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The clinical illness associated with vaccinia virus is somewhat similar to smallpox ie, a vesiculopapular rash , although exposure history can generally be used to distinguish between the two. Other rash illnesses, outlined in the table below, are included in the differential diagnosis of smallpox. See Monkeypox below. Human monkeypox is caused by monkeypox virus, which, like variola virus, is in the Orthopoxvirus genus.

Monkeypox is similar to smallpox, but illness is generally milder. Recognized cases have occurred predominantly in western and central Africa. Pertinent historic information about monkeypox in Africa is as follows:. Key findings from the outbreak are as follows:. Smallpox and monkeypox are generally quite similar, although smallpox often is more severe and the case-fatality rate is higher. Early in the clinical course, smallpox or monkeypox may be mistaken for chickenpox if the clinical suspicion for orthopoxvirus infection is low.

Also, smallpox in partially immune patients may be mild and may resemble chickenpox. An assessment of suspected smallpox cases referred to the CDC between and found that chickenpox accounted for more than half of the cases Seward Distinguishing features of the three illnesses are outlined in the table below.

Lasts days, with high fever, headache, backache, and severe prostration; vomiting and severe abdominal pain may occur. Begins on oral mucosa, spreads to face, then expands in centrifugal pattern ie, most dense on face and distal extremities. Often begins on face and spreads in centrifugal pattern although cases have been reported with centripetal pattern of spread. Occur in "crops" and may be at different stages of maturation at any given point in time.

Progress over several days from macules day 1 , to papules day 2 , to vesicles days , to pustules days 7 to about 14 , to scabs day 14 to about Progress quickly over about 24 hr from macules to papules to vesicles, then to crusted lesions. Often intensely pruritic; not usually painful unless superimposed bacterial infection occurs. Cases can be expected to occur in all age-groups; illness may be somewhat milder in adults over age 30 who were vaccinated as young children.

Cases can be expected to occur in all age-groups; illness may be milder in people who have received smallpox vaccination. The likelihood of a smallpox diagnosis determines the appropriate laboratory testing and handling of specimens. Several years ago, the CDC developed the following criteria for determining the risk of smallpox CDC : Acute, generalized vesicular or pustular rash illness testing protocol in the United States. An important caveat to this algorithm is that it is not designed to detect the most severe and atypical forms of smallpox Lucey A study indicated that physicians in the United States may be poorly prepared to diagnose smallpox.

Similarly, baseline knowledge assessment of physicians in 30 internal medicine residency programs in 16 states and Washington, DC, showed that only An algorithm developed by the CDC to rapidly evaluate patients for smallpox may prove useful.

A prospective, multicenter study used the algorithm to classify 26, cases of rash or rashlike illness at emergency departments and inpatient units of 12 acute-care hospitals in six states. Eighty-nine patients presenting with acute generalized vesicular or pustular rash were determined to be eligible for the study, and 73 were enrolled. Physicians or study staff classified none of the 73 as being at high risk, 72 as low risk, and 1 as moderate risk of having smallpox. The discharge diagnosis for 55 of the 73 patients was varicella illness.

Use of the algorithm did not result in misclassification of any patients as high risk for smallpox Hutchins The CDC has established algorithms for laboratory evaluation of patients with acute, generalized vesicular or pustular rash illnesses, based primarily on the likelihood of smallpox CDC : Acute, generalized vesicular or pustular rash illness testing protocol in the United States.

It is likely that laboratories will receive specimens from patients with possible orthopoxvirus infections without being notified of risk level for smallpox. Theoretically, properly practiced universal precautions should protect the laboratory worker and community from accidental exposure. The following table outlines collection of laboratory specimens for the diagnosis of smallpox variola and smallpox vaccine vaccinia —associated infections. Allow to air dry for 10 min. Allow to air dry 10 min.

Use varying degrees of pressure minimal, light, and moderately firm in application of each grid to unroofed lesion. Collect as appropriate, such as cerebrospinal fluid for postvaccinia encephalitis. Specific collection recommendations change and may vary depending on local policies. The LRN is a national network of approximately laboratories. The LRN structure for bioterrorism designates laboratories as sentinel, reference, or national. Designation depends on the types of tests a laboratory can perform and how it handles infectious agents to protect workers and the public.

In the past, tests for the detection and identification of variola virus included culture on egg chorioallantoic membrane, tissue culture, and direct examination of vesicle or pustular material. Laboratories that have at least BSL-2 containment facilities can perform rapid tests for diagnosis of rash illness in patients not considered at high risk for smallpox.

Local or state LRN laboratories should be contacted for testing of specimens from patients with a moderate or high risk of smallpox see "Determining the Likelihood of a Smallpox Diagnosis" in the Clinical Syndromes and Differential Diagnosis section.

The most likely alternative agents are VZV and HSV; available rapid tests for these two agents include the following:. Once smallpox is confirmed in a geographic area, additional cases can be diagnosed clinically CDC : Smallpox response plan and guidelines. In such situations, laboratory resources will be used for specimen testing in the following cases:. Accidental discovery of variola virus by a clinical virologist would constitute a danger to the laboratorians and could precipitate unintentional release to the community.

The following features of variola virus in cell culture have been described in the older literature Fenner , Kato , Marennikova :. Recent experience with progressive vaccinia following smallpox vaccination has raised questions about dosing and quantity of treatment agents stockpiled for responding to a smallpox incident.

Current estimates likely underestimate the actual amount of treatment doses that may be needed if a smallpox incident occurred CDC : Progressive vaccinia in a military smallpox vaccinee—United States, ; Hayden Because of this monitoring, the patient's treatment was modified when resistance to Arestvyr was identified, and treatment was continued for 2 to 3 weeks after the last detection of viral DNA.

This intense laboratory monitoring was crucial in developing a treatment plan and led to a successful outcome for this patient. On December 14 and 15, , the FDA Antiviral Drug Advisory Committee convened to discuss the treatment of individuals with an established smallpox infection in the event of a malicious reintroduction of smallpox.

The committee concluded that not enough information was available about these antivirals to provide recommendations to the FDA about their use under these circumstances at that time FDA Vaccination given within 4 days after exposure can modify the course of disease and reduce mortality.

The vaccine is derived from plaque purification cloning from Dryvax. A phase 2 clinical trial demonstrated that at a dose of 6. A randomized trial was conducted to compare the safety and immunogenicity of ACAM to Dryvax as well as to another clonally derived, cell-culture manufactured vaccinia strain, ACAM A dose of 1. All subjects had evidence of successful vaccination, and immune responses and adverse events were similar for the study groups Frey Currently, enough vaccine is available in the stockpile for all Americans CDC : Frequently asked questions about smallpox vaccine.

One newer approach is to develop vaccines that incorporate attenuated vaccinia—derived viruses Belyakov , Poland These vaccines are referred to as third-generation vaccines or beyond , and, because they use attenuated vaccinia viruses, they should have reduced rates of adverse reactions.

Examples of third-generation vaccines include the following:. LC16m8, which is licensed for use in Japan, is an attenuated cell culture—adapted Lister vaccinia smallpox vaccine missing the B5R protein.

One study suggests that the vaccine is well tolerated, with similar reactogenicity as Dryvax Kennedy A number of other studies on possible candidate vaccines such as cell-culture vaccines, subunit vaccines, and recombinant vaccines have been published in the last several years, and research into new vaccines is ongoing. Additionally, various smallpox vaccines first-, second-, third-, and next-generation have been reviewed Handley , Kennedy , Metzger , Nalca , Walsh The regulatory pathway for approving these third- and fourth-generation vaccines is complicated.

Well-defined animal models or correlates of immunity are not available for evaluating new smallpox vaccines Traynor These vaccines will potentially be used in a world where vaccine- and infection-related immunity to orthopoxviruses is waning and the risk of emerging orthopoxvirus infections may be increasing Golden To enhance preparedness in the event of a smallpox emergency, in October the Advisory Committee on Immunization Practices ACIP and the Healthcare Infection Control Practices Advisory Committee HICPAC recommended smallpox vaccination for persons designated by the appropriate bioterrorism and public health authorities to conduct investigation and follow-up of initial smallpox cases ie, smallpox response teams.

Thus, interim guidance on revaccination was issued by the CDC in ; it attempts to balance the smallpox threat and risk of exposure during an outbreak, the risk for adverse events in revaccinees and their contacts , and the need for a sufficient number of protected first responders CDC : CDC interim guidance for revaccination of eligible persons who participated in the US civilian smallpox preparedness and response program.

According to the CDC, 39, persons were vaccinated through the program as of October 31, , which is the last date that information is available on the CDC Web site CDC : Smallpox vaccination program status by state.

Before smallpox vaccine is administered, patients should be screened for contraindications and provided with educational information about the vaccine CDC : Smallpox pre-vaccination information packet. The vaccine is administered using a droplet of the vaccine applied to a bifurcated needle. Upon primary vaccination, all recipients experience a local reaction to the vaccine. A typical reaction occurs in the following sequence CDC: Smallpox vaccination and adverse events training module, CDC : Smallpox vaccination and adverse reactions: guidance for clinicians :.

Cutaneous reactions to subsequent vaccinations are weaker and manifest a range of the local reactions described above.

Traditionally, palpable inflammation or a pustule ie, a local response was thought to be an essential marker for successful revaccination. However, a study of 80 soldiers who participated in the Israeli smallpox revaccination campaign demonstrated that soldiers who had no local response to revaccination were successfully revaccinated against smallpox when assessed by immunologic markers. In the study, 40 subjects who developed a local response "clinical take" were individually matched for age, sex, and smallpox vaccinations with subjects who did not develop clinical take.

Immunologic evaluation 2 years after revaccination showed that both groups responded equally well to the revaccination. The authors concluded that during a mass vaccination campaign, success assessment is not needed for revaccinated individuals who do not have a clinical take Wiser Vaccinia vaccine for pre-exposure use is contraindicated for the following groups CDC : Recommendations for using smallpox vaccine in a pre-event smallpox vaccination program :.

During the smallpox eradication campaign and during smallpox outbreaks in the past, a "ring vaccination" strategy has been followed. Ring vaccination essentially involves creating a circle of vaccinated persons around each case to interrupt the chain of transmission.

The strategy involves the following steps:. Smallpox incubation period estimates from historical records have been used to determine the most appropriate quarantine period for persons exposed to smallpox. Several studies have used modeling to inform preparedness and response planning for a deliberate release of smallpox. In addition to ring vaccination, rapid voluntary vaccination of a large population may be required to:.

In the United States, large-scale voluntary smallpox vaccination would be initiated only in certain situations under recommendations from the Secretary of Health and Human Services HHS. Wide-scale quarantine of communities likely would not be effective and therefore would not be recommended Barbera Key points for vaccine use are outlined in the table below. Whom to vaccinate: —Persons exposed to the initial release of the virus —Persons who had face-to-face, household, or close contact ie, up to 6.

Persons with contraindications for vaccination but not in a situation likely to encounter a smallpox case a,b : —Persons who have ever been diagnosed with eczema or atopic dermatitis, even if the condition is mild or not presently active —Persons with other acute or chronic exfoliative skin conditions such as burns, impetigo, or varicella-zoster shingles , herpes, severe acne, severe diaper dermatitis with extensive areas of denuded skin, or psoriasis should not be vaccinated until the condition resolves —Persons with diseases or conditions that cause immunodeficiency —Persons with inflammatory eye disease being treated with steroids —Women who are pregnant or breast-feeding —Persons with serious, life-threatening allergies to the antibiotics polymyxin B, streptomycin, tetracycline, or neomycin.

This will decrease risk of contact transmission through vaccination site. Adapted from CDC : Smallpox response plan and guidelines. This guide includes the following information:.

In general, smallpox vaccine clinics should follow standard operating procedures for administration of other vaccines. Serious adverse reactions to smallpox vaccination can occur CDC : Adverse reactions following smallpox vaccination, Lane Historically, for every 1 million vaccinees, 1 to 2 deaths and hundreds of complications severe enough to require hospitalization have occurred.

If the current population of the United States was vaccinated, several hundred deaths and tens of thousands of hospitalizations might result. This small but definite risk and the absence of endemic smallpox led to the halt in routine vaccination in the United States in Kennedy Well-documented adverse reactions from historical information ie, before routine vaccination ceased in the United States in include the following:.

Adverse event rates tend to be much lower in revaccinees compared with primary vaccinees Treanor In addition to previously recognized adverse events, more recent experience with smallpox vaccine has demonstrated that myopericarditis is a potential adverse event. The etiology of postvaccination myopericarditis remains unclear, although it appears that the process is immunologically mediated rather than the result of direct viral infection of the myocardium.

Other severe adverse events following smallpox vaccination in the current era, including generalized vaccinia, progressive vaccinia, and eczema vaccinatum, appear to be rare Vellozzi Several anecdotal reports have been published regarding dermatologic adverse events following smallpox vaccination. These events include:. Malignant tumors at the smallpox vaccination site also have been reported, including basal cell carcinoma, malignant melanoma, squamous cell carcinoma, and fibrohistiocytic tumors Waibel : Smallpox vaccination site complications.

Such lesions may occur as the result of scarring followed by malignant degeneration, although a causal relationship between vaccination and dematological malignancies has not been established. Contact vaccinia refers to transmission of vaccinia virus from newly vaccinated persons to susceptible unvaccinated contacts.

Studies conducted during the s found the risk of eczema vaccinatum in contacts of vaccinated individuals ranged from 8. The risk of other accidental contact infections ranged from 3. These studies relied on appropriate recognition and reporting of contact cases; therefore, the data generated may not necessarily have reflected the true incidence of this condition.

A review article has suggested that the current risk may be somewhat higher than that observed in the s for the following reasons Neff :. Among the estimated 2.

The vast majority of these cases involved secondary transfers. Three fourths of all cases 86 involved either household contacts or intimate partners of vaccinees. Median time from exposure of the contact to clinical onset was 6 days range, 1 to 19 days. Fourteen cases required hospitalization, and one case was life-threatening. A report detailed secondary and tertiary transmission of vaccinia virus in sexual contacts Shao In that report, a recently vaccinated member of the military had sexual contact with the secondary case-patient, who sought treatment for a painful perianal rash and lesions on the lip 9 days following the encounter.

The lesions were positive for nonvariola orthopoxvirus. The secondary case-patient was hospitalized for 3 days and received VIGIV because of a history of eczema. The patient in the secondary case had sexual contact with a third person 3 days before seeking treatment. The tertiary case-patient developed lesions 2 days later and was eventually hospitalized and treated with VIGIV because of a history of childhood eczema. The vaccinated military member remained free of symptoms, and the other two patients recovered.

Two reports detailed vaccinia transmission that occurred during contact sports. CDC researchers reported a four-person cluster linked to a martial arts gym in Maryland Hughes Although the index case-patient was not identified, the researchers said he or she was likely a recent vaccinee.

Also, New York public health officials described a newly vaccinated military member who wrestled two people in matches during which his vaccination site became exposed Young The two other wrestlers became infected with vaccinia, and one of them subsequently infected a third wrestler in a match several days later. A household member of one of the first two contacts also contracted vaccinia.

One of the wrestlers developed ocular vaccinia Montgomery Nosocomial spread of vaccinia virus can occur, as summarized in another review article Sepkowitz However, among 27, healthcare workers vaccinated recently, no worker-to-patient transmission of vaccinia was documented DoD A study demonstrated that use of two occlusive dressings an initial waterproof gauze-impregnated transparent bandage and an outer waterproof semipermeable bandage to cover vaccination sites offered an excellent barrier against inadvertent transmission of vaccinia virus Talbot Treatment of the vaccination site with povidone iodine ointment, beginning 7 days after transcutaneous smallpox vaccination, appears to reduce the risks of autoinoculation or contact spread Hammarlund Detailed information on treatment of adverse reactions to smallpox vaccine can be found on the CDC Web site CDC : Smallpox vaccination and adverse reactions: guidance for clinicians.

The CDC guidance outlines the use of VIG, cidofovir a nucleotide analogue of cytosine , and topical ophthalmic antiviral drugs for ocular involvement. In more recent years, Arestvyr also has been used to treat adverse reactions associated with smallpox vaccination. VIG is the primary product available to treat complications of vaccinia vaccination. VIG is a sterile liquid immunoglobulin G obtained from immunized donors. Two intravenous forms of VIG were approved by the FDA in February to treat patients in whom serious adverse reactions to smallpox vaccine develop, including the following Wittek :.

Use of VIG is not recommended for isolated keratitis as it may cause severe corneal opacities , erythema multiforme, and postvaccinial encephalitis Rusnak Cidofovir and Arestvyr may be used under an IND protocol to treat serious smallpox vaccine reactions CDC : Smallpox vaccination and adverse reactions: guidance for clinicians, CDC Medical management of smallpox vaccinia vaccine adverse reactions.

Cidofovir will be released by the CDC in the following situations:. Off-label use of topical ophthalmic antiviral agents trifluridine or vidarabine has been recommended by some ophthalmologists to treat vaccinia infection of the conjunctiva or cornea. Use of VIG had no impact on clinical course; corticosteroids exacerbated the keratitis and should not be used Altmann Key points from Section , which went into effect in January , include the following:.

The rule clarifies eligibility standards, the process for requesting and receiving benefits, and other policies and procedures.

In addition, nonvaccinated healthcare workers should not provide care when immune healthcare workers are available.

Initial cases of smallpox are likely to not be placed in Airborne Precautions, which could increase the number of second generation cases among healthcare workers Milton All healthcare workers caring for patients with suspected smallpox should be vaccinated immediately. No disinfectant products are registered by the US Environmental Protection Agency specifically for variola virus inactivation; however, according to the CDC, products that inactivate similar lipid or medium-sized viruses such as vaccinia virus are adequate for disinfection of variola virus CDC : Smallpox response plan and guidelines.

These products include chemicals used on environmental surfaces for low- or intermediate-level disinfection and are outlined in the table below.

High-level disinfectants or liquid chemical sterilants are not indicated for cleaning large environmental surfaces eg, floors, walls, tabletops.

The Working Group on Civilian Biodefense recommends that bedding and clothing of smallpox patients should be autoclaved or laundered in hot water to which bleach has been added Henderson : Smallpox as a biological weapon: medical and public health management. Laboratory dispersion studies involving vaccinia virus as a surrogate for variola virus indicate that infectious virions are rapidly inactivated in the environment CDC : Smallpox response plan and guidelines.

Therefore, available evidence does not support air space decontamination of rooms, facilities, or vehicles eg, fumigation. Standard terminal cleaning practices are considered adequate for rooms that have housed smallpox patients. A single case of smallpox is considered a public health emergency; therefore, any patients with a likely diagnosis of smallpox should be reported immediately to the state or local health department, according to disease reporting rules.

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The probability that variola could reemerge as a threat because of unregistered growth of clandestine virus is an as yet unquantifiable parameter in estimation of the scientific utility of retaining variola virus.

Live variola virus would be required for full development of antiviral therapeutics needed to deal with such a threat. The committee's charge was restricted to assessment of scientific needs for live variola virus. It did not include consideration of risks that may be associated with retention of the existing stocks, and no attempt was made to determine whether the scientific needs identified by the committee outweigh these risks.

Furthermore, the committee did not address the likelihood that the funds and other resources needed to pursue this research, including facilities with suitable biological containment provisions, would be available. It must also be recognized that predicting the future is impossible, and while the committee has done its best to provide an assessment of future scientific needs for live variola virus, the unfolding of actual needs and opportunities is likely to depend on the emergence of unforeseeable technical developments, experimental tools, and model systems.

For these reasons, the committee expresses its findings and conclusions below in conditional form: If particular knowledge or capability were to be pursued, would the associated research require live variola virus? The committee identified six potential areas of research that could require the use of variola virus, and then evaluated for each area whether live virus would be needed for that purpose.

Before addressing these six areas, however, the committee notes a need associated with the short-term use of variola virus stocks.

Genomic sequencing and limited study of variola surface proteins derived from geographically dispersed specimens is an essential foundation for important future work.

Such research could be carried out now, and could require a delay in the destruction of known stocks, but would not necessitate their indefinite retention.

We turn now to the six areas of research examined by the committee with regard to the potential need for live variola virus. The most compelling reason for long-term retention of live variola virus stocks is their essential role in the identification and development of antiviral agents for use in anticipation of a large outbreak of smallpox. It must be emphasized that if the search for antiviral agents with activity against live variola virus were to be continued, additional public resources would be needed.

Live variola stocks would have to be maintained if the development of effective antiviral drugs for smallpox therapy and prophylaxis were to be pursued. There is currently no effective antiviral for the treatment or prevention of smallpox. Vaccination, which reduces the severity of the disease if administered within 4 days of exposure, is currently the only recourse for those infected with the disease.

Moreover, vaccine supplies have dwindled and may be deteriorating. In addition, as noted earlier, vaccinia vaccine, which is used for smallpox immunization, is a live virus and cannot be used safely with immunocompromised individuals. Having a number of antiviral agents would provide greater protection against an emergence of drug-resistant variola virus, whether the result of natural evolution or genetic engineering. If new agents were to be developed, cell culture infection assays would be important for demonstrating their activity and effectiveness, and for determining the concentration required to prevent infection or its spread.

Some of this testing could be carried out with replication-defective forms of variola virus cultured in cells engineered to complement the defect in the virus. Such replication-defective forms of vaccinia virus have been constructed. Yet other steps in this testing would require the use of live variola virus and recently isolated human cells since measurement of tissue culture activity using other orthopoxviruses or replication-defective forms of variola virus and genetically engineered cell lines could yield misleading results.

Finally, private enterprise has little incentive to undertake the development and testing of agents for smallpox prevention and prophylaxis. Therefore, such studies would be dependent on the availability of public resources. Adequate stocks of smallpox vaccine would have to be maintained if research were to be conducted on variola virus or if main tenance of a smallpox vaccination program were required.

Live variola virus would be necessary if certain approaches to the development of novel types of smallpox vaccine were to be pursued. Vaccinia virus vaccine was effective in eradicating smallpox. As noted earlier, however, current stocks of vaccinia vaccine are limited and may be deteriorating.

If it again became necessary to control smallpox with a vaccination program, the current supply would need to be replenished.

In addition, if laboratory research using variola virus were to be continued, vaccine would have to be available for laboratory workers, even in the absence of an outbreak. Retention of live variola virus for vaccine production would not be required if vaccinia vaccine supplies were replenished using established methods of manufacture.

Moreover, production of vaccinia vaccines using tissue culture could be pursued without the use of live variola virus. Vaccines derived from tissue culture could be compared with the standard vaccine by evaluation of reactogenicity and immunogenicity essentially the ''take" and immune potency of the vaccine in human subjects and by laboratory assays.

Live variola virus would be required only for testing of novel vaccine development strategies using materials other than live vaccinia virus, such as a DNA vaccine expressing selected variola genes. The above-noted concern about the safety of using vaccinia virus vaccine in populations with high levels of HIV infection or other immunosuppressive conditions is the reason for developing nonstandard vaccines.

Since definitive evidence of the protective efficacy of such vaccines could not be obtained in the absence of an outbreak, laboratory testing using live variola virus in as yet undeveloped animal models would be needed for this purpose. If further development of procedures for the environmental detection of variola virus or for diagnostic purposes were to be pursued, more extensive knowledge of the genome variability, predicted protein sequences, virion surface structure, and functionality of variola virus from widely dispersed geographic sources would be needed.

Evaluation of the specificity and sensitivity of detection methods for variola virus and other orthopoxviruses would require increased knowledge regarding the DNA sequence not only of variola virus from multiple geographic locations, but also of other orthopoxviruses, especially monkeypox.

With this order, George Washington enacted the first medical mandate in American history. Some believed this to be a mistake, and even Washington wavered on his order initially, though he was firm in his resolve in the end.

Washington declared his order to Congress that all troops must be inoculated, and he ordered that all new recruits entering Philadelphia must be inoculated upon entry. To offset the temporary loss of soldiers while they healed from the inoculation, military doctors inoculated divisions in five day intervals. The military used private homes and churches as isolation centers to control spread of the disease.

Continental military forces took a huge risk with these mass inoculations. If the British learned of these mass inoculations, they could have launched an attack on the weakened Continental Army. Therefore, these inoculations had to be kept secret in order to prevent word from getting out to the British.

Washington urged the inoculations to be completed as soon as possible so the soldiers would be ready to fight by the summer. Though some, including General Israel Putnam, followed Washington's orders and delivered the mass inoculations, several generals and governors prohibited inoculation. By disobeying Washington's orders, his own generals prevented Washington from having the number of soldiers he needed for his summer campaigns.

Washington responded with further urgency to inoculate troops: "The apologies you offer for your deficiency of Troops, are not without some Weight.

I am induced to believe, that the apprehensions of the Small pox and its calamitous consequences Though gaining support for inoculation was slow and difficult, mandated inoculations proved successful.

Initially, fear of smallpox and its fatal consequences ran rampant in the American colonies. This fear caused Bostonians to resist the inoculation procedure until the early s, and this fear also led Continental soldiers to inoculate themselves without supervision during the beginning of the Revolutionary War.

If inoculation had been socially accepted earlier, many more lives could have been saved from the painful and unnecessary death smallpox caused. By late , the procedure had been established in the Continental Army, and prevalence of the disease substantially reduced. While smallpox cases did still appear from time to time, the mandated inoculation of soldiers reduced the chance of large-scale outbreaks.

With the threat of smallpox diminished, the Continental Army saw a surge of new recruits in Despite its controversial origins in colonial American society, the publicized success of the mass inoculations made inoculations a cultural norm. Zabdiel Boylston, and Dr. Joseph Warren years ago, smallpox inoculation may have never gained widespread acceptance in the colonies. Their innovation and pioneering spirit reflects the modern spirit of medical innovation in Boston today.

And without George Washington's decisive and unpopular inoculation mandate, colonists may have lost the Revolutionary War. This simple, life saving procedure and the people who fought for it are in many ways responsible for colonists' victory in the Revolutionary War, which led to the founding of this nation.

Walter Lowrie and Walter S. Franklin, Explore This Park. This engraving depicts a developing smallpox pustule figures 1 - 7 , and the tools used for inoculation figures 8 - 9.

Boston and Smallpox Colonial Boston had faced many smallpox outbreaks throughout the s, the most severe of which occurred in , , , and Cotton Mather advocated in favor of inoculation to prevent the spread of smallpox. Inoculations became a subject of debate during the s, sparking Bostonians to write for and against the practice. In this document, Daniel Henchman shows his support for Dr. Boylston's work. Smallpox and the Canadian Campaign As the Revolutionary War progressed, smallpox continued to affect military operations.

Paper documenting the smallpox resolution passed by the Massachusetts House of Representatives regarding the outbreak of smallpox in Boston. Actions taken from this resolution included preventing ships from arriving and departing Boston to halt the spread of the disease. General Washington and Smallpox Washington understood the grave threat smallpox imposed upon the Continental Army and their chances of winning the war.

This Expedient may be attended with some inconveniences and some disadvantages, but yet I trust, in its consequences will have the most happy effects. Necessity not only authorizes but seems to require the measure, for should the disorder infect the Army, in the natural way, and rage with its usual Virulence, we should have more to dread from it, than from the sword of the enemy. Success of Inoculations Though gaining support for inoculation was slow and difficult, mandated inoculations proved successful.

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