Hepatitis B in the United States: ongoing missed opportunities for hepatitis B vaccination, evidence from the Behavioral Risk Factor Surveillance Survey, 2007.

PURPOSE: In the USA, the burden of hepatitis B disproportionately affects high-risk adults who alone account for more than 75% of newly reported hepatitis B virus infections each year. Despite the localization of new infections in identifiable high-risk groups, vaccination rates in this subgroup, with the exception of health care workers, remain consistently low. The purpose of this study was to characterize those at risk for hepatitis B transmission and quantify the association between missed opportunities and hepatitis B vaccination. METHODS: Data from the 2007 Behavioral Risk Factor Surveillance Survey (BRFSS) of adults aged 18 years and older who were at high risk for hepatitis B infection (n = 15,432) were analyzed. Multivariate regression analysis was conducted to determine factors independently associated with vaccination. RESULTS: In a nationally representative sample, 51.4% of high-risk adults remained unvaccinated against hepatitis B and more than 50% had a missed opportunity for vaccination. High-risk adults who were vaccinated against pneumonia and influenza had a higher odds ratio of being vaccinated against hepatitis B than those not vaccinated against pneumonia and influenza (OR 2.27 and 1.67, respectively). Also, high-risk adults tested for human immunodeficiency virus (HIV) at a counseling and testing site or a drug treatment facility had a higher OR of being vaccinated than those who had not been tested for HIV (OR 1.78 and 1.73, respectively). The opposite relationship was true among individuals tested for HIV at a correctional facility (OR 0.60). CONCLUSIONS: The findings of this study underscore the inadequacy of vaccination coverage in high-risk adults and highlight advantageous opportunities to bridge gaps in vaccination coverage.

Development of vaccines for bio-warfare agents.

There is a recognized need for the development of new vaccines (as well as other biologicals and drugs) to counteract the effects of a potential bio-terrorist or bio-warfare event in the U.S. domestic population and military forces. Regulation of products to protect against potential bio-warfare agents poses unique challenges since the usual measures of efficacy that require exposure to natural disease may not currently be possible, for epidemiological and ethical reasons. To help to address this issue, the FDA has published and requested comments on a proposed animal rule intended to address certain efficacy issues for new agents for use against lethal or permanently disabling toxic substances. Recent product development activity has focused on Bacillus anthracis (anthrax) and variola major (smallpox), agents that are regarded as highest priority in posing a risk to national security. FDA resources exist to assist vaccine developers with regard to the novel challenges posed in the dinical development of these products.

Developing new smallpox vaccines.

New stockpiles of smallpox vaccine are required as a contingency for protecting civilian and military personnel against deliberate dissemination of smallpox virus by terrorists or unfriendly governments. The smallpox vaccine in the current stockpile consists of a live animal poxvirus (Vaccinia virus [VACV]) that was grown on the skin of calves. Because of potential issues with controlling this earlier manufacturing process, which included scraping VACV lesions from calfskin, new vaccines are being developed and manufactured by using viral propagation on well-characterized cell substrates. We describe, from a regulatory perspective, the various strains of VACV, the adverse events associated with calf lymph-propagated smallpox vaccine, the issues regarding selection and use of cell substrates for vaccine production, and the issues involved in demonstrating evidence of safety and efficacy.

Two-dose measles vaccination schedules.

As measles continues to exact a high toll on infant mortality, particularly in developing countries, optimal strategies for the control of the disease are under discussion. As part of this debate, the place of 2-dose measles immunization schedules is reviewed regarding their potential as a strategy to improve measles control. To date, WHO has not recommended the use of a 2-dose schedule. A number of industrialized countries have already adopted a 2-dose schedule, often choosing to administer measles vaccine in the same injection as mumps and rubella vaccines. However, at present not enough is known about such schedules in developing countries to make global recommendations. Further research should include randomized controlled trials of early 2-dose schedules to investigate both technical and epidemiological issues such as the effect of blunting immunity and the duration of antibody. Long-term safety should be determined through studies of adequate size. Programmes already using 2-dose schedules are encouraged to evaluate their impact on disease incidence, cost, vaccine usage, and effect on coverage. Until further evaluation is complete, a high and timely coverage with one dose of measles vaccine in all areas remains the first priority for all immunization programmes.

PIP: Worldwide coverage of measles vaccine is about 80%, but many communities and countries have considerably lower coverage rates. WHO is concerned about measles occurring in infants between 6 and 12 months old, especially in densely populated African cities. Measles rarely occurs in infants under 6 months old, but the measles case fatality rate is greatest in the 1st year of life. WHO aims for an effective measles vaccine to be administered at 6 months old. A high titer vaccine appears to reduce survival among children receiving it. Some countries have reduced measles incidence by as much as 90% by achieving coverage levels greater than 90% with a single dose measles vaccine. Another method to prevent early measles cases and later vaccine failures is administration of the 1st dose around 6 months and a 2nd dose no earlier than 12 months. Measles vaccine policy in the US and some countries in Europe is routine 2-dose measles schedules: 1st dose between 12-19 months and 2nd dose at school entry. This schedule is appropriate in developed countries with good immunization coverage. Other countries schedule the 1st dose anywhere between 6-9 months and the 2nd dose between 12 months and 7 years. All mathematical models of the effects of 2-dose schedules indicate that 2-dose schedule are a great benefit. The literature shows that developing countries with high immunization coverage and well-managed immunization programs can effectively execute and sustain 2-dose measles schedules. Measles vaccination early in life sometimes results in a blunted antibody response. The 2-dose schedules are probably more expensive than 1-dose schedules and require more cold storage space. No field trials have looked at clinical efficacy of 2-dose measles schedules in developing countries. Ideal field trials would be randomized controlled trials. Demonstration projects can evaluate operational issues, e.g., dropout rates, cost, and vaccine usage. Case control studies can address technical and epidemiological issues.

Carnitine deficiency: a possible cause of gastrointestinal dysmotility.

An infant with delayed development and peripheral myopathy, nourished on a soy-based liquid diet deficient in carnitine, had gastrointestinal dysmotility manifested by postprandial vomiting, oral drooling, delayed gastric emptying and infrequent bowel movements. Oesophageal manometry showed a reduced lower oesophageal sphincter pressure for age with abnormal distal motility. Serum carnitine concentration was 9.9 mumol l-1. After dietary supplementation of carnitine the gastrointestinal symptoms resolved, oesophageal manometry returned to normal, and serum carnitine increased to 37.2 mumol l-1. Dietary carnitine deficiency in infancy may be a cause of smooth muscle dysmotility of the gastrointestinal tract.

Survey of public knowledge about digestive health and diseases: implications for health education.

Increasing emphasis in recent years has been placed on health promotion, prevention, and the self-management of health care. These strategies presume the public has sufficient levels of relevant health information, as well as necessary attitudes and skills for the effective use of this information in the management of their own health care. This study tests this assumption as it relates to the level of public knowledge of digestive health and disease, a major health concern affecting an estimated 1 in 10 Americans. This paper reports results of a telephone survey of a representative national sample administered to 1,250 Americans in May 1983 that was designed to assess their level of information about digestive health and disease, comfort in communicating about digestive problems, and preference for health information sources. The results indicate that the American public is largely uninformed and misinformed about digestive health and disease, and they underscore the need for disseminating relevant health information about digestive health and disease to the public to facilitate prevention of digestive health problems and self-management of digestive health care. Health information dissemination is severely complicated by the widespread stigma associated with digestive topics, manifested in the American public's general discomfort in communicating with others about digestive health. These factors necessitate development of sensitive and pervasive digestive health promotion and education programs in the United States.

Cancer precursors and their control by BCG.

I am proposing a theory which states that stimulation of the immune system at birth detects and destroys embryonic cells or components thereof, including subcellular pattern defects, molecular structure defects and so forth which may be the source of malignancy not only in infancy but throughout life. The facts are that: Fetal rests or stigmata thereof remain in many of the organs of the body--the liver, the kidney, the spleen, the brain and so forth. These rests are usually absorbed by the end of the first year of life, but recent evidence indicates that stigmata of this fetal tissue may remain throughout one's entire life and be precursors of cancer. In animals and in humans, the antigens from malignant neoplasms crossreact with anti-fetal antibodies. Many tumors express fetal antigens and secrete fetal products. Alpha-feto-protein was found in adult cancer of the liver; carcino-embryonic antigen (CEA) has been reported in cancer of the colon-rectum; fetal alkaline phosphatase has been found in many adult cancers. Fetal tissue injected into animals will immunize these animals against certain transplanted tumors. Recently, in a lecture at Salk Institute, Sir Peter Medawar, Nobel Prize winner in medicine and until recently the head of the British Medical Research Council, described the use of quasi-fetal tissue as helpful in treating cancer of the adult. The infant's immune system is not fully developed. In fact, one can transfuse an infant without typing because he has built no antibodies to the blood types in early infancy. It has been shown in individuals of any age who are immune-deficient, either by heredity or acquired that the rate of malignancy may be as high as 10,000 times that of the general population. The immune system controls cancer development to a great extent. Published data suggests that the immune system detects and destroys embryonic cells or components thereof that may be a locus for cancer development. Our studies demonstrated that in some 85,353 BCG vaccinated newborns followed over a period of 20 years, there was an overall 74 percent reduction in the death rate from all forms of cancer when compared to a similar group not vaccinated. The differences were highly significant statistically. At an International Symposium, "BCG Vaccination Against Cancer and Leukemia" held in Chicago October 4-6, 1982, papers were presented from the U.S.A. (83), Austria (7), and Israel (54) which support the thesis of a lowering of mortality from cancer and leukemia in infants vaccinated at birth with BCG.(ABSTRACT TRUNCATED AT 400 WORDS)

Thermal injury mortality in germfree and conventional animals.

Studies in germfree (GF) rats and mice demonstrated that GF animals were as sensitive if not more so to thermal injury than conventional (CV) animals. Death occurred in both groups after a similar period of time. There was no evidence of infection in either group. Using GF animals in other forms of injury such as hemorrhagic shock, others report that death occurred with equal frequency in both GF and CV animals. It is therefore postulated that sepsis cannot be the basic cause of death in severely traumatized patients. It is of utmost importance to control the toxic effect of tissue breakdown products before the vicious cycle of depressed immunological function and malnutrition ensues. A method of neutralizing the toxic effects of thermal injury by competition is described. Competitin is an "antitoxin" produced in vitro from "toxin(s)" isolated from burned human skin. Competitins to other toxin(s) have been produced and it is postulated that competitins may also be produced from the breakdown products of all forms of injury.

Cancer precursors and their control by stimulation of the immune system.

BCG vaccination at birth according to our studies and those from Montreal, Austria, and Israel, lowers the mortality from leukemia and, in my studies, to all forms of cancer followed over a period of 20 years. It has been proposed by several studies that the lymphoreticulo-endothelial system detects and destroys neoantigens such as would be the case in remnant embryonic antigens. It follows that stimulation of the immune system would be desirable at birth to augment the removal of such neoantigens. There are numerous vaccines which stimulate the immune system, and BCG is among the foremost. I propose, therefore, that the mechanism of cancer mortality reduction in those BCG vaccinated at birth was at least in part due to the detection and destruction of embryonic cells or components thereof. To prove this theory, I recommend: Retrospective studies be done in those BCG vaccinated at birth and those not vaccinated for the incidence of cancer and leukemia over the years. Test cells, sera, and urine of those BCG vaccinated and non-vaccinated for the presence of embryonic antigens or antibodies. BCG vaccinated individuals should have lower titers of fetal antigens or antibodies than the non-vaccinated. Examine the organs on post mortem of BCG vaccinated and non-vaccinated individuals who died from trauma for the presence of fetal antigens or antibodies.

Growth failure and inflammatory bowel disease: approach to treatment of a complicated adolescent problem.

Severe retardation of linear growth occurs in a minority of children with Crohn's disease. It appears to be associated with increased disease activity and decreased caloric intake. Why some children are affected and others are not is unknown, but some degree of growth retardation is probably more prevalent than is generally appreciated. The use of somatomedin-C levels may be of some future value in predicting which children will be affected. Growth failure is often difficult to treat and requires vigorous medical and nutritional support. No current treatment is without attendant problems. Proper and frequent assessment of growth and development will help ensure intervention while growth potential still exists in these children. Large cooperative studies are needed to compare the effects of various treatment plans on the growth velocity and ultimate stature of children with Crohn's disease-related growth retardation.

Burn toxin and its competitin.

A "toxic factor' has been isolated and purified from scalded normal human skin; it is lethal to mice and toxic to HeLa and HEP2 cell lines in tissue culture. The toxic factor in both crude and purified form is antigenic in rabbits, producing an antisera that neutralizes the in vivo and in vitro effects of "burn toxin', similar to that of the convalescent sera of burned human subjects. The sonicate of the toxic glycoprotein named competitin is relatively non-lethal and protects against the lethal effect of the toxic factor. The action of the purified burn toxic factor and its competitin is at the ATP site of actomyosin preparations. The data presented suggests that the purified burn toxic factor and its competitin compete for the same receptor sites in the myocardium. A thesis is presented that states that it is vital to neutralize the toxic effects of burn breakdown tissue products in severely burned subjects before the vicious cycle of depressed immunological function and malnutrition ensues. Competitin produced in vitro from toxic factor(s) generated scalded normal human skin is offered as a means of neutralizing the toxic factors(s).