Table 1.

Outbreaks providing evidence of aerial transmission of smallpox.

Year of Outbreak	Reference (s)	Country/City	Effect of the Outbreak	Findings in Relation to the Evidentiary Threshold	Main Results
1881	[8,36]	Fulham, United Kingdom	A total of 62 cases of smallpox among the residents of Fulham, of whom 32 lived within a one-mile radius of the hospital, and 23 cases had no known exposure to smallpox cases.	Conclusive	Cases occurred in the community in an area immediately around smallpox hospitals, without known contact with smallpox cases or explanatory smallpox cases in the surrounding community. As supportive evidence, the density of smallpox cases around Fulham hospital fell away proportionally to distance. In 1881, smallpox hospitals were located in densely populated urban areas. That year, WH Power, the medical inspector, showed through a series of disease maps that there was an increasing incidence of smallpox in the city with increasing proximity to the hospital. This effect was observed for at least 1 mile. He investigated the movement of hospital staff and patients and concluded that contact with patients or hospital personnel could not explain the observation. Further, the disease map patterns were not concentrated near main traffic units to and from the hospital highlighting a possible difference in the mechanism of transmission. Power was the first person to attempt to quantify this and coined the term “aerial convection”. A report in 1886, “Statistics of Smallpox Relative to the Operations of Hospitals in the Metropolis” confirmed that the same phenomenon was observed with other smallpox hospitals in London and in the provinces.
1901–1902	[8]	Orsett Union (Purfleet), Essex, United Kingdom	Hospital ships were used to treat smallpox in London. In 1901-2, during an epidemic, the hospital ships were moored in the Thames river near the Kentish shore. The Orsett Union on the other side of the river suffered an epidemic. The community closest (3/4 mile) to the river, Purfleet, had 110 households, of which 44 were infected with smallpox, without known contact with cases. The next nearest community to the ships was West Thurrock, which suffered the next largest epidemic.	Conclusive	Smallpox cases occurred in the nearby community onshore, closest to the hospital ship. Aerial convection was the only explanation, as there was no documented mixing of people from the ship with the onshore community. Some speculate there were clandestine visits by the crew to shore, but only one such instance was reported. Further supportive evidence is that the same phenomenon of epidemics in Purfleet following mooring of the hospital ships was observed in three consecutive epidemics.
1917	[37]	Salonika, Greece	The index case (an infected seaman) infected 1 person, who was half a mile away from the hospital in Greece where he was admitted, within the incubation period. As a result, there were 20 further cases and several deaths.	Conclusive	The index case was isolated in a tented camp half a mile away from any habitation. No other source of infection was identified and there were no other cases of smallpox in the nearby community. The likely mode of transmission was through aerial convection of virus particles. The flow conditions could also likely be more conducive for particulate travel due to the open ‘sandy’ terrain between cases with appropriate wind conditions.
1920	[38]	Glasgow	An epidemic in Glasgow occurred where people in the vicinity of the treating hospital became ill. A physician reported that a case of smallpox was admitted to the “smallpox compound of a hospital in a distant part of the city at a time when no other cases were occurring, and this was the only case of smallpox in that hospital.” After the incubation period, cases occurred in the scarlet fever ward, which overlooked the smallpox compound.	Partially conclusive	During this epidemic, subsequent cases occurred in the vicinity of the hospital which was treating smallpox cases. A clinician specifically recalls cases occurring in an overlooking ward across a spatial separation of much greater than 2 m from the smallpox ward (where a single smallpox patient was treated) after the incubation period.
1938	[37]	Gravesend, United Kingdom	Smallpox occurred in 6 cases in the UK, who had not been in contact with the index patient, and were located at a distance of ¼ to 1 ¾ miles from the index case. No other possible source of infection was identified.	Conclusive	The secondary cases lived at a distance ranging from a quarter of a mile to one and three-quarters of a mile from the hospital where a smallpox case was being treated, and no other source of infection was identified. There was no smallpox in the community at the time. The spread might have been an unusually dispersive type or associated with wind or other weather conditions.
1947	[39]	New York, USA	The index case travelled from Mexico to New York and was admitted to the ground floor of a hospital, with a subsequent outbreak consisting of 12 cases, 9 originating in New York City and 3 in Millbrook, N. Y. Patients who did not have contact with the index case, including one patient on the 7th floor, became infected.	Conclusive	The index case, a 47-year-old merchant who developed a rash and got admitted to Bellevue Hospital where he remained until March. He was transferred to Willard Parker Hospital, the communicable disease hospital in Manhattan. Among the patients who were in Willard Parker Hospital at the same time as the secondary cases were a male age 27 with mumps, and a 22 months old girl suffering from croup, a 2 and half-year-old boy suffering from whooping cough. All of them had been in the same building: the index case and the baby on the ground floor and the 47-year-old male on the seventh floor. Three men, aged 43, 57, and 60, all patients at Bellevue Hospital when the index case was there, got infected. A 4-year-old boy who got discharged on the day the index case died, developed rash later. He was the source of 3 other cases—a nun, aged 62, a 5-year-old boy, and a 2-year-old girl. There is a probability of airborne transmission of smallpox from the index case to 9 secondary cases residing in the same hospital building but spatially separated, including on different floors. There was no documented direct contact between the cases, with one secondary case six floors above the index case.
1947	[40]	Germany	The index case caused an outbreak of smallpox infection in 18 additional persons, both in the hospital and surrounding community.	Partially conclusive	The Army hospital in Wiesbaden, Germany received a patient with a presumptive diagnosis of smallpox. Although the patient was placed in strict isolation, there were secondary cases of smallpox in hospital patients and 7 people in the surrounding community, who did not have direct contact. The hospital cases were patients admitted in widely scattered parts of the hospital and had no known contact with the index case. There were no other smallpox cases in this area prior to the outbreak. Multiple possible means of transmission were postulated, including transfer by fomites, through laundry procedures and bed linen, contaminated blood collection equipment and aerial convection. The possibility of virus-laden dust moving in natural air currents was considered in explaining cases arising in the surrounding community and across large distances within the hospital.
1961	[41]	Monschau, Germany	The index patient was a 9-year-old girl admitted to a hospital in Germany. On that ward, 10 persons, none of whom had direct face-to-face contact with the source case, developed smallpox.	Conclusive	Infection appeared to have spread within the hospital through aerial transmission over a considerable distance along the common corridor and suggesting that air flowed from the isolation unit to the neighbouring ward.
1962	[42]	Simmerath, Northrhine-Westphalia, Germany	The index patient was a 6-year-old child admitted in the hospital who subsequently infected 10 more persons	Conclusive	At that time, a heavy wind was affecting the gable-end of the building, which has given rise to a draught in the corridor and infected people at the opposite end of the corridor. A wind tunnel effect was observed in this case, which was suggestive of aerial transmission.
1962	[43]	England, United Kingdom	There was a total of 62 infected cases, out of which no explanation of the source could be explained in 4 cases.	Conclusive	Four districts were involved: Woolwich Met. B., Hornchurch U.D. Rhondda M.B. and Penybont R.D. In the whole series of 62 cases, all but four could be attributed to clear direct sources of infection. In three of the four entirely unexplained cases, there was no evidence of contact or possible sources of infection under surveillance within 150 miles. Regarding the Penybont incident, there were three cases of smallpox, a few miles in Llantrisant not under surveillance, with no contact either direct or indirect with the Glanrhyd Mental Hospital, Bridgend, where a smallpox case was treated. This indicates a possible spread of infection from smallpox hospitals, presumably in the form of airborne infection.
1962	[26]	South Wales, United Kingdom	There were a total of 26 patients out of which 5 died.	Conclusive	This was related to a cluster of outbreaks which occurred in England in the same year [43]. The index case, a Pakistani male was infected with smallpox and was admitted to an isolation ward in a hospital in Cardiff on January 15th. He was ill with benign confluent smallpox and was discharged from hospital on March 6, 1962. In this outbreak, a woman died during childbirth of probable smallpox on February 9th. It was found out that this woman’s house was about half a mile from Penrhys Hospital, where the Pakistani patient from Cardiff was a patient. There were no other cases of smallpox in the region. The woman/s house was about half a mile from Penrhys Hospital, where the patient from Cardiff was admitted from January 16 until March 6, raising the possibility of aerial convection.
1962	[26]	South Wales, United Kingdom	20 smallpox cases and 12 deaths were reported in this outbreak	Partially conclusive	This is the continuation of the cluster of outbreaks in England [43]. A 75-year-old woman admitted in the Heddfan hospital ward for many months and probably died of smallpox infection. Many patients got infected in the Glanrhyd Hospital and this hospital is situated about half a mile from Heddfan Hospital, where the index patient was admitted. There were no other cases of smallpox in the region. There was no evidence of the transfer of virus via persons or items from inside Heddfan to the outside and there was no evidence of poor infection control by the staff members. This suggests the possibility of aerial conveyance of smallpox virus from the infected woman in the Glanrhyd hospital to the patients in the Heddfan hospital.
1963	[44,45,46,47]	Sweden	A 24-year-old sailor flew from Australia to Zurich with seven stops and contracted smallpox either on the aircraft or at an airport terminal. He eventually caused 24 secondary cases and 4 deaths.	Partially Conclusive	The index case had not been in contact with any known sources of infection. The index case was attributed to in-transit exposure either at the airport terminal or the aeroplane and this might be indicative of airborne transmission.
1967	[48]	Kuwait	A total of 41 cases and 19 deaths were recorded. Of 41 cases, at least 32 had a known close contact with unrecognized smallpox patients admitted to the hospitals.	Partially conclusive	The first case occurred in a Pakistani woman who arrived in Kuwait from Karachi by air and was admitted to the Fever hospital after she became ill. An outbreak of smallpox was, however, not suspected until a second-generation case was diagnosed. The first case caused 3 infections which subsequently caused an outbreak in the Fever hospital, Kuwait. In the third generation, there were a total of 10 cases and at least 8 of them had hospital contacts. However, for 2 of these patients, the source of infection could not be traced. One unrecognized third-generation case was transferred from the Fever Hospital to the Sabah Hospital which resulted in further hospital-associated cases in the Sabah Hospital, 25 cases occurred in the fourth generation and out of them, 4 cases did not have a definite history of contact with patients either in the Fever Hospital or in the Sabah Hospital. Three cases had previously been admitted to the Fever Hospital but had been discharged more than one incubation period previously. No family contact was involved in these four cases. The unknown source of infection in these cases may indicate aerial or airborne transmission of smallpox.
1970	[9,10,11,17,41,42,49]	Meschede, Germany	An index case in hospital infected other patients on different floors of the building, 21 cases of smallpox occurred, with 4 deaths.	Conclusive	A smoke test of the air movement in the building under similar atmospheric conditions strongly suggested aerial convection. The pattern of airflow coincided closely with the distribution of cases within the hospital. Further, through examining smoke escaping out of the window from the index patients’ room, this provided evidence of re-entry of air into the building from windows above where cases were present. The lower humidity conditions (reported in the paper) were also likely to have led to increased airborne dispersion.
1971	[50]	Aralsk, Kazakhstan (Soviet Union)	A crew member on the Lev Berg ship contracted smallpox during a voyage of the ship, which passed 15km from Vozrozhdeniye Island, a Soviet biological weapons testing site. A total of 11 secondary cases of smallpox resulted from this case.	Conclusive	The index case was a young fisheries expert who was on a biological research ship called the Lev Berg, sailing from Aralsk to multiple locations on the Aral Sea. She contracted smallpox at the end of July 1971. Official reports claim she got off the ship at several stops, but in an interview she denied it. Official policy was that only male crew were allowed to disembark. During the voyage, she spent a large amount of time outdoors on the deck, collecting samples. Dr Pyotr Burgasov, chief sanitary physician, said in an interview in the Russian press in 2001 that weaponized smallpox was being tested on Vozrozhdeniye Island (a Soviet biological weapons testing site) at the time. It seems likely this was the source of infection, with virus travelling at least 15 km to infect the index case. Whether this was the result of deliberate dispersal of the virus through smallpox “bomb” being tested, or accidental dispersion from the lab, is unknown, although Dr Burgasov is quoted as saying “The smallpox formulation—400 g of which was exploded on the island—“got her” and she became infected.”
1978	[27,28]	Birmingham, United Kingdom	A fatal case of smallpox occurred in a photographer working on the first floor of the medical school above the department of microbiology (where smallpox research was being done). She had never visited this laboratory. There were no other cases among people on the first floor.	Conclusive	Some of the smallpox laboratory work on the ground floor was carried out inside a safety cabinet, using unsafe procedures. The reports also suggest that “the opening and closing of the smallpox room door and the passage in and out by whoever was conducting work on the virus would have created the opportunity for any airborne virus to escape into the animal pox room”. The service ducts in the animal pox room and the smallpox room both had gaps which could allow the leakage of viruses. There also might have been a possibility of aerosol transmission from the ground floor to the first floor either through the air conditioning system or through an open window.