President, Staff Society Journal of Postgraduate N. A. Kshirsagar Volume 49, Issue 2, April-June, 2003 Editor Atul Goel Print ISSN 0022-3859 CD ISSN 0972-2823 Contents Associate Editors Sandeep Bavdekar Editorial Lakshmi Rajgopal Antibiotic resistance: Unless we act soon! Consulting Editors Bavdekar SB ...... 107 Nithya Gogtay Original Article Original Articles Sanjay Mehta Recruitment of subjects for clinical trials after informed consent: Does gender and Vinita Salvi educational status make a difference? Managing Editor Gitanjali B, Raveendran R, Pandian DG, Sujindra S ...... 109 D. K. Sahu Brief Reports Members Human immunodeficiency virus type 1 infection in patients with severe falciparum Amita Athavale malaria in urban India Abhay Dalvi Khasnis AA, Karnad DR ...... 114 Sucheta Dandekar Hemant Deshmukh Antimicrobial-induced endotoxaemia in patients with sepsis in the field of acute Anil Patwardhan pyelonephritis Preeti Mehta Giamarellos-Bourboulis EJ, Perdios J, Gargalianos P, Kosmidis J, Giamarellou H ...... 118 Nalini Shah A comparison of intravenous ketoprofen versus pethidine on peri-operative analgesia Lalita Tuteja and post-operative nausea and vomiting in paediatric vitreoretinal Pradeep Vaideeswar Subramaniam R, Ghai B, Khetarpal M, Subramanyam MS ...... 123 S. V. Vaidya Extended interval between enzyme infusions for adult patients with Gaucher’s Editorial Assistants disease type 1 Shilpa Abhyanakar Pérez-Calvo J, Giraldo P, Pastores GM, Fernández-Galán M, Martín-Nuñez G, Pocoví M ...... 127 Jignesh Gandhi Umbilical hernia in adults: Day case local anaesthetic repair Milind Tullu Menon VS, Brown TH ...... 132

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106 Special Article

Smallpox: Clinical Highlights and Considerations for Vaccination

Mahoney MC,1,2 Symons AB,1 Kimmel SR 3 1Depar tment of , State University of New York at Buffalo, ECMC Clinical Center, 462 Grider Street, Buffalo, New York 14215; 2Department of Social and Preventive Medicine, School of & Health P rofessions, State University of New York at Buffalo, 276 Farber Hall, Buffalo, NY 14214 and 3Department of Family Medicine, Medical College of Ohio, 1015 Garden Lake Parkway, Toledo, Ohio 43614, USA.

Abstract: Smallpox virus has gained considerable attention as a potential bioterrorism agent. Recommendations for smallpox (vaccinia) vaccination presume a low risk for use of smallpox as a terrorist biological agent and vaccination is currently recommended for selected groups of individuals such as health care workers, public health authorities, and emergency/rescue workers, among others. Information about adverse reactions to the smallpox is based upon studies completed during the 1950s and 1960s. The prevalence of various diseases has changed over the last four decades and new disease entities have been described during this period. The smallpox vaccination may be contra-indicated in many of these conditions. This has made pre-screening of potential vaccines necessar y. It is believed that at present, the risks of vaccine-associated complications far outweigh the potential benefits of vaccination in the general population. (J Postgrad Med 2003;49:141-147)

Key Words: Smallpox/epidemiology/history/physiopathology/prevention & control, smallpox vaccine/administration & dosage/adverse effects, biological warfare

The Centers for Disease Control and Prevention (CDC) clas­ two repositories: one in Atlanta (at the Centers for Disease sifies smallpox as one of several Categor y A pathogens that Control & Prevention) and a second in Moscow (at the Insti­ could pose a risk to national security as it can be easily trans­ tute for Viral Preparations).2 It is possible that more nations mitted, has the potential to cause significant morbidity and and some groups may possess additional viral stores. The prob­ mor tality, and has the ability to create social disruption. The ability of multiple owners has raised concerns regarding a last case of (natural) smallpox occur red in Somalia in 1977 potential bioterrorist threat using this agent. and the World Health Organization (WHO) announced the It is transmitted through droplet spread of viral particles onto global eradication of smallpox in 1980. The early 1980s saw the mucosal surfaces of the orophar yngeal or respiratory tract the end of smallpox vaccination all over the among susceptible persons. This transmis­ world. The decision to end smallpox vacci­ sion occurs through close personal contact nation was based upon the eradication of At present, recommendations (face-to-face within 6 feet or household naturally occur ring smallpox, resulting in a for smallpox (vaccinia) contact) for extended periods; 3-6 it has a vaccination are based upon a situation where the risk of adverse reactions lower transmission rate as compar ed to scenario of low risk for use of from the vaccinia vaccine outweighed the smallpox as a terrorist biological measles, pertussis and influenza.3,7,8 Trans­ risk of contracting smallpox. agent worldwide; accordingly, mission through casual and limited contact smallpox vaccination is currently recommended only for is unlikely. Although rare, airborne (i.e. sus­ Clinical Highlights selected medical care and public pended viral par ticles) and fomite transmis­ Smallpox is caused by the variola virus, health personnel. sion can occur. Patients with skin rash are which belongs to the genus orthopoxvirus. infectious and remain so until all the lesions Cowpox, vaccinia and monkeypox are the are scabbed. Transmission can also occur other species belonging to the same genus.1 During the pe­ during the prodromal phase through aerosolisation of viral riod of endemic smallpox infection, humans represented the particles from oral mucosal lesions. Infection cannot be spread only known viral reservoir. Variola virus is known to exist in during the incubation period or during the early prodromal phase.4,9 Survivors of natural infection have lifelong immu­ Address for Correspondence: Martin C. Mahoney, MD nity. Identification of contacts, isolation of cases and contacts, Division of Cancer Prevention & Population Sciences, vaccination of susceptible individuals, and surveillance can Roswell Park Cancer Institute – Carlton 307, 3,4,7,8 Elm and Carlton Streets, Buffalo, NY 14263, USA. help interrupt transmission. E-mail: [email protected] Most secondary smallpox infections occur among house­

141 © Copyright 2003 Journal of Postgraduate Medicine. Online full text at http://www.jpgmonline.com Mahoney et al: Vaccination Against Smallpox hold contacts and hospital personnel.3 Secondary attack rates ists across Europe, and worldwide, since most vaccination among unvaccinated household contacts range between 37% programs ceased 20 or more years ago. Few studies of long­ and 88%.10 Generations of infection typically occur at inter­ ter m immunity have been conducted. Protection has been vals of 1-3 weeks. Health care providers should use airborne noted to persist up to 30 years after administration of 3 doses (e.g. use of a NIOSH N-95 mask) and contact precautions of the Lister vaccine strain used in Israel.13 Fatality rates of (e.g. gloves, gowns, eye shields, and shoe covers) to protect 10% have been observed among those vaccinated 20 years themselves.4 previously, compared to fatality rates of up to 50% among The incubation period lasts for 10-14 days (range 7-17 unvaccinated persons.14 The determinants of long-term im­ days). This is followed by a prodromal period with manifesta­ munity are unknown. tions such as fever, chills, malaise, headaches, vomiting, and backache. Patients appear severely ill with fever exceeding 40 Smallpox Vaccine degrees Celsius. This prodrome is followed by an enanthem The smallpox vaccine is a live viral vaccine, containing an involving the tongue and oropharynx, which is followed by a attenuated vaccinia virus. Intra-dermal administration of small­ maculopapular rash involving the oral mucosa, face, and up­ pox vaccine (vaccinia virus), using a bifurcated needle, can per extremities. The rash spreads to involve the trunk and lower prevent or lessen infection if administered within five days fol­ extr emities and evolves synchronously into vesicles and then lowing smallpox exposure. umbilicated pustules. Historically, mortality rates are reported Five vaccine products are available or planned. Stockpiled to be generally about 30% among unvaccinated groups.4 While vaccine product consists of bovine products produced by there are four clinical forms of smallpox, the two forms most Wyeth (Dryvax® ) and Aventis-Pasteur (Wetvax ®, a liquid prepa­ commonly observed prior to the eradica­ ration, as compared to the lyophilized ® ® tion of smallpox wer e variola major and While contemporary experiences Dr yvax vaccine product. The Dryvax for­ variola minor.3 Variola major accounted for with vaccinia vaccination are mulation includes polymyxin B, dihydros­ based upon a limited number of about 90 percent of cases and demon­ treptomycin, chlortetracycline and neomy­ vaccinees, the rates of adverse strated the classic picture of diffuse pustu­ reactions (e.g., myopericarditis) cin as antibacterials. There are no plans to lar skin lesions.3 Variola minor, resulting have been elevated; risk of license the Wetvax® product due to prob­ complications from the smallpox from infection with a less virulent for m of vaccine are higher than for any lems with proper documentation of appro­ variola virus, exhibited fewer lesions with a other routinely used vaccine priate storage of the vaccine over the years; generally mild clinical course. While less product. it will always be used under an common, flat type smallpox and investigational protocol and only in an hemorrhagic smallpox were repor ted to have had fatality rates emergency at a 1:5 dilution. Two new tissue-based vaccine that approached 100%.2, 11 Supportive treatment is the main­ products, ACAM 2000, from the Vero cell line, and ACAM stay of treatment as there is no proven pharmacotherapy for 1000, using the MRC-5 cell line, are being produced by smallpox infection. Use of vaccinia immune globulin provides Acambis and will generate an additional 54 million doses. no benefit to persons with clinical smallpox.3 Oravax Inc., a small Massachusetts (United States) biotech­ The differential diagnosis for smallpox includes chickenpox, nology firm, is poised to enter the market. Biopreparedness disseminated herpes zoster, impetigo, erythema multiforme, plans call for a smallpox vaccine supply sufficient to vaccinate scabies, and enteroviral infections, including Hand, Foot and all U.S. citizens, the capacity to deliver millions of doses within Mouth disease. Resources comparing the clinical featur es of 12-24 hours to any state or U.S. territory, and accomplish the chickenpo x and smallpox are readily accessed (http:// distribution of 280 million doses within 5 days; this planning www.bt.cdc.gov/agent/smallpox/smallpox-images).12 has encouraged other countries to address smallpox prepar­ It is unlikely that individuals previously immunized many edness. Presently, only the Dryvax® smallpox vaccine product years ago against smallpox have adequate immunity. For ex­ (Wyeth L aboratories) is licensed by the FDA for use in per­ ample, given the 30-year inter val since widespread smallpox sons age 18 years and older. Several Investigational New Drug immunization in the United States, coupled with waning im­ (IND) protocols are under way to evaluate other smallpox vac­ munity over time, the U.S. population is considered suscepti­ cine products. ble to smallpox infection. Persons under the age of 30 years Vaccination continues to represent a primary strategy for are particularly susceptible, given the fact that they have never persons at occupational risk of exposure through culture han­ been vaccinated against smallpox.2 Similar susceptibility ex- dling or contact with animals infected with non-highly attenu­

J Postgrad Med 2003;49:141-147 142 Mahoney et al: Vaccination Against Smallpox ated vaccinia viruses (e.g. laboratory workers and health care nificant immune dysfunction represents an absolute contra­ workers) and immediately following exposures.4,5,8 indication to use of smallpox vaccine.5 CDC has defined house­ hold contacts as persons with whom the vaccinee is likely to Other Attenuated Vaccinia Vaccines have prolonged intimate contact (e.g. sexual contacts) or con­ The modified vaccinia virus Ankara (MVA) vaccine was de­ tact with the vaccination site.8 rived by taking material from a horse’s pox lesion in Ankara, Turkey and passing it in chick embryo fibroblasts.15 During Adverse Reactions the 1970s, MVA was given to over 100,000 persons in Ger­ Prior vaccine experience many and Turkey as a primer to establish basic immunity be­ Risk of complications from the smallpox vaccine is higher than fore later administering the traditional smallpox vaccine dur­ for any other routinely used vaccine product. 21 Most of our ing the final phases of a smallpox eradication program. MVA knowledge about adverse reactions to the smallpox vaccine is immunogenic in human cells and appears to have limited (vaccinia) is based upon studies completed during the 1950s capacity for replication.15 However, its efficacy in an outbreak and 1960s, a period when the general population was vacci­ situation has not been evaluated. nated as part of standard care. The defective vaccinia virus Lister (dVV Studies from the 1960s document a Lister) genetically alters the Lister strain that death rate of 1 per million primar y small­ is used for the smallpox vaccine in the The prevalence of certain pox ; rates of adverse reactions medical conditions, which United Kingdom, Europe, and Israel, so that represent contraindications for are highest among children aged less than the virus replicates in few permanent mam­ vaccinia vaccination in a pre- 5 years. Minor side effects include fever in event scenario, suggest that a malian cell lines.16 However, dVV Lister has 70% of children lasting up to 14 days.4 considerable number of been demonstrated to induce humoral and individuals will fall into one or Complication rates were higher among pri­ cellular immunity in mice and both the MVA more of these categories; mary vaccines (125 per 100,000) than in careful screening is and dVV Lister wer e tolerated in recommended. those receiving revaccination (10.8 per immunodeficient mice.16 Further develop­ 1,000,000) ment and study of these attenuated vaccines Serious adverse events, based on past in humans is required before they can be introduced on a experience, included death (1/million primar y vaccines) and large scale. post-vaccine encephalitis (range 1 to 10 cases /million). These

Vaccine Efficacy Table 1: Contraindications for use of smallpox vaccine in pre­ Vaccine efficacy is 95% among vaccinees in whom a 1-2 cm exposure situations loculated and umbilicated pustule (called a Jennerian pus­ 1. History of or current eczema or atopic dermatitis 2. Other acute, chronic or exfoliative skin condition (burns, impetigo, tule) is noted 6-8 days after inoculation.2,4,8,17 The presence of varicella zoster, herpes, severe acne, or psoriasis) 3. Immunosuppression (HIV, AIDS, leukemia, lymphoma, general­ a Jennerian pustule is considered a major reaction and indi­ ized malignancy, solid , cellular or humoral cates a successful vaccination; lesser reactions r equire immunodeficiencies, therapy with alkylating agents, anti metabolites, radiation, or high dose corticosteroids) revaccination.3 Primar y vaccination results in immunity for 5­ 4. Pregnancy 5. Breastfeeding 10 years, with revaccination yielding immunity for 10-20 6. Child less than 1 year old in household years.11 Studies examining 1:5 and 1:10 dilutions of the 7. to vaccine component (glycerin, polymyxin B, strepto­ mycin, chlorotetracycline, neomycin, and phenol) Dryvax® product show no decrease in vaccine efficacy among 8. Myocardial infarction, angina, congestive heart failure, cardio­ 18,19 myopathy, stroke or transient ischemic attack, chest pain or short­ selected populations. Clinicians should be aware of what ness of breath with activity, or other cardiac conditions being constitutes a normal cutaneous vaccination response.20 treated by a doctor 9. Presence of three or more of the following risk factors: – Hypertension – Hypercholesterolemia Contraindications – Diabetes Guidelines for pre-exposur e smallpox vaccination are given – A first-degree relative (mother, father, brother, sister) who had a heart condition before the age of 50 in Table 1. Recent r eports of myopericarditis among U.S. – Current cigarette smoker 10. Household contacts – defined as persons with whom the vac­ vaccinees have resulted in additional restrictions against vac­ cinee is likely to have prolonged intimate contact (e.g. sexual cination for persons with a histor y of cardiac disease, stroke contacts) or contact with the vaccination site with medical con­ ditions #1 though #4 above. or transient ischemic attack or cardiac symptoms, or persons Modified from reference #8 and http://www.bt.cdc.gov/agent/smallpox/ repor ting three or more risk factors for cardiac disease. Sig­ vaccination/contraindications-public.asp [accessed 21/4/03]

143 J Postgrad Med 2003;49:141-147 Mahoney et al: Vaccination Against Smallpox generally occur among infants and the elderly.4,17,22 Other com­ eral differences are apparent, including the high rate of my­ monly observed adverse reactions included a robust primary opericarditis that was not previously noted in the 1960s. The reaction (incidence of 4-18%); generalized vaccinia (240 cases/ high rate of overall adverse events and “non-serious adverse 1 million primary vaccinations) with vesicles/pustules distant events” noted for the 2003 data likely reflects a surveillance from vaccine site, and mild systemic illness. Inadvertent in­ bias and tendency to over-report relatively benign conditions oculation to other places on the body (529 cases/million), ec­ and symptoms unrelated to smallpox vaccine. Continued sur­ zema vaccinatum (1/25,000) generally occur ring among per­ veillance will be important in further characterizing these ex­ sons with a history of eczema; progressive vaccinia (1/600,000) periences. seen among persons with impaired T-cell function with necro­ The increased risk for serious adverse events among per­ sis at the vaccine site and with severe and potentially fatal sons with certain medical conditions has guided the CDC in systemic illness. In addition, transmission of vaccinia from carefully outlining contra-indications for vaccination in the pre­ vaccinees to susceptible contacts occur red at a rate of 27 in- event immunization program. However, over the last 20-40 fections/million vaccinations.4 years, the prevalence of many of these risk conditions has increased. Recent vaccine experience For example, not only have incidence rates increased for Beginning in early 2003, a pre-event smallpox vaccination many cancer sites, but also mor tality rates have remained sta­ program was initiated in the U.S. As of May 2003, 36,217 ble or even decreased, leading to an increased prevalence of civilians have been vaccinated, in addition to more than cancer (e.g. including cancer survivors and chemotherapy 240,000 military vaccinees. patients) among the general population. This has resulted in Recent experiences have revealed that one-third of 680 increased numbers of immunocompromised individuals. Also, persons who received smallpox vaccine re­ dramatic enhancements in management of ported missing school, modifying recrea­ In the event that a smallpox rejection have made organ transplantation tional activities or disturbed sleep follow­ outbreak were to occur, much more common today than in the ing vaccinia vaccination;18,19 1 in 4 recent vaccination of primary contacts 1960s and increased the numbers of pa­ and persons exposed to these vaccinees noted mild systemic reactions (B. contacts (e.g. a ring vaccination tients on immunosuppressive medications. Schwartz, CDC, June 2002). Local skin ir­ strategy) would be initiated as a HIV/AIDS was not a clinical entity prior to control strategy. ritation, satellite lesions, headache, myal­ the early 1980s. Also, although precise fig­ gia, lymphadenopathy, nausea, chills and ur es are lacking, rates of atopic dermatitis fever for 1-2 weeks post-innoculum is common.18,19 A robust are estimated to have doubled or tripled since the era of uni­ primary reaction is likely to result in either ambulatory visits versal smallpox vaccination. 26 In addition, Smith et al recently or time lost from work or school. estimated that a considerable proportion of hospitalized pa­ Six cases of myopericarditis have been confirmed with an tients might be at an increased risk for contacting vaccinia additional 18 suspect cases repor ted among vaccinees.23 These based on a review of discharge diagnoses.27 events have resulted in three deaths. Following extensive re­ Table 2: Comparison of selected adverse events following view, these data were judged to be sufficient to establish cau­ smallpox vaccination: historical and recent experience sality between the development of myocarditis/pericarditis and Recent (2003)* Lane et al. (1970) Selected adverse Cases† Rate/ Cases† Rate/ administration of the smallpox vaccine. However, no causal event s million million relationship was found between cardiac ischemic events and Eczema vaccinatum 0 – 41 24.9 smallpox vaccination.24 It is worthwhile to note that in 1968, Erythema multiforme major 0 – 118 71.6 Generalised vaccinia 1 27.6 167 101.3 only one case of transient pericarditis was reported (<1/mil- Inadvertent inoculation, 4 110.4 415 251.8 lion vaccinees).22 Aside from these cardiac events, no other nonocular Myopericarditis 6 165.7 1 0.6 serious complications have been reported in the current im­ Ocular vaccinia 2 55.2 ‡ munization program at the time of this writing.25 Postvaccinial encephalitis 0 – 10 6.1 Subtot al 13 358.9 Table 2 summarizes selected adverse events following small­ Other serious adverse event s 59 1,629.1 ‡ pox vaccination from both the 1960s22 and recent experience.23 Other non-serious event s 488 13,474.3 216 131.1 Total 560 15,462.4 972 589.8 It should be emphasized that current experiences are based Persons immunised 36,217 1,648,000 upon a limited number of vaccinees and the occurrence rates *based on MMWR report 5/23/03.23 (data: January 24-May 9, 2003), might be considered somewhat unstable. Nonetheless, sev- †Confirmed or probable cases, ‡not separately reported

J Postgrad Med 2003;49:141-147 144 Mahoney et al: Vaccination Against Smallpox

Based on experiences in the U.S., it has been estimated risk of ‘contact vaccinia.’ Recommendations for inoculation that the list of contra-indications (particularly that for atopic site management include covering the vaccination site with a dermatitis/chronic exfoliative skin conditions in the patient or semi-permeable dressing on top of gauze, with clothing to be a household contact) may result in more than 50% of the popu­ worn on top of the dressing. The dressing is to be changed lation becoming ineligible for smallpox vaccination in the first every 3-5 days, particularly if exudate collects on the gauze. stage of the pre-event vaccination program.26 The prevalence Currently most vaccinees are assessed daily and would have of medical contra-indications to smallpox vaccination is sum­ daily dressing changes. marised in table 3. Even acknowledging the possibility that individuals might have multiple contra-indications to small­ Adverse Events Reporting pox vaccine, these data suggest that a considerable number The occurrence of adverse events following smallpox vacci­ of individuals will fall into one or more of these categories nation should be immediately reported to health officials. In irrespective of cardiac history, cardiac risk factors and the U.S., severe events should be r eported electronically via contraindications among household contacts of potential the Vaccine Adverse Events Repor ts System (VAERS) at http:/ vaccinees. /secure.vaers.org/VaersDataEntry.htm or by calling 800-822- 7967 for a postage-paid paper repor t form. Post-vaccination site management Until the vaccination site is scabbed there is a risk of inoculat­ Treatment ing nonvaccinees with vaccinia virus. Although, no cases of For cases of progressive vaccinia, eczema vaccinatum, severe vaccinia transmission from civilian vaccinees have been re­ generalized vaccinia or inadver tent inoculation resulting in ported, transmission has occurred in military populations.25 extensive lesions and/or ocular involvement, vaccinia immu­ The CDC does not recommend routine administrative leave noglobulin (VIG) and cidofovir can be used. These drugs are for healthcare workers after vaccination, so vaccinees will po­ available from the CDC under investigational new drug (IND) tentially come into contact with patients who are at increased protocols.8,28 The current VIG supply is sufficient to treat about 4,000 adverse events anticipated to result from vaccination of Table 3: Estimated prevalence of medical contra-indications to smallpox vaccination in United States population 40 million persons. Condition Prevalence Annual incidence 1. Eczema or atopic dermatitis 15,000,00029 Recommendations for vaccination 2. Other acute, chronic or Recommendations for smallpox (vaccinia) vaccination are exfoliative skin condition - Burns 1,000,000 30 based upon a scenario of low risk for use of smallpox as a - Impetigo Not Available ter rorist biological agent, disease transmission consistent with - Varicella Zoster 600,000- 1,000,000 31 prior disease experience, adherence to recommended infec­ 32 - Herpes 45,000,000 tion control measures, appropriate scr eening for contra-indi- - Severe Acne 5-10% teenagers33 - Psoriasis 1 in 50 persons34 cations to vaccination, a procedure for informed consent, sur­ 3. Immunosuppression veillance of vaccinated persons, adequate supplies of vaccine - HIV/AIDS 850-900,0008 - Leukemia 30,80035 and vaccinia immunoglobulin (VIG), and voluntary vaccine - Lymphoma 60,90035 administration (http://www.cdc.gov/mmwr/preview/ 35 - Generalised malignancy 1,185,000 8 - Solid organ transplantation 24,100 mmwrhtml/r r5207a1.htm). transplants36 Accordingly, smallpox vaccination in the U.S. is cur rently - Cellular or humoral immunodeficiencies 1 in 5,00037 recommended for persons pre-designated by the appropriate - Therapy with alkylating bioterrorism and public health authorities to conduct investi­ agents,antimetabolites, gation and follow-up of smallpox cases. Smallpox vaccination radiation and/ or high dose corticosteroids Not Available is also recommended for selected personnel in facilities pre­ 4. Pregnancy 3,043,500 designated to serve as r eferral centers to provide care for the 5. Breast feeding 150,000 6. Child <1 year old in initial cases of smallpox. Personnel within these facilities would 38 household 4,058,000 be designated for vaccination by the hospital. As outlined in 7. Allergy to vaccine component Not Available 8. Cardiac conditions/risk factors Not Estimated the CDC Interim Smallpox Response Plan and Guidelines (see URL above), state bioterrorism response plans should desig­ The United Census Bureau estimated the overall U.S. population as 290,000,000 persons in 2003. nate initial smallpox isolation and care facilities.

145 J Postgrad Med 2003;49:141-147 Mahoney et al: Vaccination Against Smallpox

In the event that a smallpox outbreak were to occur, vacci­ JA, et al. Clinical recognition and management of patients exposed to biological warfare agents. Clin Lab Med 2001;21:435-73. nation of primar y contacts and persons exposed to these con­ 10. Mack TM, Thomas DB, Muzaffar Khan M. Epidemiology of smallpox tacts (e.g. a ring vaccination strategy) would be initiated as in West Pakistan. II. Determinants of intravillage spread other than outlined in the CDC Draft Smallpox Response Plan. In addi­ acquired immunity. Am J Epidemiol 1972;95:169-77. 11. Fenner F DH, I Arita, Z Jezek, ID Ladnyi. Smallpox and its eradica­ tion, if circumstances warrant, vaccination of communities may tion. Geneva: World Health organization; 1988. be under taken based upon existing biopreparedness plans. 12. Kimmel SR, Mahoney MC, Zimmer man RK. Vaccines and bioterrorism: smallpo x and anthrax. J Fam P ract 2003;52:S56-61. Surveillance and containment, including ring vaccination, rep­ 13. el-Ad B, Roth Y, Winder A, Tochner Z, Lublin-Tennenbaum T, Katz E, resent the primary strategy for the control and containment of et al. The persistence of neutralizing antibodies after revaccination a smallpox outbreak. In addition, local, federal, and against smallpox. J Infect Dis 1990;161:446-448. 14. Mack T. Smallpox in Europe, 1950-1971. J Infect Dis 1972;125: international public health agencies would be able, if neces­ 161-9. sary, to expand immunisation to additional groups, up to and 15. Blanchard TJ, Alcami A, Andrea P, Smith GL. Modified vaccinia vi­ rus Ankara undergoes limited replication in human cells and lacks including the entire population, in a timely manner. several immunomodulatory proteins: implications for use as a hu­ Since prompt identification of a smallpox case is critical to man vaccine. J Gen Virol 1998;79:1159-67. initiating a public health response, the CDC has developed a 16. Ober BT, Bruhl P, Schmidt M, Wieser V, Gritschenberger W, Coulibaly S, et al. Immunogenicity and safety of defective vaccinia virus lister: rash assessment algorithm to assist medical and public health comparison with modified vaccinia virus Ankara. J Virol 2002;76: professionals in evaluating the likelihood of smallpox in pa­ 7713-23. 17. Lane JM, Ruben FL, Neff JM, Millar JD. Complications of smallpox tients with febrile rash illnesses. Poster copies of this algorithm vaccination, 1968. N Engl J Med 1969;281:1201-8. are available at http://www.bt.cdc.gov/agent/smallpox/diagnosis 18. Frey SE, Newnman FK, Cruz J, Shelton WB, Tennant JM, Polach T, In the event of a documented outbreak, use of smallpox et al. Dose-related effects of smallpox vaccine. N Engl J Med 2002;346: 1275-80. vaccine for post-exposure prophylaxis warrants clinical judg­ 19. Frey SE, Couch RB, Tacket CO, Treanor JJ, Wolff M, Newman FK, et ment since the benefits resulting from use of vaccine would al. 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Announcement New Website for the journal The Journal of Postgraduate Medicine is pleased to announce the launch of a new version of its website from August 2003. The site address would remain same [www.jpgmonline.com]. The features of the new site include: • Free full text availability of articles form 1980 (to be added over next couple of months) • Direct link to abstracts and full text from the cited references • Link from text of articles to various databases and search engines • Facility to submit comments on articles • Email notifications on new issue release • Statistics of articles download and visits • Better user interface • New structure based on OpenURL, DC Metadat a and other international standards

147 J Postgrad Med 2003;49:141-147