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Chapter 4

Infectious Disease Control

Looking Back
In the mid-20th century. conside red the golden age
for antimicrob ial advances, Ame ricans came to believe
that infectious disease~ might be conquered for all time.
Vaccines held many scourges at bay in advanced industrial
n:uions, where once-fatal d iseases, slIch as measles, polio
and diphtheria, were no longer ser ious threats. The year
\977 marked success in tbe global era di ca tion of smallpox,
olle of the g reatest achievements o f public health. Some
medical researchers grew to believe that an infectious
agent only needed to be identified before effective
counte rmeasures could be iden tifi ed and implemented.

A rude awakening lay ahead, however. The ea rl y years

, of the 21 st century have al ready seen widespread outbreaks
ofSARS, avian flu, and Ebola virus, debilitating and
ofte n f.1tal emerging infec ti ous diseases. Tuberculosis has
re-emerged as a threat to th e public's health, the number of
H [V infections continues to mount, and growing antibioti c

, resistance threatens hospitals and communit ies throughout

the Uni ted States. ~ Who would have thought in the
1950s, as the Salk vaccine effectively eliminated the threat
Who would have of polio, that so many othe r infectious diseases would
thought in the emerge JUSt 50 years later? [n an age of rapid global travel
19505, as the Salk and a revolution in the developmellt of the rapeu tics and
vaccine effect ively public education, we have reached an uneasy sta ndoff
eliminated the between microbes and man's best efforts to crea te a world
threat of polio, free of infectioLls diseases.
that so many
other infectious Re:l.l :l.dv:l.Tlces in infectious dise:l.se con trol beg:l.n in the
diseases would second h:df of the 19th century, but medical C:l.re did not
emerge just 50 become truly transformed until antibiotics were discovered
years later? in the 1940s, ushering in dramatic reductions in illness and
death frol11 infectious diseases. For exa mple. in 1850 t he
infant mortality rate in Massach use m was 130 deaths per
1,000 live-born infants, with many of these deaths due to
inrra- and postpartum sepsis. By 2003, the inf.1Tlt mortality
rate ill Massachusetts had dropped to 4.8 deaths per 1,000
liv(' births.
For :I tim e in the mid-19th century, sanitary reforms
helped comrol diseases. A hygienic movemcnt arose from
the squa lor of urban slum s, trying to eliminate dirt and
sewcr stenches . While th e effort had some effect, it failed
to counter diseases spread by fl eas and mosquitoes or by
personal contact, and it oftcn failed to separate drinking
water suppli es from sewage. Fortunately, the breakthroughs
of Louis Pasteur and Robert Koch and the germ theory of
disease were soon to corne.

In 1346, the world's most famo us scourge, bubonic plague,

spread by rats to fleas to humans at first in Asi:t, migrated
to thc population centets of Europe
with devastating effect. It is thought
that as much as half of Europe's popula-
tion succumbed to the disease in the
ensu in g years. The disease - a highly
con tagio us, virulent bacteria - caused
high fever and :lttackcd the lungs, turn-
ing the body black before death. Once
the "blac k death " ep id emic died out of
its own accord, th e relieved but dimin -
ished population of Europe moved on
to the R enaiss:tncc, one of th e great
ages in human history.

In 1530, the Itali an physician Girolamo Fracastoro wrote

a poem to ex press his ideas about the origin of sy philis,
positing that this sexu all y transmitted disease w:ts spread
through intimate contact by "seeds." H e ex p:tnded th is
earl y theory of contagion in later writings to include
indirect contact, through cloth in g and even through the
air. I n giving voice to his ideas, Fracastoro anticipated by
350 years the pionee ring work of LOllis Pasteur, Robert
Koch and their contempora ri es in the late 18705. Their
big breakthrough came with the ge rm theory of disease.

In 1627,Jesuit missionaries 111 mal aria-ridden Peru began

carrying the bark of the Cincho na tree back to Europe.
They had observed th:H native Indian s used the bark to
fight malaria, not yet realizing that the active ingredient.
quinine, had anri-ITularial properties. When the bark proved
to lessen malaTlal fevers in Europe, quinine gained a spot
on the rare list of pharmaceu ticals - opium, digitalis,
willow b:trk, and little else - that provided patients so me
relief pri or to the modern era.
 In 1683 in rhe Nethe rlands, with one of h is new micro-
scopes in h:l11d, Anton van Leeuwenhoek visualized bacteria
among the (ll/illll//w/es - microscopic animals that cannot be
seen by rhe naked eye - he harvested from his own teeth.
H e was the first to see and describe bacteria, yeast plants,
the teeming life III a drop of water and the circulation of
blood co rpuscles in capillaries. The invention of the micro-
scope opened the way to visualize some of the microbial
agel1ts causing contagious diseases, but not until the invell-
tion of the d ectrotlmicroscope in the 1930s did the
A rrM/! 1'1111 molecular structure of microbes - nucleoids, ribosomes,
LrcI/1/I{'/lJ/Od: cell walls and membranes, flagella - become discernible.
The electron micro~copc gave rise to a fl omishing era for
molecular biology.

[n 171)6, in Hertfordshire, Engl:l.lld, Edward JenneT devel-

oped the first vaccine after observmg that milkmaids
exposed to cowpox were so mehow immulle to smallpox.
Jentler concluded thlt exposure to a form of the animal
infection protects a persOIl (i'om contracting a full -blown -
and Illuch Illorc devastating - form of the human disease.
and his cnlpirical observation and successfu l experimcnts
became thc basis for vaccincs that followed.

The ge rm theory of disease arose from research by a

French che mist. Louis Pasteur. and a German bacteriolo-
gist, Robert Koch, which established the s:ll1itary condi-
ti ons necessary for isola tin g and studying b:lcte ria. In the

-"" '

Dr. K!,c/,:'- IrCIIIIIICIII j." (l lI SI Wlplim, (1IIhf((III(lsis).

late 1870s, Pa~teur invented pasteurization, the process of
heating milk to kill dangerous microorganisms, and invent-
ed vaccines against anthrax and rabies. Koch's contributions
were procedu ral and have been handed down as " Koch's
Postulates," criter ia necessary for a particular organism to
be proven to cause a particular disease. In 1882, Koch iden-
tified the bacterium that causes tuberculosis, and a yea r
later, he did the same for cholera. Koch's discoveries began
a golden age of microbiology marked by headlong compe-
tition among medical researchers to isolate and identify the
microorganisms that ca use diseases. uw;s Pasteur u",rks 011

(III cxperimclIf.
This ger m theory led to advances in treating infectious
diseases in western Europe and the United States. Dy
the turn of the century, typhus had virtually disappeared,
tuberculosis had started a long decline, and life ex pectan cy
began to increase. Nonetheless, annual mortality in the
advanced industrial nations remained at two percent,
much of it caused by infection. Diseases such as diphther ia,
measles, whooping cough, scarlet feve r, puerperal fever,
tuberculosis and infectious diarrhea remain ed major killers.
In some cases, notably mortality from childhood infectious
diseases, such as scarle t feve r, little would change until the
advent of antibacterial agents in the mid-20th century.

I n th e 1890s, the Russian mj crobiologist Dmitri lvanowski

and the Dutch botanist Martinus Deijerinck independen tl y
discovered tiny infectiou s agents that could pass through
baCleria-stopping filters. .. Too small to be seen with
conventional microscopes, these age m s were named
,
"viruses." Unlike bacteria, which replicate independendy, a Too small to
virus lIlvades an existing celJ and replicates using that cell's be seen with
genetic code. Research in viruses, thought to cause at least conventional
half of human infections, has unleashed a new sphere of mIcroscopes,
co mpetition among microbe hunters. these agents were
named "v iruses ."
In the 20th ce ntury, great advances in fighting infectious
diseases we re made possible by the discovery of sulfon-
amides, penicillin and anti -tuberculosis agents . Vaccine
development and smallpox eradi cation were also great
achieve ments during the centmy. H owever, the great
infectious disease cha!!engcs of the century - influenza
pandemics, the H IV pandemic, and failure to control
malaria, tube rculosis and worldwide inf:1nt mortality-
sti!! haunt us at the start of the 21 st ce ntury.

1\'kdiclll+sm.'cllillg
WIU/1<I(~1I Jor", lapiIiS
sirki/('ss" ill Glll/iI.
While an timi crobial agen ts play an important role in
reducing deaths caused by infect ion, much of this reduced
mortality comes frOIll cO lltinued improvements in nutri-
tion, housing and environmental hygie ne. Vaccination. cul-
minating in the global eradication of smallpox in 1977, also
bas had a profound impact in reducing the global burden
of diseases such as polio, measles, diphtheria and tetanus.
Early ill the 21 st century, polio and gum ea worl11 arc ve ry
close to eradica tion , while onchocerciasis and lymph:Hic
filariasis are also t:trgets for elimina tion.
Approxinutely 25 percent of phys ician visits ill the
United St:Hes today :tre to identify :tnd treat infectious
dise:tses, including H[V infection alld related illnesses, with
both direct and indirect costs estimated to be S 120 billion
annually. An estimated 600,000 cases of pneumonia occur
each year in the United States and ca use as many as 50,000
deaths. 111 other parts of the world, in fectious diseases
rcmam the leading caLIse of morbidity and mortality.
Each year, malaria claims the lives of
more than olle million children in sub-
Saharan Afri ca. Worldwide, each year 35
million to 60 million people con tract
dengue, and approximately 200 milli on
people have sc histosomiasis (also called
bilharz ia or snail fever, a tropical disease
made widespread through the LIse of
contaminated water, characterized by
illfection and gradual destruction of the
tissues in th e kidneys, liver and other
organs). [n Russia, 1110re t h:lI1 10,000
cases of diphtheria have occu rred since 1993 due to a fall-
off in lInlllunization levels. [n 1998, the World Health
Organization estimated that infectious diseases ca used
almost a quaner of the 54 milliol1 deaths worldwide - ove r
13 million deaths. Three diseases that had been COlllmon ill
the developed world at the beginning of the 20th cC I1tt1ry
- pneumonia, diarrheal disease, and tuberculosis - account-
ed for nearly half of these deaths. Still, since the advcm of
microbiology in the late 19th century, progress against
infectious diseases has been remarkable.
The emergence of infectious diseases in this cemury,
despite man's best efforts to eradicate them, cOllies in part
from demographic factors. As people live lon ger, they arl'
 . - ~ 'r"'" .
64 M,Ie'lonc, Chal'ln4 lnfccnuus n><~"<~ Comrul lookmllli.lCk · ~.~ • _' ',' > ~•
. .L ,.~~~ ___ -,._ _, ...... ~....,. •. -.t _ .

more apt to be hospitalized in old age and become suscep-

tible to bacterial pathogens lurking on wards, Hospit:tl per-
sonnel can spread these pathogens from one patie nt to
another, ca using what are knowll as "nosocomial infections."
~ Ironically, ill the developed wo rld, old people are
mOSt at risk of infectious diseases; while in the develop in g
,
world, infants and young chi ldren remain Illost at risk. Iro nicall y, in the
deve loped world ,
JoshU:l Ledc rberg, Nobel Laurea te in mediCIne, observes, old people are
"As infectio us diseases have assumed lower rankings in most at risk of
mortality statistics, other ki llers - mostly diseases of old infectio us dis-
age, amuence and civilization - have moved up the ladde r. eases; while in the
H eart disease and cancer, for example, have loomed as developing wo rld,
larger threats over the past few decades. H ealthier lifestyles, infan ts and young
including less smoking, sparer dices, more exercise and children remain
bener hygiene, h:lVe been important countermeasures . most at risk.
Prophylactic llledic:Hiol1s, such as aspirin, as well as medical
and surgical interventions, have also kept people alive
longer." []
Case Study
HIV/AIDS
The myste r ious constellation of symproJlls that beg.:m [Q
appC:lf in gay men in rh e late 1970s and C3r1y 19805 harned
the medical world at first, but not for long. The symptollls
consisted of opportll!l1sric infections or cance rs - candid ia-
sis in the mOllth, pneumocystis carinii pneumonia in the
lungs, toxoplasmosis in the brain, Kaposi's sarcoma lesions
on the skill and elsewhere, to name a few - that hinted at
compromised immune systems as the underlying cause.

The medical cOl1lmunity set to work to identify the c ulprit.

Fortunately, cach individual infection presenting in g;ty men
had been identified in tbe early years of tbe 20th CC !HUT Y
and by tbe 1970s, for different rCJ$Ons, had been linked
to an underlying defect of the immune system. Doctors.
therefore, understood the complexity and implications of
wh:lt they now confronted. [n New York City and Los
Angeles, where the first ca~es of rh e new "gay plaguc" or
gay-related immunodeficie ncy (GR [D) were tre:Hcd, doc-
tors astutely noted that a defect in the immune system was
the undet lying rcason why this constellation of infectious
diseases :l11d cancers was occurring.
In 1981 , CDC beg~1.Il to formally track cases. Th e next year,
public hea lth offi cials in the Uni ted States began to usc th e
term "acquired immunodefi ciency syndrom e" (AIDS) to
identify tbe new occurrences of opportunisti c infections,
cancers and othe r co ndition s. In 1983, Drs. Francois-13arre
Sinoussi, Lu c Momaigner, and colleagues at th e Institut
Pasteur in Par is isolated and identifi ed the ca use of AIDS,
a virus th ey named "lymphadenopathy-associa ted virus"
(LAV). Additionally, discover ies by Dr. R.obe rt G:lllo and
his colleagues at the National Institutes of H ealth that sam e
year provided co nclusive evidence that this vi rus indeed
caused AIDS. A few years la ter, th e virus was renamed
" human immunod efi ciency viru s" (H IV).

Although the public health cOlllmunity speculated over

the years that the source of H IV must be connected to
primates in Afri ca, the origin of the virus in humans was
not settled until 1999 . That year, a team of researchers
reported they had discove red H I V- I in chimpan zees in
west equato rial Africa. H IV- I, the predo minant strain of
H IV in th e developed world , has a cOllsin , HI V-2 , whi ch
is a slower-ac ting strain that o cc urs primarily in wes tern
Africa. Th e researchers idelHified a particular subspecies
of chimpanzees as the li kely o riginal source of H IV-1 and
concl ud ed that th e virus must have passed to humans from Au AIDS reseaTe/lcr
this so urce. dril l/)ing blood jf(/m
1/ chilllplln:uc.
Th e properties of HJ V arc unique. A retroviru s, H IV repli-
cates by binding to the outer sllTface of the C D4 + T cell
(also known as a helpe r T lym phocyte, a white blood cell
that fights lllfectio ns and is critical to a healthy immun e
system). After binding to thi s ce ll , H IV enters th e ce ll and
remains hidden and protected from other immun e system
cells. On ce inside, HI V copies its RNA , creating a new
viral DNA that is ilHcgrated into the host ce ll's DNA.
Empowe red by th e host cell, HIV repli cates new virions
(si ngle viruses). Th e new virions leave the host ce ll to
infect othe rs, and th e host CD4+ T ce ll dies. Whil e the
body produ ces about 10 bill io n new virions daily, the
immune system kills and removes most o f them, leavin g
about 100 million virions that arc infectiou s. Although the
body crea tes C D4 + T cells eve ry day, virions kill others
off. leading to a struggle for balance of power between
H IV and C D4+ T cel ls.
 H IV is transmitted in the following ways:
• Sexual comact with an mfected partner, includin g
vaginal, anal and oralmtercourse; HIV ente rs the body
through the lining of the female and male genitalia, the
rectulll, and through the mouth (men hav ing sex with
men remain the population at highest risk, although
the growth rate of HI V infection in women in the
U.S. has in some years outstripped that in gay and
bisexual men).
• Sharing needles or syringes contaminated with tnfected
blood (the number of cases in injected drug use rs is
second only to gay and bisexual men in the U.S.).
• From infected woman to fe tus during pregnancy or to
newborn during birth.
• Ureast-feeding by mfected mothers to newborns.
• Transfusion of infectcd blood or blood products.

Based on available ev idence, HI V is not t ransmitted throu gh

saliva , sweat, tears, urine or feces. No transmission has been
attributed to biting insects, and only rarely through mu cosal
or casua l contact with blood or body fluids. Casual contact
docs not includc sitting next to someone, shaking hands,
hugging, eari ng in the same restaurant, sw imming in the
same pool, using the same shower or rub, and using the
same toilet seaL

How do people infected with HJ V know if they have

AIDS? ~ When monitoring a pe rson with H IV,
twO blood tests shou ld be done periodically. a C D4 + T
When monitoring cdl count and a viral load count. If the C D4 count drops
a perso n with below 200 cells/mm3, or an AIDS- defining condition
H IV, two blood develops, th e person bas AIDS. AIDS-defining conditions,
tests should be listed below, would be ve ry unusual in someone not
done periodically, infected with HI V.
a CD4+ T cell
count and a viral • Candidiasis (knowil as rhrush ,:I fungus in the mouth)
load count. • Invasive ce rvical cancer in women
• Coccidi oidomycosis, cryptococcosis. cryptosporid iosis
• Cytomegalovirus disease
• Encepha!opathy (H IV- related)
• H erpes si mplex (severe infection)
 • HistoplasmoSIS
• lsosporiasis
• Kaposi's sarcoma (a rare skin lesion ca llsed by
a type of herpes virus)
• Lymphoma (ce rtain types)
• Mycobacte rium avium complex
• Pnel1mocystis carinil pn el111l0l1 ia
• Pneumoni a (recu rrent)
• Progressive 111l1lrifocal leukoencephalopathy
• Salmon ella septi cemia (recur rent)
• Toxoplasmosis of the brain
• Tubercul osis
• Wastin g syndrom e

The immediate conce rn for som eo ne infected with HIV,

even before he or she develops AIDS, is treatment. Today,
people with H IV should be followe d clinically with lab
tests to assess their need for anciretroviral th erapy and to
mo nitor their progress. The viral load count beco mes an
important meas ure in determining when and how to pro-
ceed. Gene ra[[ y, anti- HIV medi catiollS are ca[[ ed fo r if th e
viral load is 100 ,000 copies/ mL or more or if the CD4+T
cell count decli nes rapidly. Systemic f:1ctors also playa role.

Treatment of H I V in th e early 1980s consisted mainl y of

palliative ca re, sin ce rhe o ri gills and cO Llrse of th e disease
were still a mystery and drugs to fight it effectively had ye t
to be developed . ~ Until 1987, when th e m edi catio n
AZT was li ce nsed for LIse, death usuall y occurred within 18
month s of diagnosis, often from pn eulllonia after a period Until 1987, when
o f :1larming weigh t loss . P:1tients often had more £11:111 o ne the medication
oppo rtunisti c infection or can ce r at a time - slI ch as can - AZT was li ce nsed
didi:1sis, diarrheal disease, Kaposi's sa rcoma an d, in the end, for lise, death
pn ellmocystis carini i pnelll11on i:1. Not all people with HIV usually occurred
develo p symptoms rapidly, however. Th e median time lag within 18 months
for developing sy mptom ~ is estimated to be tell ye:trs, but of diagnos is ..
so me peopl e in fec ted with 1-11 V develop symptoms very
quick ly while othe rs st:ty free of symptoms for many yc:t rs.
Dr. Jun es Curran, dean of R o [[ins School of Pu blic Hl'a lth
at Emo ry University and forme r head ofche H1V/ A1DS
 unit a\ CDC. observes, ~ "Unfortunately. most people
in the world with HIV still get no trcatme nt."
" Unfortunately,
most people in The pubhc health respon$t' \0 the H I V/ Al DS pandemic in
the world wi th its early days included education, testing and partner notifi-
HI V still get no cation. So little was known about the disease that the pub-
treatment." lic cl:l111orcd for information. Could kissing transmit HI V?
Who was most at risk? As CDC began collecting data on
every reported case before the discovery of HI V and the
avaibbility of testing, new populations surfaced as being
potentially at specia l risk - Haitians, injecting drug users
and hemoplu liacs. Almost from the start of the epidemic,
some hospitals beg:l.n to separate :It-risk popubtiotls and
AIDS cases and recommended that staff be fully gowned,
ma5ked and gloved when treating patients . Since the
exchange of blood through needles was known to transmit
AIDS. special precautions became neCl'ssary for drawing
blood.

Some of the mo re controversial public health measures to

address the emerging epidemic 11lcluded anonymous and
voluntary I-II V resting, partner notification and bhnded
seropreva1ence surveys. Early on, the public health commu-
ni ty encouraged indiVIduals who were at risk of infection
to le;'lrll about their HI V status through :l.nonymous testing
sites th:l.t were established at local and st:l.te health de part-
nH:nts. Individuals who tested positive we re encouraged to
notify their partner{s). For those who tested positive and
were reluctant to notify their part ner{s), State and local
health departmcnts set up systcms for notifying partners,
collecting the names and notifying them while shielding
the n:1Ine of the index case. Finally, CDC developed :l
Sl'ri('S of validated or blinded seroprevalcnce surveys - in
pregnant women, in newborns, in STD clinic patients - in
order to better unde rst:lnd the epidemIC and how It was
ch anging. Controvnsy developed when sta tes began to fed
pressure to identify the positive caSt'S in order to notify
them of their I-l tV st:ltuS and the need for thcrapy. In some
scates, such as New York, the newborn seroprevalence su r-
vey Ius bee n "un blinded" so that the names of the babit:s
are made known to pedia tricians and mothers who are
referred for therapy. Since the early 1990s, the U.S. Public
Health Services has recomll1ended that all pregnant women
in the U.S. receive voluntary Ht V testing during pregn:lncy.
... Today, after conce ntrated research and development
by ph armaceutical co mpani es, the U.S. Food and Drug
,
Admini stration (FDA) has approved more t han 20 anti- HIV ... t he U.S.
medications for adults an d adolescents. Th e U. S. Depart- Food and Drug
ment of Health and H uman Se rvices (DHH S) provides Administration
HI V-treatmcnt guidelines co physicians an d pati ents and has approved
updates th em as the FDA approves new treatment protocols. more than 20
Th e guidelines recommend that three or more medications anti - H IV med ica-
be taken together in a reg imen call ed Hi ghly Active Anti- tions for adults
retroviral Therapy (HAART). Because th e choices of com- and adolescents.
binations of drugs are now numerous, each case requires
careful , methodical analysis and periodic adjustment by
a physic ian.

Four classes of antiretroviral medi catio ns now exist:

• Nucleoside R eve rse Tra nscr iptase Inhibitors: NRT ls,
faulty ve rsion s of bu ilding blocks needed by H IV to
rep licate, lure HI V away from normal building blocks
and stall reprod uction of the virus (first FDA approval:
March 1987).
• Protease Inhibitors: Pis disable protease, another
protei n needed by H IV to replicate (first FDA
approval: Dece mber 1995).
• Nonnucleoside R everse Tra nscriptase Inhibitors:
NNRTi s bind to reverse transcriptase and disabl e
t his protein needed by HI V to replicate (first FDA
approval: June 1996).
• Fusion Inhibitors: Fis preve nt HI V from ente ring cells
(fi rst FDA approval : March 2003).

For treatment to be etTective, patients must adhere to a

strier regi men . T hey must observe an unwavering daily
tim eta ble for ingesting pills and be carefu l about what
they eat and drink . For patients who adhere to the strict
reg imen, remarkable successes are becoming the norm in
keeping HIV and symptoms in check. In f.1Ct, AIDS is
often now a chronic, treatable d isease rather t han one that
carries an au tomatic dea th se ntence. H oweve r, even now
in the Un ited States, ove r 15,000 deaths frOIll AIDS occur
each year, and th ere is still 110 cure.

III addition to their foclls Oil providing !lew antiretroviral

medications, pharmaccutical companies havc focllse d on an
H IV vaccine since the discovery of the vi rus. Until a
 proven vaccine clears the hurdles of clinic:!.1 trials, however,
the only sure mcthod to fight AIDS continues to be pre-
vention. The view of A IDS as a chronic, treatable diseasc,
paired with a curren t epidemic of tllethamphetalllllle use in
the gay community, has led many young and middle-aged
gay men to resume unprotected sex, a g rave concern to the
public health communi ty. Public health expe rts note that
messages need to resonate in the teen and young adult
pOPllbti on stating that thc only sure way to prevent AIDS
is abstinence and avoidance of needle-sharing. Although
morc than twO dozen clinical trials of experiment:"d AIDS
vaccines arc being conducted worldwide, only one has
made it to Phase 3 clinical trials. ~ A viable AIDS
vaccme is not yet in Sight.
A viable AIDS
vaccine is not yet The up and down mood swings felt by the scie nt ific and
in sight. public hea lth comlllllllities and by the public as the A[DS
pandemic unfolds - from pessimism and depression to
optimism and euphor ia and now back to:l new re:llisl11 -
accur:ltcJy capture thc repeated cycles of questions that afe
unique to AIDS. Unlike nUI1Y other infect ions, A[DS dC:lls
with taboos and denials and a greater :lIllOUllt of fear and
uncert:lillty. Eve n so, many middle :md high schools today
o penly te:lch H [V prevention, integrating the latest infor-
mation about th e epidemic into their health :lnd wellncss
curricula.

Sobering statistics accoulH for the fe:lr and uncert:linty.

More dl:ll1 600,000 cases of AIDS h:lvc been reported
in the United St:ltes since 1981. An estimated 850,000
to 950,000 Al1IeriC:lns arc currently infected with HIV,
with African-America ns :!.ffected disproportionately.
~ Included in this estimate are 180,000 to 250,000
people who don't kn ow th ey :Ire infected. From 1985
Included in this to 1996, AIDS C:lSCS In women incre:lsed threefold. Citi ng
estimate are 1999:1s the low point in incidence of AID S, CDC
180,000 to reported in July 2003 rh:lt A[DS in g:ly :llld b isexual men
250,000 people h:ld increased lle:lrly 18 percent since thell. Wh il e the rate
who don't know of H [V infections ill the U.S. continues to incrc:lsc, the
they are infected. number of AIDS c:lses has t:,llen dr:llllatically since [996.
In that year, HAA RT c:lme into comlllon usc :lnd the
de:lth rate from AIDS in t he u.s. began to level off.

Thc rest of the world is :mother matter. however. A[DS

is now rhe fourth le:lding caUSe of death worldwide and
th e No.1 cause of death du e to infectious di sease. AIDS
has surpassed malaria as th e leadin g killer in Afri ca. [n
2003,38 million people were thou ght to be li vin g with
HIV/ AIDS and an estimated five million peopl e acquired
HIV that year, more th:ll1 in any prior year. More th an
three million people were killed by AJDS in 2003, brin g-
in g the total number of people who have died fro m AIDS,
sin ce the first ca se~ of A IDS were identifi ed in 198 1, to
more than 20 million.
Child rccrilies till
Yes , these statisti cs are sobering . On th e other hand , aromillhempy maSSi/,llI'
remarbb[e progress has bee n made against a disease that ill il l/ arpllallage filr
emerged from nowh ere in 198 1. Th e behavior o f gay men child,!'" !IIilh A IDS.
in th e developed wo rld changed qui ckly ; HIV itself was
isolated and identifi ed almost imm ediately, and new med-
Ications and other therapi es were di scovered and llsed. Th e
accumu lated knowledge o f th e co mplex mechanisms of
AIDS enabled ever more effecti ve cOllnterm easures to be
d eveloped th :1t extend and enri ch lives prev io usly viewed
as imperiled. In rhe developed wo rld , AID S has becom e an
often chroni c, treatable condition rath er th an a rapid death
se ntence. This progress mu st be celebrated as a signal
achievement of th e SC ientifi c and publi c health communi -
ties. But as Dr. Curran points out, " We still have a long
way to go in the world . Th ere is still neith er a cure nor a
vacc in e. Science and public health canno t rest." 0 Dr.Jaml's Cr i mm,
Deall of lire Rollills
School r1 PI/b/ie H ('II/I/I,
Emory UlliI/t'rsiIY.
 73

Vignette
Development of Penicillin
Sir Al exander Fleming discovered penicilli n by accident at
St. Mary's Hosp ital in London in Se ptember 1928. The sto ry of
how he stumbled on 3n ext raordinary advance in public health
illustr:ttes the role serendip ity can play in the often painfully slow
process that accompanies great advances in scientific history.

As he was about to discard a culture plate while cleaning up his

laboratory in the Inoculatio n Department of the hospital, the
young Scottish physician noticed somethin g fun ny. He remembered
streaking the pla ce som e weeks befo re with staphylococci and now
noticed a cont:llllin ant mold grow ing ncar o ne edge of the plate.
Around the mold, the co loni es of sraplly/ocQ((i wefe translu cent
and smalle r; whi le further away on the plate, the colonies conti nu ed
to grow in their norm:!.l way, robust and snowy white . Dr. Fl eming
realized that someth in g in the mold \Vas destroying th e disease-
causing bacteria.

What was this mold? With the help of the mycology lab one floor
below, Alexander Flemi ng identified it as PellicilliulII, and the sub-
stance in it, as penicillin. H e began to
ex periment with penicillin and discov-
ered that its properties also destroyed
other disease-causing bacteria. Fleming
realized that penicillin would be an
effec tive treatment against infectious
diseases, yet other scie nti sts shun ned
his p resentations at scientific meetings
and his journal articles. R ather th an
fight to overcome the skepticism of
the scie ntifi c communi ty, Fleming
turned his attention to o the r areas of
research. H e owed much in his wo rk
to Sir Almroth W right, who estab-
lished the Jnocu lation Department in
1907 to produce and sell vaccilH:s. The
diminutive, reticent Fleming was no
Sir Ale.\"<lIIfler F/cmillg receillill<~ match for the brilliant and abundant
Ihl' 1945 Nobel Prize for Scit'lIlijil eccentricit ies of Wright, but after
"t/,iell{'lIIelll from Ki/J,~ GIIS/III' 1/ Fleming earned his degree in surgery,
(YSlIl{'fll'lI . it was Wright who gamely kept
74

Fleming on staff and encouraged the ingenuity that became a hall-

mark of Fleming's experimental techniques.

Twelve years elapsed before Howard Florey and Ernst Chain at

Oxford Universi ty resuscitated Fleming's findings and vindicated hi s
claims for penicillin. Ironically, it was Alexander Fleming who
gained fame after penicillin
began to be produced
commercially III the early
1940$, saving countless
wounded on the battle-
fields of Europe and Asia
with its disease-destroying
properties. Fleming had, in
fact, become an expert on
trea tin g waf wounds with
antiseptics during his World
War r service at Boui ogne,
111 WW II, II UlQll/ldeli soldier is illjeaed France. [n 1945,A lex:t nder
wirh penicilliuo
Fleming was awarded a
Nobel Prize in m edicin e, and by staying at St. Mary's Hospital for
the remain der of his career, he gained fame for the hospi tal as the
site of his discovery.

Under constant threat of German air raids and a possible invasion,

the Oxford gro up sought help in the United States for continued
resea rch and production of penicillin. In the f.1.ll of 1942 in
Brooklyn , the Charles Pfizer Company dedicated its citri c acid
production fac ilities to penicillin. Military demand was paramount,
and Pfi ze r's production eased supply sho rta ges, helping to make
penicillin the miracle drug it became on World War II battlefields.

M eanw hile, at Brooklyn's J ewish H ospital, Dr. Leo Loewe and his
associates were participating in a clinical trial of penicillin for the
treatment of streptococcal subacute bacterial endoca rditis, an infec-
tion of heart valves damaged by rheumatic feve r. Th e mortality o f
this disease was 97 percent, and the results for penicillin were not
encourag in g. Of 17 patients t reated, fOllr died, 10 showed no
Ilnprovemcnt, and two of the three who showed improvement had
relapses as soon as treatment stopped . Dr. Loewe now confronted a
34-year-old man for whom his team had tried everythi ng for six
months - huge doses of sulf.1. drugs, artificial fever therapy, heparin,
and moderate doses of penicillin. Desperate, they tried a larger dose
of penicillin - 200,000 units per day instead of th e standard 40,000
 75

units (milliscule by today's standards) - by intravenous drip. The

alpha-hemolytic streptococc us disappeared from the patient's blood,
reappeared after treatmenc sto pped and d isappeared for good after a
second several-week course of treatment. Dr. Loewe had proved that
endocarditis could be cured w it h aggressive t reatmen t with peni-
cillin, bur he and his associates now faced a shortage of available
penicillin, all of it earmarked for the military. Fortunately, the sen ior
execu tive of nearby Pfizer, John L. Smith, co ntributed a supply from
his research allotment, and another seve n pati ents were treated and
cured. Smith visited eac h of the seven pe rsonally and , thereafter,
continued to supply Dr. Loewe with penicillin fro m Pfizer's research
allotme nt , despite the risk of being found in violation of the War
Department's requ irement t hat al\ manufactured penicillin be dedi-
cated to military lise.

Fleming's di scovery of penicillin was also not without controversy.

Othe rs trying to duplicate his expe riment f.1.iled, and not until 1940,
under a microscope at Oxford, was it determined that penicillin
wo rked against microorganisms only w hen they were actively in the
stage of division. What's more, it was later determined that Fl eming's
serendipi tolls strai n of Pellicil/illlll ha ppened to be one of the three
most effective in its disease-destroying properties . R ece nt recon-
stru ctions of Fleming's discovery have also determi n ed th:at the
weather co nditions in Septembe r 1928 were ideal - a cold snap
followed by warm tem peratures - for the phenomena obse rved by
Fleming to occur. Without those ideal co nditio ns, he may neve r
have discovered penicillLn. D
76 M,l, ,""'"' (h 'pkr 4 ]nfecu"u, J)1<~<l<e (om",l LOll!.:"'!: Ahe"iI

Looking Ahead
Antibiotic Resistance

Antibioti cs, whi ch are also known as antimi crobial drugs,

fi ght in fections caused by bacteria . I n the decades since
their discovery in the 19405, t he an tibi oti cs that normally
coTltrol bacteria have become less effec tive as the bacteri a
have become increasingly resistant. Penicillin - the miracle
drug that saved couTltl ess wounded on \Vorld War 11 battle-
field s - today faces the fie rcest strain of resistant bacteria.
... In [1ct, virtuall y eve ry important bacteri:tl infection
in the United States and throughou t the world is now
,
becoming resistant, to one degree or another, to antibiotics. In fact, vinuaUy
For this reaso n, Ce nters for Disease Control and Prevention eve ry important
(CDC) considers antibiotic resistan ce one of its top con- bacterial infection
cerns, and the U.S. Food and Dru g Administration (FDA) in the Un ited
see ks ways to stream lin e the approval process for new anti- States and
biotics to replace those that have bee n compromised by throughout th e
resistant bactetia. wo rld is now
becoming resist-
13acte ria develop resistance through genetic mutation. No ant, to one degree
one antibiotic kills every last targe ted bacteria. The bacteria or another, to
that survive, already displaying resistance, pass th elr ge nes antibiotics,
to a llew and more numerous ge neration, renderin g the
antibiotic even less effective for the patient t he next time
it is Llsed. Sometim es, resistant bacteria even exchange their
geneti c code with unrelatcd b:tcteri:t, causing unforeseen
resistance to oth er an tibiotics.

How did this problem develop? Th e reasons are Illulti -

facto rial and include the overuse and incorrect use of
antib ioti cs. Parenrs often request antibiotics to treat the ir
children's colds or ea r infections before allowing these COI1-
ditions to cl e:t!" up on their own. Ag:tinst their own better
judgment, physicians often acquiesce to a patient's demand
for alltibiotic tre:Lt!11ent. Eage r for quick results, physicians
sometimes prescribe antibiotics to treat conditions for
which they are not appropriate. 130th patients and physici:llls
must be educated about the appro pri ate usc of antibiotics .

In 1999. the U.S. Department of Heal th and H uman

Services (D H HS) formed :t task force alllong fede ral agen-
cies to tack le the problem of antimicrob ial resistance. CDC,
 FDA and National InsritU[cs of Health co-chai red the
task force, which in 2001 issued a plan of action. Known
as the Public Health Action Pbn to Combat Antimicrobial
R.esistanct', the pbn's success depends all the cooperation
of state and local ht!alrh agencies, universities, professional

, societies. pharma ceutical companies, health Clfe profes-

sionals, agricultural producers and the public. ... The
plan's primary foellS is to fa cilitate the development of new
The plan 's amimic robi:Jl therapies wbile preserving the lIse fulne ss of
primary foc us is curre nt and new drugs.
to facilitate the
developmellt of C DC developed ItS own Campaign to Prevent Anti-
new antimicrobial microbial R.esistan ce. which :li!l1s to prevent antimicrobi:ll
therapies while resist:lnce in hC:llth C:lre settings. The c:llllpaign h:ls four
preserving the Il1:1in strategies: prt'vcrlt infection, di:lgnose and treat infec-
usefulness of tion, use antimicrobials wisdy and prevent transmission.
current and new The campaign is developing multiple 12-step progr:lrllS
drugs. that target spec i:llty clinici:lllS who rre:lt specific patient
populations, including hospitalized c hildren and adults,
dialysis and surgic:ll p:Hients :lnd lon g-term care p:ltiems.
The campaign is developing educationa l tools :lnd materials
for each patient population.

The American College of Physicians has issued guidt'lines

for patients, physici:llls and other health care providers.

G uidelines for Preve nting

A ntin'lic robial R e sistanc e From the
Alnerica n College of Physicians
For p a ti e n ts:

• Ins ist that antib iotics be presc r ibed (for yourself or

your ch ildren) only when th ey c:ln be useful; know
rhe risks :IS well as th e benefits.

• R. e membet that an tibiotics work only against bacteria.

Most colds, coughs, sore throats (except strep throat)
and runny noses arc ca used by vIruses and cannot be
cured by antibiotics.
• Don't use antibiotics left over from an old presc r iption
without a doctor's permission, :Inc! never sh:ln;~ antib i-
otics with f:1111ily members or friends.
 • Wash hands thoroughl y with soap and hot water, and
tea ch your children to do the sa me. Antih3cter i31 soap
is not necessary - ord inary soap win eliminate resistam
bacteria and help preve nt illn esses.
• Make sure immunizations are up to date. Peo ple older
than 65 and people with chronic illnesses sho uld be
vaccinated against pn eutllOllla and influenza.
• Fin ish a prescribed antibio tic eve n if you feel better.
By stoppin g treat ment befo re the full course, some
partly resistant bacteria will remain and multiply, mak -
ing th e antibioti c less effective the next time.
• Wash fruits and vegetabl es thoroughly, and avo id raw
eggs and und ercoo ked meats, especially ground mea ts.

For physic ian s:

• Don't overp rescr ibe antibiotics.
• C hoose narrow- over broad-spectrum antibiotics,
usin g the most specific, narrowly targeted (" narrow-
spectrum ") antibiotics possibl e if you know the
causal agent. Save th e newer, broad-spectrum drugs
for infectio ns that resist th e older dr ugs.
• Wash hands thoro ughl y with soap and hot water
between each patient visit.
• Edu ca te pati ents about t he risks of antibiotic resistan ce .
• Make sure that a!l pati ents have the app ropriate
imlllu nizations.

Fo r h ospi tals:
• Improve infection COntrol.
• Use ultraviolet ligh ts, insist on consistent han d-washin g
by staff, and improve sani tation.
• Quickly identify and iso late patients with drug-resist-
ant infections.

For h ealth syste m s a nd h ealth d e p a r tme n t s:

• Encourage and fac ilitate appro priate immunizations for
chi ldre n , adolesce nts, adults and the elderly.
• Monitor ove rall use or antibi otics to spOt possible
overuse of broad-spect rulll antibiotics.
 For the fed eral governm ent:
• Require that product labels on antibiotic drugs contain
the Illost currellt surveillance information on antibiotic
resist:lI1ce as well as prudent usc informa tion .
• Adequately fund national su rvei!!:ll1cc programs.
Develop a system of electronic l:lbo r:ltory reporting
by hospit:lls :lnd labor:ltories. Est:lblish :l comnlllniC:l-
tion link to publLc health and medic:ll communities
to provide timely up(btes on :lggn::g:lte (b ra and their
interpretation.
• Adequately fund immunization programs.
• Strengthen the public health infrastrucHlre to facilitate:
rapid identification of :md response to infectious
disease outb re:lks. Enhance laboratory capabilities and
fund tr:lining programs for laboratory, epidemiology
and infectioll control personnel.
• Fund research progra ms to develop new vaccines and
antibiotics to prevent or treat d iseases resulting from
viral. bacterial, fungal and p:lTasitic pathogens.
• Fund researc h progr:lI11S to study mic robial patho-
genesis and molecular mechanisms responsible for
drug res istance.
• Sponso r publi c health messages to the medical
COIlHllt1nity and the public about the sco pe of
the resista nce proble m and the prude nt lise of
'Hltimicrobial drugs.
• Monitor antimicrobial drug use in food-producing
animals in order to protect human health.

For state governlTIents:

• Adequately fund state surveillance efforts to study

antibiotic resistant and othe r diseases.
• Include in state survcillance prog rams diseases that arc
notified nationally, and report collected informacion to
CDC.

For researchers:
• Con tinuc to develop and search for new antibio tics or
:mribiotics that work in flew ways .

._ ' >'. -.'.,.....

,
I
 • Develop new vaccines Jgainst common microbial
diseases to prevent infection in the first place.

For phannaceuti c al manufacturers :

• On product labels, include messages about
Jntibiotic resistance and informJtion on prudem
lise of Jntimicrobial drugs. Discourage unnecessary
and inappropriate Lise of products.
• Continue efforts to develop new vaccines and drugs
to prevenr or treat infectious diseases.

For agriculture:
• R educe widespread use of antibiotics in animal feeds
and food produ cti o n.

For world h ealth:

• Develop J global strategy for infectious diseases, and
massively increase resources to prOtec t, diagnose and
treat people around th e world.
• FJcilit:He the development of surveillance in addition
to prevention and control measures.
• Improve sewage systems and waH.'r purity in develop-
ing nations.

The FDA is working on a variety of approaches to encour-

age the development of new antibiotics and new classes of
antibiotics and other antimicrobials. One approach is exclu-
sivity ri ghts to protect a mJnufacturer's drug frolll gcneric-
drug competition for a specific length of time. The FDA
hopes exclusivity will help stimu late new antimicrobial
drug development, even while it discourages overuse of
antibiotics. ~ Th e FDA also has a variety of existing
regulatory tools to help developers of antimicrobial drugs.
,
One of these is an accelerated approval process for drugs The FDA also
that treat severely debilitating or life-threatening diseases; has a var iety of
another is for drugs that show meaningful benefit over exist in g regub-
existing prescription drugs to CUfe diseases. tory tools to
help developers
The FDA is investigating other approaches for speeding of antimicrobial
the antimicrobial ap proval process as well. One approach IS drugs.
to expand the nll!l1ber of clinical trials while reducing the
number of participants in each clinical trial program. In

.' , • - < . , " ! . . ' {. ~-

 this way. the FDA hopes to streamline the review process
without compromising s:lfety and effectiveness.

ScientiSTS and health professionals generally agree that a

way to decrease antibiotic resistance is to use antibiot ic
drugs more cautiously and to Illonitor outbreaks of drug-
resistant infections. Research is critical to understanding
the variolls mechanisms that pathogens lISC to evade drugs.
Once these mechanisms afC understood. new drugs can be
designed that are morc effective.

To that end, the FDA's National Ceme r for Toxicological

R esearch (NCTR) has been studying the mechanisms of
resistance to antibiotic "-gems alllo ng bacteria from the
human gastroimestinal tract. These bacter ia are known to
ca use serio us infenions. The NCT1\. has also tabulated the
amount of aIHibioti c residues that people consume in food
from food-producing animals and has studied whether
these residues affect human intestinal baneria. The FDA
is also r('viewlllg drugs for food animals with all eye on
assessing the safety of antibiotic dnlg residues in people.
An important mission of CDC is to promote the guidelines
noted above to the public and health care provider C0111-
lIlunity. Fortun;ltdY,;l grow ing number ot' public health
organizations have joined the chorus in alerting th e public
to the proper use of ;llltibiotics :md blsic infcniol1 comrol
practices.

Much of t he knowledge lbol1t l1ltibiotic resistance flows

fr0111 NIH, rhe FDA ;lnd CDC. the fedcrll 1ge1lcics thlt
conduct research, develop solutions and educate the public
:lbOl1t this eme rging problem. As well, these agencies COI11-
l11ulliclte to all levels of the public health infrastructure.
The public hellrh work force is committed to educating
the public and health care providers l bout how to reduce

, transmission of infectious agents and how to usc antibiotics

;lppropriatdy. ... Th e ability to counteract resistance.
however. startS at the individ ual level. To strengthen the
OUf ability to c hances for ;llltibiotics to defeat infcctiollS diseases the way
counter:lcr resist- they arc meant to, each person must usc antibiotics wisely
ance, however, lnd only when they arc necessary, prJcticc good personll
starts at the indi- hygiene and st;ly current with immunizations. Antibiotic
vidual level. resistance, ;l phellomenon rhat's here to stay, can be made
more manageable if t.';lcb person does his or her part. c
H2 M,le,wnc, (h'ptn.t lnkeuou, Ill"'"'' Comrol
.. '
.
. ;

PholO c redi ts
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