J. Michael Lane

Clinical Efficacy of Intramuscular Vaccinia Immune Globulin: A Literature Review

BACKGROUNDnNumerous literature reports describe clinical efficacy of intramuscular vaccinia immune globulin (VIG) for complications of smallpox vaccination, prophylaxis of individuals with contraindications to vaccination, and prevention of smallpox among close contacts of patients with smallpox.nnnMETHODSnWe reviewed the literature regarding VIG treatment and prophylaxis of smallpox vaccine complications and the use of VIG as a preventative measure for close contacts of patients with smallpox.nnnRESULTSnData regarding intramuscular administration of VIG for treatment of smallpox vaccine complications occurred in 16 articles, none of which reported formal controlled trials. The indications for treatment include generalized vaccinia, progressive vaccinia, eczema vaccinatum, and certain accidental implantations. Six publications suggest VIG efficacy for prophylaxis of vaccinial superinfection of eczema, burns, chickenpox, immunosuppression, pregnancy, or certain skin conditions. Prophylactic VIG has also been used in healthy military recruits to reduce the incidence of postvaccinial encephalitis. The use of intramuscular administration of VIG to prevent smallpox in contacts of patients with documented cases of smallpox is reported in 4 studies that compare contacts who received intramuscular administration of VIG with those who did not and in 1 observational study, with varying but promising results.nnnCONCLUSIONSnAlthough controlled clinical trials do not exist to support the use of VIG for treatment of vaccinia-related complications or prophylaxis among individuals with contraindications to smallpox vaccination, available data suggest that VIG reduces morbidity and mortality associated with progressive vaccinia (vaccinia necrosum) and eczema vaccinatum. Furthermore, VIG seems to prevent vaccinial superinfection in patients with inflammatory skin diseases or burns, given the low incidence of vaccina-related complications associated with these conditions.

Myocarditis, Pericarditis, and Dilated Cardiomyopathy after Smallpox Vaccination among Civilians in the United States, January-October 2003

Myocarditis was reported after smallpox vaccination in Europe and Australia, but no association had been reported with the US vaccine. We conducted surveillance to describe and determine the frequency of myocarditis and/or pericarditis (myo/pericarditis) among civilians vaccinated during the US smallpox vaccination program between January and October 2003. We developed surveillance case definitions for myocarditis, pericarditis, and dilated cardiomyopathy after smallpox vaccination. We identified 21 myo/pericarditis cases among 37,901 vaccinees (5.5 per 10,000); 18 (86%) were revacinees, 14 (67%) were women, and the median age was 48 years (range, 25-70 years). The median time from vaccination to onset of symptoms was 11 days (range, 2-42 days). Myo/pericarditis severity was mild, with no fatalities, although 9 patients (43%) were hospitalized. Three additional vaccinees were found to have dilated cardiomyopathy, recognized within 3 months after vaccination. We describe an association between smallpox vaccination, using the US vaccinia strain, and myo/pericarditis among civilians.

Myocarditis: the unexpected return of smallpox vaccine adverse events.

adults in their 20s or 30s, and the complication rate increases with age with vaccinia and many other viral infections. Finally, earlier studies were mostly retrospective surveys for known complications. During 2003, active surveillance complementing enhanced passive surveillance of the recent US military and civilian vaccinees was done for both known and unknown adverse events. It is increasingly essential to monitor and respond to vaccine safety concerns, because as national immunisation programmes mature with high vaccine coverage, there is decreased incidence of target diseases, increased visibility of adverse events, and possible loss of confidence (figure, stage 3). Tragically the classical paradigm of eradicating a vaccine-preventable disease and then stopping vaccinations to eradicate adverse events (figure, stage 5) may now be obsolete in the face of bioterrorism. Historically, susceptible native populations have been decimated by introduction of new diseases, and it would now seem unwise to deliberately create an immunity vacuum. Unfortunately, continuation of immunisation means that much of the cost savings initially envisioned to justify disease-eradication programmes no longer exist. We need therefore to strive to develop safer vaccines and/or safer vaccination strategies, including for smallpox, which can be used indefinitely with minimum risk.

Development of a Risk-Priority Score for Category A Bioterrorism Agents as an Aid for Public Health Policy

In developing public health policy and planning for a bioterrorist attack or vaccination of military personnel, the most common method for assigning priority is using the probability of attack with a particular agent as the single criterion. Using this approach, smallpox is often dismissed as an unlikely threat. We aimed to develop an evidence-based, systematic, multifactorial method for prioritizing the level of risk of each category A bioterrorism agent. Using 10 criterion, anthrax scored the highest, followed by smallpox. Tularemia was the lowest scoring agent. We suggest that such a system would be useful for developing public policy, stockpiling of vaccines and therapeutics, vaccination of military personnel, and planning for public health responses to a bioterrorist attack.

Evaluating Public Health Responses to Reintroduced Smallpox via Dynamic, Socially Structured, and Spatially Distributed Metapopulation Models

The risk of smallpox reintroduction has motivated preparations in potential target countries. After reproducing the spatiotemporal pattern after the 1972 importation into Yugoslavia via coupled, biologically realistic systems of ordinary differential equations, we developed dynamic population models with current US age distributions and typical spatially distributed social structures. Surveillance and containment (S&C) coupled with vaccination of 95% of hospital-based health care workers (HCWs) within 2 days after the first diagnosis (estimated to be 18 days after aerosol release) were modeled after simulated exposure of 10, 50, or 10,000 people in various settings. If 90% of patients were isolated within days after symptom onset and 75% of contacts were vaccinated and monitored, S&C would reduce cases by 82%-99%. Preemptive immunization of HCWs, closing of schools, and even vaccination of as many as 80% within 1 week would have small marginal benefits. Preparations should emphasize stockpiling vaccine, training HCWs, improving laboratory capacity, and fostering an understanding of S&C.

Severe Headaches Following Smallpox Vaccination

Headaches are common following smallpox vaccination; the re‐introduction of civilian vaccination necessitates better understanding of the clinical features and outcome of postvaccination headache. We identified patients reporting headache following vaccination from among those reported to the U.S. Vaccine Adverse Events Reporting System to characterize demographic and clinical features. One‐hundred and eight reports were obtained from among 627 smallpox vaccine‐related reports, including 15 hospitalized persons. None had neurologic dysfunction or acute laboratory abnormalities; headache resolved in all except 2 hospitalized patients within 3 months. Severe headache following smallpox vaccination is generally transient, but debilitating headache may occur and further characterization is needed.

SAHEL NUTRITION SURVEYS, 1974 and 1975

The Sahel region of.West-Central Africa consists of an area approximately 300 miles wide extending from 13 to 20 degrees north latitude, and including parts of Mali, Mauritania, Upper Volta, Niger and Chad. The total population of these countries is approximately 20 million in an area of 2 million square miles. Shipments of food and relief supplies to the Sahel began in 1973 following several years of inadequate rainfall. The need for a scientific evaluation of the impact of the drought on the nutritional status of the population was recognised, and the United States Agency for International Development (USAID) asked the Centre for Disease Control (CDC) of the US . Public Health Service to undertake such an evaluation. After methodological problems were worked out in 1973, the first formal survey of nutritional status took place in May, June and July of 1974. In order to measure changes since 1974, two surveys were conducted in 1975, the first after the annual harvest, and the second immediately before the rainy season, approximately one year after the 1974 survey. The results of these three surveys are the subject of this paper. The objective of the surveys was to quantify the extent of acute proteinenergy malnutrition in the rural population of that part of each country estimated to be most affected by

Nutrition Surveillance in Developed Countries: The United States Experience

Nutrition surveillance can be defined as the continuous monitoring of both the nutritional status of population groups and the economic- and food-related variables which may be predictive of the possibility of change in nutritional status. Nutrition surveillance differs from nutrition surveys in that surveillance data are collected, analyzed, and utilized in an ongoing manner while nutrition status surveys are most frequently conducted at single or multiple discrete points in time. Surveillance can also be interpreted as the analysis of time trends obtained from the results of periodic nutrition status surveys. We would suggest that this type of activity be termed monitoring. This chapter deals with surveillance in the context of a continuous ongoing system of data collection, analysis, and utilization. Although the mechanics of implementing and carrying out a nutrition surveillance system in developed countries may differ from those in developing countries, the principles remain the same.

Smallpox as a Weapon for Bioterrorism

Smallpox, the only disease ever eradicated, is one of the six pathogens considered a serious threat for biological terrorism (Henderson et al., 1999; Mahy, 2003; Whitley, 2003). Smallpox has several attributes that make it a potential threat. It can be grown in large amounts. It spreads via the respiratory route. It has a 30% mortality rate. The potential for an attack using smallpox motivated President Bush to call for phased vaccination of a substantial number of American health care and public health workers (Grabenstein and Winkenwerder, 2003; Stevenson and Stolberg, 2002). Following September 11, 2001, the United States rebuilt its supplies of vaccine and Vaccinia Immune Globulin (VIG), expanded the network of laboratories capable of testing for variola virus, and engaged in a broad education campaign to help health care workers and the general public understand the disease (Centers for Disease Control and Prevention, 2003a). This chapter summarizes the scientific and theoretical bases for use of smallpox as a bioweapon and options for preparation for defense against it.