Prevention of infections hepatitis by gamma globulin

Infectious hepatitis, a viral disease, has become increasingly more important in recent years. It is believed that the great increase in reported cases is not due entirely to better reporting, but that there has been an actual increase in the incidence of this disease. The comparatively long incubation period in infectious hepatitis, the high incidence in persons in close contact with patients who have the disease, and the fact that in most instances contact between persons is the mode of spread, makes this disease particularly suitable for the use of an immunizing agent which would be administered after exposure. From the studies reviewed it is apparent that gamma globulin is of value in preventing hepatitis both when administered as mass prophylaxis in an epidemic, and when given to persons in close contact with a person who has the disease. Widespread use of gamma globulin prophylactically among persons who have been in close contact with the occasional patients with infectious hepatitis seen by practicing physicians might often obviate the need for mass immunization. It should be stated that there is little evidence for the effectiveness of gamma globulin in the therapy of infectious hepatitis. In a study in which very large amounts (average dose 45 cc.) of gamma globulin were given very early in the disease, no significant difference was observed between those injected and a control group.     

INFECTIOUS HEPATITIS—Report of an Outbreak of 24 Cases

In an epidemic of 24 cases of infectious hepatitis in a small lumbering community, the majority of cases occurred in children. Sixteen of them were pupils in one school. The school apparently was the focus for the spread of infection, which is thought to have been through contact between persons. Five multiple case households with eight secondary cases were observed. With one exception, gamma globulin was not used for the prophylaxis of infectious hepatitis in families in which one member had the disease.     

Infectious hepatitis; report of an outbreak of 24 cases

In an epidemic of 24 cases of infectious hepatitis in a small lumbering community, the majority of cases occurred in children. Sixteen of them were pupils in one school. The school apparently was the focus for the spread of infection, which is thought to have been through contact between persons. Five multiple case households with eight secondary cases were observed. With one exception, gamma globulin was not used for the prophylaxis of infectious hepatitis in families in which one member had the disease.     

Effect of multiple gamma globulin administration on the effectiveness of seroprophylaxis in hepatitis A

The data provided by immunological and epidemiological studies carried out to determine the influence of the multiple injections of 10% commercial gamma globulin on the level of antigamma globulin formation and, in this connection, on the effectiveness of the prophylaxis of hepatitis A are discussed. A sharp increase in the titers of antigamma globulin in persons receiving multiple gamma globulin injections is shown. The increased amount of antibodies to gamma globulin, appearing as the result of the multiple use of this preparation, decreases the effectiveness of the seroprophylaxis of hepatitis A.     

Specific immune adherence assay for human hepatitis A antibody application to diagnostic and epidemiologic investigations.

A specific immune adherence (IA) test for hepatitis A antibody in human serum was described employing liver extract of marmosets infected with CR326 strain human hepatitis A virus. Persons with hepatitis A, but not hepatitis B, developed hepatitis A IA antibody soon after onset of the acute illness and this persisted thereafter. There was very close agreement in the tests for human hepatitis A immune adherence, complement fixing (CF) and neutralizing antibodies. IA antibodies appeared to develop somewhat later than CF or neutralizing antibody. A limited epidemiologic study of a family outbreak of hepatitis A and B in Costa Rica showed simultaneous occurrence of the two diseases and was supportive of the concept that susceptible persons in a country with high hepatitis A prevalence generally acquire their infections at an early age and are immune thereafter. Most persons of high socioeconomic level in an area of low hepatitis A incidence may proceed to adulthood without experience with hepatitis A. Person of low socioeconomic level, however, such as commercial blood bank donors and prisoners, show high incidence of hepatitis A antibody. Hepatitis IA and CF antibodies persisted in human subjects for at least 7 hr after hepatitis A virus infection. Captive chimpanzees and grivet and rhesus monkeys, not given hepatitis A virus, showed evidence of previous experience with human hepatitis A or an antigenically related virus based on tests for hepatitis A antibody. Other subhuman primates, rodents, and swine, not given hepatitis A virus, were without hepatitis A antibody. The IA test provides an excellent tool for diagnostic and epidemiologic investigations of hepatitis A and should be of considerable value to detect hepatitis A virus in attempts to propagate the virus in cell culture. There was considerable difference in hepatitis A IA antibody content of different lots of commercial human immune globulin, though the majority titered 1:4000 or 1:8000.     

Advisability of carrying out mass prevention of infectious hepatitis with gamma globulin

In Vilnius 15,183 pupils in 20 schools were observed for two years; in October, 1966, gamma globulin prophylaxis of infectious hepatitis was carried out among all the pupils of these schools. 17.062 pupils in 27 schools, who received no gamma globulin, were used for control. At the end of the first year of observation morbidity rate among the immunized children was found to be considerably lower than among the school children of the control group. During the second year of observation morbidity rate among the children of the "old" immunized group increased 3.5-fold and did not significantly differ from morbidity rate among the children of the control group. The latter increased 1.8-fold. The authors have come to the conclusion that the effect of gamma globulin prophylaxis on the epidemic process depends on the method of such prophylaxis. The method of prophylaxis by introducing gamma globulin immunization with universal coverage, as the use of the former method is not followed by an increase in total morbidity (i.e. among both immunized and nonimmunized children) during the second year after immunization, which is observed after prophylaxis by universal immunization.     

Effectiveness of the seroprophylaxis of tick-borne encephalitis depending on the titer of homologous gamma-globulin antihemagglutinins

To give a rationale for using homologous gamma globulin with antihemagglutinin titers of 1 : 20 to 1 : 80 for the prophylaxis of tick-borne encephalitis, 5-year observations covering all persons attacked by ticks in one of the intensive natural foci of the disease in the Western Urals have been made. The threefold statistically significant difference in the morbidity rate of tick-borne encephalitis between groups of persons immunized and not immunized with gamma globulin has been shown.     

Hepatitis A outbreak in Anchorage,Alaska, traced to ice slush beverages.

The Alaska Department of Health and Social Services investigated a community outbreak of hepatitis A in Anchorage. A total of 57 persons who had hepatitis A between June and September 1988 were studied. Patients ranged from 1 to 54 years of age. A market was implicated as the source of the outbreak. An employee who prepared beverage mixtures in a bathroom was a contact of a person who had had hepatitis A 2 months before the outbreak; the employee was reported to have been jaundiced 3 to 4 weeks before the peak of the outbreak. The administration of immune globulin had an efficacy of 100% (95% confidence limits 69, 100%) in preventing hepatitis A among household contacts of primary cases. Similar beverages are sold by convenience markets and many other businesses nationwide. It is important to ensure that safe food-handling practices are followed by such establishments.     

Viral Hepatitis: Problems of Incidence and Control in Military Personnel

(A) Hepatitis B virus (HBV) is now the major cause of infectious viral hepatitis in U.S. military personnel and probably also in the civilian population over 15 years of age. (B) The incidence of icteric, viral hepatitis is much higher in U.S. military personnel than in comparable age groups in the civilian population. The 17-to 20-year-old enlisted men show the highest rates. (C) In parts of the world (e.g., U.S.A., Germany) where most of the inapparent infection is caused by the adw subtype of HBV, most of the acute clinical disease is caused by the ayw subtype. In the U.S.A. and Germany, 95% or more of HB_s Ag isolates from U.S. military personnel with acute hepatitis is ayw. (D) It may be many years before one can expect to have sufficient data for a decision as to the possible availability of an effective HBV vaccine. Accordingly, a decision is urgently needed regarding either the immediate use of the best practically available hepatitis immune gamma globulin, that can be prepared by modern techniques, for the prevention of hepatitis in U.S. military personnel or postponement of such use until an adequate and properly controlled trial can be carried out in active duty military personnel in an area of high incidence.     

Clinico-epidemiologic characteristics of infectious hepatitis in a populated area where hepatitis had not been reported for a long time

The analysis of the clinico-epidemiological characteristic of infectious hepatitis in a populated area in the Kashkadarya region of the Uzbek SSR, where the cases of infectious hepatitis were not formerly registered for a long time, is presented. The epidemic process was found to take and intensive course with the formation of a large number of foci with 2 or more patients, an in the age groups of 20-29, 40 years and older a comparatively high morbidity rate, exceeding that among the total population 2-3 times, was registered. A low proportion of patients under 14 years (21.1%) was probably due to the planned preventive gamma globulin immunization carried out in this area.     

Epidemiology of viral hepatitis in the Estonian SSR

The epidemiological peculiarities of viral hepatitis in the Estonial SSR as a whole, as well as in Tallinn and in the surrounding Harju region were studied. The study revealed that during the last 10 years the total decrease of morbidity in viral hepatitis was observed due to a decrease in infectious hepatitis, pronounced periodic and seasonal morbidity fluctuations being absent. A sharp decrease in infectious hepatitis morbidity had been achieved by carrying out planned gamma globulin prophylaxis among children. Viral hepatitis morbidity in the republic was determined by the adult population and manifested as sporadic cases of infectious and serum hepatitis. Infectious hepatitis was transmitted mainly through every day contacts, while the leading factor in the transmission of serum hepatitis consisted in various injections. The relatively high morbidity level of serum hepatitis was mainly determined by morbidity in large cities.     

Assessment of British Gammaglobulin in Preventing Infectious Hepatitis

A series of 87 controlled trials of the effectiveness of British gammaglobulin in preventing infectious hepatitis in schools and other institutions showed that gammaglobulin is very effective in these circumstances. No protection was given for the first two weeks after injection, probably because it was given during the incubation period of the hepatitis.The risks of developing hepatitis in contacts was found to vary greatly. In day schools there was usually little tendency for the disease to spread among the population, but the pupils in closest contact were at greater risk. In mental hospitals and children''s homes, on the other hand, the tendency for the disease to spread was more pronounced.     

Chemoprevention trial of human hepatitis with selenium supplementation in China

A three-year study has been conducted for prevention of infectious hepatitis with supplementation of table salt fortified with 15 ppm anhydrous sodium selenite to the general population of 20,847 persons in a township M.Z. at Qidong County, Jiangsu Province, China. The results showed that the incidence of virus hepatitis infection in the test township was significantly lower than that of controls provided with normal table salt. The incidence rate of infectious hepatitis in the treated township M.Z. was 1.20 and 4.52 per 1,000, whereas the average incidence in the 6 surrounding control townships was 2.96 and 10.48 per 1,000 in 1986 and 1987, respectively. The incidence of hepatitis B surface antigen (HBsAg+) was 13.2% vs 19.23% for males and 10.42% vs 12.24% for females in the supplemented vs nonsupplemented neighboring township, respectively. Epidemiological studies have demonstrated that a low grain Se content is associated with a high regional incidence of hepatitis B virus infections.     

Outbreak of Hepatitis A on an Offshore Petroleum Platform,Alaska

An outbreak of 8 cases of hepatitis A among the 36-member crew of an offshore Alaska petroleum production platform was linked to a previous outbreak in an urban day-care center. Transmission of hepatitis A on the platform related most plausibly to refrigerated food items contaminated by a cook with mild disease. Control efforts included identifying and treating contacts of case patients who had traveled far from the platform before becoming ill. Early serologic confirmation of diagnosed cases and rapid reporting to public health authorities are essential to prevent disease transmission. Timely investigation can limit the administration of immune globulin to persons at high risk of contracting the disease.     

Detection of core antibody in hepatitis B infection.

Hepatitis B core antigen (HBcAg) is found on the decoated Dane particle and on a morphologically similar particle detected mainly in the nucleus of hepatocytes of patients with hepatitis B. HBcAg prepared from the liver of a chimpanzee infected with hepatitis B virus was used to test human serum for core antibody (anti-HBc) by complement fixation. Anti-HBc was found in serum collected from patients with hepatitis B in both the acute and convalescent stages, from carriers of hepatitis B surface antigen (HBsAg) and from patients with chronic liver or renal disease who were carriers of HBsAg. It was not found in patients with hepatitis A or infectious mononucleosis, or in healthy persons who were not carriers of HBsAg.     

Models for transmission of disease with immigration of infectives

Simple models for disease transmission that include immigration of infective individuals and variable population size are constructed and analyzed. A model with a general contact rate for a disease that confers no immunity admits a unique endemic equilibrium that is globally stable. A model with mass action incidence for a disease in which infectives either die or recover with permanent immunity has the same qualitative behavior. This latter result is proved by reducing the system to an integro-differential equation. If mass action incidence is replaced by a general contact rate, then the same result is proved locally for a disease that causes fatalities. Threshold-like results are given, but in the presence of immigration of infectives there is no disease-free equilibrium. A considerable reduction of infectives is suggested by the incorporation of screening and quarantining of infectives in a model for HIV transmission in a prison system.     

Medical Survey of the Local Human Population to Determine Possible Health Risks to the Mountain Gorillas of Bwindi Impenetrable Forest National Park,Uganda

There has been increasing contact between mountain gorillas (Gorilla gorilla beringei) and the human population surrounding Bwindi Impenetrable Forest National Park (BIFNP) in Uganda. Due to the close taxonomic relationship between humans and gorillas there is potential for disease transmission between them. Preventing the introduction or spread of transmissible diseases to the gorillas is essential to protect them. We interviewed 301 villagers living in close proximity to BIFNP with a medical questionnaire in July, 2000. We collected information on demographics, vaccination and health history, and human/gorilla interaction. Our objectives were to estimate the prevalence of several diseases in the human population and to evaluate the risk of anthropozoonotic transmission from humans to gorillas. We found a high prevalence of disease symptoms such as coughing (72.1%) and fever (56.1%) compatible with acute infectious diseases; over half of the respondents (59.1%) had a specific disease diagnosis within the 6 mo preceding the study. We compared villagers who had visual contact with gorillas in the 6 mo preceding the study (53.5%) to villagers who had no visual contact (46.5%). Men were 2.3 times more likely than women to have visual contact with gorillas. In general, the frequency of disease history and symptoms was similar for people with and without contact. The high prevalence of acute infectious diseases in the population surrounding BIFNP and the high rate of contact with gorillas creates the potential for anthropozoonotic disease transmission.     

Significance of Rh-sensitization during Pregnancy: Its Relation to a Preventive Programme

A study of the incidence of Rh-sensitization showed a 6.5% incidence of anti-D appearing for the first time during the last trimester of pregnancy. In 24 of the 29 subjects these antibodies were weak, and were found only when a sensitive technique using enzyme-treated Rh-deletion test cells was employed. The remaining five, however, had high-titre antibodies, which were associated with a positive Coombs test on cord blood.Rh-immune globulin administered at delivery resulted in disappearance of the anti-D in all but one of the subjects with weak antibody to whom it was given, suggesting that this treatment can reverse early sensitization. There was no effect when Rh-immune globulin was given to one subject with a high anti-D titre.Since sensitization has been found to occur frequently during the last trimester of pregnancy, an antenatal schedule of prophylaxis is advocated.     

Generation interval contraction and epidemic data analysis

The generation interval is the time between the infection time of an infected person and the infection time of his or her infector. Probability density functions for generation intervals have been an important input for epidemic models and epidemic data analysis. In this paper, we specify a general stochastic SIR epidemic model and prove that the mean generation interval decreases when susceptible persons are at risk of infectious contact from multiple sources. The intuition behind this is that when a susceptible person has multiple potential infectors, there is a "race" to infect him or her in which only the first infectious contact leads to infection. In an epidemic, the mean generation interval contracts as the prevalence of infection increases. We call this global competition among potential infectors. When there is rapid transmission within clusters of contacts, generation interval contraction can be caused by a high local prevalence of infection even when the global prevalence is low. We call this local competition among potential infectors. Using simulations, we illustrate both types of competition. Finally, we show that hazards of infectious contact can be used instead of generation intervals to estimate the time course of the effective reproductive number in an epidemic. This approach leads naturally to partial likelihoods for epidemic data that are very similar to those that arise in survival analysis, opening a promising avenue of methodological research in infectious disease epidemiology.     

Epidemiologic and clinical features of infectious hepatitis in children against a background of massive prevention of the disease with microdoses of gamma-globulin]

The authors analyzed epidemiological and clinical peculiarities of infectious hepatitis in children aged under 11 years in conditions of mass-gamma-globulin prophylaxis in microdoses the last 5 years in Voronezh. It appeared that the incidence of the disease fell and that its clinical course became milder. In connection with reduction of the incidence of infectious hepatitis in the age group of under 10 years, the incidence of the disease was relatively higher in children aged from 10 to 14 years, with a tendency to levelling-out the periodic autumno-winter elevations among preschool children. Introduction of decreased gamma-globulin dose for hepatitis prophylaxis led to a lesser expenditure of the preparation and thus permitted to vaccinate more children.