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PubMed2004

Smallpox: what every otolaryngologist should know.

OBJECTIVE: In light of recent terrorist events and the potential threat of smallpox as a biological agent, we present information concerning smallpox to better inform the otolaryngologist concerning this disease and its prevention. STUDY DESIGN: We performed a review of the smallpox and smallpox vaccination literature over the past 200 years using MEDLINE, PREMEDLINE, Centers for Disease Control and Prevention Internet site, World Health Organization Internet site, and references found in previous publications not found in MEDLINE or PREMEDLINE. Our search focused on the pathogenesis, clinical presentation, course, unique manifestations in the head and neck, diagnosis, and treatment of smallpox, as well as the method of smallpox vaccination, vaccination contraindications, and complications. RESULTS: Smallpox is a viral disease with a high mortality rate. Its clinical course, manifestations, and methods of prevention are carefully analyzed in light of otolaryngology practice. CONCLUSION: Smallpox manifestations in the head and neck often presented as acute airway obstruction and also as long-term sequelae such as ectropion, nasal vestibular stenosis, conductive hearing loss, and blindness. Most chronic sequelae involve the head and neck. Smallpox vaccination is effective but not without potential serious risks.

Adult↗
PubMed2003

Smallpox and live-virus vaccination in transplant recipients.

Recent bioterrorism raises the specter of reemergence of smallpox as a clinical entity. The mortality of variola major infection ('typical smallpox') was approximately 30% in past outbreaks. Programs for smallpox immunization for healthcare workers have been proposed. Atypical forms of smallpox presenting with flat or hemorrhagic skin lesions are most common in individuals with immune deficits with historic mortality approaching 100%. Smallpox vaccination, even after exposure, is highly effective. Smallpox vaccine contains a highly immunogenic live virus, vaccinia. Few data exist for the impact of variola or safety of vaccinia in immunocompromised hosts. Both disseminated infection by vaccinia and person-to-person spread after vaccination are uncommon. When it occurs, secondary vaccinia has usually affected individuals with pre-existing skin conditions (atopic dermatitis or eczema) or with other underlying immune deficits. Historically, disseminated vaccinia infection was uncommon but often fatal even in the absence of the most severe form of disease, "progressive vaccinia". Some responded to vaccinia immune globulin. Smallpox exposure would be likely to cause significant mortality among immunocompromised hosts. In the absence of documented smallpox exposures, immunocompromised hosts should not be vaccinated against smallpox. Planning for bioterrorist events must include consideration of uniquely susceptible hosts.

Bioterrorism↗
PubMed2004

Smallpox: clinical features, prevention, and management.

OBJECTIVE: To describe a general overview of smallpox, clinical presentation, diagnosis, adverse events, and management of both pre- and postexposure vaccination. DATA SOURCES: Literature was identified by search of MEDLINE (1966-June 2003) and International Pharmaceutical Abstracts (1966-May 2003) databases using the key terms smallpox, bioterrorism, biological warfare, and smallpox vaccine. STUDY SELECTION AND DATA EXTRACTION: Articles identified from data sources were evaluated, and relevant information was included in this review. DATA SYNTHESIS: Smallpox is spread by human-to-human contact with an infected host and therefore can be contagious. The mortality rate for smallpox is approximately 30%. While the disease was completely eradicated by 1980 with successful use of smallpox vaccine, concern has been raised that smallpox may emerge as a tool of bioterrorism. This concern, combined with the reality of current smallpox vaccination programs in the military and selected civilian populations, mandates a clear understanding of vaccination-related adverse events and contraindications by all healthcare professionals. The vaccine may cause moderate to severe adverse events such as eczema vaccinatum, progressive vaccinia, and generalized vaccinia. CONCLUSIONS: The balance between the risks and benefits of mass vaccination in prevention of an epidemic is not clear. The Centers for Disease Control and Prevention has established a guideline for appropriate use of smallpox vaccine in the civilian population.

Antiviral Agents↗
PubMed1999

[Biohazards due to Orthopoxvirus: should we re-vaccinate against smallpox?].

Although the WHO declared global smallpox eradication in 1980, the Orthopoxvirus remains a source of concern for several reasons. Firstly, stocks of the smallpox virus have been preserved for experimental use (at least officially in the USA and Russia) so that an escaped isolate could lead to reemergence and spread of the disease worldwide. Secondly discontinuation of smallpox vaccination programs has led to dwindling acquired immunity in the world population thus raising the risk of epidemic extension of several Orthopoxvirus zoonoses (e.g., monkeypox). Thirdly stocks of camelpox virus which is very similar to Smallpox virus and was intended for biological warfare were discovered during the Gulf War in 1991 and pose a potentially serious threat. Finally official stocks of Smallpox virus could be stolen and used by bioterrorists. Thus reemergence of Orthopoxvirus including smallpox, monkeypox, cowpox, and camelpox is a real danger and contingency planning is needed to define prophylactic and therapeutic strategies to prevent and/or stop an epidemics. Adverse effects from earlier smallpox vaccine (vaccinia) in healthy people or immunocompromised people (congenital or acquired as in HIV infected patients) are absolute contraindications to smallpox vaccination at this time. Further research is needed to develop new vaccines (e.g., attenuated isolates of vaccinia) and effective treatment. This is the only valid reasons for postponing planned destruction of remaining Smallpox virus stocks.

Biological Warfare↗
PubMed2002

[Smallpox, bioterrorism agent].

A CONSIDERABLE RISK: Among the infectious agents that might be used as terrorist weapons, the smallpox virus represents a sufficiently high risk, which is difficult to manage and must be seriously taken into account. FROM A MICROBIOLOGICAL POINT OF VIEW: Two viral strains of the smallpox virus, which belong to the Poxviridae and orthopoxvirus-type families, are known. They are associated with various clinical presentations of smallpox, i.e., variola major and variola minor or "alastrim". VARIOLA MAJOR: Five clinical forms of varying prognosis are described. Common smallpox, haemorrhagic smallpox (the most severe form of the disease), mild smallpox (predominantly observed in vaccinated patients), flat-type smallpox (defined by coalescent and slowly progressive lesions) and so-called "sine eruptione" smallpox. VARIOLA MINOR: This form is not as severe as variola major and the mortality rate is lesser. DIAGNOSIS: Smallpox must be systematically evoked on clinical elements and confirmed by electronic microscopy of a sample of liquid from a vesicle or pustule or a scab. The strains can be characterised by PCR (Polymerase Chain Reaction). TREATMENT: It is symptomatic. Early vaccination, within 4 days following exposure to the virus, permits the reduction in mortality by 50%. The only efficient prevention is vaccination prior to any exposure to the virus. In the case of a bioterrorist attack, the United States and most of the EC countries propose to vaccinate only the health professionnals most exposed to the virus and those having contacted identified cases.

Bioterrorism↗
PubMed2003

Smallpox: a review of clinical disease and vaccination.

The clinical course of smallpox infection and the current and future roles of vaccination and strategies for controlling smallpox outbreaks are reviewed. Close personal contact is required for transmission of variola, the DNA virus that causes smallpox. Following an incubation period, infected persons have prodromal symptoms that include high fever, back pain, malaise, and prostration. The eruptive stage is characterized by maculopapular rash that progresses to papules, then vesicles, and then pustules and scab lesions. The mortality rate for smallpox is approximately 30%. Patients having a fever and rash may be confused with having chickenpox. The most effective method for preventing smallpox epidemic progression is vaccination. Until recently, only 15 million doses of smallpox vaccine--manufactured 20 years ago--were available in the United States. The vaccine is a live vaccinia virus preparation administered by scarification with a bifurcated needle. The immune response is protective against orthopoxviruses, including variola. Vaccination is associated with moderate to severe complications, such as generalized vaccinia, eczema vaccinatum, progressive vaccinia, and postvaccinial encephalitis. Efforts for vaccine production are now focused on a live cell-culture-derived vaccinia virus vaccine. Although smallpox was eradicated in 1980, it remains a potential agent for bioterrorism. As a category A biological weapon, its potential to devastate populations causes concern among those in the public health community who have been actively developing plants to deal with smallpox and other potential agents of biological warfare. The only proven effective strategy against smallpox is vaccination.

Bioterrorism↗
PubMed1983

Five years of freedom from smallpox.

In 1967, when the intensified global eradication programme was launched, smallpox was still endemic in 35 countries with a total population of 1200 million and caused an estimated 10-15 million cases, resulting in 2 million deaths. Ten years and ten months later, on 26 October 1977 through intensified public health activities, the chain of smallpox transmission was finally broken in Merka, south Somalia; the World Health Organization missed its ten-year target line by ten months. In December 1979, the Global Commission concluded that the global eradication of smallpox had been achieved and the Organization formulated its policy for the post-eradication era. In May 1980, the 33rd World Health Assembly endorsed the Commission's conclusion and officially confirmed the international acceptance of smallpox eradication as the most outstanding achievement in international public health. This achievement has unmistakably demonstrated that the concept of disease eradication is correct and feasible. WHO encouraged countries to discontinue smallpox vaccination and/or the need for a smallpox vaccination certificate from international travellers. However, WHO is continuing its vigilance over the disease and promoting further research on orthopox viruses. Globally, US$ 313 million were spent on the eradication of smallpox from the world. However, conservative calculations indicate that in the post-eradication era, concrete economic returns resulting from the eradication of smallpox throughout the world, are estimated at US$ 1000 to 2000 million, annually. For the last five years of smallpox-free status, savings of about US$ 5000-10 000 million could be diverted for other health projects, which has had a major impact on international public health. However, there are other dividends similarly worthy as those of economic value. The most important of these are the hundreds of thousands of experienced and dedicated health workers who remain now in the countries as a solid base for implementing other important public health programmes.

Adult↗
PubMed2004

Development and experience with an algorithm to evaluate suspected smallpox cases in the United States, 2002-2004.

Concerns that smallpox, an eradicated disease, might reappear because of a bioterror attack and limited experience with smallpox diagnosis in the United States prompted us to design a clinical algorithm. We used clinical features of classic smallpox to classify persons presenting with suspected smallpox rashes into 3 categories: those with high, those with moderate, and those with low risk of having smallpox. The classification guides subsequent diagnostic strategies, limiting smallpox laboratory testing to high-risk persons to minimize the number of false-positive test results. From January 2002 through June 2004, the Centers for Disease Control and Prevention (CDC) received 43 consultations regarding suspected smallpox cases. No patient was at high risk for having smallpox. One patient was tested for the presence of variola virus. Varicella was the diagnosis for 23 cases (53%). The algorithm worked well to guide clinical and public health responses to suspected smallpox cases. The poster is available from CDC, and an interactive version and laboratory protocol are available at http://www.bt.cdc.gov/agent/smallpox/diagnosis/riskalgorithm/index.asp. We recommend use of the algorithm in the United States and elsewhere.

Adolescent↗
PubMed2004

Chickenpox or smallpox: the use of the febrile prodrome as a distinguishing characteristic.

BACKGROUND: The ability to differentiate chickenpox from smallpox is important for early recognition of bioterrorism events and prevention of false alarms. The febrile prodrome is a clinical feature used to differentiate these conditions. However, the prevalence of prodromal manifestations in chickenpox has not been well established. METHODS: We evaluated prodrome characteristics of all chickenpox cases identified through an active varicella surveillance program over a 21-month period. The frequencies of various prodromal manifestations among vaccinated and unvaccinated case patients were assessed, and the impact of other demographic features on these manifestations was evaluated. Data were analyzed to determine what proportion met the smallpox febrile prodrome criteria as elaborated in the Centers for Disease Control and Prevention algorithm for evaluating patients suspected of having smallpox. Finally, we compared our data with historical data on smallpox prodromes. RESULTS: Data on prodrome characteristics were available for 932 chickenpox cases. Prodromal fever was present in 37% of unvaccinated chickenpox case patients and in 25% of vaccinated case patients. Among unvaccinated case patients, adults were 70% more likely than children to have fever in the prodrome period. We found that prodromes are less common and less severe in chickenpox than in smallpox. Nevertheless, 7%-17% of unvaccinated chickenpox case patients meet the smallpox febrile prodrome criteria. CONCLUSIONS: Febrile prodromes occur in a significant proportion of patients with chickenpox, particularly among unvaccinated case patients and adults. Therefore, the febrile prodrome alone is not a sufficient marker of smallpox risk. All major and minor smallpox criteria should be considered together in assessing the likelihood of smallpox.

Adolescent↗
PubMed2005

Knowledge about the initial presentation of smallpox among emergency physicians in Washington, DC.

OBJECTIVES: To assess the current knowledge of full-time emergency physicians in Washington, DC, regarding the initial diagnosis of smallpox and the initial care of the patient with smallpox. METHODS: A written true/false test was prepared based on information accessed from the current Centers for Disease Control and Prevention (CDC) Web site on smallpox. The 20-question test was administered to full-time emergency physicians practicing emergency medicine in all seven adult civilian hospitals in Washington, DC. RESULTS: The overall response rate was 81% (52 of the 64 eligible full-time emergency physicians). The average score was 59% correct. The facts most likely to be known were 1) that the symptoms of smallpox begin with a two- to four-day prodrome of fever and myalgia (before the appearance of any rash), 2) that no antiviral treatment is of more proven value than vaccination of contacts, and 3) that a person with smallpox may be contagious before any rash appears (average, 90% correct). The facts least likely to be known were 1) that when dealing with a known case of smallpox, fit-tested N95 masks are not needed by treating personnel if they have been vaccinated; 2) that the rash of smallpox begins with 24-48 hours of flat, erythematous macules (not papules or vesicles); and 3) that very typically the rash of smallpox begins in the mouth (average, 22% correct). CONCLUSIONS: Some facts from the current CDC Web site on smallpox are known by a large majority of full-time emergency physicians in Washington, DC, whereas questions based on other facts were answered incorrectly by a majority of the physicians tested.

Academic Medical Centers↗
PubMedDate not supplied

[Smallpox--in the past or not?].

Smallpox is a potentially deadly illness caused by the variola virus, an orthopoxvirus. Severe illness followed by blister-like body rash is the sign of smallpox. Smallpox symptoms develop about 12 days after exposure. V. variole can spread very readily by aerosol, which may lead to explosive epidemics. For centuries, smallpox has been a worldwide cause of death, killing about 30% of the infected people. In 1972, the epidemic of smallpox in ex-Yugoslavia was the largest postwar smallpox epidemic in Europe. The total number of the affected was 175, out of whom 35 with fatal outcome, accounting for 20% of mortality. However, after a decade-long vaccination effort, the last natural case of smallpox occurred in 1977. The only way to prevent smallpox epidemic is by vaccination and patients' isolation. The possibility of future bioterrorism attacks, which may cause a new outbreak of smallpox and return variola, is very serious. World population is not immune, because of lack of vaccination. In 1980, the World Health Organization (WHO) declared the disease fully eradicated.

Humans↗
PubMed2000

[20 years without smallpox].

It is 20 years since the 33rd World Health Assembly (WHA) declared that "worldwide eradication of smallpox" was achieved. This was the outcome of many years intensive work of the World Health Organization (WHO) and its member countries. In 1958 the WHA adopted the recommendation that WHO should initiate the eradication of smallpox on a worldwide scale. In 1967 the eradication activities in hitherto endemic countries became more intense. Smallpox affected 31 countries and 15 countries recorded from occasional cases. Every year more than 10 million people contracted the disease and two million of them died. A ten-year limit for the eradication was set. Gradually smallpox were eradicated in South America, then in Asia and last in Africa where the last case of endemic smallpox was recorded in 1977 in Somalia. WHO ensured international collaboration, close coordination of activities and mobilization of financial, personal and material resources. It ensured also that tested methods were fully applied in the affected countries regardless of their political, religious and cultural differences. In the eradication activities participated hundreds of thousands of local and 700 health professionals from abroad, incl. 20 Czechoslovak epidemiologists. The worldwide costs of eradication amounted to some 300 million dollars, i.e. some 23 million per year. The most important contribution of the eradication of smallpox was in addition to the termination of human suffering, worldwide financial savings estimated to 1-2 billion US dollars per year. These saved personal and financial resources could be used for other important health projects. The eradication of variola was defined as eradication of clinical forms of smallpox not as the final eradication of the variola virus. The importance of laboratories keeping the variola virus increased steeply at the time when clinical cases of smallpox were eradicated. From the beginning of the eighties WHO made an effort to reduce their number to a minimum. Since 1984 strains of variola are officially kept only in two centres collaborating with WHO. The Organization suggested destruction of the kept viruses in 1987, i.e. ten years after the eradication of smallpox. Unfortunately some political and scientific circles did not agree with this intention. Even recommendations to destroy the virus in 1993 and again in 1999 were not accepted. In the nineties fear of bio-terrorism and secret modernization of biological weapons influenced some member countries to change their opinion on the intended destruction of the virus. Despite this in May 1999 the WHA adopted a resolution that the final destruction of all variola strains is the objective of all member countries of WHO and recommended to postpone the destruction of the virus to the year 2002. The reason for postponement is current research of new antiviral preparations and better vaccines. There is again hope that all that will be left of the variola virus will be magnetic signals on computer diskettes.

Bioterrorism↗
PubMed2003

US military smallpox vaccination program experience.

CONTEXT: The United States recently implemented smallpox vaccination of selected military personnel in a national program of preparedness against use of smallpox as a biological weapon. The resumption of smallpox vaccinations raises important questions regarding implementation and safety. OBJECTIVE: To describe the US military smallpox vaccination program. DESIGN: Descriptive study of the vaccination program from its inception on December 13, 2002, through May 28, 2003. SETTING: US Department of Defense (DoD) fixed and field medical treatment facilities on multiple continents and ships at sea. SUBJECTS: US service members and DoD civilian workers eligible for smallpox vaccination. MAIN OUTCOME MEASURES: Numbers of vaccinations and rates of vaccination exemptions, symptoms, and adverse events. Data were collected via reports to headquarters and rigorous surveillance for sentinel events. RESULTS: In 5.5 months, the DoD administered 450 293 smallpox vaccinations (70.5% primary vaccinees and 29.5% revaccinees). In 2 settings, 0.5% and 3.0% of vaccine recipients needed short-term sick leave. Most adverse events occurred at rates below historical rates. One case of encephalitis and 37 cases of acute myopericarditis developed after vaccination; all cases recovered. Among 19 461 worker-months of clinical contact, there were no cases of transmission of vaccinia from worker to patient, no cases of eczema vaccinatum or progressive vaccinia, and no attributed deaths. CONCLUSIONS: Mass smallpox vaccinations can be conducted safely with very low rates of serious adverse events. Program implementation emphasized human factors: careful staff training, contraindication screening, recipient education, and attention to bandaging. Our experience suggests that broad smallpox vaccination programs may be implemented with fewer serious adverse events than previously believed.

Adolescent↗
PubMed2003

Emergency physicians' perspectives on smallpox vaccination.

OBJECTIVE: To evaluate emergency physician (EP) attitudes toward smallpox vaccination, the treatment of patients with suspected smallpox, and the threat of a bioterrorist attack. METHODS: This was a prospective study utilizing a standardized survey instrument that was distributed on November 16, 2002, and collected by February 1, 2003. EPs from a sample of 50 accredited emergency medicine programs were surveyed regarding their perspectives on smallpox vaccination. RESULTS: A total of 989 surveys were collected from 42 emergency medicine programs. Of the respondents, 43.4% would currently volunteer for smallpox vaccination. EPs previously vaccinated against smallpox were 1.46 times more likely to volunteer for vaccination (95% CI = 1.14 to 1.93). EPs who believed they were at risk for complications were less than half as likely to volunteer for vaccination. EPs who perceived a significant risk of a bioterrorist attack were 2.7 times more likely to volunteer for the vaccine compared with those who thought the risk was minimal (95% CI = 2.06 to 3.47). Of the respondents, 34.4% believed the risks of the vaccination outweighed the benefits, 33% did not, and 32.6% were unsure. CONCLUSIONS: Currently, fewer than half of EPs surveyed would volunteer for smallpox vaccination. Factors associated with a willingness to be vaccinated include previous smallpox vaccination and the perceived threat of a bioterrorist attack. The variation in EP attitudes toward smallpox vaccination may be due to uncertain risk-to-benefit ratio. The opinions and actions of EPs may be influential on current and future government policy and public opinion.

Adult↗
PubMed2003

Attitudes of healthcare workers in U.S. hospitals regarding smallpox vaccination.

BACKGROUND: The United States is implementing plans to immunize 500,000 hospital-based healthcare workers against smallpox. Vaccination is voluntary, and it is unknown what factors drive vaccine acceptance. This study's aims were to estimate the proportion of workers willing to accept vaccination and to identify factors likely to influence their decisions. METHODS: The survey was conducted among physicians, nurses, and others working primarily in emergency departments or intensive care units at 21 acute-care hospitals in 10 states during the two weeks before the U.S. national immunization program for healthcare workers was announced in December 2002. Of the questionnaires distributed, 1,165 were returned, for a response rate of 81%. The data were analyzed by logistic regression and were adjusted for clustering within hospital and for different number of responses per hospital, using generalized linear mixed models and SAS's NLMIXED procedure. RESULTS: Sixty-one percent of respondents said they would definitely or probably be vaccinated, while 39% were undecided or inclined against it. Fifty-three percent rated the risk of a bioterrorist attack using smallpox in the United States in the next two years as either intermediate or high. Forty-seven percent did not feel well-informed about the risks and benefits of vaccination. Principal concerns were adverse reactions and the risk of transmitting vaccinia. In multivariate analysis, four variables were associated with willingness to be vaccinated: perceived risk of an attack, self-assessed knowledge about smallpox vaccination, self-assessed previous smallpox vaccination status, and gender. CONCLUSIONS: The success of smallpox vaccination efforts will ultimately depend on the relative weight in people's minds of the risk of vaccine adverse events compared with the risk of being exposed to the disease. Although more than half of the respondents thought the likelihood of a bioterrorist smallpox attack was intermediate or high, less than 10% of the group slated for vaccination has actually accepted it at this time. Unless new information about the threat of a smallpox attack becomes available, healthcare workers' perceptions of the vaccine's risks will likely continue to drive their ongoing decisions about smallpox vaccination.

Adult↗
PubMed2005

Neurologic adverse events associated with smallpox vaccination in the United States, 2002-2004.

CONTEXT: Neurologic illness is an infrequent but severe adverse event associated with smallpox vaccination. The reinstatement of smallpox vaccination in the United States in response to possible bioterrorism renewed concerns about vaccine-related adverse neurologic events. OBJECTIVE: To determine rates and describe the clinical features of neurologic events associated with smallpox vaccination. DESIGN AND SETTING: We assessed reports of adverse events obtained through active case reporting and review of data reported to the Vaccine Adverse Event Reporting System among 665,000 persons vaccinated against smallpox by the Departments of Defense (n = 625,400 [corrected]) and Health and Human Services (n = 39,400 [corrected]) during the 2002-2004 US Smallpox Vaccination Program. MAIN OUTCOME MEASURE: Adverse neurologic events temporally associated with smallpox vaccination. RESULTS: Between December 16, 2002, and March 11, 2004, 214 neurologic adverse events temporally associated with smallpox vaccination were reported; 111 reports involved Department of Health and Human Services and 103 involved Department of Defense vaccinees. Fifty-four percent of these events occurred within 1 week of vaccination, and 53% were among primary vaccinees. The most common neurologic adverse event was headache (95 cases), followed by nonserious limb paresthesias (n = 17) or pain (n = 13) and dizziness or vertigo (n = 13). Serious neurologic adverse events included 13 cases of suspected meningitis, 3 cases of suspected encephalitis or myelitis, 11 cases of Bell palsy, 8 seizures (including 1 death), and 3 cases of Guillain-Barré syndrome. Among these 39 events, 27 (69%) occurred in primary vaccinees and all but 2 occurred within 12 days of vaccination. CONCLUSIONS: During the 2002-2004 smallpox vaccination campaign, reported neurologic events were generally mild and self-limited, and no neurologic syndrome was identified at a rate above baseline estimates. Serious neurologic adverse events, such as postvaccinal encephalitis, Bell palsy, and Guillain-Barré syndrome, occurred in accordance with expected ranges.

Adverse Drug Reaction Reporting Systems↗
PubMed2004

Smallpox and measles: historical aspects and clinical differentiation.

Smallpox and measles have ravaged native populations worldwide for centuries. Millions of people have succumbed to smallpox or measles or suffered from their effects. Clinicians wonder how their predecessors confused measles with smallpox. The difficulty was in differentiating smallpox and measles in their early phases, which had important public health implications. The prodromal rash of smallpox sometimes resembled measles. Clinicians through the ages learned to differentiate smallpox and measles in their early stages. Osler's careful clinical description of prodromal smallpox is a classic in infectious diseases. Koplik's appreciation of the diagnostic significance of the spots on the buccal mucosa was another advance in the early diagnosis of measles. The clinical features and effects of measles and smallpox on history are reviewed.

Diagnosis, Differential↗
PubMed2005

Antiviral treatment is more effective than smallpox vaccination upon lethal monkeypox virus infection.

There is concern that variola virus, the aetiological agent of smallpox, may be used as a biological weapon. For this reason several countries are now stockpiling (vaccinia virus-based) smallpox vaccine. Although the preventive use of smallpox vaccination has been well documented, little is known about its efficacy when used after exposure to the virus. Here we compare the effectiveness of (1) post-exposure smallpox vaccination and (2) antiviral treatment with either cidofovir (also called HPMPC or Vistide) or with a related acyclic nucleoside phosphonate analogue (HPMPO-DAPy) after lethal intratracheal infection of cynomolgus monkeys (Macaca fascicularis) with monkeypox virus (MPXV). MPXV causes a disease similar to human smallpox and this animal model can be used to measure differences in the protective efficacies of classical and new-generation candidate smallpox vaccines. We show that initiation of antiviral treatment 24 h after lethal intratracheal MPXV infection, using either of the antiviral agents and applying various systemic treatment regimens, resulted in significantly reduced mortality and reduced numbers of cutaneous monkeypox lesions. In contrast, when monkeys were vaccinated 24 h after MPXV infection, using a standard human dose of a currently recommended smallpox vaccine (Elstree-RIVM), no significant reduction in mortality was observed. When antiviral therapy was terminated 13 days after infection, all surviving animals had virus-specific serum antibodies and antiviral T lymphocytes. These data show that adequate preparedness for a biological threat involving smallpox should include the possibility of treating exposed individuals with antiviral compounds such as cidofovir or other selective anti-poxvirus drugs.

Animals↗