bacteria expelled linger in the air for XmX`cXYc\mXZZ`e\#9:>#`jfecpgXik`Xccp
hours, ready to invade the next victim effective, and the most commonly used
young man had lesions on K_`j`jn_pK9_Xjjff]k\eY\\eX [`X^efjk`Zk\jk`j(''p\Xijfc[%
the inside of his skull, the disease of the poor, because it is at its most 9lk`ek_\gXjk(,p\Xij#i\j\XiZ_feK9
imprint of brain membranes [\X[cp`efm\iZifn[\[#lejXe`kXipZfe[`- _Xj\eafp\[Xi\eX`jjXeZ\%=fccfn`e^X
`eÕXd\[n`k_K9Çgiff] k`fej%@e)''-#K9`e]\Zk\[0%)d`cc`fe ]i`^_k\e`e^\g`[\d`Z`eE\nPfib:`kp`e
g\fgc\nfic[n`[\#ZcX`d`e^k_\c`m\jf](%, k_\(00'j#k_\E@?ÇXe[#`egXik`ZlcXi#
that the disease has been d`cc`fe#dfjk`ek_\[\m\cfg`e^nfic[%@e jZ`\ek`jkj`eE\nPfibÇY\^XegXp`e^
ravaging humans for much some parts of South Africa, as many as 70 Zcfj\iXkk\ek`fekfk_\[`j\Xj\%J\m\iXce\n
longer than anyone had ever g\iZ\ekf]k_fj\n`k_K9Xi\Xcjf`e]\Zk\[ [il^jXe[mXZZ`e\jXi\efn`ek_\g`g\-
suspected. n`k_?@M#Y\ZXlj\K9`jfggfikle`jk`Z% c`e\#Xe[i\j\XiZ_\ijXi\nfib`e^fek\jkj
Most bacteria or viruses that attack k_XkZXe[`X^efj\K9dfi\\Xj`cp%
8e\jk`dXk\[)Y`cc`feg\fgc\Çe\Xicp the body elicit a robust immune response Lek`ci\Z\ekcp#Èk_\[`j\Xj\nXj`egffi
fe\$k_`i[f]k_\nfic[ËjgfglcXk`feÇXi\ n`k_`eX]\n[Xpj%=fiK9#k_\\Xic`\jk Zfleki`\jXe[k_\k\Z_efcf^pnXj`ei`Z_
thought to harbor Mycobacterium tubercu- [\k\ZkXYc\i\jgfej\kXb\jn\\bj#Ypn_`Z_ countries,” says Suman Laal, Ph.D., asso-
losis (M. tb #k_\YXZk\i`ldk_XkZXlj\jK9% time the bacteria have multiplied to nearly ciate professor of pathology and microbi-
@k^ifnjjcfncp#clib`e^`ek_\cle^j]fi (''#'''k`d\jk_\`i`e`k`XceldY\i% fcf^p%ÈEfnk_\i\Ëjk_`ji\Xc`qXk`fek_Xk
p\Xij#Xe[flkn`kjk_\Yf[pËj`ddle\ “What are you doing in the meantime?” \`k_\ipfljkXdg`kflk\m\ipn_\i\fipfl
jpjk\d#`egXikYpnX`k`e^]fik_\_fjkËj asks Dr. Joel Ernst, chief of the Division of jkXdg`kflkefn_\i\%É
[\]\ej\jkfn\Xb\e%@edfjkg\fgc\#k_Xk @e]\Zk`flj;`j\Xj\j%ÈEfk_`e^Ç^\kk`e^ ;i%<iejk#k_\A\]]i\p9\i^jk\`eGif]\jjfi
fggfikle`kpe\m\iXi`j\j#Xe[k_\pj_fn j`Zb%K_\`ddle\jpjk\d`jefk[f`e^X of Medicine and professor of microbiology
efjpdgkfdjf]k_\[`j\Xj\%9lkfeZ\M. tb very good job of handling the infection.” Xe[gXk_fcf^p#Y\ZXd\`ek\i\jk\[`eK9`e
k_\d`[$(0/'j%8kk_\k`d\#k_\E@?]le[\[
fecpX_Xe[]lcf]K9gifa\Zkj%DXepf]k_\
ZXj\j`eE\nPfibn\i\i\j`jkXekkfk_\
available drugs, underscoring the urgency
]fiZc`e`ZXci\j\XiZ_fee\nki\Xkd\ekjXe[
basic research to understand the progres-
j`fef]k_\[`j\Xj\%;i%<iejkjffenfe
^iXekjkfjkl[pn_pk_\Yf[pËjZXi\]lccp
constructed defenses are no match for M. tb.
@k_Xjcfe^Y\\ek_fl^_kk_Xkn_\eXm`-
iljfiXYXZk\i`ld`e]\Zkjk_\Yf[p#k_\Ôijk
response is from dendritic cells, gatekeepers
that initiate the immune response, dispatch-
`e^KZ\ccjfeXj\XiZ_$Xe[$[\jkifpd`jj`fe%
9lki\j\XiZ_\ijjljg\Zk\[k_Xkk_\Yf[p
marshaled another kind of initial response
kfK9%K_\p_X[Y\c`\m\[k_Xk`ek_\cle^j#
dXZifg_X^\jÇZ\ccjk_XkljlXccp\e^lc]

22 NYU PHYSICIAN
+ FALL 2007
 P H OTO G R A P H E R S C R E D I T:

2 NYU PHYSICIAN
+ SPRING 2008
NYU PHYSICIAN
+ SUMMER 2008 21
Xe[[`^\jkgXk_f^\ejÇXi\k_\Ôijkkf\e-
counter M. tb and that the bacteria live and
multiply in these macrophages. But some
bacteria, such as M. tb, have devised ways to
\mX[\k_XkgifZ\jj%ÈN\cffb\[Xkk_XkXe[
jX`[#ÊN\cc#k_\pZXeËkYfk_Y\Zfdgc\k\cp
right,’ ” says Dr. Ernst.
Dr. Ernst and graduate student Andrea
Nfc]Zi\Xk\[M. tbkX^^\[n`k_XÕlfi\j-
cent green label to allow them to track
the bacteria’s progress through the body.
They found that, in fact, the bacteria
infect different kinds of cells and that the
predominant type of cell infected changes
over time. At the earliest point there is
a three-way tie in the cell types infected
with M. tb: macrophages, dendritic cells,
Xe[e\lkifg_`cjk_\Ôijk`ddle\Z\ccjkf
arrive at a site of infection). By the third
week, dendritic cells, not macrophages,
are the cell type predominantly infected
with M. tb, they reported. “That certainly
calls into question the TB dogma that mac-
rophages are the only cells that harbor M.
tb,” says Dr. Ernst. “It says TB immunity
is in line with the rest of contemporary
cellular immunology.”
The researchers also found the bacteria
in lung-draining lymph nodes, but up to 80
percent of the bacteria were once again in
[\e[i`k`ZZ\ccj%;li`e^k_\Ôijk]\nn\\bj
of infection, Dr. Ernst explains, a large
number of infected dendritic cells carry the
bacteria from the lung to the lymph nodes.
It’s only after the bacteria appear in these
lymph nodes that T cells are activated. The
T cells then have to be transported back to
the lung, the main site of infection. M. tb
takes advantage of this lost time, multiply-
ing to overwhelming numbers. “I think
that’s one of the reasons TB wins,” says Dr.
Ernst. “It rigs the system so that by the time
the T cells are recruited into the lung, there
are a million bacteria.”
Getting the bacteria to the lymph nodes,
which has to happen before the immune
response kicks into gear, appears to be the
time-dependent step that slows down the
whole process. Dr. Ernst says the bacteria
may have evolved to survive in a part of
the lung from which they can’t easily be
moved to the lymph nodes. Some people’s
bodies may be able to get around this bet-
ter than others, which potentially explains
why not everyone exposed to TB develops
a full-blown infection. Unfortunately,
even the infected cells in the lymph nodes
are rather inept at inducing an adequate
immune response.
;i%<iejkËjÔe[`e^j_Xm\jfY\i`e^`d-
plications for vaccine development. If the
`ddle\jpjk\dZXeËk\]]\Zk`m\cpÔ^_kk_\
infection, vaccines designed to activate im-
mune cells may prove powerless — at least
without additional methods to foil M. tb’s
evasive tactics.›
22
05
Fighting Drug- BY: APOORVA
MANDAVILLI
Resistant TB in
DOCTOR:
WILLIAM ROM
New York City
FOR A FEW WEEKS LAST SUMMER,
Americans were riveted by news that Andrew Speaker,
k_\eX*($p\Xi$fc[8kcXekXeXk`m\#dXp_Xm\Y\\eÕp`e^
on commercial airplanes, exposing hundreds of people
to a virtually untreatable type of tuberculosis (TB).
They could be forgiven for having thought of TB as strict-
ly a third-world disease. In 2006, 13,767 people in the U.S.
had TB — the lowest prevalence in the country recorded
since 1953 — while else- the 1960s, and that the available drugs
where 1.5 million people were powerless against some new strains
died of the disease. of M.Tb.
Multi-drug resistant (MDR) TB develops
Speaker was diagnosed in early May when patients don’t complete the pre-
)''.#YlkX^X`ejkd\[`ZXcX[m`Z\_\Õ\n scribed six-month course of isoniazid and
to Greece for his wedding later that month. rifampicin. About one in 20 new cases of TB
Tracked down in Rome on his honeymoon, nfic[n`[\`ji\j`jkXekkfÔijk$c`e\[il^j#
he was told he had extensively drug-resis-
tant tuberculosis (XDR-TB) and was asked
Dr. William Rom stands at the
to stay put. entrance of the Chest Service
@ejk\X[#_\Xe[_`jn`]\#JXiX_#Õ\n on Bellevue’s 7th floor.
to Prague and Montreal and then drove A Bellevue security officer stands
kfE\nPfib:`kp%FeDXp)+#f]ÔZ`Xcj guard in the foreground.
from the Centers for Disease Control and
Prevention directed Speaker to report to
Bellevue Hospital, where he was served
with a federal warrant that isolated him for
d\[`ZXc\mXclXk`fe#k_\ÔijkjlZ_]\[\iXc
order issued in 44 years.
Bellevue is no stranger to TB. The hos-
pital’s Chest Service, established in 1903
to treat the disease, has contributed a great
deal of knowledge about its pathophysiol-
ogy, clinical behavior, and treatment. In
the late 1980s and early 1990s, Bellevue
endured a long bout with this familiar foe,
grappling with nearly 4,000 cases in New
York City, many of them homeless people
addicted to drugs and infected with HIV.
“I came here and I found everything was
XccK9Xe[8@;J#Éi\ZXccjN`cc`XdIfd#
M.D., M.P.H., director of the Chest Service.
He came to NYU in 1989 after a long stint
at the Rocky Mountain Center for Occupa-
tional and Environmental Health, where
his primary experience had been with coal
miners and asbestos workers. Dr. Rom,
the Sol and Judith Bergstein Professor of
Medicine and professor of environmental
medicine, quickly discovered that TB treat-
ment and care had barely changed since
NYU PHYSICIAN
+ SUMMER 2008