Smallpox as an actual biothreat: lessons learned from its outbreak in ex-Yugoslavia in 1972

Abstract

Variola (smallpox) virus is classified as class A of potential biological weapons, due to its microbiological, genetic, antigenic and epidemiological characteristics. The potential danger is more real because vaccination against smallpox has stopped since disease eradication in 1979. That is why we want to share our unique, rich experience and acquired knowledge in the fight against this highly contagious and deadly disease during the smallpox outbreak in ex-Yugoslavia in 1972. It was the largest postwar outbreak in Europe when there were officially registered 175 ill patients, 35 of them with lethal outcome. This outbreak was specific by the time of its occurrence, the affected territory, dimensions and some epidemiological characteristics, but also by the well-organized, synchronized and efficient reaction of the competent state services in the fight against it.

Full text

Original art icl es and rev ie ws
587
Key words
• smallpox-variola
• outbreak
• Yugoslavia
• bioweapons
Smallpox as an actual biothreat:
lessons learned from its outbreak
in ex-Yugoslavia in 1972
Elizabeta Ristanovic1, Ana Gligic2, Sonja Atanasievska1, Vesna Protic-Djokic1,
Dragutin Jovanovic1 and Miodrag Radunovic3
1Institute of Microbiology, Military Medical Academy, Belgrade, Serbia
2Institute for Virology, Vaccines and Sera Torlak, Belgrade, Serbia
3Faculty of Medicine, University of Montenegro, Podgorica, Montenegro
Ann Ist Super Sanità 2016 | Vol. 52, No. 4: 587-597
DOI: 10.4415/ANN_16_04_21
Abstract
Variola (smallpox) virus is classied as class A of potential biological weapons, due to
its microbiological, genetic, antigenic and epidemiological characteristics. The poten-
tial danger is more real because vaccination against smallpox has stopped since disease
eradication in 1979. That is why we want to share our unique, rich experience and ac-
quired knowledge in the ght against this highly contagious and deadly disease during
the smallpox outbreak in ex-Yugoslavia in 1972. It was the largest postwar outbreak
in Europe when there were ofcially registered 175 ill patients, 35 of them with lethal
outcome. This outbreak was specic by the time of its occurrence, the affected territory,
dimensions and some epidemiological characteristics, but also by the well-organized,
synchronized and efcient reaction of the competent state services in the ght against it.
SMALLPOX AS A HISTORICAL HEALTH
THREAT
Variola is considered one of the most deadly diseases
in human history that decimated the population and
signicantly changed the course of civilization develop-
ment. The origin of smallpox is unknown. It is believed
that it rst appeared about 10 000 BC in northeast Afri-
ca, from where it spread to the Far East, up to India and
China. The oldest credible conrmation of the smallpox
presence in Africa was found in 1500 BC in Sanskrit
writings about the deity-protectors of smallpox, while
on the mummy of Egyptian ruler Ramses V (1100 BC)
were observed lesions that indicated that he died of
smallpox [1, 2].
Hippocrates (460-370 BC) did not mention this dis-
ease, while Galen described it in the 2nd century [3]. In
the 6th century the epidemic in Mecca was mentioned.
It is believed that the virus was introduced into Europe
in the period between the 5th and 7th century, during
the invasion of the Saracens from North Africa, across
the Pyrenees, but variola might have arrived in Europe
through natural ways of communication from Asia Mi-
nor. It caused frequent outbreaks during the Middle
Ages and the New Age, when smallpox was the most
deadly disease in Europe causing the death of about
400 000 Europeans annually, including 5 rulers [1]. In
the 15th century Spanish conquerors brought a smallpox
virus to the territory of Cuba and Mexico, where in the
rst outbreak wave the entire tribes of native inhabit-
ants perished. At the time when the European coloniz-
ers conquered the New World, smallpox was used as a
strong biological weapon against powerful empires of
the Aztecs and the Incas, and many Indian tribes [4]. In
Australia the variola appeared in the 19th century, when
the epidemic broke out in Sydney [3].
During the 20th century a smallpox virus caused 300-
500 million deaths in the world. In the period between
1950 and 1971, smallpox found its way into Belgium,
Canada, Czechoslovakia, Denmark, French, East and
West Germany, Spanish, England, Italy, Holland, Po-
land, Switzerland, Sweden and the USSR, mostly via
travelers from endemic foci causing many outbreaks. In
each of the mentioned epidemics the number of regis-
tered cases was under one hundred [5].
This is why, in 1967, the World Health Organization
(WHO) launched a global campaign for the disease
eradication, when the vaccination against smallpox in-
cluded all current and potential foci [6]. The campaign
was successfully completed in 1979, and on the 8 May,
1980, WHO proclaimed the eradication of smallpox.
It was recommended that only two laboratories in the
world (in Russia-the former Soviet Union and the Unit-
ed States) retain the virus, while others were obliged to
destroy it. The time of its destruction in these laborato-
Address for correspondence: Elizabeta Ristanovic, Department of Microbial Genetics and Immunology, Institute of Microbiology, Military Medical
Academy, 17 Crnotravska St., Belgrade, Serbia. E-mail: elizabeta.ristanovic@vma.mod.gov.rs.

Elizabeta Ristanovic, Ana Gligic, Sonja Atanasievska et al.
Original art icl es and rev ie ws
588
ries was not denitely determined. After eradication, the
mass vaccination against smallpox was terminated [7].
BACKGROUND INFORMATION
AND TODAY’S CHALLENGE
Variola virus is classied as the genus Orthopoxvirus,
family Poxviridae, together with some animal poxviruses
such as vaccinia virus, monkeypox, camelpox, mouse-
pox, rabbitpox, and others [8]. The origin of variola vi-
rus is unknown and there is no evidence that the nature
of smallpox during the centuries has undergone some
changes [9]. In the 20th century, numerous researchers
investigated correlation among smallpox and another
animal poxviruses with the aim of explaining its origin
and thus nding the most biological, immunological
and epidemiological similarity between smallpox and
monkeypox which can induce illness in humans, and
be transmitted from human to human. It was also very
hard to conrm differences of smallpox and camelpox-
“white poxvirus” [10-17]. During smallpox epidemic
in 1975 Lourie et al. from trapped rodents-Gerbil in
North Africa isolated pox virus that was biologically
more similar to variola minor (alastrim) than variola
major [18]. According to these ndings there is pos-
sibility that monkeys or rodents could be natural reser-
voirs of the smallpox virus in Equatorial Africa, or they
could also be infected from some unknown reservoirs in
wilderness [19] The infected persons are usually virus
reservoirs during the disease outbreaks.
Until the discovery of Marburg and Ebola viruses it
has been described as the biggest human virus, whose
size is 150-360 nm. It is surrounded with a symmetrical
capsid envelope with lipoproteins and hemagglutinins
and contains a double-stranded DNA with 200 000
base pairs. Smallpox is spread by direct contact with
an infected person, as well as through air-droplets and
aerosols. The virus is relatively stable in the environ-
ment, so that in the form of an aerosol it preserves the
infectivity even for several hours. The disease can be
transmitted via contaminated clothes and some other
items, when the risk of infection is less [20]. The in-
cubation period usually lasts 7-17 days, after which
u-like symptoms appear: fever, malaise, headache,
prostration, back pain, and sometimes abdominal pain
and vomiting. The characteristic rash appears after 2-3
days, rst on the face, hands, forearms, and later on
the body. Lesions occur on the mucous membranes of
the nose and mouth quickly transforming into ulcers,
then progressing from the macula into the papules, pus-
tules and vesicles nally appearing in the form of the
crusts that fall off, leaving typical scars. There are two
basic clinical forms of the disease: variola major, which
has a more difcult clinical course and mortality up to
30% and variola minor (alastrim), which has a milder
clinical course and mortality of less than 1% [21]. The
hardest forms of the disease are hemorrhagic and ma-
lignant (at) variola, characterized by severe toxemia
with at conuent lesions and high mortality rate up to
96-100%, after 5-6 days. The infected persons are most
contagious during the temperature rise and in the rst
week of rashes, when the virus is released via the respi-
ratory tract. Contact with the sick in the later stages of
the disease rarely leads to infection.
Microbial diagnostics of smallpox includes a direct
electron microscopy of all stages of skin lesions samples
as well as virus isolation, using in vivio (chicken embryo)
and in vitro (cell culture) systems. Detections of anti-
gens and antibodies in the patient blood are also very
useful methods to conrm infection. The methods of
molecular genetics such as PCR, which can rapidly and
reliably detect the virus particles are certainly of the
greatest signicance nowadays. Laboratory work with
infectious material, containing smallpox virus, should
be conducted using the highest level of biological safety
containments (BSL4) [20].
The treatment of a smallpox patient is conducted by
symptomatic therapy while the vaccine can be used in
the post-exposure prophylaxis in 4 days after exposure
for obtaining protective immunity, preventing infection
and alleviating the symptoms of the disease. Specic
monoclonal antibodies can be used for treatment of im-
munocompromised persons. It is also worth mentioning
that the smallpox vaccine was the rst vaccine in history
made by Edward Jenner in 1796 [22]. The rst Law on
vaccination against smallpox was adopted in 1874 in
Germany. The vaccination in Serbia began in 1881 with
the imported vaccines while since 1901 home-made
vaccines produced at the Pasteur Institute in Nis, Ser-
bia were used [23]. After rst vaccination, the protec-
tion level is high in the rst ve years, after revaccina-
tion it is maintained longer, while it lasts about 30 years
after the 3rd dose. The vaccine against smallpox causes
a large number of adverse effects, especially in infants
and people with immunodeciency and in persons with
chronic diseases.
Due to its microbiological, epidemiological and
clinical characteristics, then the possibility of the virus
spreading with aerosol and among people, the smallpox
virus is classied by the CDC in class A of potential
biological agents. According to available data, this vi-
rus entered the arsenals of biological weapons of the
most powerful countries in the world during the Cold
War and was the subject of serious research, includ-
ing its recombination with Ebola virus [24]. The virus
is well-studied at the molecular level and it can easily
be genetically modied in order to prevent the effects
of the vaccine or to increase the virulence. The virus
as the biological weapon can be easily cultivated and
it is possible to produce large quantities in a relatively
short period. It is very resistant to the environmental
agents and can survive their impacts for months and
years [25]. The use of smallpox as a biological agent is
also supported by the fact that a large portion of the
world population is vulnerable, susceptible to this virus,
since the vaccination was terminated after its eradica-
tion, mortality is high, and there is no specic therapy
[26]. The real fear of the application of smallpox virus
as a potential biological agent is also supported by the
fact that in the last years of the 20th century in some
countries in the world began the intensive production
of vaccine against smallpox. Considering that this is a
highly contagious agent where one infected person can
transmit the infection to 10 or 20 others, special pro-
tection measures are required in the management of

Lessons Learned in the Largest smaLLpox postwar outbreak in europe
Original art icl es and rev ie ws
589
patients (room-isolators with negative air pressure and
accompanying protective equipment that prevents the
infection spreading) as well as during microbiological
processing of the samples (BSL 4 laboratories) so that
its breakout might lead to big problems in health care
activities, as well as in all other public services, espe-
cially in undeveloped countries [25, 27].
In today’s world of global contradictions, the use of
biological weapons, including smallpox, poses a real
danger, both in war and in bioterrorist actions when the
agent has been acquired by individuals or groups with
nefarious intentions over which no one has any control.
This danger has particularly come to the fore after 11th
September, 2001, and the attack on the World Trade
Center in New York-USA and a subsequent anthrax
campaign leaving in its wake 11 victims. In this con-
text, the smallpox virus could again become an obvious
present-day danger. In view of all the above-mentioned,
it is extremely important to strengthen the awareness
of this problem, monitor the epidemiological situation
and take preventive measures, and, above all, to have
adequately prepared human and material resources
for the response in case of disease occurrence. In that
regard the unique experience and lessons of the previ-
ous epidemics and responses of the relevant services in
these situations are extremely valuable.
An outbreak of smallpox that engulfed the former Yu-
goslavia in 1972 was combated quickly and efciently.
The circumstances under which the outbreak started,
the number of cases reached before smallpox was iden-
tied, the economic damage it caused, as well as the
taken measures need to be analyzed carefully.
VARIOLA IN YUGOSLAVIA IN 1972:
EPIDEMIOLOGICAL DATA
AND ANTI-OUTBREAK MEASURES
The outbreak of smallpox in Yugoslavia broke out
just in a period of intense campaign for disease eradica-
tion. It was the largest post-war outbreak in Europe.
Both then and now, there were doubts and speculations
that it might have been a bioterrorist attack on Tito’s
Yugoslavia as well as many other interpretations [28],
although scientic facts do not support these claims.
The beginning of outbreak was registered on Febru-
ary 16th, and the last case was reported on April 11th,
1972. The outbreak affected a total of 175 persons, 35
of whom (20%) died. Among the patients there were 99
(56.6%) men and 76 (43.4%) women. The 174 patients
were registered in the Republic of Serbia (Central Ser-
bia: 49 cases, 8 of them with lethal outcome; Autono-
mous Province of Kosovo: 124 ill persons, 26 of them
died; the Autonomous Province of Vojvodina: 1 person
was infected and died), while one case was recorded in
the Republic of Montenegro [29]. Spreading of disease
across the country is shown in Figure 1.
Epidemiological data and serological tests showed
that a pilgrim Ibrahim H. from the village of Danjane
(Orahovac near Djakovica) brought the smallpox into
Yugoslavia. He visited Mecca and Medina (Saudi Ara-
bia) with another 24 pilgrims from Kosovo and returned
by bus across Iraq, visiting dervish shrines around Basra
and Baghdad where at that time there were more pa-
tients suffering from smallpox [30]. Upon returning
to the village, the pilgrim Ibrahim H., according to his
own testimony, had some mild symptoms of fatigue and
Figure 1
Smallpox in Yugoslavia. Spreading of disease from primary focal point in Kosovo.

Elizabeta Ristanovic, Ana Gligic, Sonja Atanasievska et al.
Original art icl es and rev ie ws
590
chills, and several small pimples on the face that also
conrmed the barber who would not do Ibrahim’s face
treatment. However, a month later, on his face and body
were not found any scars, and no traces of vaccination,
although it was carried out in December 1971 in the
Institute for Health Protection in Skopje (Macedonia),
before traveling to Holy places. Following law, all hajj
participants were previously vaccinated against small-
pox by lyophilized vaccine produced in the Institute
of Immunology in Zagreb (Croatia), as well as against
cholera. After vaccination, all of them received certi-
cates, under the provisions of the WHO International
Health Regulations, but the success of vaccination was
not controlled. By testing the sera of passengers who
travelled on the pilgrimage by bus in which was the rst
infected person, it was found that 20 of them had no
satisfactory vaccination antibody titer, which opened up
a number of issues related to the failures in the imple-
mentation of measures of immunization against small-
pox [2, 30].
According to the WHO estimates, in Yugoslavia the
measures of control of all the passengers coming from
infected areas were implemented and pilgrims were
treated as a particularly risky group. So it was required
that a pilgrimage be organized by plane, with pre-sanita-
tion and checking, health control during the trip, as well
as health surveillance after return. All those recommen-
dations were generally enforced, in agreement with the
Islamic community, but nevertheless there were some
private arrangements, such as the one with the person
who travelled on pilgrimage by bus and subsequently
brought in the disease [31]. Otherwise, in the WHO’s
report Iraq rst appeared as the smallpox infected area
in March of 1972. All pilgrims stated that during the
trip they were healthy. They were revaccinated during
the outbreak. Serological examination of their samples
was performed before revaccination at the Institute of
Virology, vaccine and sera in Belgrade, the national ref-
erence laboratory for smallpox in Yugoslavia, as well as
in the laboratories of the Center for Disease Control
and Prevention (CDC) in Atlanta (USA). The results
showed signicant differences of positive ndings in
the sera of Ibrahim H. compared with sera of other
pilgrims. Therefore, it was considered that Ibrahim H.
as an index case was a probable source of infection for
next 9 cases [2, 30]. The scheme of infection origin and
further spreading is shown in Figure 2.
The outbreak in the Province of Kosovo developed
into three generations: 9 cases in the rst, 100 in the
second, and 14 cases in the third, plus the index case.
The number of secondary infections from one source
was closely connected with the length and intimacy of
contact between patients and vulnerable people, and
depended on the clinical form and stage of the disease at
a time when the contact was established. Patient Ljatif
M, one of 9 contacts with index case developed severe
atypical changes in the skin and mucous membranes
and caused the largest number of secondary infections.
He had hemorrhagic and always deadly but unrecogniz-
able form of smallpox. Diagnosis was established post
mortem on the basis of virologically conrmed smallpox
infection in numerous contacts, the number of plate-
lets and reduced amount of blood coagulation factors.
Since he was found to be severely allergic to penicil-
lin, the patient was introduced before his death to the
groups of students and also stayed in several medical
institutions. Thus, 38 persons were infected in direct
contact with him which represents the largest number
of infections from one person as reported in the world
literature [32].
Figure 2
The origin and spread of smallpox epidemic. Source: Dovijanić P, et al. Social-medical character of combating against smallpox out-
break in Belgrade. Proceedings of the Symposium Smallpox Outbreak in Belgrade. 1972. p. 15. [In Serbian]

Lessons Learned in the Largest smaLLpox postwar outbreak in europe
Original art icl es and rev ie ws
591
Out of 175 patients, 105 of them (60%) were previ-
ously vaccinated, 66 (37.7%) were unvaccinated, while
in 4 of them (2.3%) the vaccination status was unknown
as it is shown in the Table 1. It is necessary to emphasize
the big difference in the fatality rate among previously
vaccinated (8%) and unvaccinated persons (35%). Oth-
erwise the compulsory vaccination of children in Yugo-
slavia was carried out at the age of 6 months to 3 years
(primary vaccination), with mandatory revaccination at
7 and 14 years. The control of vaccination success in
some areas was not adequate, so the signicant decline
of vaccine immunity after primary vaccination and the
lack of revaccination led to disease occurrence in the
young population [33].
One of the specicities of this outbreak was a rela-
tively high percentage of hemorrhagic forms of dis-
eases as it is shown in Table 2. Early and late hemor-
rhagic forms appeared in 8.0% of registered smallpox
cases with severe pain, bleeding and temperature. All
patients died in the rst week of illness. This form of
disease appeared in both vaccinated and unvaccinated
persons. The standard anti-shock therapy did not give
positive results, due to continuing increase in viral load
and new tissue damage [34]. In the sample of a nurse
from Belgrade, with this form of smallpox, just before
death, were registered 21 750 viral particles in 1 ml of
blood [2]. The other authors previously published simi-
lar results but the number of virus particles was never
at any time over 10 000 particles in 1 ml of blood [1,
35, 36]. Malignant (at) form appeared in 19 cases,
including 7 under one year of age. Only one person
among them, a pregnant woman, had a vaccination scar
[37]. Three patients with this smallpox form received
a transfusion of fresh blood of vaccinated people and
convalescents, which had favorable therapeutic effects,
and represented a signicant contribution to the prac-
tice of treating the disease [38]. Ordinary forms of dis-
ease were registered in 72 cases. The prognosis in this
form was relatively good. Death outcome occurred in
the elderly, immunocompromised, and those with im-
pairments of other organs. In the four of seven deaths,
the immunization scarring was not detected. Modied
smallpox form was detected in 67 patients, without a
single fatality. Most of them, 61, were with the old vac-
cine scars. This form did not represent a problem in
therapy, but it was a diagnostic challenge because the
rash drying happened in the stage of papules or vesicles,
while pustulisation was rare and did not affect any efo-
rescence. Due to the scarcity of material the cultivation
of the virus became more difcult, while the serologi-
cal diagnosis was the only available option, although in
most patients antibody titers were low. These forms had
a good prognosis and required only symptomatic treat-
ment [39]. Variola sine exanthemata was identied in
3 cases on the basis of clinical and serological criteria
[40]. It is assumed that there were more patients with
subclinical forms of disease, but serological tests were
not performed. Eight of 14 affected infants died. The
affected children were mostly from Kosovo, they were
not vaccinated, but the vaccination status of mothers
affected the occurrence of the disease, its manifestation
and prognosis [41].
Different clinical manifestations of smallpox in Yugo-
slavia are shown in Figure 3. The previous state, genetic
predispositions, immune and vaccination status had a
major impact on clinical picture of patients. Three of 6
patients with previous hepatitis infection died, as well
as two patients with pertussis, and the patient with tu-
berculous meningitis. The previous vaccinations had the
biggest impact on the clinical manifestations of disease.
Ordinary forms occurred more frequently in unvacci-
nated people, as well as the at forms, while the modi-
Table 1
Vaccinal status and age distribution of diseased and deceased persons in the smallpox outbreak
Age groups
0 1-6 7-14 15-19 ≥ 20 TOTAL
Diseased persons
Vaccinated 1 6 7 91 105
Not vaccinated 12 14 13 6 21 66
Unknown 4 4
Total number of diseased persons 12 15 19 13 116 175
Fatal cases
Vaccinated 1 1 6 8
Not vaccinated 8 3 3 2 7 23
Unknown 4 4
Total number of fatal cases 8 3 4 3 17 35
Lethality (%) 66.7 20 21 23 15 20
Table 2
Diseased and deceased from various clinical forms of smallpox
during Yugoslav outbreak in 1972
Clinical form Number
and percent
of diseased
Number
and percent
of fatal cases
Early hemorhagic 13 (7.4%) 13 (100%)
Late hemorhagic 1 (0.6%) 1 (100%)
Flat (variola maligna) 19 (10.8%) 14 (73.7%)
Ordinary 72 (31.2%) 7 (9.7%)
Modified 67 (38.3%) 0 (0%)
Variola sine exanthemate 3 (1.7%) 0 (0%)

Elizabeta Ristanovic, Ana Gligic, Sonja Atanasievska et al.
Original art icl es and rev ie ws
592
ed forms and variola sine exanthema appeared only in
people with vaccine scars. Lethality was also three times
higher in people without immunization scars [42].
During Yugoslav smallpox outbreak, microbiological
diagnosis was performed in the National reference lab-
oratory for smallpox in the Institute of Virology vaccine
and sera in Belgrade using electron microscopy (EM) −
method of negative staining, poxvirus antigen detection
by immunodiffusion precipitation method in agarose
gel (AGID), virus isolation on chorion-allantoic mem-
brane (CAM) of chicken embryos and serologic assays
of hemagglutination inhibition (IHA), complement
xation (CF) and neutralization test (NT). The same
choice of diagnostic procedures at that time was carried
out by the laboratories for smallpox of CDC Atlanta,
which had a long experience in combating and eradica-
tion of smallpox in West Africa and Brazil [43, 44].
Skin lesions of 93 patients suspected of smallpox
were tested. Virus isolation on CAM chicken embryo
gave a high percentage of positive results (over 90%) as
well as the data about the nature of pox virus isolates
(variola or vaccinia). This method was very suitable for
the isolation of the virus from the blood in the early
days of the disease and especially valuable in fulminant
hemorrhagic form, when the patient did not have sig-
nicant skin lesions or death occurred quickly. The dis-
advantage of the method was the long duration of the
process (48 to 72 hours). The method of EM with nega-
tive staining proved to be a fast, highly sensitive and
accurate method, but it did not distinguish variola virus
from other poxviruses, particularly a vaccinia virus that
was used as vaccine in mass. AGID method for detec-
tion smallpox infection was also a very fast method, but
gave the lowest percentage of positive results (below
60%) and required a greater amount of material. There-
fore, the combination of EM and isolation in chicken
embryo CAM gave the best result in the virology diag-
nostics [44]. Serological methods are used for examina-
tion of 410 blood samples taken from 124 patients. It
was found that the signicant antibody titers (1:80 and
1: 160) were registered on the fourth day of the disease,
depending on the used methods, while the highest an-
tibody levels were recorded between the third and sev-
enth week of the onset of the disease, which was consis-
tent with results of other authors. The combination of
the listed diagnostic methods provided an opportunity
for retrograde diagnosis of smallpox, which was par-
ticularly important for nding sources of infection and
detection of subclinical infections. According to these
criteria it was determined that a pilgrim, Ibrahim H.,
was the index case in the Yugoslav outbreak. In addition
to the high positive ndings in the IHA, CF and NT, his
serum samples taken on March 16, 1972, were positive
in agar-gel precipitation with vaccinia and variola anti-
gen. The serum was positive in NT even in the dilution
1: 4.096 that was not registered in any other sera of
pilgrims. The obtained results with applied AGID test
using variola antigen were different from all published
data so far. Precipitins antibodies in our patients were
found from the rst day of illness up to 4 months. It
was also observed that patients with low values of vi-
rus neutralizing antibodies, and with the high values of
IHA, CF and AGID antibodies died of smallpox. Previ-
ous vaccination status had a visual impact on the time
of occurrence, as well as the value of antibodies that
inhibit haemagglutination, which x complement and
antibodies that neutralize the virus, but had no tangible
impact on results in the AGID reaction. Serology tests
had important role in discovering of unapparent infec-
tions, atypical smallpox cases and discovering source of
infection [2].
About 52% or 91 people were infected outside the
hospital, while 84 patients or 48% were infected in hos-
pitals. The exception to this percentage represents the
focal point in the province of Kosovo, where the outpa-
tient cases were twice as frequent. Otherwise, a com-
mon feature of postwar smallpox outbreaks in Europe
was that most of the patients were infected in hospitals
(index 2.4:1.6), while in the Yugoslav outbreak the situ-
ation was reverse (ratio 1.1: 2.0) [45]. Another specic
feature of the outbreak in the primary focus referred
to the fact that the focus of nosocomial infections in
this area, in addition to infective was a maternity ward,
although the exact way how virus entered the maternity
hospitals was not determined. The characteristic of the
outbreak was the great number of the affected infants,
14, or 8% of the total number of patients, which was the
largest number of the diseased children of this age in all
postwar smallpox outbreaks in Europe [41].
Vaccination in the rst foci started already on 16th
Figure 3
Dierent clinical manifestations of smallpox in Yugoslavia A: early hemorhagic variola with purpuric skin changes; B: ordinary form:
variola pustulosa conuens, 9th day of the illness; C: intrahospital infection; 4-months old baby died on the 14th day of the illness.
(Photo: V. Šuvaković, M.Kecmanović; source: Variola in Yugoslavia in 1972. Proceedings of the Yugoslav Symposium on Smallpox,
Primošten: 1972. [In Serbo-Croatian])

Lessons Learned in the Largest smaLLpox postwar outbreak in europe
Original art icl es and rev ie ws
593
March, one day after virology conrmation of smallpox
diagnosis. By the decision of the competent authority,
the Federal Epidemiologic Commission, vaccination
was later extended to the entire population of Yugo-
slavia, so that the measure covered a total of 18 mil-
lion people. Among vaccinated, were many pregnant
women. In 180 of them, the blood samples were taken
from mothers and from umbilical cord of their new-
borns, for detecting of IHA antibodies. In 95 of tested
pair sera higher values of vaccinia antibodies (from
2-16 times) were conrmed in new born children than
in mothers’ sera. The concentrations of IgA and IgM
immunoglobulins were higher in sera of mothers, while
IgG concentrations were higher in sera of newborns.
The isolation of vaccinia virus was tried from fetal tis-
sue of vaccinated mothers after abortion, but it was not
successful. Herpes virus was isolated from one tissue
sample. Among vaccinated women, we found the data
related to about 110 women vaccinated within rst 3
months of pregnancy and 300 women vaccinated after
3 months. As most women from the rst group had an
abortion, the destiny of newborns from 247 vaccinated
mothers was monitored. All children were healthy and
had normal constitution that is particularly important
[46-48].
The treatment by Marboran and vaccinia gamma
globulin, hyperimmune anti-variola serum was also
conducted during the outbreak [49]. All health institu-
tions in the country undertook adequate measures to
combat smallpox and stop bad effects of vaccination on
the entire population. Health surveillance of hot spots
in the province of Kosovo included the daily tour of the
population, temperature taking and checking of the
skin and the oral mucosa. In the search for contacts,
nearly 3000 surveys were carried out in Belgrade [50].
Contacts were taken care of in special quarantine in-
stitutions, but there were also quarantined individual
households and whole villages. Restrictions on popula-
tion movements from infected areas, the control of vac-
cination success and prohibition of public gatherings
were widely applied measures. As the primary immuni-
zation after contact was the main protective measure,
many people who subsequently came in contact with
smallpox patients did not get the disease. Yet primary
immunization after contact in the Yugoslav outbreak
had no greater impact in terms of reporting milder
clinical forms of the disease, which was contrary to the
then available literature data on the existence of clinical
modications after the primary vaccination in the rst
six days after risk contact [51]. But the persons with old
scars in most cases had a clearly modied clinical pic-
ture, regardless of whether a booster shot after contact
was successful or not [52].
ORGANIZATION OF THE YUGOSLAV HEALTH
SERVICE AND THE WHOLE SOCIETY IN THE
FIGHT AGAINST SMALLPOX
The health service in Yugoslavia was seriously pre-
pared for the case of importing smallpox virus within an
organization ghting quarantine diseases. The National
Reference Laboratory for smallpox was founded in 1966
at the Institute of Virology, Vaccine and Sera “Torlak”
in Belgrade, Serbia. Already in 1967 in the laboratory
was isolated and studied the Marburg virus imported
with shipment of 300 monkeys from Africa [53]. The
adequate equipment including electron microscope was
procured. Diagnostic procedures were also being test-
ed. The laboratory team consisted of two experts and
one medical technician responsible for virology work
and two experts for electron microscopy. Previously, the
experts for training visited the laboratories that were in-
volved in the diagnosis of this disease in England and
West Germany. The laboratory did not have a separate
building. It was located in the same place as a laboratory
for arboviruses and hemorrhagic fevers at the building
for the entire virology, including the production of viral
vaccines. The entire staff of virology sector was vacci-
nated against smallpox. Once or twice a year the labora-
tory tested the working methodology, restored positive
sera and control antigens and several times intervened
in cases of suspicion of smallpox being imported: an ill
sailor stranded in Split (Croatia) with suspicious erup-
tive skin changes, then a suspicious ill passenger from
the train from Ljubljana (Slovenia) to Belgrade (Serbia)
and a sick female coming from the area where variola
was registered. In all three cases the results on smallpox
were negative [2].
The rst smallpox case in our country in 1972 was
atypical; in addition, the majority of doctors had no
practical experience in the diagnosis of this disease,
since last smallpox case in Yugoslavia was registered in
1930. At the beginning, it was thought that the out-
break would have a local character, although the pos-
sibility of its spreading was not neglected, so the taken
measures were adequate to the situation. The contami-
nated areas were identied, and movement of people
there was prohibited. The plan of detection and isola-
tion of patients, as well as isolation of persons from con-
tacts was also established, in accordance with the inter-
national sanitary regulations and practices. The plan of
progressive vaccination of the entire population of the
Autonomy Province of Kosovo was also in line with the
potential spread of infection. Throughout the Republic
of Serbia and other republics of the Former Yugoslavia
at the same time began vaccination of all workers in
the medical sector, transport, catering industry, internal
affairs, and a wider range of the population, according
to the epidemiological indications. A plan of taking and
sending samples for laboratory testing was made ac-
cording to the possibilities of a competent laboratory
in Belgrade [54].
A state of emergency and the regime of 24 hours
duty had been introduced in the laboratory. The staff
was vaccinated again and a greater amount of equip-
ment for sample taking was acquired. During labora-
tory processing of samples, a special regime of per-
sonal and collective protection in the laboratory was
organized (suits, gowns, masks, goggles, gloves, boots,
bathing after work, permanent sterilization of working
rooms, strictly controlled transport and sterilization or
incineration of all infectious items and materials as well
as ceasing the contact of laboratory personnel with the
external environment). In this regard it is important to
mention that in the course of investigating and isolat-

Elizabeta Ristanovic, Ana Gligic, Sonja Atanasievska et al.
Original art icl es and rev ie ws
594
ing smallpox and during prior experience with Marburg
virus in the laboratory there were no cases of laboratory
infections. This fact indicates the good training and or-
ganization of work since then the biosafety standards as
we know them today were not in force [55].
Patient samples were taken by a well-trained team
that consisted of three experienced microbiologists
and epidemiologists who brought the samples to the
laboratory in specially prepared sets which contained
a list with a pen for a patient’s data, a plastic syringe
and blood tube, equipment for skin lesions sampling
(scalpel, lancet, tweezers, scissors), capillary tube for
taking uid from the vesicles and pustules, small bottles
for crust and slides for smear. The taken samples were
packed into impervious plastic bags and transported to
the laboratory by appropriate transport means (heli-
copter, plane, car) provided by the republic or federal
civil protection staff. During sample collection, the
staff wore appropriate suits for personal and collective
protection. Such procedure of professional sampling
and safe transport was important for the reliability of
laboratory tests and presented an adequate biosecurity
precaution. In cases of suspected smallpox, on the ba-
sis of clinical and epidemiological parameters, a nega-
tive answer obtained by one test did not exclude the
diagnosis, so it was necessary to wait for the results of
virus isolation (3 days), or sub-passaging (3-6 days).
The whole working process was documented in details.
The efciency and results of the laboratory were highly
rated by the WHO [55].
On the basis of acquired experience during the out-
break, it was clear that a specially equipped laboratory
center for working with dangerous pathogens was nec-
essary and that it should be located within a separate
building providing adequate conditions for sterilization
of the stale air and wastewater as well as the conditions
that would provide safety and security of laboratory
workers and the environment. The quarantine hospitals
or isolation units were required to be preferably placed
within these laboratory buildings in terms of major out-
breaks. The learned lesson related to the fact that it was
necessary to have a larger number of laboratory workers
acquainted with working procedures. Providing perma-
nent professional training abroad and adequate funding
to maintain the readiness of laboratories and scientic
research in this area were supposed to be a priority in
the planning allocations [54, 56]. These requirements
do not lose its relevance even nowadays, when the con-
ditions for working with dangerous pathogens such as
smallpox, are precisely dened.
The isolation of patients during the outbreak was
carried out in accordance with the principle of accom-
modation in special conditions (isolation in hospitals,
hotels, motels, spas) in situations where there were no
special facilities for the medical treatment of quaran-
tine diseases. Accommodation of persons who were in
contact with diseased patients was also performed ac-
cording to local conditions. Federal headquarters for
the ght against smallpox brought a precise decision on
the infected areas and the measures which had to be
implemented, on the movement of people, trafc etc.
Requirements for a sanitary blockade of the whole re-
gion of Province Kosovo were without any professional
justication, because since the outbreak was conrmed
there was no single case of transmission of disease from
its territory [57].
Requirements for vaccination of the entire Yugoslav
population at that time were not realistic because the
infected areas had priority and the amount of vaccines
was inadequate. However, the emergence of disease out
of affected areas in other cities of Serbia (Novi Sad, Ca-
cak, Belgrade, Sid) and Montenegro, which occurred
due to contacts with infected persons in the province
before the ofcial start of the outbreak as it is shown
in Figure 1, gave basis for the decision of the Federal
Executive Council of Yugoslavia to start gradual vac-
cination of the entire population and to take adequate
measures for importing of vaccines and hyperimmune
gamma-globulin [52].
The public was being informed all the time by the
competent professionals about the occurrence and
spreading of the disease and the measures that should
be taken from the rst days of the outbreak. Daily
newspapers continuously published the adequate bul-
letins. The WHO was informed about all facts and its
experts were invited in order to coordinate informing of
the world public [58].
The work and coordination of all management bodies
and state administrative bodies responsible for health
affairs were at a high level. The Federal Executive
Council followed the work and gave full support to the
Federal Headquarters for the ght against smallpox,
whose task was to collect and publish data about the
disease, coordinate the work of national and provin-
cial headquarters, acquire and distribute vaccines and
other means and to dene the other measures based
on the evaluation of the epidemiological situation. The
staffs in the republics and provinces were organs of the
Executive Councils or Municipal Assemblies. Medical
Service of the Yugoslav National Army (JNA) at full ca-
pacity was the integral part of the response of the health
service and society in general [59, 60].
CONCLUSIONS: VALUBLE AND ACCURATE
LESSONS LEARNED IN YUGOSLAV
OUTBREAK
Without neglecting the organizational, technical and
other weaknesses, and the lack of practical experience,
we can say that the Yugoslav health service quickly and
efciently carried out the task of combating the out-
break, which was large in the number of cases (175)
and geographical spread (25 foci) and caused a severe
disruption of life and economy in the country. The re-
markable commitment of health workers and other
social actors, as well as the disciplined behavior of the
population certainly signicantly contributed to this
success. The omissions were related to the undetected
rst smallpox case (inadequate medical and sanitary
control), late detection (only at the beginning of the
second wave, when there were already 11 patients in 6
foci) and inadequate implementation of prescribed vac-
cination of certain categories of the population which
facilitated the outbreak spreading (46% of the cases
were found among the people which should have been

Lessons Learned in the Largest smaLLpox postwar outbreak in europe
Original art icl es and rev ie ws
595
protected in the regular vaccination, and 8% among
staff of health institutions). The problem was that the
basic anti-outbreak measure - vaccination in focus was
not implemented quickly enough, as well as the absence
of a unique approach about the quarantine, control and
restriction of people’s movements to and from infected
areas, as well as within them.
The recorded lessons are related to the facts that it is
necessary to strengthen the capacities for rapid labora-
tory diagnosis, provide facilities for isolation and treat-
ment of the patients and develop uniform medical pro-
cedures in order to combat the contagious infectious
diseases effectively. It is also important to keep enhanc-
ing the capacities of the Institute for Health Protection
with the training of mobile teams for eld work, con-
stant reinforcement of sanitary-epidemiological service
and the sanitary inspection, with constant monitoring
of the situation in the world and achievements in the
eld of science. It was emphasized that special point
should be given to education and training of person-
nel, and health education of the population [61]. Key
contribution in relatively rapid outbreak suppression
had the integrated efforts of specially formed bodies
for ghting smallpox at all levels, good organization of
health services, support of the Yugoslav National Army
(JNA), as well as international solidarity and the WHO
support.
Considering all the above-mentioned, it is clear that
the variola virus is a dangerous pathogen, which has an
important place on the list of potential biological agents
due to its characteristics and possible consequences
that it might cause. In times of growing threats from
bioterrorism and possible misuse of science, all com-
petent bodies must pay special attention to the preven-
tion as well as the preparation of resources for medical
treatment in the event of the occurrence of the disease.
This include training of the personnel, and improving
diagnostic capabilities with respect to prescribed bio-
safety standards and other capacities required for medi-
cal care, as well as knowledge of the necessary tools for
crisis management and crisis communications.
Conict of interest statement
As the authors of the paper with full legal responsi-
bility we state that there does not exist any conict of
interest that could inappropriately bias conduct and
ndings of this study.
Received on 26 July 2016.
Accepted on 11 October 2016.
REFERENCES
1. Downie AW. Smallpox. In: Horsfall FI, Tamm I, Rivers
TM (Eds). Viral and rickettsial infections of man. Philadel-
phia: JB Lippincott Co; 1965.
2. Gligić A. Dynamics of antibody titers in patients suffering
from smallpox, vaccinated persons and experimentally in-
fected animals measured by different methods. Doctoral
(PhD) thesis. Medical Faculty, University of Belgrade;
1979. [In Serbian].
3. Dixon CW. Smallpox. London: Churchill; 1962.
4. Fenn E. Biological warfare in eighteenth-century
North America: Beyond Jeffery Amherst. J Am Hist
2000;86(4):1552-80. DOI: 10.2307/2567577
5. Mack TM. Smallpox in Europe from 1950-1971. J Infect
Dis 1972;125(2):125-61. DOI: 10.1093/infdis/125.2.161
6. WHO. Smallpox eradication. Geneva: WHO; 1968.
(Technical Report Series: No.393).
7. WHO. The global eradication of smallpox: nal report of the
Global Commission for the Certication of Smallpox Eradi-
cation. Geneva: WHO; 1980.
8. Fenner F. The Classication and nomenclature of vi-
ruses. Arch Virol 1976;51(1-2):141-9. DOI: 10.1007/
BF01317843
9. Hughes AL, Irausquin S, Friedman R. The evolutionary
biology of poxviruses. Infect Genet Evol 2010;10(1):50-9.
DOI:10.1016/j.meegid.2009.10.001
10. Gispen R, Brand-Saathof B. “White” poxviruses from
monkeys. Bull World Health Organ 1972;46(5):585-92.
11. Gispen R, Brand-Saathof B. Three specic antigens
produced in vaccinia, variola, and monkeypox infec-
tions. J Infect Dis 1974;129(3):289-95. DOI: 10.1093/
infdis/129.3.289
12. Foster SO, Brink FW, Hutchins DL, Pifer JM, Lourie B,
Moser CR, Cummings EC, Kuteyi OEK, Eke REA, Titus
JB, Smith EA, Hicks JW, Foega WH. Human monkey-
pox. Bull World Health Organ 1972;46(5):569-76.
13. Ladnyj ID, Ziegler P, Kima I. A human infection caused
by monkeypox virus in Basankusu territory, Demo-
cratic Republic of the Congo. Bull World Health Organ
1972;46(5):593-7.
14. Lourie B, Bingham PG, Evans HH, Foster SO, Nakano
JH, Herrmann KL. Human infection with monkeypox vi-
rus: laboratory investigation of six cases in West Africa.
Bull World Health Organ 1972;46(5):633-9.
15. Marennikova SS, Šeluhina EM, Mal’ceva NN, Čimiškjan
KL, Malcevič GR. Isolation and properties of the causal
agens of a new variola-like disease (monkeypox) in man.
Bull World Health Organ 1972;46(5):599-611.
16. Marennikova SS, Šeluhina EM, Mal’ceva NN, Ladnyj
ID. Poxviruses isolated from clinically ill and asymptom-
atically infected monkeys and a chinpanzee. Bull World
Health Organ 1972;46(5):613-20.
17. Cho CT, Werner HA. Monkeypox virus. Bacteriol Rev
1973;37(1):1-18.
18. Lourie B, Nakano JH, Kemp GE, Setzer HW. Isola-
tion of poxvirus from an African rodent. J Infect Dis
1975;13(6):677-81. DOI: 10.1093/infdis/132.6.677
19. Marennikova SS. The results of examinations of wildlife
monkeys for the presence of antibodies and viruses of the
pox group. Vopr Virusol 1975;3:321-6.
20. Kuljić-Kapulica N. Viruses as bioweapons. In: čobeljić
M, Kuljić-Kapulica N, Mirović V, Lako B, Bulajić N,
Ristanović E, Šuljagić V, Jovanović D, Lazić S. Biological
weapons. Belgrade: Military Publishing Center; 2003. [In
Serbian]
21. Creighton C. A history of epidemics in Britain. Cambridge:
The University Press; 1891.
22. Riedel S. Edward Jenner and the history of smallpox and
vaccination. Proc (Bayl Univ Med Cent) 2005;18(1):21-5.
23. Antić B, Udički S, Debeljković N. Mass vaccination − ba-
sic protective measure against smallpox. In: Krajinović S,
Perišić Z, Antić B, Jocić R, Prelić A (Eds). Smallpox out-
break in Belgrade. Proceedings of the Symposium. Belgrade:

Elizabeta Ristanovic, Ana Gligic, Sonja Atanasievska et al.
Original art icl es and rev ie ws
596
November 14-16, 1972. p. 41-6. [In Serbian]
24. Ristanovic E. Bioterrorism: prevention and response. Bel-
grade: Odbrana Media Center, University of Defence,
Military Book. 1932; 2015.
25. Henderson DA, Inglesby TV, Bartlett JG, Ascher MS,
Eitzen E, Jahrling PB, Hauer J, Layton M, McDade J,
Osterholm MT, O’Toole T, Parker G, Perl T, Russell PK,
Tonat K. Smallpox as a biological weapon: medical and
public health management. Working Group on Civilian
Biodefense. JAMA 1999;281(22):2127-37. DOI:10.1001/
jama.281.22.2127
26. Nishiura H, Schwehm M, Eichner M. Still pro-
tected against smallpox? Estimation of the dura-
tion of vaccine-induced immunity against smallpox.
Epidemiology 2006;17(5):576-81. DOI:10.1097/01.
ede.0000229196.41862.c2
27. Tucker JB. Scourge: the once and future threat of smallpox.
New York City: Grove Press; 2002.
28. Šuvaković U, Baljošević S, Obradović Z. Smallpox and
globalization or the rst achieved planetary goal. Vojnosa-
nit Pregl 2014;71(3):301-6. DOI 10.2298/VSP1403301S
29. Čobeljić M. Smallpox outbreak in Yugoslavia in 1972. Vo-
jnosanit Pregl 2004;61(5):569-71.
30. Borjanović S, Heneberg Đ, Lindner R, Stojković Lj,
Borđoški M, Gligić A, Maksimović S. Investigation of
the source of infection (index case) in smallpox outbreak
in Yugoslavia in 1972. In: Stojković Lj, Birtašević B,
Borjanović S, Litvinjenko S, Perišić Z, Šuvaković V (Eds).
Variola in Yugoslavia in 1972. Proceedings of the Yugoslav
symposium on smallpox. Primošten: November 21-24,
1972. p. 32-42. [In Serbo-Croatian]
31. Lane JM, Brandling-Bennett D, Francis DP, Gibson JJ,
Goldstein JA, Stenhous DH, Townsend TR. Smallpox in
Yugoslavia. Atlanta: Public Health Service Report; 1972.
Available from: www.nlm.nih.gov/nichsr/esmallpox/Small-
poxYugoslavia - EPI-72-91-2.pdf.
32. Litvinjenko S, Arsić B, Borjanović S. Epidemiologic as-
pects of smallpox epidemic in Yugoslavia in 1972. In:
Stojković Lj, Birtašević B, Borjanović S, Litvinjenko
S, Perišić Z, Šuvaković V (Eds). Variola in Yugoslavia in
1972. Proceedings of the Yugoslav symposium on smallpox.
Primošten: November 21-24, 1972. p.19-31. [In Serbo-
Croatian]
33. Litvinjenko S, Arsić B, Borjanović S. Epidemiological as-
pects of smallpox in Yugoslavia in 1972. Geneva: WHO;
1973. Available from: http://apps.who.int/iris/han-
dle/10665/67617.
34. Kecmanović M, Šuvaković V, Pavlović J, Mijušković P,
Mironicki Z, ćirić B, Frtunić P. Primary hemorrhagic form
of smallpox. In: Stojković Lj, Birtašević B, Borjanović S,
Litvinjenko S, Perišić Z, Šuvaković V (Eds). Variola in Yu-
goslavia in 1972. Proceedings of the Yugoslav symposium on
smallpox. Primošten: November 21-24, 1972. p. 147-54.
[In Serbo-Croatian]
35. Mitra AC, Chatterjee SN, Sarkar JK, Manji P, Das AK.
Viraemia in haemorrhagic and other forms of smallpox. J
Indian Med Assoc 1966;47(3):112-4.
36. Mitra AC, Sarkar JK, Mukherjee MK. Virus content of
smallpox scabs. Bull World Health Organ 1974;51(1):106-
7.
37. Šuvaković V, Kecmanovć M, Serhati A, Gazideda K. Flat
type of smallpox-presentation of 12 cases. In: Stojković
Lj, Birtašević B, Borjanović S, Litvinjenko S, Perišić Z,
Šuvaković V (Eds). Variola in Yugoslavia in 1972. Proceed-
ings of the Yugoslav symposium on smallpox. Primošten: No-
vember 21-24, 1972. p.155-63. [In Serbo-Croatian]
38. Kecmanović M, Šuvaković V. Transfusions of fresh blood
taken from persons vaccinated against smallpox and re-
convalescents in the treatment of severe forms of small-
pox. In: Stojković Lj, Birtašević B, Borjanović S, Litvin-
jenko S, Perišić Z, Šuvaković V (Eds). Variola in Yugoslavia
in 1972. Proceedings of the Yugoslav symposium on smallpox.
Primošten: November 21-24, 1972. p.197-206. [In Ser-
bo-Croatian]
39. Šuvaković V, Kecmanović M, Imami O, Gazideda K,
Serhati A. Modied type of smallpox (clinical presenta-
tion 53 cases. In: Stojković Lj, Birtašević B, Borjanović
S, Litvinjenko S, Perišić Z, Šuvaković V (Eds). Variola in
Yugoslavia in 1972. Proceedings of the Yugoslav symposium on
smallpox. Primošten: November 21-24, 1972. p. 164-72.
[In Serbo-Croatian]
40. Mijušković P, Bošković R, Gligić A. Variola sine exanthe-
mate. In: Stojković Lj, Birtašević B, Borjanović S, Litvin-
jenko S, Perišić Z, Šuvaković V (Eds). Variola in Yugoslavia
in 1972. Proceedings of the Yugoslav symposium on smallpox.
Primošten: November 21-24, 1972. p. 173-7. [In Serbo-
Croatian]
41. Kecmanović M, Šuvaković V, Huziak T, Serhati A,
Mijušković P, Gazideda K. Smallpox in newborns and in-
fants. In: Stojković Lj, Birtašević B, Borjanović S, Litvin-
jenko S, Perišić Z, Šuvaković V (Eds). Variola in Yugoslavia
in 1972. Proceedings of the Yugoslav symposium on smallpox.
Primošten: November 21-24, 1972. p. 178-87. [In Serbo-
Croatian]
42. Šuvakovic V, Kecmanović M, Pavlović J, Mijušković
P, Janković T. Clinical picture and experience in treat-
ment of smallpox in Yugoslavia in 1972. In: Stojković
Lj, Birtašević B, Borjanović S, Litvinjenko S, Perišić Z,
Šuvaković V (Eds). Variola in Yugoslavia in 1972. Proceed-
ings of the Yugoslav symposium on smallpox. Primošten: No-
vember 21-24, 1972. p. 95-101. [In Serbo-Croatian]
43. Bordjoški M, Stojković Lj, Gligić A, Bošković R, Stefanović
Ž, Pecić J, Petrović R. Laboratory diagnosis of smallpox
during epidemic in 1972. In: Stojković Lj, Birtašević B,
Borjanović S, Litvinjenko S, Perišić Z, Šuvaković V (Eds).
Variola in Yugoslavia in 1972. Proceedings of the Yugoslav
symposium on smallpox. Primošten: November 21-24,
1972. p. 215-27. [In Serbo-Croatian]
44. Gligić A, Bordjoški M, Bošković R, Pecić J, Lesić Lj,
Stojković Lj. Haeminhibiting antibodies in smallpox pa-
tients and vaccinated persons. In: Stojković Lj, Birtašević
B, Borjanović S, Litvinjenko S, Perišić Z, Šuvaković V
(Eds). Variola in Yugoslavia in 1972. Proceedings of the Yu-
goslav symposium on smallpox. Primošten: November 21-
24, 1972. p. 232-8. [In Serbo-Croatian]
45. Senker K, Kecmanovic M, Šuvakovic V. Intrahospital
smallpox infections in the Kosovo epidemic. In: Stojković
Lj, Birtašević B, Borjanović S, Litvinjenko S, Perišić Z,
Šuvaković V (Eds). Variola in Yugoslavia in 1972. Proceed-
ings of the Yugoslav symposium on smallpox. Primošten: No-
vember 21-24, 1972. p. 89-92. [In Serbo-Croatian]
46. Gligić A, Stojanović D, Stojković Lj, Stefanović Ž. Iso-
lation of vaccinia poxvirus from fetal tissue of pregnant
women vaccinated against smallpox. Jugosl Ginekol Opstet
1975;XV(6):329-34. [In Serbo-Croatian]
47. Gligić A, Stojković Lj, Kanjuh B, Mašić R, Dodić-Savić
M, Polak D, Djukić-Tadić M,Petronijević A. Comparison
of antibody levels for some viruses in the sera of mothers
and the sera of umbilical cord of their newborns. In: 3.
Congress of Microbiology of Yugoslavia. Proceedings. Bled:
October 5-9, 1976. p. 526-7. [In Serbo-Croatian]
48. Ilić V, Gligić A. Vaccination of pregnant women and new-
born infants against smallpox. In: Stojković Lj, Birtašević
B, Borjanović S, Litvinjenko S, Perišić Z, Šuvaković V
(Eds). Variola in Yugoslavia in 1972. Proceedings of the Yu-
goslav symposium on smallpox. Primošten: November 21-

Lessons Learned in the Largest smaLLpox postwar outbreak in europe
Original art icl es and rev ie ws
597
24, 1972. p. 372-6. [In Serbo-Croatian]
49. Janković T, Šuvaković V, Kecmanović M, Džibo
Dž, Lazarević P, Ristić S, Ranitović S, Banković A,
Radovanović Z. Experiences with marboran and vac-
cinia immune globulin in the smallpox epidemic in 1972.
In: Stojković Lj, Birtašević B, Borjanović S, Litvinjenko
S, Perišić Z, Šuvaković V (Eds). Variola in Yugoslavia in
1972. Proceedings of the Yugoslav symposium on smallpox.
Primošten: November 21-24, 1972. p. 275-9. [In Serbo-
Croatian]
50. Dovijanić P. Social-medical aspect in controlling smallpox
outbreak in Belgrade. In: Krajinović S, Perišić Z, Antić
B, Jocić R, Prelić A (Eds). Smallpox outbreak in Belgrade.
Proceedings of the symposium. Belgrade: November 14-16,
1972. p.13-25. [In Serbian]
51. Rao AR. Smallpox. Bombay: The Kothari Book Depot;
1972.
52. Ranitović S. Experience in mass vaccination-postvacinal
reactions and complications. In: Stojković Lj, Birtašević
B, Borjanović S, Litvinjenko S, Perišić Z, Šuvaković V
(Eds). Variola in Yugoslavia in 1972. Proceedings of the Yu-
goslav symposium on smallpox. Primošten: November 21-
24, 1972. p.267-74. [In Serbo-Croatian]
53. Stojković Lj, Bordjoški M, Gligić A, Stefanović Ž. Two
cases of Cercopithecus-monkey-associated haemorrhagic
fever. (Some data on etiology, epidemiology and epizo-
otology) In: Martin GA, Siegert R (Eds). Marburg virus
disease. Berlin-Heidelberg: Springer-Verlag;1971.
54. Jakovljević Dj, Vukmanović Č, Dovijanić P. Organization
of control of quarantine diseases in Yugoslavia based on
the last smallpox epidemic. In: Stojković Lj, Birtašević B,
Borjanović S, Litvinjenko S, Perišić Z, Šuvaković V (Eds).
Variola in Yugoslavia in 1972. Proceedings of the Yugoslav
symposium on smallpox. Primošten: November 21-24,
1972. p.253-9. [In Serbo-Croatian]
55. Stojković Lj, Bošković R, Bordjoški M. The organisation
of virological diagnostic service during smallpox epidem-
ic in Yugoslavia in 1972. In: Stojković Lj, Birtašević B,
Borjanović S, Litvinjenko S, Perišić Z, Šuvaković V (Eds).
Variola in Yugoslavia in 1972. Proceedings of the Yugoslav
symposium on smallpox. Primošten: November 21-24,
1972. p. 228-31. [In Serbo-Croatian]
56. Hrabar A, Weisz-Maleček R. Protection against smallpox
in the future. In: Stojković Lj, Birtašević B, Borjanović
S, Litvinjenko S, Perišić Z, Šuvaković V (Eds). Variola in
Yugoslavia in 1972. Proceedings of the Yugoslav symposium on
smallpox. Primošten: November 21-24, 1972. p. 307-12.
[In Serbo-Croatian]
57. Zdravković A, Andjelković N, Vujošević N, Vuković B,
Djurdjević D, Zonjić S, Lazarević P, Ljumović V, Otašević
Z, Radovanović Z, Ristić S, Tmušić K, ćirić Ž, Celina
D, Džibo Dž. Experiences with quarantines during
smallpox epidemic in Yugoslavia in 1972. In: Stojković
Lj, Birtašević B, Borjanović S, Litvinjenko S, Perišić Z,
Šuvaković V (Eds). Variola in Yugoslavia in 1972. Proceed-
ings of the Yugoslav symposium on smallpox. Primošten: No-
vember 21-24, 1972. p. 280-91. [In Serbo-Croatian]
58. Prelić A, Jocić R. The role and importance of the media
in combating the epidemic of smallpox in Belgrade. In:
Krajinović S, Perišić Z, Antić B, Jocić R, Prelić A (Eds).
Smallpox outbreak in Belgrade. Proceedings of the sympo-
sium. Belgrade: November 14-16, 1972. p. 356-60. [In
Serbian]
59. Kulenović H, Vračarić B, Arsić B. Epidemic of small-
pox and national defence. In: Stojković Lj, Birtašević B,
Borjanović S, Litvinjenko S, Perišić Z, Šuvaković V (Eds).
Variola in Yugoslavia in 1972. Proceedings of the Yugoslav
symposium on smallpox. Primošten: November 21-24,
1972. p. 260-5. [In Serbo-Croatian]
60. Vučić D, Ljubojević S. The work of City Assembly, mu-
nicipalities and services in combating the epidemic of
smallpox in Belgrade. In: Krajinović S, Perišić Z, Antić
B, Jocić R, Prelić A (Eds). Smallpox outbreak in Belgrade.
Proceedings of the symposium. Belgrade: November 14-16,
1972. p. 352-5. [In Serbian]
61. Ristanovic E. Infectious agents as a security challenge:
experience of typhus, variola and tularemia outbreaks in
Serbia. Bezbednost (Security). Gazzetta of Serbian Minis-
try of Interior 2015;LVII(2):5-20. DOI:10.5937/bezbed-
nost1502005R