James Martin Center for Nonproliferation Studies
Combating the spread of weapons of mass destruction with training & analysis

CNS Occasional Papers: #9 Commentaries

Richard Clover, M.D.
Dean of the School of Public Health
University of Louisville
Louisville KY 40292

The epidemiological analysis of the 1971 smallpox outbreak in Aralsk, Kazakhstan by Alan Zelicoff raises many interesting, troubling, and unanswered questions about the biological weapons program of the former Soviet Union. Clearly this warrants further investigation to determine the real source of the smallpox outbreak at Aralsk. The analogy to Sverdlovsk is great--official reports that deny any association with a biological weapons program and facts that come out years later pointing to Soviet biological weapons activities as having been responsible for a disease outbreak. It seems unquestionable that the Soviet biological warfare program developed the smallpox virus as a biological weapon. Ken Alibek has reported on that program and claimed that it had been scaled to an enormous production capacity. Reports of testing at Vozrozhdeniye Island are consistent with the fact that the Soviet Union had an extensive biological weapons program that must have involved outdoor testing of biological weapons agents. One sign of such programs and testing would be unusual disease outbreaks--such as the 1971 smallpox outbreak in Aralsk.

With regard to the epidemiological analysis by Zelicoff, the data are consistent with exposure of patient 1 between July 29 and 31, 1971. The manifestation of disease in patient 1 was more likely about August 11 rather than the official report of August 6 as this would fit with the occurrence of smallpox onset in patient 2 on August 27; i.e., it would match the approximate 11-15 day incubation period for smallpox and would be consistent with the incubation period of about 2 weeks seen for subsequent patients. If patient 1 had developed disease on August 6 as in the official report there would have been a 21 day lapse from the exposure of patient 2 to the onset of disease in patient 2 and exposure of patient 1 would have had to have been during the portion of the cruise while the ship on which Patient 1 worked was at sea and not near land. While an extended incubation period is possible, as is the possibility that patient 2 was not exposed until several days after onset of disease in patient 1, this scenario is less likely. Hence, exposure of patient 1 seems to have occurred during the period when members of the ship's crew went ashore in Uyaly on July 29 and again in Komsomolsk-on-Ustyurt on July 31. During this period the ship also passed near Vozrozhdeniye Island on July 30, raising the specter that exposure occurred while patient 1 was on deck during the time the ship passed the island. Knowledge of the wind and weather conditions, as well as how close the ship really came to Vozrozhdeniye Island, could help resolve the likelihood of this scenario. It is difficult 30 years later to resolve the differences between the recollections of patient 1 and the official record regarding whether she went onshore or remained on the ship. More important would be to clarify what activities were ongoing on Vozrozhdeniye Island during that period. That is likely the only way the actual source of exposure will be resolved, as was the case for Sverdlovsk when only official admissions finally exposed the accidental release of anthrax spores from a biological weapons facility.

Regardless of what occurred in late July 1971 in the Aral Sea, the knowledge of the Soviet program, the fear that Iraq, North Korea and, perhaps, other nations possess clandestine stocks of smallpox virus, and given the deadly and contagious nature of smallpox, have catapulted smallpox virus to the top of the biological agents threat list. It has led to the decision by the United States government to stockpile sufficient smallpox vaccine (vaccinia produced in human cell culture) to vaccinate all Americans and the decision by the Advisory Committee on Immunization Practices to recommend that the primary strategy of "ring vaccination" be used in the event of a smallpox outbreak in the United States and that a limited number of health care workers be pre-vaccinated. In the case of a terrorist attack with smallpox, "ring vaccination" would likely extend throughout the community that might have been exposed, i.e., a broad definition of "contacts" would be used in determining who would be vaccinated. Such practice of "ring vaccination" is consistent with the procedure that followed the 1971 outbreak of smallpox in Aralsk, as well as the practice employed in Yugoslavia in 1972. In both cases, restricted movement of people and mass vaccination of potential contacts was used to contain the outbreak and to prevent epidemic spread. Regardless of whether the index case in Aralsk contracted smallpox from an infected individual while onshore or, as suggested by Zelicoff, from an air-release of smallpox virus in a biological weapons test on Vozrozhdeniye Island, the practice of extensive vaccination and isolation was successful in halting the epidemic spread of smallpox in 1971 in Aralsk.

The reasons for the somewhat unusual nature of the Aralsk smallpox outbreak, namely the occurrence in some vaccinated individuals and the high incidence of the deadly hemorrhagic form of the disease, remain unclear. The Soviet vaccination program may have suffered from quality control issues, either with the vaccine or its administration. The data in the report on the smallpox vaccination program indicated that there had been a low immunity--only 31.6% of the residents of Aralsk had been vaccinated. Among first and second grade schoolchildren, 24% had not been vaccinated, and 31.6% showed a primary vaccination reaction when they were vaccinated again following the Aralsk outbreak, indicating a low immunity even among those who had been previously vaccinated. Many of the children who had contacted patient 2 had no vaccination scars even though their medical records indicated that they had been vaccinated against smallpox. Thus, although several of the individuals who contracted smallpox had supposedly received vaccinations, there is evidence that the many receiving the vaccine did not develop immunity. Hence, it seems more likely that there was inadequate immunity in those exposed than the possibility that the strain of smallpox virus was immune-resistant. This viewpoint that proper vaccination would afford protection against the strain of smallpox virus that caused the Aralsk outbreak, even if it came from the Soviet biological weapons program, is supported by the fact that mass vaccination was used to contain the outbreak.

With regard to the high prevalence of the hemorrhagic form smallpox, as Dr. Zelicoff notes, it is not clear whether host factors or the nature of the virus are primarily responsible for causing this form of the disease. Whether or not the smallpox virus came from a natural source as concluded in the official reports or from a biological weapons test on Vozrozhdeniye Island, as Dr. Zelicoff suggests, the virus may well have been especially virulent--although not especially infective. Any suggestion that the virus was genetically engineered, however, is incorrect as the outbreak occurred a decade before the era of recombinant DNA technology began. The strain, though, could have been selected for its virulence from prior natural outbreaks. The assumption of any biodefense program must be that the strain used for a smallpox attack would have a high mortality rate and that an epidemic outbreak from such an attack could cause mass casualties in a susceptible population, such as now exists in the United States. The Advisory Committee on Immunization Practices clearly took this into account when it modified its position to recommend vaccination for some health care workers. The committee held that the basic strategy of vaccinating individuals who may have been exposed after an outbreak remained the best approach based upon prior historical and scientific evidence--including the 1972 outbreak in Yugoslavia. The results of vaccination following the 1971 outbreak in Aralsk would only strengthen the conclusion of the advisory committee; i.e., that a "ring vaccination" strategy that allows for extension to broader vaccination administration (e.g., community-based, target population based vaccination) can be used to stop transmission rapidly following confirmation of a smallpox case. Thus, the epidemiological analysis of the Aralsk outbreak would not alter the claim that a "ring vaccination" strategy can limit the smallpox epidemic and should be used as a primary response strategy.

Neither the 1971 Aralsk outbreak of smallpox nor the Advisory Committee on Immunization Practices' recommendation deal with responding to an imminent attack with smallpox (as determined by intelligence sources) nor of the possibility that recombinant DNA technology could be used to make a more virulent form of the virus and even one that was resistant to the immune response. Should the threat of a smallpox attack with a naturally occurring strain of smallpox virus be deemed very high, it would be prudent to consider a wider vaccination program using the stockpiled vaccine. This would have to be done in a manner that would minimize adverse reactions. The Advisory Committee on Immunization Practices likely will need to consider recommendations for that scenario. In the event that a strain of smallpox virus proves to be able to overcome immunity, a separate containment strategy will be necessary. A new generation vaccine might help if it provided multiple epitopes so as to make engineering a resistant virus more difficult. The greater value of a new vaccine may be reducing the rate of adverse reactions.

But, as shown by the IL-4 mousepox experiments in Australia, a new vaccine may not be able to totally eliminate the possibility of engineering a smallpox virus that could totally circumvent the immune system. In such an event, isolation procedures may be the only way of stopping the epidemic spread of smallpox. Joshua Epstein has been modeling such a strategy and it appears that isolation can be as effective as "ring vaccination" in interrupting a smallpox epidemic. Dr. Zelicoff suggests that such isolation may have been an important factor in halting the spread of smallpox in the 1971 Aralsk outbreak.

In conclusion, the analysis of the 1971 Aralsk smallpox outbreak suggests a possibility that the source was an outdoor bioweapons experiment on Vozrozhdeniye Island and that patient 1 (the index case) contracted the disease while on the deck of a ship passing the island on July 30. The outbreak of disease seems to have caused a higher than expected rate of hemorrhagic smallpox. This may indicate that the virus, regardless of its source, had a high virulence. Evidence that the virus may have circumvented immunity induced by vaccination is speculative--a more likely probability is that the vaccination program in the Soviet Union was inefficient and that even vaccinated individuals who were exposed may have had a marginal immune response. Thus, while a continuing investigation as to the nature of the Soviet biological weapons program is warranted, with particular interest in revealing activities on Vozrozhdeniye Island and any smallpox related tests, there is no reason based upon the analyses presented in Occasional Paper # 9 to suggest altering the recommendation of the Advisory Committee on Immunization Practices smallpox for the U.S. vaccination strategy nor of the NIAID Advisory Committee recommendation for a research and development program to develop a new and safer smallpox vaccine.

Return to Occasional Paper #9.