For centuries it was assumed that infectious diseases were spread primarily by airborne miasms. Contemporary concepts of disease transmission include direct contact spread, indirect contact spread (primarily via hands or fomites), endogenous infection, droplet contact spread, airborne spread (droplet nuclei, skin squames and fungal spores), common vehicle spread and vector spread. Prevention of transmission of viral infection in day care and the home requires a firm understanding of how pathogens are transmitted. Three viral pathogens provide insight into current understanding of the transmission of infectious diseases, as well as remaining knowledge gaps. Respiratory syncytial virus appears to be spread primarily by hands contaminated by contact with contaminated respiratory secretions. There is still considerably controversy regarding the principal mode of transmission for rhinovirus. Some investigators believe that contamination of the hands followed by inoculation of the eyes or nose is of paramount importance, whereas others favor transmission by droplets and droplet nuclei. The controversy regarding transmission of influenza centers on whether or not this virus can be spread by airborne droplet nuclei. Experiments in animals and natural experiments in humans provide considerable support for airborne spread.
Rational infection control measures require a clear understanding of how pathogens are transmitted. Research performed during this century has radically transformed our knowledge of the epidemiology and transmission of microorganisms. We now recognize that transmission often is complex and multifactorial, whereas scientists and laymen in earlier centuries were fixated on the dangers of airborne spread. They were convinced that disease was transmitted by miasms, clouds of noxious vapors emanating from sewage and rotting organic matter. Accordingly those brave souls who cared for victims of the plague wore hoods with long beaks into which they placed herbs to mask the odors of putrefying flesh and, ostensibly, to protect them from contagion. The massive cholera epidemic in London in 1849 provided a particularly good test of the role of miasms in spreading disease. William Farr, a noted epidemiologist who campaigned side by side with Florence Nightingale for improved hygiene in hospitals, believed that miasms from the polluted Thames River were responsible for the outbreak. He demonstrated a remarkably close inverse correlation between elevation of habitation above the Thames and risk of disease. However compelling these data may have seemed at the time, John Snow proved that cholera was spread by contaminated water, not putrid air, when he halted the epidemic by removing the handle from the Broad Street water pump. Belief in the importance of miasms in transmitting infection succumbed slowly to advances in science and epidemiology. Even at the turn of the century, yellow fever and malaria (literally, from the Italian for “bad air”) among workers digging the Panama Canal was attributed to miasms rising from the muck in the canal bed.
Just as air polluted with miasms was felt to be important in contagion, so was clean air believed to be critical in preventing and curing infectious diseases. Fresh air and rest were the mainstays of tuberculosis therapy in the preantimicrobial era. In the early part of this century, hospital construction featured pavilions with ready access to the outdoors. At Children’s Hospital in Boston, for example, children routinely were wheeled out onto sun porches in their individual carts even on the coldest days so that they would have the benefit of fresh air (Fig. 1). In summer children were placed on a ship (the original Boston Floating Hospital, from which the New England Medical Center originated) and sent out to Boston harbor so that they would not be exposed to the foul air that enveloped the city. This boat plied the waters of Boston Harbor until it burned in 1927. A similar hospital ship operated out of Southport in Manhattan.
The work of Wells and his protégé Riley at Johns Hopkins Hospital in Baltimore radically transformed our understanding of airborne transmission of infection. 1 They demonstrated that tiny droplet nuclei produced by talking, coughing or sneezing could carry microorganisms over considerable distances. These droplet nuclei were just a few micrometers in size and could easily waft on air currents and evade upper respiratory tract host defenses. Their classic studies demonstrated clearly that tuberculosis is transmitted primarily via airborne droplet nuclei. Meanwhile understanding of other mechanisms of transmission was expanding quickly. Building on the work of Semmelweiss, epidemiologists explored the role of transmission of microorganisms via the hands. The role of contaminated food, water and fomites played was clarified. It was recognized the large respiratory droplets were important in the spread of some pathogens, such as meningococci.
CURRENT UNDERSTANDING OF TRANSMISSION OF MICROORGANISMS
Widely recognized mechanisms of transmission can be classified as follows: direct contact spread (including bloodborne transmission); contact spread (including fecal-oral transmission); endogenous infection (autoinfection); droplet contact spread; airborne spread (droplet nuclei, skin squames or “rafts,” fungal spores); common vehicle (common source) spread; vector spread.
Direct contact spread results from direct contact with an infected individual, as might occur when one sibling spreads streptococcal impetigo to another during play. Indirect contact involves contamination of an intermediate object. Most often this “object” is the hands. For example a mother who puts a dressing on her child’s staphylococcal boil and does not wash her hands might transmit staphylococci to another child during diapering. Or a father who changes the diaper of a child with Shigella gastroenteritis might transmit this pathogen to the rest of the family if he prepares lunch without washing his hands. Environmental objects, or fomites, may also be involved in indirect contact spread of infection. For example cytomegalovirus can be spread in day care if a child drools on a toy and another child snatches it away and puts it in his mouth. Campylobacter may be transmitted if a chopping block used to cut up contaminated raw chicken is subsequently used to prepare salad. Droplet contact spread occurs over distances of no more than 3 or 4 feet because these relatively large droplets quickly settle out of the air. Large respiratory droplets can harbor pathogens such as Bordetella pertussis, group A Streptococcus and Neisseria meningitidis. Endogenous infection is caused by an individual’s own microbial flora. For example if a father chokes on a piece of purloined Halloween candy and aspirates oral secretions into his lungs, he may develop pneumonia from his own oral flora. Airborne spread via droplet nuclei already has been explained. Airborne transmission can also occur rarely via skin squames, or flakes, shed from the skin of individuals heavily colonized with pathogens such as staphylococci. British investigators use the more picturesque term, “rafts,” which provides a vivid picture of how skin squames ferry microorganisms through the air. Fungal pathogens, such as coccidioidomycosis, can be transmitted over amazingly long distances via fungal spores stirred up by the wind. Fungal spores of pathogens such as Aspergillus pose an airborne threat to immunocompromised patients. Common vehicle transmission occurs when many people are exposed to a contaminated item. For example common vehicle transmission might occur among children who consume improperly processed apple cider contaminated with Escherichia coli O157. Finally vector spread refers to transmission via insects. This is rarely a problem in the home, but it is worth noting that the feet of flies, ants and other insects can become contaminated with pathogens in the environment and very rarely can spread infection to humans. Of course mosquitoes can transmit malaria, yellow fever, dengue and West Nile encephalitis, and ticks carry Lyme disease and Rocky Mountain spotted fever, to name just a few of the legion of vector-borne infections.
Three viral respiratory pathogens, respiratory syncytial virus, rhinovirus and influenza virus, that are commonly encountered in the home provide excellent illustrations of the basic principles of transmission of microorganisms. They also demonstrate that significant gaps persist in our understanding of the epidemiology of common viral pathogens.
RESPIRATORY SYNCYTIAL VIRUS (RSV)
RSV is the major cause of viral respiratory infection in young children worldwide. Attendance in day care virtually guarantees that an infant will be infected with RSV within the first year or two of life. Bronchiolitis is the major clinical manifestation, resulting in hospitalization of 0.5 to 1.0% of infected infants.
Although it would seem logical that a respiratory virus would be spread primarily by droplets or droplet nuclei, this does not appear to be the case with RSV. In a classic study Hall et al. 2 in Rochester demonstrated that direct and indirect contact transmission were far more important. Highly symptomatic infants who were producing abundant secretions were placed in cribs. Three categories of nurse volunteers were brought into the room. “Cuddlers” played with the infant, changed his or her diaper and performed other routine care. “Touchers” did not touch the baby but had extensive contact with the child’s environment, which had been heavily contaminated with secretions. “Sitters” sat next to the crib reading a book for 3 h but did not touch anything in the immediate environment. Five of the 7 cuddlers, 4 of 10 touchers and none of 14 sitters developed RSV infection. In retrospect the reasons for these striking findings are clear. Infants with RSV excrete prodigious concentrations of virus in their nasal secretions for a number of days. 3 RSV survives quite well on inanimate objects, more than 5 h on impervious surfaces such as a countertop, providing caregivers with abundant opportunities to contaminate their hands (Fig. 2). 4 Once the hands are contaminated, virus can be spread by indirect contact to other children. In addition if caregivers touch their eyes or nose before washing their hands, they can infect themselves, with attack rates during the annual fall/winter RSV season approaching 50%. 5 RSV in adults often is manifested as a severe cold, and sick caregivers subsequently can infect others by direct contact.
Studies of nosocomial RSV infection conducted at Children’s Hospital provide additional support for the importance of indirect contact spread. 6 Surreptitious surveillance of nurses’ compliance with gown and glove precautions demonstrated complete adherence in only 38.5% of encounters with symptomatic infants. After open surveillance was initiated, compliance reached 95% and remained at that level even after open surveillance was discontinued. Improved compliance resulted in a dramatic decline in the rate of nosocomial RSV infection, from 6.4 to 3.1 cases per 1000 patient days. Although the attack rate increased as the number of patients with community-acquired RSV infection on the ward increased, the slope of this relationship decreased dramatically (Fig. 3). The impact of strict compliance with gown and glove precautions was most impressive during the height of the seasonal epidemic in the community. Thus barrier precautions are an extremely effective deterrent to the transmission of RSV, provided that they are observed on contact with both the infected infant and its contaminated environment. Presumably gloving was more important than gowning because it is difficult to imagine extensive indirect contact transmission via clothing.
It is entirely reasonable to assume that careful handwashing after contact with infected babies and their environment would have been equally effective in reducing the risk of nosocomial RSV infection. Handwashing agents containing detergents or alcohol are quite effective at killing RSV, although chlorhexidine without alcohol is not. 7
Some investigators have advocated performing rapid tests for RSV on all symptomatic infants during the annual RSV season and cohorting RSV-positive patients with contact precautions. This approach was more effective than gowns and gloves or cohorting alone in one study, 8 although compliance was not measured. In another study the rate of nosocomial infection in a newborn nursery declined when rapid testing was combined with cohorting, visitation restrictions and gowns, gloves and masks. 9 However, it may not be cost effective to test routinely all symptomatic infants for RSV, because a child presenting with bronchiolitis during the annual RSV season is very likely to have RSV infection.
The common cold is an extraordinarily noisome impediment to everyday quality of life. Children can expect to suffer approximately four to eight episodes per year, and adults might have three to five episodes annually. Although many viruses can produce the symptoms of a cold (e.g. parainfluenza viruses, RSV, coronaviruses), rhinovirus is the most frequent cause of the common cold and the best studied from an epidemiologic point of view. Unfortunately there are more than 100 distinct serologic types of rhinovirus, and exposure to one rhinovirus does not confer significant immunity against other serotypes.
Work at the Common Cold Research Unit in Salisbury, England, after World War II definitively established that colds could be produced by inoculating secretions from infected patients into the nose or eyes of volunteers, who were happy to have a vacation in a facility with central heating and a fine view. 10 When rhinovirus was established as an etiologic agent for the common cold, these findings were replicated by inoculating volunteers with live virus. 11 Interestingly subsequent work demonstrated that it was exceedingly difficult to transmit the virus orally or by kissing. 12
The question remained as to whether rhinovirus is transmitted primarily by direct contact, indirect contact, droplet contact or droplet nuclei. This seemingly innocuous issue has produced intense controversy, primarily between investigators from the University of Virginia (who believe that contact with secretions is the principal mode of spread) and researchers at the University of Wisconsin (who have found evidence for airborne spread). The Virginia group (Hendley and Gwaltney) demonstrated that most subjects with experimental colds had rhinovirus on their hands and that rhinovirus could be recovered from 43% of plastic tiles they touched. 13 When the Virginia group studied natural rhinovirus colds, virus was found on 39% of hands of symptomatic individuals and on 6% of objects in their immediate environment. 14 Virus could survive for hours or even days on environmental surfaces and for at least 2 h on human skin. Volunteers who had contact with contaminated objects or with fingers of individuals with rhinovirus colds had a high rate of infection if they inoculated their own nose or eyes. Any doubt about the tendency of individuals to put their potentially contaminated fingers in their nose or eye was dispelled by Hendley et al., 14 who found that one-third of grand rounds attendees picked their nose and one in 2.7 rubbed their eyes during the 1-h lecture. Perpetrators tended to repeat these maneuvers. Transmission could be interrupted by treating surfaces with disinfectant or applying iodine to the fingers. 15
In a randomized trial of families with children, Hendley and Gwaltney 15 found that prophylactic treatment of mothers’ fingers with iodine reduced the incidence of secondary respiratory infections in these mothers. Specifically when illness occurred in the family, mothers were instructed to dip their fingers in iodine or a colored placebo upon awakening in the morning, then every 3 or 4 h or after activities that washed the iodine from the skin. Because iodine has residual activity on the hands, it was hypothesized that if virus-laden secretions contaminated fingertips, it would be killed on contact. In 4 years of evaluation the secondary attack rate in mothers was 7% in the iodine group and 20% in placebo families. No confirmed rhinovirus infections occurred in susceptible mothers after 11 exposures to an index case with proven rhinovirus infection in the iodine group, vs. 5 infections after 16 exposures in the placebo group (P = 0.1).
In contrast to these studies, which emphasized the importance of indirect contact spread of rhinovirus via contaminated fomites and fingers, the Virginia group found little evidence for transmission via droplets or droplet nuclei. Exposure of volunteers to infected individuals across a small table (providing an opportunity for both droplet and droplet nucleus transmission) resulted in only an 8% infection rate, far less than the rate with self-inoculation via contaminated hands. 16 Moreover no infection was seen when infected and uninfected volunteers faced each other through a wire mesh.
Meanwhile the Wisconsin group was performing very intriguing studies in various “natural” models of exposure to rhinovirus colds. In one model sick volunteers were housed with susceptible volunteers in a room 11.9 by 5.8 by 2.7 m 17 (Fig. 4). The volunteers played board, card and video games during the study. The pool of virus “donors” was constantly replenished with highly symptomatic volunteers when nasal secretions began to diminish. A somewhat surprising result of these studies was the length of exposure required for infection in the recipients; 200 h of exposure was required to achieve a 50% attack rate (Fig. 5). Dick and his colleagues contended that the exposure times in the Virginia studies were inadequate to rule out droplet and airborne transmission.
The Wisconsin group extended these studies in an ingenious experimental model in which donors and recipients played poker for 12 h sitting at round tables 18 (Fig. 6). Three trials were performed, which included 24 donors and 36 recipients. One-half of the recipients were fitted with diabolical restraints, either arm braces that allowed them to play cards but not touch their face or a shield that left the hands free but kept them away from the face. The attack rates for rhinovirus infection in the restrained and unrestrained recipient volunteers were 56 and 67%, respectively, strongly supporting transmission via the air, not the hands. Furthermore when 12 susceptible volunteers were removed to a separate room and compelled to play stud poker with chips and cards heavily contaminated with secretions from ill volunteers, none became ill. Surprisingly, relatively low titers of virus were found even on chips and cards that were sticky with secretions. The Wisconsin group argued that the high rate of transmission via the hands in the Virginia experiments might be attributable to intensive contact with fresh wet secretions produced by volunteers who essentially blew their nose into their hand.
The explosive spread of influenza after the annual introduction of virus into a community suggests airborne transmission. However, there are surprisingly few studies that shed light on this issue.
The ferret model of influenza provides a convenient system in which to study the transmission of influenza. 19 Efficient transmission of infection from ill to susceptible ferrets was documented regardless of whether the ferrets were separated by a long straight air duct or by ducts in the shape of a “s” or “u.” Presumably, large respiratory droplets could not negotiate the bends in the ducts, whereas aerosols of droplet nuclei could. Studies in a mouse model of influenza also supported transmission by droplet nuclei. 20 These experiments were replicated in a natural human experiment in the Veterans Administration Hospital in Livermore, CA. 21 Patients with tuberculosis were housed either in a building with ceiling ultraviolet radiation or in a nonirradiated building, depending on the stage of their tuberculosis management. The attack during the 1957 to 1958 influenza season was only 2% in the irradiated group, compared with 19% in the nonirradiated patients and 18% in hospital personnel.
Perhaps the most dramatic evidence for airborne spread of influenza occurred during a flight from Anchorage to Kodiak, with an intermediate stop in Homer, AK. 22 The plane experienced mechanical difficulty in Homer and had to remain on the ground, its ventilation system inoperative, for a number of hours. Within 72 h 72% of the 54 people on the plane became ill with typical symptoms of influenza. The attack rate was highest in those who remained on the crippled plane the longest; the 6 passengers who immediately deplaned remained well. This point-source outbreak was initiated by a 21-year-old woman who boarded the flight in Homer and developed fever, chills and cough within 15 min. During her stay on board, people on the plane moved about frequently, but few had close contact with her. It appeared that airborne spread was responsible for this outbreak, perhaps aided by the relatively low humidity, which prolongs survival of influenza virus.
Respiratory viruses in the home exploit multiple modes of transmission. RSV is transmitted primarily by contact with ill children and contaminated objects in the environment. Influenza appears to be spread mainly by airborne droplet nuclei. Despite many years of study, from the plains of Salisbury, to the hills of Virginia, to the collegiate environment of Madison, WI, the precise routes rhinovirus takes to inflict the misery of the common cold on a susceptible population remain controversial.
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