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****** DATA-MEDICOS **********
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LA GUERRA QUE AUN NO GANAMOS, LA VIRUELA
THE WAR THAT WE HAVE NOT STILL WON, THE SMALLPOX
**************************************
***** DERMAGIC-EXPRESS No.26 ******** 
****** 30 DICIEMBRE DE 1.999 ********* 
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EDITORIAL ESPANOL
=================
Hola amigos dermatólogos del Cyber, en esta ocasion DERMAGIC hace una
interesante revisión sobre la Viruela, LA GUERRA QUE AUN NO GANAMOS. Se
preguntaran el porque de esta afirmación y les voy a dar claras respuetas.

La viruela, enfermedad terrorifica que en el siglo pasado y hasta los años
60-70 cobró innumerables victimas fue practicamente eliminada de la faz de
la tierra en los años 70. Edward Jenner Descubridor de la vacuna hace 200
años se inmortalizó con ello, por otro lado, Ali Maalin oriundo de Somalia,
quedo para la historia como el ultimo caso reportado de la enfermedad
adquirida en forma natural, año 1977. (Ver Attachment)

A partir de esa fecha comenzaron álgidas discusiones en el seno de la
Organización Mundial de la Salud, sobre el destino que se les debia dar a
las cepas del mortifero Virus, Actualmente almacenadas en ATLANTA Georgia
CDC, y Russia, Koltsovo, las dos gran superpotencias.

En principio se habia acordado destruirlas totalmente en 1.995, pero
vinieron posteriores aplazamientos, los cientificos estan divididos en dos
bandos: Unos claman 
por la destrucción total de las cepas almacenadas, otros dicen que hay que
preservarlas para futuras investigaciones, de hecho el virus ya fue
CLONADO, pero dicen ellos que es inofensivo.

Lo que me motivo a hacer esta revisión justificó mi esfuerzo en la busqueda
de información, siempre pense que habia sido UN ERROR, dejar de vacunar a
la población contra la VIRUELA, y mucho más, si no existen casos, DEJAR
almacenes con 600 cepas del Virus. Porque ???

1.) Principalmente porque puede usarse como armamento BIOLOGICO, les pongo
dos segmentos de las referencias encontradas en el Cyber:

"It touched lightly on bioterrorism, although some think smallpox could be
a weapon." 

"- the escape of the virus from the laboratories and its use for terrorist
purposes would be a serious risk as an increasing proportion of the
population lack immunity to the disease "

2.) Puede desatarse una epidemia fácilmente si se manipula mal el virus y
se disemina 
rapidamente, recordemos el evento de Jannet Parker, murió tomando una
fotografias en un laboratorio, ello ocurrio 1 AÑO DESPUES DEL CASO DE ALI
MAALIN !!!

"Janet Parker, a British photographer, became accidentally infected while
taking pictures in a Birmingham University Medical School lab in
which some samples were stored. Hers was the last recorded death by smallpox. 
This incident is the "practical example [of accidental infection] that
everyone points to,"

3.) La vacuna contra la viruela (ortopoxvirus) confiere resistencia contra
otros virus relacionados como el virus monkeypox humano, del cual se han
descrito numerosos casos

"Human monkeypox: clinical features of 282 patients."

Recordemos que hace años se decidio ERRONEAMENTE en USA eliminar la vacuna
contra la Tuberculosis... y ya todos conocemos las consecuencias, LA TBC
volvió con gran impetu, y de nuevo se asumio la vacunación.

La OMS, decidio que en junio 30 de 1.999 seria la fecha seleccionada para
la destrucción total de los almacenes de virus que quedan,,, donde ???

"The last stocks of the smallpox virus have been kept
frozen in laboratories at the Centers for Disease
Control and Prevention in Atlanta and the Russian
State Research Center of Virology and Biotechnology
in Koltsovo, Russia."

Pero es ahora en ENERO Y en MAYO 1999, cuando se dara el veredicto final,
sabian ustedes eso ???, dentro de pocos dias sabremos que haran con el
VIRUS DE LA VIRUELA nuestros grandes mandatarios,,, Y que estaría pensando
ahora Edward Jenner !!!!

"Destruction is scheduled for June 30, 1999, according
to a plan that representatives of 190 countries
approved at the final day of the week-long annual
meeting of the health organization. 

Final approval is required by member countries of
WHO, the United Nations agency in Geneva, at their
May 1999 meeting." 

Seran nuestros "lideres" capaces de dar ese gran paso y olvidarse de la
loca carrera armanentista, de pensar verdaderamente en la salud de la
humanidad, de evitar un "escape" accidental del virus ??? matandolo
totalmente ????

Por ello, creo que esa guerra TODAVIA no esta ganada. Estara ganada cuando
cesen las bombas BIOLOGICAS y NO BIOLOGICAS,, y el VIRUS no exista en la
faz de la tierra.

Feliz año nuevo para todos, !!!!, y esperemos no oir las voces agoreras de
que la VIRUELA volvio porque "alguien" dejo escapar el virus de sus manos,,,

Saludos,,, la copia va para CNN en español.

Dr. Jose Lapenta R. 


EDITORIAL ENGLISH
=================
Hello friends dermatologist of the Cyber, in this occasion DERMAGIC makes
an interesting revision on the SmallPock, THE WAR THAT not yet WIN. You
wondered the cause of this statement and I will give clear answers. 

The Smallpock, terrifying illness that in last century and until the years
60-70 kill a lot of people it was practically eliminated of the face of
the earth in the seventies. Edward Jenner who Discovered the vaccine 200
years ago was immortalized with it, on the other hand, Ali Maalin, born in
Somalia, pass for the history like the one finishes reported case of the
illness acquired in natural form, year 1977. (See Attachment) 

Starting from that date algid discussions began in the World Organization
of the Health (WHO), on the destination that should be given to the strains
of the murderous Virus, At the moment stored in ATLANTA Georgia CDC, and
Russia, Koltsovo, the two great superpowers. 

In principle they had remembered to destroy them totally in 1.995, but
later postponements came, the scientists are divided in two decrees: Some
clamor 
for the total destruction of the stored strains, others say that it is
necessary to preserve them for future investigations, in fact the virus was
already CLONED, but they say them that it is inoffensive. 

What I motivate myself to make this revision justified my effort in the
search of information, I always thought that it had been AN ERROR, to stop
to vaccinate the population against the SMALLPOCK, and much more, if cases
don't exist, to LEAVE warehouses with 600 strains of the Virus. Why ??? 

1.) Mainly because it can be used as BIOLOGICAL armament, I put them two
segments of the references found in the Cyber: 

"It touched lightly on bioterrorism, although some think smallpox could be
to weapon." 

" the escapes of the virus from the laboratories and its it uses for
terrorist purposes would be to serious risk ace an increasing proportion of
the population lack immunity to the disease" 

2.) An epidemic can to take place easily if it is bad manipulated the virus
and it is disseminated quickly, let us remember Jannet Parker's event, she
died taking a pictures in a laboratory, it happened it LATER 1 YEAR OF THE
CASE OF ALI MAALIN!!! 

"Janet Parker, to British photographer, grant a scholarship me accidentally
infected while taking pictures in to Birmingham University Medical School
lab in 
which some samples were stored. Hers was the last recorded death by
smallpox. 
This incident is the practical example [of accidental infection] that
everyone points to," 

3.) The vaccine against the Smallpock (orthopoxvirus) it confers resistance
against other virus related as the virus human monkeypox, of which numerous
cases have been described: 

"Human monkeypox: clinical features of 282 patients." 

Let us remember that some years ago in USA decided ERRONEOUSLY to eliminate
the vaccine against the Tuberculosis... and already all know the
consequences, THE TBC returned with great impulse, and again the
vaccination was assumed. 

The OMS, decide that June 30 of 1.999 was the date selected for the total
destruction of the virus warehouses that they still exist,,, where??? 

"The last stocks of the smallpox virus have been kept 
frozen in laboratories at the Centers for Disease 
Control and Prevention in Atlanta and the Russian 
State Research Center of Virology and Biotechnology 
in Koltsovo, Russia." 

But is it now in JANUARY AND MAY OF 1999, when the final verdict will be
given, you knew that???, in few days we will know that they will make with
the VIRUS OF THE SMALLPOCK, our big leaders, AND.... What he would be
thinking Edward Jenner now !!!! 

"Destruction is scheduled for June 30, 1999, according
to a plan that representatives of 190 countries
approved at the final day of the week-long annual
meeting of the health organization. 

Final approval is required by member countries of
WHO, the United Nations agency in Geneva, at their
May 1999 meeting." 

Will our " leaders " be able to take that great step and to forget the
crazy arms career, of truly thinking of the humanity's health, of avoiding
an accidental escape of the virus??? killing them totally ????

For it, I believe that the war is NOT STILL won. It will be won when the
BIOLOGICAL and NOT BIOLOGICAL bombs cease, and the VIRUS doesn't exist in
the face of the earth. 

Happy new year for all!!!!, and let us hope to not hear the prophetic
voices the SMALLPOCK returned because to "somebody" allow to "escape" the
virus from his hands !!! 

Greetings to all, the copy goes for CNN spanish. 

Dr. José Lapenta, 

================================================================
DERMAGIC/EXPRESS(26)
================================================================
LA GUERRA QUE AUN NO GANAMOS, LA VIRUELA
THE WAR THAT WE HAVE NOT STILL WON, THE SMALLPOX
================================================================
1.) Smallpox, the disease
2.) Smallpox, the vaccine
3.) Smallpox vaccine
4.) The World Health Organization Smallpox Eradication Programme
5.) World Health Day, 1997 Emerging Infectious Diseases, Global Alert -
Global Response
6.) Scene is set for destruction of Smallpox Virus
7.) Smallpox Stores
8.) The End to Smallpox
9.) Smallpox Extermination Proposal Stirs Scientists
10.) Sparing smallpox virus from destruction helps research, scientists say
11.) Should My Child Get the Smallpox Vaccine? 
12.) [Danger to the human caused by animal poxvirus following
discontinuation of mandatory vaccination against smallpox]
13.) The confirmation and maintenance of smallpox eradication.
14.) [Lethal animal pox virus infection in an atopic patient simulating
variola vera]
[Letale Tierpockeninfektion bei einem Atopiker unter dem Bild einer
Variola vera.]
15.) Human monkeypox: clinical features of 282 patients.
16.) Smallpox: emergence, global spread, and eradication. 
17.) Smallpox: the triumph over the most terrible of the ministers of death. 
18.) Edward Jenner and the eradication of smallpox. 
19.) The smallpox saga and the origin(s) of vaccination. 
20.) The Jenner bicentenary: the introduction and early distribution of
smallpox vaccine. 
21.) Smallpox Virus Faces Own Death
========================================================================
1.) Smallpox, the disease
========================================================================

This week we look at the virus responsible for smallpox, a highly
contagious and
often fatal infection, and the only one to have been officially eradicated. 

Smallpox virus is one of the largest viruses known. It is brickshaped with
a thin
membrane on its outer surface. Inside it has a single molecule of DNA and a
variety of viral proteins that it needs to take with it into human cells. 

Smallpox only affects humans. It infects through broken skin, and then
spreads to
the internal organs. The first symptoms include high fever and weakness,
followed
by a rash on the hands, face and feet. Later characteristic skin pustules
form which
eventually crust over. Death usually results if the virus reaches the
brain, heart or
lungs. 

In ancient Chinese medicine people were deliberately infected with 'mild'
smallpox
to protect them against severe smallpox, although this was very risky. In
the 19th
century Edward Jenner found that material from the pustules of cowpox, a
related
disease, could be used to make people immune to smallpox itself. This
marked the
beginning of the search for vaccines. 

In 1967 the World Health Organisation launched a campaign to eradicate
smallpox
using a combination of vaccination, surveillance and containment. By 1979 they
had rounded up the last few cases and declared it eradicated - a major
achievement
for mankind. 

Now the only stocks of smallpox virus are kept in high security vaults in
Atlanta,
USA and Moscow, Russia. These were retained in case the disease ever appears
again and further research needs to be done. Recently many scientists have
argued
that we should get rid of them altogether, and in the last few months it
has finally
been agreed that they will be destroyed in April 1995. 
========================================================================
2.) Smallpox, The vaccine
========================================================================
Licensed Product: 
----------------------- Smallpox Vaccine (Vaccinia) 
Countermeasure to 
----------------------- Variola virus (smallpox), a member of the
Orthopoxvirus 
Status 
----------------------- Licensed, Wyeth Laboratories 
Expected Route of
Exposure 
----------------------- Inhalation or direct contact 
Availability 
----------------------- Currently available 
Manufacturer 
------------ Repository at Centers for Disease Control and
Prevention,Atlanta,Georgia 
POC 
Joint Program Office for Biological Defense,
Medical Program
---------------------- Manager, 703-756-0467, DSN 289-0467 
Product Description 
---------------------- Live, attenuated vaccine 
Effectiveness 
--------------- By Route of Exposure: Reliable data are surprisingly
sparse as to
efficacy and durability of protection. Indirect evidence
indicates a
highly effective vaccine. 
Immune Response in Humans: > 95% of primary vaccinees
develop neutralizing or hemagglutination inhibition
antibody titers
greater than or equal to 1:10. 
----------------------
Dose & Administration 
---------------------
Primary Immunization Dose/Schedule: 1 dose by the scarification
Technique 
Minimum Time/&num Doses to Protection: 14 days/ 1 dose 
Booster Schedule: Repeat dose every five to ten years for
protection against variola major virus 
-----------------------
Side Effects 
Infrequent other than short-lived mild temperature
elevation.
Occurrences of complications are as follows: 

Cases/1,000,000 Vaccine Recipients: 

Accidental autoinoculation: 25.4 primary, 0.8 booster
Generalized vaccinia: 23.4 primary, 1.2 booster
Eczema vaccinatum: 10.4 primary, 0.9 booster
Progressive vaccinia: 0.9 primary, 0.7 booster
Post-vaccinal encephalitis: 2.9 primary, < 0.1
booster 
------------------------
Shipping/Handling
Requirements 
------------------------
Maintain at 2-8 degrees C, reconstitute with sterile
water. May be
used for three months after reconstitution if stored below
0 degrees
C. Sterilize vials and syringes prior to disposal. 
-------------------
Other Available
Countermeasures 
-------------------
Vaccinia immune globulin - 0.6 mg/kg IM, or primary
vaccination
within 3-4 days of exposure yields some protection.
Vaccinia
immune globulin should be kept available for potential
complications. 

Contingency Protocol 
--------------------- Not required 
========================================================================
3.) Smallpox vaccine
========================================================================
Excerpted from United States National Library of Medicine Datafile 

Last update: April 17, 1996 

Also known as 
--------------
Dryvax [AHFS Drug Information 1995] ; 

Manufactured by: 
----------------
Wyeth-Ayerst 

Classification 
--------------
Immunizing agent 

MODE OF ACTION: Used to promote active immunity to smallpox in individuals
exposed to the
disease or virus. The vaccine contains vaccinia virus which is
antigenically similar to variola virus, the
causative agent of smallpox. Administration of vacciniavirus promotes the
production of specific
antibodies which confer immunity against smallpox. Following administration
of vaccine, local
replication of vaccinia virus occurs; replication of the vaccinia virus may
occur in the regional lymph
nodes.Protection that results from immunization is probably the result of
both T and B cell-mediated
antibodies. Following primary immunization, antibody appears in the serum
within 4-5 days, peaks
within 4 weeks, and persists for several yearss. The skin response to
immunization appears within
3-5 days, peaks within 4 weeks, and may show evidence of change for up to
20 years following
immunization. Appearance of antibody in serum without a skin response
occurs rarely following
primary immmunization; however, absence of a skin response usually
indicates an inadequate
immune response to the vaccine. Immunization is highly protective, although
the exact mechanism of
protection has not been fully established. Nearly 100% of the individualls
who receive vaccine are
protected during the first 1-3 years following immunization. The duration
of immunity has not been
definitely established, but the vaccine generally provides substantial but
waning immunity for 10
years or more. Individuals 

Uses in HIV-related Illness
-----------------------------
Control in vaccine studies 
Comparative study of HIVAC-le and the smallpox vaccine in previously
vaccinated and
unvaccinated volunteers 

Interactions with other medications
------------------------------------
In general, individuals receiving immunosuppressive therapy (e.g.
corticotropin, corticosteroids,
alkylating agents, antimetabolites, radiation therapy) may have a
diminished response to smallpox
vaccine and replication of the virus may be potentiated. [AHFS Drug
Information 1990].
Concomitant smallpox vaccination and dexamethasone therapy and concomitant
smallpox
vaccination and prednisone therapy have been reported to result in
immunosuppression produced
by corticosteroids and impairment of theresponse to smallpox vaccine,
increasing the risk of
generalized vaccinia. Concomitant indomethacin and smallpox vaccination has
been reported to alter
the response to smallpox vaccination. Concomitant methotrexate and smallpox
vaccinationn has
been reported to impair the immunologic response to smallpox vaccine and
result in generalized
vaccinia. [AHFS Drug Information 1995] [Drug Interactions 3rd ed, 1975]
[Drug Interaction 4th
ed., 1979] 

Contraindications
-----------------
Contraindicated in pregnant women. [NIAID VEU 022] 

Related Adverse Effects
-----------------------
Adverse effects may include nausea, hallucinations, confusion, depression,
loss of balance, isomnia,
orthostatic hypotension, increased akinetic involuntary movements,
agitation, arrhythmia,
bradykinesia, chorea, delusion, hypertension, new or increasedangina
pectoris and syncope,
headache, leg pain, back pain, tinnitus, migraine, supraorbital pain,
burning throat, chills , numbness
in fingers and toes, taste disturbance, constipation, weight loss,
anorexia, dysphagia, diarrhea, rectal
bleeding,slow urination, urinary frequency, increased sweating,
diaphoresis, facial hair, hair loss,
hematoma, rash, and photosensitivity. [PDR 1995] 

Delivery
--------
MODE OF DELIVERY: Administered intradermally by the multiple pressure
technique,
preferably over the deltoid region of the arm. [AHFS Drug Information
1995] 
STORAGE: Lyophilized smallpox vaccine should be refrigerated at 2-8 C.
[AHFS Drug Information 1995] 


Physical Properties
--------------------
DRUG DESCRIPTION: Lyophilized preparation of live vaccinia virus
prepared from calf
lymph and grown in the skin of a vaccinated bovine calf AHFS Drug
Information 1995 
STABILITY: Stable for 10 days at room temperature. Under
refrigeration, the product has a
shelf life of 18 months; after reconstitution, the vaccine may be
stored for 3 months
refrigerated AHFS Drug Information 1995 
STABILITY: Trace amounts of antibiotics added during manufacturing to
eliminate bacterial
contamination may be present in the final reconstituted vaccine AHFS
Drug Information
1995 
PHYSICAL DESCRIPTION: The lyophilized vaccine occurs as a yellow to
grayish pellet
which may become fragmented upon shaking AHFS Drug Information 1995 

References
----------
Slade HB. HIV immunotherapy [letter] [published erratum appears in
Vaccine 1994
Aug;12(11):1055]. Vaccine. 1994 Apr;12(5):476. 
Hart JF. Smallpox and AIDS [letter; comment]. Can Med Assoc J. 1994 Aug
1;151(3):271. 
Tartaglia J, Cox WI, Taylor J, Perkus M, Riviere M, Meignier B,
Paoletti E. Highly
attenuated poxvirus vectors. AIDS Res Hum Retroviruses. 1992
Aug;8(8):1445-7. 
Graham BS, Belshe R, Clements ML, Dolin R, Fernie B, Stablein D,
Wright P, Koff W.
HIV-GP160 recombinant vaccinia vaccination of vaccinia-naive adults
followed by
RGP160 booster immunization. Int Conf AIDS. 1991 Jun 16-21;7(2):88
(abstract no.
F.A.1). 
Baxby D. Smallpox. Int J STD AIDS. 1991;2 Suppl 1:8-12. 
Graham B, Belshe R, Midthun K, Dolin R, Fernie B, Stablein D, Wright
P, Koff W. HIV
gp160 recombinant vaccinia in vaccinia-naive adults. Int Conf AIDS.
1990 Jun
20-23;6(2):346 (abstract no. 1131). 
Keefer MC, Bonnez W, Roberts NJ Jr, Lambert J, Dolin R, Reichman R. HIV-1
rgp160-specific cellular immune responses by recipients of a live
vaccinia-rgp160
vaccine. Int Conf AIDS. 1990 Jun 20-23;6(2):326 (abstract no. 1051). 

Coded for WWW distribution by Robert Throop, Project Coordinator for
Canadian HIV AIDSMentorship Program 06/27/96 

========================================================================
4.) The World Health Organization Smallpox Eradication Programme
========================================================================

Smallpox is the only major human disease to have been eradicated. Epidemics
of smallpox had
inflicted mankind throughout history, and as recently as 1967, some 10-15
million cases were still
occuring annually in more than 30 endemic countries (Fenner et al 1988). Of
these some two million
died and millions of survivors were left disfigured or even blind. There is
no treatment for smallpox
once it has been contracted. The more serious strain of the smallpox virus
(variola major) causes
fatality of 20-40 percent among unvaccinated persons. 

On January 1, 1967, the World Health Organization launched the Intensified
Smallpox Eradication
Programme. At that time the plan was to rely entirely on mass vaccination
of susceptible persons in
endemic countries -- the problem was defined as one of mass vaccination.
The mass vaccination
strategy had successfully eradicated smallpox in programs in Western
Europe, North America,
Japan and other areas. The WHO Expert Committee on Smallpox in 1964 had
recommended that
the goal should be to vaccinate 100% of the population, based on the
observation in India that
smallpox persisted in some areas despite vaccinations reported to be 80% or
more of the
population (80% was then assumed to be the acceptable target of a
well-conducted vaccination
program). In hindsight, one might have asked whether the sample size of
successful vaccination
campaigns was adequate, whether results obtained in insulated areas (such
as tests on the island of
Tonga) could be replicated elsewhere, and to what extent campaigns in
Europe and North America
were helped by better controlled conditions (Hopkins 1989). A review of the
programmes
conducted after 1967 suggests that mass vaccination alone could have
eliminated smallpox in South
America and most African countries, but not in the densely populated
countries of Bangladesh,
India, Indonesia, and Pakistan (Fenner et al 1988).

A 1966 outbreak in Nigeria started the evolution of a new strategy. In
Western Nigeria, where over
90 percent of the population had been vaccinated, another smallpox outbreak
had occurred,
apparently originating in a religious group which had resisted vaccination.
Vaccine supplies were
delayed, forcing program staff to quickly locate new cases and isolate
infected villages which could
then be vaccinated with the limited supplies. A reporting network using the
available radio facilities
was established to locate new cases. Containment teams moved swiftly to
isolate infected persons
and to vaccinate susceptible villages. The Nigerian experience demonstrated
that an alternative
strategy of surveillance and containment could break the transmission chain
of smallpox, even when
less than half the population was eventually vaccinated (Hopkins 1989).

In 1970, a major epidemic had begun in the Gulbarga district of Karnataka
in southwestern India,
claiming over 1,300 victims (including 123 deaths) in more than 1,000
villages and five
municipalities. To prevent the epidemic from spreading to more populated
areas, "prompt detection
of all cases in an area of two million people was required. All available
health personnel, not just
smallpox health workers, were mobilized for a weeklong, house-to-house
search of the area. By
carefully focusing containment vaccination around each newly discovered
case, they eliminated
smallpox from the district within weeks." (Brilliant 1985, p. 27) The
Gulbarga experience was
India's first real success with surveillance-containment, and showed that
it could work even in a
densely populated country. The new strategy evolved gradually and were
accepted slowly as local
campaigns controlled outbreaks with their own variations of
surveillance-containment. In India for
example, when a village-by-village search in Uttar Pradesh and Bihar in
1973 identified 10,000 new
cases, surveillance first shifted to a house-to-house search, and then to
market surveillance:
smallpox disappeared in some 19 months before the strategy was ever fully
worked out (Hopkins
1989). 

The initial definition of the problem as mass vaccination was a classic
symptom of a confusion
between ends and means. The goal of the program was the complete
eradication of smallpox, and
mass vaccination was a means to achieve that end. With the epidemiological
experience available in
1966, the choice of mass vaccination as a strategy appeared rational.
National governments also
favored mass vaccination partly because it was a highly visible display of
government action, and
partly because of the substantial investments already made in creating the
vaccination infrastructure
(including jobs and salaries). Fortunately, the smallpox campaign learned
quickly from its
experiences in Nigeria, India and elsewhere and was able to recast the
problem and evolve a new
surveillance-containment strategy through experimentation and innovation in
the field. 

The process of institutional learning and local adaptation was central to
the campaign's success:
"Indeed, that process, more than any other element in the campaign, is the
key explanatory factor of
the ultimate success of the program." (Hopkins 1989, p. 74, italics in
original.) The surveillance and
containment strategy was not a single policy deliberately planned for or
even envisioned by WHO.
Instead, it comprised a broad array of measures that emerged over time from
the local practices of
field teams who had to invent procedures that not only blended with local
customs and conditions,
but were also genuinely effective in providing early detection and
enforcing isolation and control.
What eventually eliminated smallpox was the combined approach of using mass
vaccination to
reduce disease incidence so that detection and containment could eliminate
the remaining endemic
foci (Brilliant 1985).

To achieve the large-scale vaccination in the program required the high
volume production of
potent, reliable vaccines and an efficient, inexpensive means of delivering
the vaccine. Three major
technological innovations greatly facilitated the smallpox eradication
program by addressing these
needs. Perhaps the most significant was the development of the capacity to
mass produce high
quality freeze-dried vaccine in many countries. Edward Jenner had
discovered as long ago as
1796 that humans inoculated with cowpox became immune to smallpox. An
earlier 1959 WHO
smallpox program had depended on a liquid vaccine that had to be used
within 48 hours and was
easily contaminated. The new freeze-dried vaccine, which had the potency
and stability needed for
mass vaccination, was developed mainly at the Lister Institute in London
using modest resources.
The first apparatus for heat-sealing the ampoules of freeze dried vaccine
on a production scale was
built from a child's toy construction kit (Hopkins 1989). The final
production method was
subsequently made freely available. Since the quality of the vaccine was
crucial, WHO established
two regional vaccine reference centers in Canada and the Netherlands to
test vaccine quality. Within
a few years, several countries achieved self-sufficiency in vaccine
production. 

Apart from the vaccine, the program also had to solve the problem of
developing an efficient
technique of introducing the smallpox vaccine into humans. The traditional
vaccination technique was
to scatch a drop of the vaccine into the superficial skin layers, employing
a rotary lancet or a needle,
which sometimes resulted in serious wounds. The scratch method was clearly
inadequate for
large-scale vaccinations that were to be accomplished in compressed time
frames. Starting in 1963,
the US National Communicable Disease Center tested a hydraulic-powered jet
injector that could
do over 1,000 vaccinations in an hour. The jet injector proved too
expensive for house-to-house
vaccination in densely populated countries.

The third major technological innovation was the bifurcated needle. The new
freeze-dried vaccine
required a different method of presenting single doses of the vaccine.
Because the vaccine had to be
reconstituted each time and dispensed in tiny quantities, the traditional
method of storing liquid
vaccine in capillaries was no longer tenable. In developing a new solution,
Benjamin Rubin of Wyeth
Laboratories worked with Gus Chakros of the then Reading Textile Machine
Company in needle
design. It occurred to Rubin that a prolonged needle with a loop would
provide both the capillarity
activity and the scarification action required (Hopkins 1989). He suggested
the use of a sewing
needle in which the loop end was ground into a prolonged fork, creating two
bifurcated prongs. A
piece of wire suspended between the prongs was designed to hold a constant
amount of vaccine by
capillarity. By 1968, the bifurcated needle had replaced traditional
methods in most countries, and
by 1970 it was in use everywhere.

Although the development of the freeze-dried vaccine, the jet injector, and
the bifurcated needle
were milestones in the smallpox campaign, the program would not have
succeeded without the
ingenuity and creativity with which the field staff surmounted a host of
local problems. Important
innovations such as smallpox recognition cards, watchguards, rewards, rumor
registers, and
containment books all came from fieldworkers (Brilliant 1985). Managers and
supervisors
encouraged the creative solving of problems as they arose, and adopted an
attitude of supporting
problem-oriented practical experimentation in the field. New techniques or
improvements of existing
procedures were then disseminated through surveillance newsletters and
periodic review meetings.

Staff training was another major component of the campaign. Epidemiologists
from various
backgrounds and nationalities, including academic epidemiologists, had
typically never worked in
rural villages, and so required special training. In India, part of the
training program included two
simulation exercises. The first was a hypothetical outbreak that required
the trainee to trace the
source of infection, locate all contacts, and carry out containment
operations. An example scenario
involved an infectious disease hospital as a source of infection. Academic
epidemiologists were
incredulous, but realized when they reached the field that poorly guarded
hospitals were notorious
for spreading the disease they were trying to control. In the second
exercise, the trainee played the
role of the chief of a state smallpox program who had to watch against
infection from neighbouring
areas, investigate sources of infection, and make sense of conflicting
reports. Following the
exercises, the entire training group then went out to a nearby village with
a chickenpox outbreak and
proceeded to vaccinate and contain the infection. The field training was
highly practical and was
conducted not by a ranking administrator but by a junior paramedical
assistant who had intimate
knowledge of village-level epidemiology.

At the strategy level, the smallpox eradication programme of 1966 was
guided by a plan that
embraced two complementary approaches: mass vaccination campaigns which
employed
freeze-dried vaccine of assured quality to substantially reduce the
incidence of smallpox in endemic
areas, and surveillance systems which detected and reported cases early
enough to permit the
containment of outbreaks and the analysis of occurence patterns so that
appropriate vaccination and
surveillance activities could be taken. The WHO program functioned in a
collegial structure of many
independent national programs, each developing its own administrative
traditions and adapting to
local social and cultural conditions. As a result, programs differed
greatly from one country to
another, as well as from one time period to another. 

Unambiguous standards of performance were stipulated from the outset and
refined as the program
advanced. Mass vaccination campaigns were expected to result in more than
80% of the population
in each area having a vaccination scar. Independent assessment teams could
easily ascertain the
proportion of the population with such a scar. From 1974, standards for
surveillance and
containment were added: 75% of outbreaks should be discovered within 2
weeks of the onset of
the first case, and that containment of the outbreak should begin within 48
hours of its discovery and
that no new cases should occur more than 17 days after containment had
begun. Fenner et al
(1988) concluded that "the various standards were of the greatest value
when the data were
promptly collected, analysed and used as management guides for programme
action. The
knowledge by those collecting the information that their data were being
promptly put to use
contributed greatly to the development of the system and to better
performance." (p. 1354) 

Each national program developed its own set of standard operating
procedures that were tuned to
the local task environment. In India, Operation Smallpox Zero was launched
in 1975 with a
closely specified set of rules and procedures (Brilliant 1985).
Village-by-village searches were
changed to house-to-house. In one state capital room-to-room searches were
done to prevent an
epidemic from spreading. Every case of rash with fever was recorded,
monitored, and treated as
smallpox until proven otherwise. A rumor register was maintained at the
Primary Health Center.
Uncertain diagnoses were followed with containment by default. Four
watchguards were posted at
infected homes. All villages within 10 miles of a case of known or
suspected smallpox were
searched. Everyone inside a one-mile radius was vaccinated. Market searches
were intensified.
Medical officers were posted to live in infected villages. The stringent
procedures paid off. The
average size of an outbreak fell to fewer than 5 cases from 7 six months
before. The number of
infected villages fell by 40% each month. 

An important innovation which preceded Operation Smallpox Zero was the use
of the infected rural
village or urban neighborhood as an assessment index, and in effect, as a
decision premise for
allocating resources. A village in which any case of smallpox was recent
enough to be potentially
infective was labelled a 'pending outbreak' and placed on the pending lists
of active outbreaks
maintained at the smallpox control offices. If no new cases were found at
the end of the pending
outbreak period (4-6 weeks), the outbreak was removed from the lists with
fanfare. By specifying a
standard complement of resources for each incident (jeep, vaccine,
gasoline, staff), pending
outbreaks were an ideal tool for resource allocation, invariably the most
pressing management
decision when an outbreak was first identified.

Throughout the program, the pursuance of clear and stringent rules and
standards concerning
vaccination, detection and containment, was matched by an equally fervent
spirit of innovation and
experimentation in the implementation of those procedures. Many people in
WHO today believe
that the program had bent many rules, and indeed, many at WHO viewed the
smallpox program
negatively because it ran outside the regular WHO system. Hopkins (1989)
recounts how one
WHO official commented that if the India campaign were successful, he would
"eat a tire off a
jeep." When the last case was reported, Donald Henderson, director of the
smallpox program, sent
that person a jeep tire. 

There were many instances of cutting corners. Obtaining cash for the
program required voluminous
paperwork, and often cash flowed simply on the director's assurance that
funds would be
forthcoming. The regional finance officer in India often had to cover such
advances, but considered
them as "an act of faith well justified." In Bangladesh, traditional steps
in the health service hierarchy
were bypassed when the mobile surveillance teams drew personnel from their
other regular
assignments and gave them authority and powers that exceeded their service
ranks. In India,
relations in the joint WHO-government of India central command became
characterized by an
open, informal atmosphere developed from months of working closely in the
field and office. Junior
staff frequently leaped over formal hierarchical levels in order to
expedite action, so much so that
nearly every senior Indian health official cited 'level jumping' as one of
the reasons for the program's
success. At the core of the campaign in India (as well as many other
countries) was a logic of
learning by experimenting and sharing that learning quickly. 

WHO had recognized early on the critical role of concurrently evaluating
the performance of the
various campaigns by independent teams so that deficiencies could be
discovered and remedied
while the campaigns were still active. Evaluation and assessment procedures
constantly evolved in
response to new experience and lessons learned from the field. Evaluation
measures were kept
flexible so that they could be changed to fit each local environment.
Initial output-based measures
such as the number of people vaccinated proved unuseful and were replaced
by outcome-based
measures such as trends in the incidence of smallpox. More specific
indicators were used at lower
levels. In India for example, attention shifted to pending outbreaks in
1974; the focus then changed
to the outcome of surveillance searches in 1975; and finally search
efficiency was stressed in the
closing years of the campaign. A sensitive feedback and control system was
thus established, relying
on the extensive, accurate and rapid collection of data from the field.
Field data were rapidly
analyzed and acted upon in order to influence the campaigns while they were
still in progress. The
smallpox program excelled in careful planning and administration, creating
hierarchical levels of
control and reporting systems that were nevertheless simple enough for the
field teams to
understand. Regular feedback was provided through periodic review meetings
at all levels and
through special publications and research papers.

In 1977, the last case of smallpox was reported in Somalia. For the first
time, a major disease has
been completely vanquished. Dr H. Mahler, WHO director-general, described
the smallpox
program as "a triumph of management, not of medicine." It is said that at a
meeting in Kenya in
1978 the then director-general, on announcing the end of smallpox, had
turned to Donald
Henderson who had directed the smallpox program, and asked him which was
the next disease to
be eradicated. Henderson reached for the microphone and said that the next
disease that needs to
be eradicated is bad management (Hopkins 1989).
=======================================================================

5.) World Health Day, 1997 Emerging Infectious Diseases, Global Alert -
Global Response
=======================================================================

Under the leadership of WHO, all the countries of the world
united to
destroy the killer virus. 

Although a vaccine to fight smallpox had already been
discovered 200
years ago, the disease was still endemic in the 1960s. In
1967, WHO
launched a global smallpox eradication campaign, systematically
vaccinating entire populations in endemic countries - an
enormous
and complex exercise. The strategy soon became "
surveillance and
containment": every time a new case was discovered, it was
isolated
and contacts of the patient traced and vaccinated. Where
cases were
detected, local immunization was intensified. The last caseof
naturally
acquired smallpox was reported from Somalia in 1977, and in
1980,
WHO declared the world free from the scourge. In its 1996
session,
the World Health Assembly recommended that the last smallpox
stocks would be destroyed in 1999. 

Source: WHO, Emerging Infectious Diseases. Global Response,
Global Alert. April 7, 1997. 

========================================================================
6.) SCENE IS SET FOR DESTRUCTION OF SMALLPOX VIRUS 9 September 1994 
========================================================================

The last remaining stocks of smallpox (variola) virus should be destroyed,
says a WHO international
group of experts. This was the unanimous verdict pronounced today by the Ad
Hoc Committee on
Orthopoxvirus Infections during its final one-day meeting here in Geneva.
This confirms the
recommendation of the preceding Committee meetings, in March 1986 and
December 1990. 

A majority of the Committee agreed that the time of destruction should be
30 June 1995, allowing
the World Health Assembly to confirm this recommendation at its meeting of
May 1995. The stocks
include clinical specimens and other materials containing infectious
variola virus. These materials are
being held in the WHO Collaborating Centres for Smallpox and other Poxvirus
Infections in the
Centres for Disease Control and Prevention in Atlanta, Georgia, United
States of America and in
the Institute for Viral Preparations in Moscow, Russian Federation.
Recommendations on the
procedure for destroying the variola virus and for the certification of its
destruction were also issued.

Cloned DNA fragments of variola virus genome are themselves not infectious
and provide a useful
resource for analysing variola virus genes and protein structure and
function. The members of the
Ad Hoc Committee recommended that such cloned material be kept. The Committee
recommended the establishment of two international repositories for the
storage, distribution and
monitoring of the cloned material - at the WHO Collaborating Centre for
Smallpox and Other
Poxvirus Infections, CDC, Atlanta, and at the Russian State Research Centre
of Virology and Biotechnology in Koltsovo. 

The Committee also recommended that smallpox vaccine (500,000 doses) be
kept by WHO in
case of an emergency and that the vaccine seed virus (strain Lister
Elstree) be maintained in the WHO Collaborating Centre on Smallpox Vaccine
at the National Institute of Public Health and
Environmental Protection in Bilthoven, The Netherlands. 

Commenting on the results of the meeting, Dr Ralph Henderson, WHO Assistant
Director-General,
said: "The Ad Hoc Committee had a very difficult task before it. The basic
problem was to weigh
the potential risks of this virus escaping with the potential benefits to
science from retaining it. This is
a matter of best judgement, not scientific certainty. The next step is to
seek as broad a consensus as
possible concerning this recommendation. We will be doing this by widely
publicizing the
Committee's recommendations and by asking them to be reviewed by the WHO
Executive Board in
January 1995 and put for final decision to the World Health Assembly in May
1995." 

The eradication of smallpox is among the greatest public health
achievements of all time. This
success resulted from an unprecedented international effort coordinated by
WHO and was
recognized by the 33rd World Health Assembly which declared on 8 May 1980
the global
eradication of smallpox. The last known natural case of smallpox was
detected in Somalia in
October 1977. 

Less than 30 years ago, smallpox was endemic in 31 countries. At that time,
between 10 and 15
million people were stricken with the disease each year: of these nearly
two million died and millions
of survivors were disfigured or blinded for life. Smallpox was the first
disease ever to be eradicated.

Since that time, the stock of variola viruses has been gradually reduced
and is now restricted to two
WHO Collaborating Centres at the Centres for Disease Control and Prevention
in Atlanta, and at
the Institute for Viral Preparations in Moscow. 

The concept of total global eradication calls not only for the elimination
of the disease but also for
the complete removal of the causative agent. During their first meeting in
March 1986, members of
the WHO Committee on Orthopoxvirus Infections unanimously recommended
destruction of the
virus stocks kept in the two laboratories. 

The Committee also recommended however that the genetic blue-print of the
variola virus should be
determined and archived prior to destruction of the remaining stocks of the
virus. In order to further
understanding of this highly virulent virus and to be able to conduct
proper diagnostic tests, if need
be, it was decided to carry out complete sequencing of the genome. 

At the end of the last meeting of the WHO Technical Committee on the
Analysis of Nucleotide
Sequences of Variola Virus Genomes, held in Geneva in January 1994, Dr
Bernard Moss, of the
National Institute of Health in Bethesda, Maryland, United States of
America, concluded: "Now we
are fully satisfied that the genetic blue-print of variola virus has been
properly archived for posterity.
Should the need arise, we will be able to conduct diagnostic tests with
100% accuracy". 

The publication of the Ad Hoc Committee's recommendation to destroy the
variola viruses had,
however, triggered mixed reactions from both the public and the scientific
community. The
arguments for and against destruction can be summarized as follows: Against
destruction: 

- all possibility of future studies on the virus will be lost; 

- destruction of the viruses in the two known repositories does not
guarantee the complete removal of the virus from the earth (preserved
corpses of smallpox cases, forgotten or hidden stocks elsewhere); 

- the decision to destroy the virus is politically, and not scientifically,
motivated. 

For destruction: 

- the escape of the virus from the laboratories from the laboratories and
its use for terrorist purposes
would be a serious risk as an increasing proportion of the population lack
immunity to the disease; 

- the sequence information and the cloned DNA fragments of full genome of
several strains of
variola virus allow further scientific research on the properties of the
viral genes and proteins to
continue. The cloned DNA fragments of the virus genome are non-infectious
and can be handled in
complete safety. 

- the decision to eradicate smallpox was a collective decision of the world
community, based on
public health considerations. Eradication is an absolute term and includes
not only the elimination of
the disease, but also the complete removal of the causative agent. 

========================================================================
7.) Smallpox Stores
========================================================================
Author: Susan G Robbins, Date: March 6, 1995 

My opinion is that all known stocks of the smallpox virus should be
destroyed as soon as possible. I
disagree with the premise of the late Bernard Fields's argument (quoted in
K.Y. Kreeger, The
Scientist, Nov. 14, 1994, page 1) that "destroying it ends the whole issue
of possibly understanding
it in the future." The only moral, humane reason for a scientist to study a
virulent microbe is to obtain
the minimum amount of information needed for its eradication_that is, how
to create an effective
vaccine or treatment. Since the virus has been eliminated from humans, why
let it "live" and risk its
release by accident or intent?

Those who think it desirable to pursue further knowledge of smallpox
replication for what it might
shed on understanding other known or emerging viruses are trading a
certainty (getting closer to
total destruction of smallpox) for a possibility and risking the lives of
the living in favor of the unborn.
Is it better to save smallpox on the chance that we might learn about other
viruses, such as HIV, or
to kill smallpox and look for other ways to understand HIV? At least in the
latter scenario we're
assured of some success. Any emerging viruses will have to be studied on
their own, regardless of
what has been discovered about smallpox.

There are also those who, in the name of preserving biological diversity,
oppose deliberate
extinction of any virus. Don't they realize that the alternative could be
extinction of humankind?

Susan G. Robbins 
University of Arkansasfor Medical Sciences 
4301 W. Markham St.Mail Slot 523 
Little Rock, Ark. 72205 
E-mail: [email protected] 

========================================================================
8.) The End to Smallpox
========================================================================
Shelly Cummings

The World Health Organization (WHO) proclaimed smallpox eradicated in late
1977, with the only
existence of the disease well contained in medical laboratories. (See
http://www.cac.washington.edu:1180/alumni/columns/top10/calling_the_shots.ht
ml) This was the
first time humankind had triumphed over a disease of this magnitude. In
December of 1994,
geneticists had fully characterized the microbe's genetic code. These
achievements did not end the
struggle against smallpox. In the early 1990s, a debate erupted over the
still existing smallpox
samples. Government medical experts are still arguing whether to destroy
the small quantities of the
disease still in their possession. Many public health experts are asking
the question, why does the
Centers for Disease Control and Prevention in Atlanta, Georgia and the
Russian State Research
Center of Virology and Biotechnology in Koltsovo still have over 600 vials
of the virulent germs
stockpiled for use by researchers? WHO announced this June that research
stocks of smallpox
virus will be destroyed on June 30, 1999. 

Some public health defenders feel this date is not acceptable and the two
earlier proposed
deadlines, should not have been allowed to pass. The earlier extinction
dates, in 1993 and
1995-were postponed amid protests that stocks should remain for research
purposes. Most experts
believe the risk to public health outweighs the research value. The recent
lack of attention that the
WHO committee has been paying to the eradication of the stocks of smallpox
could be due to the
controversies surrounding mad cow disease in the United Kingdom. Also, a
tight budget caused the
committee's annual meeting to be shortened, preventing alternatives to the
1999 date to be
considered. Destroying the only smallpox viruses in existence sounds like
an excellent idea. But how
can we be sure that in some remote corner of the world, there isn't a
village that will someday
reintroduce the dreaded smallpox into society? 

A brief history of the smallpox virus can be found in Chapter 14 in Human
Heredity. The news
piece discussing the eradication of the smallpox virus is: Kaiser J (ed.),
Smallpox Destruction Set for
1999, Science:272:1253, 1996. 
=======================================================================
9.) Smallpox Extermination Proposal Stirs Scientists
=======================================================================

Author: Karen Young Kreeger

Eminent virologists from around the world are reacting strongly--both for
and against--a
recommendation made in September by a World Health Organization (WHO)
committee to destroy
all remaining stores of the smallpox virus. 

At a September 9 meeting in Geneva, the 10-member WHO Ad Hoc Committee on
Orthopoxvirus
Infections unanimously agreed that the potential costs to humanity from
biological warfare or
inadvertent outbreaks of the disease outweigh its research benefits to
science--especially when there
are alternatives to using the live virus for scientific investigations. 

Advocates of preserving the viral stores argue, however, that given the
powerful microbiological
tools that have been devised in the recent past, it is short-sighted and
foolish to get rid of the live
virus just yet. They contend that information that is likely to be
discovered in the smallpox genome
could help fight other deadly viral pathogens, most notably HIV. 

"To me, on a scientific basis, we're taking an extremely precious resource
and destroying it," asserts
Bernard Fields, chairman of the microbiology and molecular genetics
department at Harvard
Medical School in Boston. While he does not advocate that researchers
"immediately start doing
experiments with the virus," Fields stresses that "destroying it ends the
whole issue of possibly
understanding it in the future." 

On the other hand, David Baltimore, Ivan R. Cottrell Professor of Molecular
Biology and
Immunology at the Massachusetts Institute of Technology in Cambridge,
maintains that "we can get
a lot of information from a variety of other routes, which I think
scientists will be prepared to take
because they're safe." 

He adds, referring to concerns that terrorists might use the virus in
biological warfare: "Balance
[these alternative methods] against the fact that there are nuts in the
world, and I would just as soon
get rid of it." 

If the recommendation to exterminate the stores by June 30 is carried out,
it also means that the
smallpox virus--more specifically, the variola strain, which is deadly to
humans- -would have the
distinction of being the first species to be intentionally eliminated. 

Before the remaining stocks are autoclaved and incinerated, health
ministers from around the world
will vote on the ad hoc committee's recommendation at the annual meeting of
the World Health
Assembly--the decision-making body of WHO--next May in Geneva. Currently,
live viral stocks
are held in freezers in high-containment laboratories at the Centers for
Disease Control and
Prevention (CDC) in Atlanta and the Institute for Viral Preparations in
Moscow. 

Diseases And Detente
====================
Smallpox was once the scourge of almost every inhabited continent on Earth,
with hundreds of
cases appearing in the former Yugoslavia as late as the early 1970s. In
1967, WHO launched an
aggressive vaccination campaign to eradicate the disease. Ten years later,
a man from Somalia was
the last known person in the general populace to die of smallpox. In 1979,
WHO announced that
the Earth was smallpox-free, making the virus the only contagious pathogen
ever to be eradicated. 

WHO first suggested that the virus be destroyed in 1986. According to Frank
Fenner, chairman of
the current WHO committee, there were no strong objections from the
scientific community. But, he
adds, in the interests of detente, a United States-Soviet Union
collaboration was proposed in 1990
to sequence the virus, thus giving smallpox a reprieve until December 1993. 

"The U.S. Na-tional Academy of Sciences and the Russian Academy of Sciences
got together and
thought a way of softening Cold War attitudes might be to set up a
collaborative enterprise of
sequencing the genome of the variola virus," notes Fenner, who is also a
professor, emeritus, at the
John Curtin School of Medical Research of the Australian National
University in Canberra. 

To date, two strains have been totally sequenced along with portions of
five others. Another strain is
currently being collaboratively sequenced by CDC and the Moscow institute,
says Joseph Esposito,
director of the WHO Collaborating Center for Smallpox and Other Pox Virus
Infections at CDC.
Should the virus be destroyed, the collaborating laboratories in Moscow and
Atlanta will remain
open, says Esposito. Among other responsibilities, he reports, the CDC
center will continue
working with other poxviruses. The WHO committee also recommended that CDC
and the
Moscow institute become repositories for cloned smallpox DNA stored in
recombinant plasmids. 

But in mid-1993, Fenner says, a "small minority" of mostly U.S. scientists
whose "words carry a lot
of weight" expressed reservations about the standing directive to eliminate
the virus after it was
sequenced. These scientists voiced their hesitation despite the endorsement
of the WHO
committee's recommendation by several groups, including the American
Society for Microbiology
and the Council of the International Union of Microbiological Societies. 

Although the committee listened to the pleas from the scientific community
to save the virus, Fenner
says, the committee represents 156 nations and couldn't justify keeping the
virus on hand because of
a few vocal, yet eminent, virologists. "It was a small minority, and I
think that weighed in the
consideration of the committee," he remarks. 

Why Destroy It?
================
To the WHO committee, the most compelling argument to get rid of the
smallpox stores is the
potential for the virus to be used by terrorists for biological warfare
(B.W.J. Mahy et al., "The
remaining stocks of smallpox virus should be destroyed," Science,
262:1223-4, 1993). "Political
stability is a relative thing," Baltimore observes. "In a perfect world we
would have a perfect
repository where we could keep it just in case we were wrong [about
destroying the smallpox
virus], but I don't think that makes any sense now, since all of its
information is decoded." 

But Fields views this reasoning as political rhetoric, not a scientific
dilemma at all. Moreover, he
says, this objection can be addressed through concomitant political
solutions: "There are political
ways to deal with that. Remove it from CDC and Moscow and put it in a
neutral country under
extremely safe conditions." 

Nonetheless, Fenner maintains, the committee's responsibility to the people
it represents is
justification for destroying the virus: "There are more countries in the
world experimenting with
bacterial warfare than there were a few years ago, and many countries feel
more comfortable if
there weren't these 600-odd strains of virus just [kept] in a deep freezer." 

Advocates of saving the virus, however, contend that, in any case,
eliminating lab-controlled stocks
doesn't mean that the threat of a smallpox outbreak is gone forever. Three
potential sources, they
say, exist: possible stocks unwittingly or intentionally stored in non-WHO
laboratories; possible
preservation of the virus in the tissues of smallpox victims buried in the
Russian permafrost region;
and possible re-emergence through a monkeypox variant. Given these
circumstances, they ask, why
not maintain the stores for study? 

Committee chairman Fenner counters that the likelihood that a vial of
smallpox virus would be found
in storage somewhere unbeknownst to WHO "gets more and more remote as time
goes on" and if
someone is keeping it secretly, there's "no way of knowing that, anyway."
He also calls the chances
that an epidemic would be initiated from permafrost cadavers "remote" and
points out that easy
transmission of the monkeypox virus in humans "hasn't happened in the whole
human occupation of
the rainforests of western, central Africa." 

In that unlikely event, WHO officials add, they have about 500,000 doses of
vaccine readily
available, with more capable of being produced in a matter of weeks. 

On the other hand, the possibility of accidental release from the lab is
significantly less remote,
according to the committee and its backers. "It can get out; it's proven
its ability to get out," says
Baltimore, referring to a 1978 isolated case that stoked early debates of
what to do with the
remaining stores. One year after the "last" death in Somalia, Janet Parker,
a British photographer,
became accidentally infected while taking pictures in a Birmingham
University Medical School lab in
which some samples were stored. Hers was the last recorded death by smallpox. 

This incident is the "practical example [of accidental infection] that
everyone points to," he observes.
"Even if that wasn't the case, we know that containment is never perfect.
That's the problem with human beings--they're fallible." 

Supporters of retaining the virus, however, claim that the Birmingham
incident couldn't happen in today's highly secure facilities in which the
remaining smallpox stocks are stored. 

Why Save It?
==============
Opponents of the committee's recommendation maintain that biomedical
researchers would forever
lose unique scientific knowledge if the virus is destroyed, especially at a
time when molecular
biological techniques are just beginning to reveal so much about viral
pathogens (W.K. Joklik et al.,
"Why the remaining stocks should not be destroyed," Science, 262:1225-6,
1993; L.S.
Sandakhchiev, "We'd Better Think Twice Before Eradicating All Smallpox
Virus Stocks," The
Scientist, Aug. 23, 1993, page 11). They say that preserving the variola
virus--at least for the next
five to 10 years-- for future study will aid in understanding the way other
such other deadly viral
pathogens as HIV operate and also in developing antiviral drugs. 

"Twenty years ago we didn't know anything about [smallpox] proteins,"
Wolfgang Joklik, James B.
Duke Professor of Microbiology at Duke University in Durham, N.C., points
out. "Twenty years
ago we thought all the information present in a [human] viral genome was
only to enable the virus to
multiply. Now we know that half the information is to defeat the human
defense mechanism." The
smallpox virus infects humans exclusively. 

However, proponents of destruction say that genetic studies can be done
without the live virus
because the base-pair sequence of smallpox DNA has been mapped and that
cloned smallpox viral
DNA is being kept in recombinant plasmids. (As a precautionary measure, WHO
also urged that no
more than 20 percent of the plasmid fragments be housed in any one
laboratory--with the exception
of CDC and the Moscow institute--and that no studies be performed in labs
where other poxviruses
are kept.) 

But, Joklik counters: "To study smallpox pathogenesis, the complete virus
is required, not just
plasmid clones and a sequence. How viruses cause disease at a biochemical
and molecular level is
little understood, and in smallpox, viral proteins mimic or interfere with
host immune and regulatory
functions. Clones don't suffice for study because encoding regions of the
smallpox DNA are
separated from regions that control expression." 

Fields concurs: "Anyone who says the sequence is enough doesn't understand
virology, and that
includes some famous virologists. We have to understand holistic parts of
this virus and how these
work together. There are many other poxviruses [to work on], but not this
one. This one is the key
pathogenic virus in its family. It's qualitatively different." 

Even if the virus is destroyed, current pox research will proceed apace,
according to Fenner: "Pox
virologists are now working primarily with vaccinia [an avirulent strain of
smallpox] and other pox
viruses as vectors for novel vaccines" against diseases unrelated to
poxviruses. Currently, the live
smallpox virus is being used only in the sequencing project. 

A Dubious Distinction
=====================
One issue that does seem to trouble both camps in the debate is that, if
the recommendation is
carried out, smallpox will be the first species to be deliberately wiped
out by humans. 

"I think that makes everybody a little unhappy," remarks Baltimore. "I do
think that biological
diversity is one of the great positive aspects of our planet and that we
should be maximizing it rather
than destroying it, so I think that that's a real concern. 

"On the other hand, it's very hard to find a positive side of viruses. As a
virologist, that's always
bothered me. If [eradicating] any species can be justified it's a species
that has no obvious positive
side to it, either aesthetic or any other." 

For the champions of sparing the virus, of course, this aspect of the
smallpox debate is also of
concern. 

"I don't mind containing things," Joklik says, "but I don't think we should
destroy them. With the
variola virus, obviously it's taken millions of years for nature to make
it, and why should 10 guys
sitting around a table say, 'Let's destroy it'? 

"It just doesn't make any sense to me because it's just such an admission
of defeat to say we can't keep it safe." 

========================================================================
10.) Sparing smallpox virus from destruction helps research, scientists say
========================================================================
Saturday, November 21, 1998

WASHINGTON -- Scientists pleaded for the life of the smallpox virus Friday,
telling an
Institute of Medicine committee that stocks of the virus that caused the
now-vanished disease are needed for research that could unlock the secrets
of the human immune system 
Smallpox, a deadly disease that killed 2 million people a year as
recently as 1968, was
declared eradicated in 1980. Stores of the virus are kept in Atlanta and
Moscow. The World
Health Organization would like to destroy the leftover virus, but
scientists do not agree whether
that's a good idea. 
Destruction is scheduled for June 1999, but that decision may be
re-examined at a
WHO board meeting in January. 
The Institute of Medicine, part of the National Academy of Sciences,
is preparing a report
on the possible scientific uses of the smallpox virus, also known as
variola. A final report assessing
the need to keep the virus around for research is expected in a few months;
the panel had no
opinion Friday. 
A workshop Friday on the issue -- attended by representatives of the
Department of
Defense and White House, as well as scientists -- did not focus on the pros
and cons of destruction.
It touched lightly on bioterrorism, although some think smallpox could be a
weapon. 
Most research dealt with pure lab work into the genetics and mechanics of
the virus, not the
kind of human based research that probably would be considered unethical by
most institutional
review boards. Smallpox is so dangerous researchers dealing with the live
virus must use full
protective equipment. 
Some researchers discussed the possibility of creating an animal model
for the disease,
despite the fact that what made smallpox eradicable was the fact it was
limited to humans. 
Researchers told the panel that having the virus around would enable
them to test new drugs
more effectively, better understand what makes viruses become deadly and
learn more about how
the human immune system works. Few had reasons why they would not need the
virus. 

Doug Lundberg 
========================================================================
III. Conclusion
========================================================================
A. The arguments for destroying the smallpox virus are
not strong enough to warrant its destruction

1. Threat of using smallpox for biological warfare is
small

2. Sequence data and cloned fragments do not
provide enough information

3. Risk of accidental laboratory infection is minimal

B. There should be much more concern for destroying the
smallpox virus than for the study of it in one or two
responsible laboratories

C. The risks associated with keeping the smallpox virus
are negligible compared with the opportunities for gaining
insight into the mechanisms of smallpox pathogenesis

D. For these reasons, research on the smallpox virus
should be supported, and decisions concerning its
destruction should at least be postponed

========================================================================
11.) Should My Child Get the Smallpox Vaccine? 
========================================================================
Answered by Robert Steele, MD 

Q: I would like to ask about the dangers of smallpox. The
outbreak of "monkeypox" has me concerned. Should we
re-instate the requirement to have children vaccinated
against
smallpox or at least let parents have the option of
choosing this
form of protection for their children?

What are the dangers of smallpox? 

Smallpox is a virus which used to cause severe illness
and death.
The 1960's saw over 2 million people/year die of this
disease.
However, an aggressive vaccine campaign world-wide allowed
for this devastating infection to be completely
eliminated. In 1980,
the World Health Organization declared the population of the
entire earth to be safe from this infection, and immunization
against smallpox was discontinued. However , the smallpox
virus
itself was not completely eliminated. A small quantity of
the virus
was kept under extreme security in two locations: The
Centers for
Disease Control in Atlanta and the Institute for Viral
Preparation
in Moscow, Russia. 

The reason for keeping the virus around was research.
Scientists
were concerned that eliminating the virus would cut off
our
opportunity to study it, completely understand it, and
then apply
that knowledge to cure other viral infections such as
HIV for
example. Since that time, though, these scientists have
been able
to completely identify its DNA structure. Because of
this, many
argue that keeping the whole virus around is
unnecessary. The
other side says no matter what our capabilities and
knowledge
are, nothing can substitute for having the whole virus
around with
respect to possible research in the future. 

But something happened. One year after the "last" man
on earth
died from smallpox, a British photographer became
infected and
died of smallpox which she contracted while taking
pictures in a
lab at a medical school where some of the virus was
stored.
Those who do not want the virus destroyed say this
could never
happen again since the only samples are kept under
such tight
security in only 2 places in the world. Nonetheless, the
possibility
of it accidentally escaping, or worse, it being taken by
terrorists
still exists as long as there is this virus still around. So,
in 1994, a
10-member committee from the World Health
Organization met in
Geneva to discuss what to do with these remaining
samples and
unanimously agreed that the dangers of it's escape
outweighed
the potential benefits of future research. They
therefore
recommended that all remaining samples be destroyed. But
resistance has continued, so to date, samples of
smallpox still
remain in Atlanta and Moscow. A final decision about
what to do
with these samples is expected in 1999. 

So, what's the deal with Monkeypox? 

A virus which is similar to smallpox but isolated to
monkeys in
Africa was noted to be able to jump from monkey to human
through contact. And until recently, it was felt that
monkeypox
could not be transmitted easily from human-to-human.
Jump to
October 1997 and you'll find the largest outbreak of
monkeypox
through human-to-human contact which occurred in
Africa. This
was primarily isolated to the Democratic Republic of
Congo. 

The vaccine against smallpox is highly effective in
preventing
monkeypox infection; however, at present, the
outbreak does not
seem to be large enough to warrant vaccination with the
smallpox
vaccine. Nonetheless, very diligent surveillance of this
infection is
ongoing by the World Health Organization. 

So...what does this all mean as far as the risk of
getting one of these infections? 

The likelihood of anyone in the United States getting
either smallpox or monkeypox is currently so remote that
vaccination against them with the smallpox vaccine is
really not a
worthwhile consideration. Why? First, the only
plausible way
smallpox could be introduced back into humans is
through a
terrorist obtaining samples either in Atlanta or Moscow.
I'll be the
last person to say this is impossible, but it is at least
extremely
unlikely. Second, even though monkeypox has now been shown
to be able to be transmitted human-to-human, it is still
felt to occur
only about 10% of the time. This implies that the only
reasonable
way to continue an epidemic of monkeypox infection
would be to
also have ongoing contact with animals that are
infected. Since
monkeys are not indigenous to the U.S., a sustained
outbreak of
this infection is remote at best. 

I hope this helps.

========================================================================
12.) [Danger to the human caused by animal poxvirus following
discontinuation of mandatory vaccination against smallpox]
========================================================================
TT - [Zur Gefahrdung des Menschen durch Tierpocken nach Aufhebung der
Pflichtimpfung gegen Pocken.]
SO - Hautarzt 1985 Sep;36(9):493-5
AU - Mayr A
MC - English Abstract
PT - JOURNAL ARTICLE
AB - The discontinuation of smallpox vaccination will lead to a gradual
decrease or disappearance of immunity to poxviruses of the genus
Orthopoxvirus. It is discussed whether orthopoxviruses of animals may then
constitute a potential danger to man, with respect to their mutagenic and
adaptation capabilities as well as their possible genetic interactions.
Infection of man with these viruses is generally possible, but at present,
not of acute importance. Monkeypox and cowpox viruses, as well as their
variants occurring in carnivores and rodents, are of primary interest for
individuals who have not been vaccinated against smallpox. Suggestions are
put forward on how the human population, as well as domestic and laboratory
animals, may be protected against infection with orthopoxviruses
originating from animals. In particular, it is recommended that endangered
groups of people should receive voluntary vaccination with genetically
stable, attenuated vaccinia virus strains.

========================================================================
13.) The confirmation and maintenance of smallpox eradication.
========================================================================
SO - N Engl J Med 1980 Nov 27;303(22):1263-73
AU - Breman JG; Arita I
PT - JOURNAL ARTICLE
AB - In December 1979, an independent scientific commission certified
global eradication of smallpox. This conclusion was accepted at the 33d
World Health Assembly of the World Health Organization (WHO) in May 1980.
After WHO's intensified eradication program began in 1967, special
certification procedures were used in 35 countries where the disease had
been endemic and in 44 others at special risk. Six laboratories are known
to retain variola virus; efforts have been made to ensure strict
containment of these strains. There is no evidence that smallpox will recur
as an endemic disease. Nevertheless, WHO will promote surveillance of
smallpox-like disease and selected laboratory research on certain
orthopoxviruses. These efforts will maintain confidence that smallpox has
been eradicated and confirm that there are no animal reservoirs of variola
virus. A more complete understanding of the orthopoxviruses, including
monkeypox virus, should also be obtained.

========================================================================
14.) [Lethal animal pox virus infection in an atopic patient simulating
variola vera]
[Letale Tierpockeninfektion bei einem Atopiker unter dem Bild einer
Variola vera.]
========================================================================
SO - Hautarzt 1991 May;42(5):293-7
AU - Pfeiff B; Pullmann H; Eis-Hubinger AM; Gerritzen A; Schneweis KE; Mayr A
AD - Dermatologische Abteilung, Krankenhauser des Markischen Kreises,
Ludenscheid.
MC - English Abstract
PT - JOURNAL ARTICLE
AB - An 18-year-old patient requiring steroid treatment for severe
bronchial asthma and with atopic dermatitis acquired a cowpox-like virus
infection clinically similar to smallpox from a domestic cat as carrier. In
spite of intensive care, with controlled pressure breathing and the last
available vaccinia hyperimmunoglobulin, the patient died of pulmonary
embolism although viral spread had ceased some days before.

========================================================================
15.) Human monkeypox: clinical features of 282 patients.
========================================================================
SO - J Infect Dis 1987 Aug;156(2):293-8
AU - Jezek Z; Szczeniowski M; Paluku KM; Mutombo M
MT - Female; Human; Male
PT - JOURNAL ARTICLE
AB - We present the clinical features and course of 282 patients with
human monkeypox in Zaire during 1980-1985. The ages of the patients ranged
from one month to 69 years; 90% were less than 15 years of age. The
clinical picture was similar to that of the ordinary and modified forms of
smallpox. Lymphadenopathy, occurring in the early stage of the illness, was
the most important sign differentiating human monkeypox from smallpox and
chickenpox. The symptoms, signs, and the course of the disease in patients
who had been vaccinated against smallpox differed significantly from those
in unvaccinated subjects. Pleomorphism and "cropping" similar to that in
chickenpox occurred in 31% of vaccinated and 18% of unvaccinated patients.
The prognosis depended largely on the presence of severe complications. No
deaths occurred among vaccinated patients. In unvaccinated patients the
crude case-fatality rate was 11% but was higher among the youngest children
(15%).

========================================================================
16.) Smallpox: emergence, global spread, and eradication. 
========================================================================
Author 
Fenner F 
Address 
John Curtin School of Medical Research, Australian National
University, Canberra. 
Source 
Pubbl Stn Zool Napoli [II], 15(3):397-420 1993 
Abstract 
Speculatively, it is suggested that variola virus, the cause of
smallpox, evolved from an
orthopoxvirus of animals of the central African rain forests (possibly
now represented by
Tatera poxvirus), some thousands of years ago, and first became
established as a virus
specific for human beings in the dense populations of the Nile valley
perhaps five thousand
years ago. By the end of the first millennium of the Christian era, it
had spread to all the
densely populated parts of the Eurasian continent and along the
Mediterranean fringe of north
Africa. It became established in Europe during the times of the
Crusades. The great voyages
of European colonization carried smallpox to the Americas and to
Africa south of the
Sahara. Transported across the Atlantic by Europeans and their African
slaves, it played a
major role in the conquest of Mexico and Peru and the European
settlement of north
America. Variolation, an effective preventive inoculation, was devised
as early as the tenth
century. In 1798 this practice was supplanted by Jenner's cowpox
vaccine. In 1967, when
the disease was still endemic in 31 countries and caused ten to
fifteen million cases and about
two million deaths annually, the World Health Organization embarked on
a programme that
was to see the disease eradicated globally just over ten years later,
and the world was
formally declared to be free of smallpox in May 1980. Smallpox is
unique--a specifically
human disease that emerged from some animal reservoir, spread to
become a worldwide,
severe and almost universal affliction, and finally underwent the
reverse process to
emergence, namely global eradication. 

========================================================================
17.) Smallpox: the triumph over the most terrible of the ministers of death. 
========================================================================
Author 
Barquet N; Domingo P 
Address 
Centre d'Assist`encia Prim`aria Gr`acia, Institut Catal`a de la Salut,
Barcelona, Spain. 
Source 
Ann Intern Med, 127(8 ( Pt 1)):635-42 1997 Oct 15 
Abstract 
More than 200 years ago, Edward Jenner performed an experiment that
laid the foundation
for the eradication of smallpox and transformed humankind's fight
against disease.
Smallpox afflicted humankind as no other disease had don; its
persistence and diffusion
were without parallel. The disease brought down at least three
empires. Generations watched
helplessly as their children succumbed to the disease or were
disfigured or blinded by it.
Attempts were made to contain smallpox by isolating its sufferers and,
later, by using
variolation with varying degrees of success. However, the definitive
solution was not found
until Jenner's work was done at the end of the 18th century. Milkmaids
who had developed
cowpox from contact with cow udders informed Jenner that they were
protected from the
human form of the disease; he listened to their folk wisdom and raised
it to the status of
scientific fact. Jenner did not discover vaccination, but he was the
first to demonstrate that
this technique offered a reliable defense against smallpox. It was
also a reliable defense
against other illnesses, such as poliomyelitis, measles, and neonatal
tetanus, although this was
not known in Jenner's lifetime. 
========================================================================
18.) Edward Jenner and the eradication of smallpox. 
========================================================================
Author 
Willis NJ 
Address 
Ninewells Hospital and Medical School University of Dundee. 
Source 
Scott Med J, 42(4):118-21 1997 Aug 
Abstract 
Edward Jenner's careful investigations into the usefulness of cowpox
vaccination for the
prevention of smallpox during the late 1790s, and his enthusiastic and
continued advocation
of vaccination despite the scepticism of critics, laid the foundations
for the growth of
understanding about the nature of infectious disease and the
development of immunity during
the 19th century. He began the long process which resulted in the
successful eradication of
the smallpox virus in 1980. His life story remains an inspiration to
physicians facing an
uncertain future as viruses and bacteria not yet eradicated adapt to
the antibiotic age. 

========================================================================
19.) The smallpox saga and the origin(s) of vaccination. 
========================================================================
Author 
Cook GC 
Address 
Hospital for Tropical Diseases, London. 
Source 
J R Soc Health, 116(4):253-5 1996 Aug 
Abstract 
Two hundred years ago--in May 1796--Edward Jenner carried out a
pioneering feat in the
history of "clinical investigation' which not only paved the way for
the eventual elimination of
one of the world's most terrifying infections (variola), but also
heralded widespread
vaccination campaigns and the foundation of the discipline of clinical
immunology.
Vaccination superseded the formerly used technique of variolation
which had been
introduced into England by Lady Mary Wortley Montague.
Under-recognised is the fact that
the first clinical trial(s) of this new development were carried out
under the supervision of
William Woodville at the St Pancras Smallpox Hospital (situated at
Battle Bridge--now
King's Cross); this work was crucially important in the 'vaccination
saga' and deserves far
greater acceptance than is currently the case. 

========================================================================
20.) The Jenner bicentenary: the introduction and early distribution of
smallpox vaccine. 
========================================================================
Author 
Baxby D 
Address 
Department of Medical Microbiology, Liverpool University, UK. 
Source 
FEMS Immunol Med Microbiol, 16(1):1-10 1996 Nov 
Abstract 
This review describes the background to Jenner's first vaccination,
his later work, and the
dissemination of information about vaccination and the vaccine itself.
Although based on
relatively slender evidence, Jenner's theories were basically sound
and he merits the credit
given him. Given the circumstances, particularly the slow speed of
travel and the lack of
information about the duration of immunity, vaccination became
established very quickly in
many countries. 
========================================================================
21.) Smallpox Virus Faces Own Death
========================================================================

Newer Information: November 22, 1998

Two hundred years after a vaccine was first used to
stem the spread of smallpox. the World Health
Organization has decided to destroy the last remaining
stocks of the smallpox virus, one of the biggest killers
in history. 

Destruction is scheduled for June 30, 1999, according
to a plan that representatives of 190 countries
approved at the final day of the week-long annual
meeting of the health organization. 

Final approval is required by member countries of
WHO, the United Nations agency in Geneva, at their
May 1999 meeting. 

WHO declared smallpox eradication in 1980 after a
worldwide program of immunization and case hunting.

Smallpox remains the only naturally occuring disease
ever wiped out from the human population. 

Destruction of the smallpox virus known as variola,
would be the last step in the smallpox eradication
program and the first deliberate extinction of a
species. 

The last stocks of the smallpox virus have been kept
frozen in laboratories at the Centers for Disease
Control and Prevention in Atlanta and the Russian
State Research Center of Virology and Biotechnology
in Koltsovo, Russia. 

Beginning in 1986, committees of virologists
appointed by WHO have repeatedly recommended
destroying the virus after scientists determined the
complete genetic blueprint of at least one strain of the
smallpox virus. 

Scientists have exceeded the committees' minimum
request, fully analyzing the genetic structure of two
strains and finding them identical. Additional strains
have been analyzed in part. 

WHO plans to allow scientists to keep cloned DNA
fragments of variola, which themselves cannot cause
infection, to permit further research on the virus'
genes, protein structure and function. 

Several scientific groups backed the move to destroy
the smallpox virus. It received a stay of execution
from its original destruction date of December 31,
1993, on several occasions after leading virologists,
reacting to new research findings, said the virus should
be preserved. 

While the genetic blueprints were being mapped,
scientists began identifying surprising links between
genes in the virus and natural immune substances,
including some involved in cancer. 

In January, the governing board of the health
organization voted to destroy the virus in 1999 and
recommended that the entire membership take up the
issue this wee (May 1996). 

======================================================================
DATA-MEDICOS/DERMAGIC-EXPRESS No.(26) 30/12/98 DR. JOSE LAPENTA R. 
======================================================================

Produced by Dr. Jose Lapenta R. Dermatologist 
            Maracay Estado Aragua Venezuela 1.998  
         Telf: 0416-6401054- 02432327287-02432328571