EDITORIAL ESPANOL:

====================

Hola amigos dermatólogos del Cyber, en esta ocasión DERMAGIC hace una interesante revisión sobre la Viruela, LA GUERRA QUE AÚN NO GANAMOS. Se preguntaran el porque de esta afirmación y les voy a dar claras respuestas.

La viruela, enfermedad terrorífica que en el siglo pasado y hasta los años 60-70 cobró innumerables víctimas fue prácticamente 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, quedó para la historia como el último 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 debía dar a las cepas del mortífero Virus, Actualmente almacenadas en ATLANTA Georgia CDC, y Rusia, Koltsovo, las dos gran superpotencias.

En principio se había acordado destruirlas totalmente en 1.995, pero vinieron posteriores aplazamientos, los científicos están 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 búsqueda de información, siempre pensé que había 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 BIOLÓGICO, les pongo dos segmentos de las referencias encontradas en el Cyber:

"It touched lightly on bioterrorism, although some think smallpox could b e 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 rápidamente, recordemos el evento de Jannet Parker, murió tomando una fotografías en un laboratorio, ello ocurrió 1 AÑO DESPUÉS 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 (orthopoxvirus) 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 decidió ERRÓNEAMENTE en USA eliminar la vacuna contra la Tuberculosis... y ya todos conocemos las consecuencias, LA TBC volvió con gran ímpetu, y de nuevo se asumió la vacunación. 

La OMS, decidió 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 dará el veredicto final, sabían ustedes eso ???, dentro de pocos días sabremos qué harán 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." 

Serán nuestros "líderes" capaces de dar ese gran paso y olvidarse de la loca carrera armamentista, de pensar verdaderamente en la salud de la humanidad, de evitar un "escape" accidental del virus ??? matándolo totalmente ????

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

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

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

Dr. José Lapenta R. 

 EDITORIAL ENGLISH:

===================

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

The Smallpox, 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 SMALLPOX, 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 Smallpox (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 SMALLPOX, 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 SMALLPOX 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: srobbins@acer.uams.edu 

========================================================================

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

======================================================================

Produced by Dr. José Lapenta R. Dermatologist
Venezuela 1.998-2.024

Producido por Dr. José Lapenta R. Dermatólogo
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