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PubMed1970

A study of New and Old World monkeys to determine the likelihood of a simian reservoir of smallpox.

The author presents data indicating that three species of New World monkeys (Cebus apella, Ateles paniscus, Lagothrix lagothricha) are not susceptible to Brazilian variola minor. Although the number of animals tested was not large, no experimental evidence was obtained to suggest that these species could form a non-human reservoir for smallpox in the Western Hemisphere. The results also indicate that Cercopithecus aethiops are not very susceptible to infection with either variola major or minor. Haemagglutination-inhibition tests of sera from monkeys from South America, Africa and the Philippines failed to reveal significant levels of poxvirus antibody. Previous studies have shown that Macaca irus, although susceptible to experimental infection with variola major, are not able to maintain the infection for more than a few generations of disease. The author concludes that there is as yet no clear experimental, serological or epidemiological evidence to support the hypothesis that smallpox can exist in wild simian populations.

Africa↗

PubMed1973

Virus excretion in smallpox. 1. Excretion in the throat, urine, and conjunctiva of patients.

Excretion of virus in the throat, urine, and conjunctiva of smallpox patients was studied daily for 2-3 weeks after the onset of fever. The virus titre in the throat and urine of haemorrhagic and confluent cases was higher than in discrete cases. The duration of virus excretion was also greater in confluent cases than in discrete cases. Conjunctival swabs from all 12 smallpox patients with conjunctivitis were positive for virus. The duration and titre of virus excretion in the throat, urine, and conjunctiva of patients were not related to their age or sex and did not depend on whether or not they had received a primary vaccination.

Adolescent↗

PubMed1973

Virus excretion in smallpox. 2. Excretion in the throats of household contacts.

Throat swabs of 34 of 328 family contacts of 52 smallpox cases, examined 4-8 days after the onset of the disease in the family, were positive for variola virus. The log titre of virus per swab ranged from 2 to 3.95. A higher proportion of unvaccinated than of vaccinated contacts excreted the virus. Only 4 of the virus-positive contacts developed clinical smallpox; this occurred 5-7 days after their swabs were examined. Excretion of virus in the throats of these contacts, a few of whom were in the incubation period of the disease, suggests the possibility that they could have spread the infection. This possibility, if kept in mind, may help in tracing the source of infection or in determining the incubation period in a few instances when difficulty is experienced.

Adolescent↗

PubMed1973

Evaluation of virological laboratory methods for smallpox diagnosis.

Between July 1966 and May 1972 the Vesicular Disease Laboratory, Center for Disease Control, Atlanta, Ga., USA, tested specimens from 849 suspected smallpox cases by at least 2 methods, electron microscopy and chick embryo chorioallantoic membrane (CAM) cultures. A smaller number of specimens was tested by each of 4 methods: electron microscopy, CAM culture, agar gel precipitation, and tissue culture. For specimens handled in the field the CAM culture method was less sensitive than electron microscopy because the adverse conditions often inactivated the virus. CAM cultures were valuable for identifying members of the poxvirus subgroups, however, particularly when supplemented by tissue culture. The agar gel precipitation test was the least sensitive but was of value in confirming the results of electron microscopy. The latter was highly effective for the diagnosis of varicella, but dependably identified only about half of the vaccinia infections; for vaccinia, the CAM technique was essential. The occurrence of human monkeypox cases in West Africa emphasized that the usual smallpox diagnostic methods were inadequate. More sophisticated tests, such as the rabbit dermal sensitivity test, are necessary for accurate diagnosis of these cases as monkeypox.

Adult↗

PubMed1973

Evaluation of the precipitation-in-gel reaction in the diagnosis of smallpox.

Specimens of vesicular or pustular fluids and of scabs from patients with smallpox as well as emulsions of variola-infected chorioallantoic membrane (CAM) were tested for virus titres and by the precipitation-in-gel (PIG) reaction. They were also tested after exposing them directly to sunlight and after keeping them at temperatures of -20 degrees C, 4 degrees C, and 25 degrees C. It was found that when extracts of fresh specimens were diluted to the point where the PIG reaction became negative there was still a titre of 10(4)-10(5) infectivity in the swab extracts and 10(3)-10(4) infectivity in the scab extracts. It was also found that the PIG reactions were all negative on specimens that were kept for 14 days at 25 degrees C, and that several were negative after only 7 days; the loss in infectivity titre, however, was only slight in all the specimens tested. It is concluded that the laboratory diagnosis of smallpox by virus inoculation of CAM is more reliable than by the PIG test.

Animals↗

PubMed1972

The effect of residual moisture in lyophilized smallpox vaccine on its stability at different temperatures.

In a study of the influence of residual moisture on the potency of freeze-dried smallpox vaccine, vaccine lots with moisture contents between 0.36% and 6.7% were used. These lots were stored at 4 degrees C, 24 degrees C, and 37 degrees C for up to 6 months, or were exposed to 100 degrees C for up to 3 hours, and were sampled at regular time intervals for assay. No loss in potency occurred at 4 degrees C where the moisture content was 4.8% or less. At 24 degrees C the critical moisture level was 2.5%, and at 37 degrees C it was 0.36%. At 100 degrees C the potency loss was more rapid and there were significant losses after 1 hour at a moisture level of 2.4% or more. A residual moisture content of less than 1% seems to be essential for satisfactory storage of freeze-dried smallpox vaccine.

Drug Stability↗

PubMed1970

The international standard for anti-smallpox serum.

At the request of the WHO Expert Committee on Biological Standardization, the National Institute for Medical Research, London, obtained 63 samples of convalescent human plasma from patients recovering from smallpox. The sera were pooled and distributed into ampoules and freeze-dried.The freeze-dried material was examined in 11 laboratories in 6 countries in an international collaborative assay during 1964 and 1965.The results from 10 laboratories were more or less consistent, but relative potencies in terms of the proposed international standard estimated by one of the laboratories were exceptionally low. Since this laboratory used a strain of virus different from that used in all the other laboratories, it was suspected that antigenic properties or avidity of the virus might have caused the divergence of results; this is being investigated.After considering the report of the international collaborative assay, the WHO Expert Committee on Biological Standardization established the material as the International Standard for Anti-Smallpox Serum, and a unitage was assigned so that 1 International Unit of activity was contained in 0.08416 mg, and each ampoule contains (on average) 1000 IU of activity.

Animals↗

PubMed1965

Smallpox frequency and severity in relation to A, B and O blood groups.

The results of routine determination of the blood group of smallpox patients admitted to a Madras hospital over a six-month period suggest that the distribution of blood groups among such patients and the severity of illness among patients of various blood groups do not support the hypothesis that susceptibility or resistance to this disease is associated in any direct way with the possession of A or B blood group substances or antibodies to them. The results reported and other considerations discussed make it improbable that the distribution of blood groups among the population of South India has been influenced by the endemic prevalence of smallpox in that part of the world.

Blood Group Antigens↗

PubMed1979

[Plexus paresis and smallpox vaccination (author's transl)].

Paresis of the left side upper plexus brachialis is diagnosed to a boy of 2;8 years. The trouble appeared after a smallpox vaccination, which had been carried out successfully. There are no symptoms of CNS-disturbance. serumneuritis and virogenic radiculatis are discussed as pathogenic variants. Although postvaccinal peripheral nervous lesions very seldom occur, it does seem possible that the ailment in question could be a consequence of the smallpox vaccination.

Brachial Plexus↗

PubMed1977

[Study of allergic reactions in the body after experimental smallpox vaccination].

Experiments on guinea pigs demonstrated a mixed cellular-humoral character of allergy in smallpox vaccination. The ratio of cellular and humoral components depended on the site of the vaccina application. Skin manifestations in smallpox vaccination (hyperemia, infiltration, papula) were due to the multiplication of the virus proper, increased sensitivity of the surrounding tissues to the live vibrio, and specific immunological reconstruction. The skin of the sensitized animal after the anaphylactic shock in response to the intracardiac injection of the challenging dose of the vaccine virus acquired areactivity to its subsequent application.

Anaphylaxis↗

PubMed1978

Remission of chronic lymphocytic leukemia after smallpox vaccination.

A 78-year-old man with untreated chronic lymphocytic leukemia (CLL) was revaccinated for smallpox. A severe local reaction and generalized rash followed that responded to treatment with vaccinia immune human globulin. After recovery, the leukocyte count fell to normal and all evidence of CLL disappeared. He remains in complete remission three years after smallpox vaccination.

Aged↗

PubMed1983

Stimulation of cynomolgus peripheral blood lymphocytes with tetanus toxoid and smallpox vaccine.

The cynomolgus monkey was studied as an animal model to investigate the cell-mediated immunity induced by vaccines. Optimal conditions are described to isolate peripheral blood lymphocytes. Lymphocyte transformation tests were performed with tetanus toxoid and smallpox vaccine. Antigen-specific lymphocyte transformations with smallpox vaccine could only be demonstrated when lymphocytes were obtained from vaccinated monkeys. Tetanus toxoid appeared to be a weak antigen. However, after adsorption of the toxoid to aluminum phosphate, a significant antigen-specific lymphocyte transformation was observed.

Adsorption↗

PubMed1981

[Humoral and cellular immune responses to brain tissue in animals immunized with ADPT and smallpox vaccine].

Experiments on guinea-pigs showed that 3 subcutaneous injections of adsorbed DPT vaccine resulted (on days 7-14 of the experiment) in the accumulation of cells, sensitized to brain extract, in the lymphoid tissue. The production of circulating anticerebral autoantibodies occurred, as revealed by the indirect immunofluorescent method, during the whole time of the experiment (35 days). On days 28-35 of the experiment cellular immune reaction to autologous erythrocytes was detected in the peripheral blood of the immunized animals. The intracardiac injection of smallpox vaccine to the animals resulted in the appearance of lymphoid cells, sensitized to brain extract, on days 3-7 of the experiment, as well as in the appearance of anticerebral autoantibodies, detected by immunofluorescence, which circulated in the blood for 28 days. Cellular immune reaction to autologous erythrocytes in the peripheral blood of the guinea-pigs immunized with smallpox vaccine was registered on days 3-28 of the experiment.

Animals↗

PubMed1978

Urban hospital and rural village smallpox in Bangladesh.

Smallpox mortality at Dacca, Bangladesh Infectious Diseases Hospital during 1972 and 1973 was 46 per cent. To determine if this was the actual rate within the population, data were compared to those collected from village populations in Noakhali District. Age/sex adjusted smallpox mortality for the rural population was 23 per 100 cases as compared to 52 per 100 for the hospital population. Analysis of the difference identified a selection bias of the hospital for severe disease.

Adolescent↗

PubMedDate not supplied

[Moscow Research Institute of Viral Preparations tissue-culture smallpox vaccine in a coded control experiments of adult revaccination by scarification].

Comparative studies of tissue culture and dermal smallpox vaccines were carried out in a strictly controlled coded trial by revaccination of adults by scarification. Two lots of tissue culture and one lot of dermal vaccines with a similar infectious titer (8.0 lg PFU/ml) were used. All the lots tested "took" in 100%. In the group revaccinated with tissue culture vaccine seroconversion was observed in 94.2 +/- 2.8%--95.0 +/- 2.8%, with a 4.6 +/- 5.3-fold rise in geometric mean antibody titer; the dermal smallpox vaccine produced seroconversion in 85.7 +/- 4.4% with 4.3-fold rise in geometric mean antibody titer. Febrile reactions in revaccines with the tissue culture vaccine were observed in 23.1%--26.1% which did not exceed this parameter in the group revaccinated with the dermal vaccine (25.2%); in all the groups febrile ractions were of mild degree (37.1 degrees--38 degrees C). Local reactions of the type of confluent erythema were observed 1.8--5.3-fold more frequently among those revaccinated with the dermal vaccine than among those revaccinated with the tissue culture vaccine. Thus, the tissue culture vaccine used epicutaneously was as good as the dermal one by the take rate and antigenic activity, but had less remarked reactogenic properties which allows to recommend it for public health practice.

Academies and Institutes↗

PubMed1993

The dynamics of smallpox epidemics in Britain, 1550-1800.

Time-series analysis, a valuable tool in studying population dynamics, has been used to determine the periodicity of smallpox epidemics during the seventeenth and eighteenth centuries in two contrasting representative situations: 1) London, a large city where smallpox was endemic, and 2) Penrith, a small rural town. The interepidemic period was found to be two years in London and five years in Penrith. Equations governing the dynamics of epidemics predict 1) a two-year periodicity and 2) that oscillatory epidemics die out quickly. It is suggested that epidemics were maintained by a periodic variation in susceptibility linked either to a five-year cycle of malnutrition or to an annual cycle. Computer modeling shows how the very different patterns of epidemics are related to population size and to the magnitude of the oscillation in susceptibility.

Disease Outbreaks↗

PubMed1964

RESPONSE OF VOLTA CHILDREN TO JET INOCULATION OF COMBINED LIVE MEASLES, SMALLPOX AND YELLOW FEVER VACCINES.

An earlier study established that Upper Volta children respond to vaccination with the Enders live attenuated measles strain in the same general fashion as do children in the USA. The present report describes a second pilot project carried out in Ouagadougou, Upper Volta. During this investigation various mixtures of live measles, smallpox and 17D yellow fever vaccines were introduced into susceptible infants by jet injection. Combining the attenuated virus vaccines did not alter or accentuate the characteristic clinical reactions elicited by the individual components, nor was there evidence of significant immunological interference. From this experience it is concluded that combined vaccination with these agents may be safely and effectively employed in larger programmes as the need dictates.

Africa↗

PubMed2001

Human monkeypox and smallpox viruses: genomic comparison.

Monkeypox virus (MPV) causes a human disease which resembles smallpox but with a lower person-to-person transmission rate. To determine the genetic relationship between the orthopoxviruses causing these two diseases, we sequenced the 197-kb genome of MPV isolated from a patient during a large human monkeypox outbreak in Zaire in 1996. The nucleotide sequence within the central region of the MPV genome, which encodes essential enzymes and structural proteins, was 96.3% identical with that of variola (smallpox) virus (VAR). In contrast, there were considerable differences between MPV and VAR in the regions encoding virulence and host-range factors near the ends of the genome. Our data indicate that MPV is not the direct ancestor of VAR and is unlikely to naturally acquire all properties of VAR.

Amino Acid Sequence↗