At-birth immunisation against hepatitis B using a novel pre-filled immunisation device stored outside the cold chain.

We evaluated the immunogenicity of hepatitis B (HB) vaccine in UniJect, a pre-filled, non-reusable injection device, stored at tropical temperatures for up to one month and used to give the first dose of HB vaccine to newborns. Infants in Tabanan district, Bali, Indonesia, were given their first dose of HB vaccine with UniJect stored out of the cold chain, UniJect stored in the cold chain; or standard syringe, needle and multidose vial stored in the cold chain. Subsequent doses were given by usual means and blood samples drawn 4-6 weeks after the third dose. No significant differences were found in seroconversion rates or geometric mean titres of HB surface antibody between the three groups.

The introduction of new vaccines into developing countries.

The development and introduction of new vaccines is a costly and time consuming process. Unfortunately, those most in need--individuals in developing countries--are the last to receive these powerful disease preventing products. From the time a vaccine is first licensed in a developed country to the time most of the poor in developing countries have access to the vaccine can be 20-30 years. This delay is unacceptable. There is a great need to reduce this time span. This paper examines five ways of reducing the time span. Each of the five is essential and achieving success on all five will require a heightened level of international effort and coordination.

Lombok Hepatitis B Model Immunization Project: toward universal infant hepatitis B immunization in Indonesia.

The Lombok Hepatitis B (HB) Model Immunization Project was the first mass infant HB immunization project in Indonesia. Key aspects were the procurement of low-cost HB vaccine, integration into routine infant immunization services, and delivery of the first dose in the home within 1 week of birth. The project achieved > 90% coverage with 3 doses of vaccine. The prevalence of HB surface antigen was 1.4% in infants who received 3 doses (with the first dose within 7 days of birth) and 3.0% in those who received the first dose > 7 days after birth, compared with a baseline prevalence of 6.2% (P < .001 in each case). Most vaccine failures occurred in children born to HBe antigen-positive mothers. Antibody prevalence and titers did not correlate with protection. HB vaccine can be successfully integrated into the Expanded Programme on Immunization (EPI), strengthening the EPI and significantly reducing chronic HB infection.

Recovery of hepatitis A virus from a water supply responsible for a common source outbreak of hepatitis A.

An outbreak of hepatitis A occurred in a north Georgia trailer park served by a private well. Of 18 residents who were serosusceptible to hepatitis A virus (HAV), 16 (89%) developed hepatitis A. Well water samples were collected 3 months after illness onset in the index case and 28 days after illness onset in the last trailer park resident. Hepatitis A virus antigen (HAVAg) was detected in the samples by enzyme immunoassay from three of the five cell lines following two 30-day passages and from a fourth cell line following a third passage of 21 days.

Hepatitis B: global importance and need for control.

Hepatitis B is a disease of global importance, with greater than 300 million carriers of the virus world-wide. Hepatitis B virus (HBV) is the cause of up to 80% of cases of primary liver cancer, the single most important cause of mortality globally. In countries where HBV carrier rates reach 10%, HBV infection may account for 3% of total mortality, a level which exceeds polio-related mortality before the introduction of polio vaccine. The only means by which hepatitis B can be eventually eliminated is mass vaccination of infants with hepatitis B vaccine as part of the Expanded Programme on Immunization (EPI) in areas of the world where the HBV carrier rate exceeds 2.5%. With recent dramatic increases in hepatitis B vaccine production and decreases in per-dose price, there are grounds for optimism that global HBV infection rates may be reduced by as much as 90% over the next 10 years.

A common-source outbreak of fulminant hepatitis B in a hospital.

A nosocomial outbreak of fulminant hepatitis B infection at a medical center in Haifa, Israel, between 7 and 26 June 1986, involved five patients who had been hospitalized previously in the medical ward in late April and early May (first generation). This outbreak had an unusual clinical course, with fulminant hepatic failure associated with acute renal failure from acute glomerulonephritis, leading to death within a few days. The onset dates of hepatitis were tightly clustered temporally and incubation periods were short. Extensive laboratory and epidemiologic evaluation showed that the probable common-source vehicle of transmission was a multiple-dose vial of heparin and normal saline flush solution that may have been contaminated by blood of a known HBsAg carrier, who was positive for anti-HBe, hospitalized at the same time. A sixth patient died in August 1986 (second generation), after his initial admission in June that coincided with the terminal hospitalizations of three first-generation patients. Those patients had marked coagulopathies, and transmission to the sixth patient most probably occurred through environmental contamination by patients or through cross-contamination between patients through staff. The unusually high mortality rate (5 of 6) in this outbreak has not been definitely explained.

Global control of hepatitis B through vaccination: role of hepatitis B vaccine in the Expanded Programme on Immunization.

Hepatitis B is a disease that affects people throughout the world, and over 200 million are persistent carriers of the hepatitis B virus (HBV). The chronic sequelae of this infection include chronic active hepatitis, cirrhosis, and primary hepatocellular carcinoma. The development of safe and highly effective hepatitis B vaccines now provides the means by which HBV infection, including the HBV chronic carrier state, can be prevented and the related mortality significantly reduced. The cost of these vaccines has significantly decreased and will soon approach levels at which the cost-effectiveness (cost per death prevented) of hepatitis B vaccine will be similar to that of other childhood vaccines. Integration of hepatitis B vaccine into the Expanded Programme on Immunization for mass vaccination of infants in areas where HBV infection is endemic and morbidity is high would be the most effective means of providing the coverage necessary for effective control and prevention.

Hepatitis A in Mauritius: an apparent transition from endemic to epidemic transmission patterns.

Between January 1984 and December 1985 a large outbreak of viral hepatitis occurred in the island nation of Mauritius (population 986,000). No hepatitis epidemics had occurred there since the 1930s. The outbreak involved 2428 reported cases; however, reporting levels were thought to be extremely low. All of the island's nine geographical districts were affected, but cases were concentrated in five districts mostly in the central and northern parts of the island. The highest attack rate occurred in children aged five to nine; persons above age 14 were almost unaffected. The male:female ratio of cases was 1.1:1. Evidence to support hepatitis A virus (HAV) as the infecting agent included; (1) clinical illness was compatible with hepatitis A; (2) the age profile of cases was typical for community-wide hepatitis A outbreaks; (3) the rate of positive tests for hepatitis B surface antigen in suspected hepatitis patients did not increase during the outbreak; and (4) nine of nine clinically ill children tested were serum-positive for IgM anti-hepatitis A virus antibody. Transmission was probably by the person-to-person route; no common source was implicated. The outbreak appears to represent a transition from a 40-year pattern of endemic HAV transmission on the island to an epidemic pattern.

Appearance of immune complexes during experimental hepatitis A infection in chimpanzees.

Circulating immune complexes (CICs) were detected during the course of experimental hepatitis A virus (HAV) infection in 8 of 9 chimpanzees. In all cases, the predominant class of antibody detected in the CIC was IgM. The appearance of IgM-CIC usually preceded the onset of liver enzyme elevations, and in all instances, the appearance of IgM-CIC correlated with the presence of IgM anti-HAV. Six of 8 animals tested had significant depression of C3 concentrations during the course of infection, and this depression occurred at the peak of CIC activity. Immunohistologic studies demonstrated granular deposits of IgM localized in sinusoidal cells during peak of IgM-CIC activity. IgM-CICs appear to be a fairly consistent finding during HAV infection and probably represent the viremic phase of the disease. However, they do not appear to mediate hepatocellular injury by direct action on hepatocytes.

The epidemiology and clinical outcome of hepatitis D virus (delta) infection in Jordan.

The epidemiology and clinical outcome of hepatitis D viral infection in HBsAg-positive acute hepatitis, chronic liver disease, primary hepatocellular carcinoma and the symptomless carrier state was studied in Jordan. The prevalence of hepatitis D viral infection was significantly higher in patients with chronic liver disease (18/79, 23%) and acute hepatitis (17/108, 16%) than in symptomless HBsAg carriers (2/136, 2%). The highest prevalence of hepatitis D viral infection was found in patients with primary hepatocellular carcinoma (10/15, 67%) who were also significantly older than such patients without hepatitis D viral infection. Antihepatitis D virus IgM was detected persistently in 83% of patients with antihepatitis D virus-positive chronic liver disease and transiently in 41% of patients with acute hepatitis. A trend to increased mortality was observed in acute hepatitis D viral superinfection (25%) compared to hepatitis D viral coinfection (0%) and to antihepatitis D virus-negative HBsAg-positive acute hepatitis (4%). In patients with established chronic liver disease, however, neither survival nor histological parameters of disease activity were significantly different in the antihepatitis D virus-positive and antihepatitis D virus-negative groups. While the early stage of hepatitis D viral superinfection is associated with increased mortality, it appears that in patients with late-stage chronic liver disease, severe histological activity subsides, and survival is no longer influenced by the factor of hepatitis D viral infection. However, primary hepatocellular carcinoma appears to complicate the course of those antihepatitis D virus-positive patients surviving beyond this stage.

Enterically transmitted non-A, non-B hepatitis: serial passage of disease in cynomolgus macaques and tamarins and recovery of disease-associated 27- to 34-nm viruslike particles.

An experimental model of enterically transmitted non-A, non-B hepatitis (ET-NANBH) was established in tamarins (Saguinus mystax mystax) and cynomolgus macaques (Macaca fascicularis). First-passage animals were inoculated with two different stool suspensions obtained from human patients with well-defined ET-NANBH that originated from Burma and Pakistan, where epidemics of ET-NANBH occur. Both inocula contained 27- ato 34-nm-diameter viruslike particles (VLPs) that were specifically aggregated by acute-phase ET-NANBH sera. ET-NANBH was subpassaged in both tamarins and cynomolgus macaques by using pools of stool suspensions from first-passage animals. One additional passage of disease in cynomolgus macaques resulted in a significantly shortened incubation period and increased severity of disease. VLPs similar to those found in the human inocula were observed in stool specimens of first-, second-, and third-passage cynomolgus macaques and in first- and second-passage tamarins. Our findings indicate that cynomolgus macaques are particularly suitable experimental models for studies of human ET-NANBH. The 27- to 34-nm VLPs found in infected human and primate stools appear to be etiologically linked to disease.

Hepatitis delta virus infection and Labrea hepatitis. Prevalence and role in fulminant hepatitis in the Amazon Basin.

To define more exactly the epidemiology of delta virus infection and confirm its role in causing fulminant Labrea hepatitis in the Amazon Basin, we studied the prevalence of delta virus infection among persons with acute and chronic hepatitis B virus infection in the Boca do Acre district of the southern Amazon Basin. Delta virus infection was found in 24% of asymptomatic hepatitis B virus carriers, 29% of acute nonfulminant hepatitis B cases, 74% of fulminant hepatitis B cases, and 100% of chronic hepatitis B cases. Chronic delta virus infection occurred primarily in older children and adults, while acute and fulminant delta virus infection occurred in young children as well. In fulminant hepatitis cases, delta virus superinfection of hepatitis B virus carriers was the most common serological pattern; histopathologic examination showed features identical to those described in fulminant hepatitis cases of similar etiology in Colombia and Venezuela. Delta virus infection is highly endemic in the southern Amazon Basin and is the principal cause of Labrea hepatitis.

Epidemic non-A, non-B hepatitis in patients from Pakistan.

Epidemic non-A, non-B hepatitis was diagnosed in three young Pakistani men during a 10-month period at the Los Angeles County-University of Southern California Medical Center. All three patients had recently visited or lived in Karachi, Pakistan. None had serologic markers of hepatitis B virus infection or IgM antibody (acute-phase) to hepatitis A virus. A liver biopsy from one patient showed marked cholestasis and cholangiolar transformation of hepatocytes, a pattern previously described in patients with epidemic non-A, non-B hepatitis. Immune electron microscopy of a stool specimen obtained from this patient 10 days after the onset of symptoms showed virus-like particles, 27 nm in diameter, that were specifically aggregated by antibody contained in acute-phase sera from the three Pakistani patients, from patients with non-A, non-B hepatitis in Burma and Nepal, and from an experimentally infected marmoset. Recognition of three separate cases of probable epidemic-type non-A, non-B hepatitis in patients at one institution during such a short time suggests that Pakistan is endemic for this infection and that the disease may be more commonly spread to the United States than is now presumed.

The effect of underreporting on the apparent incidence and epidemiology of acute viral hepatitis.

To determine if passively reported cases of acute viral hepatitis are representative of the affected population, an active surveillance system was set up that identified all persons in Pierce County, Washington, who had been diagnosed by a physician as having acute viral hepatitis in the period March 1 through August 31, 1984. In this county, this was part of an ongoing epidemiologic study of viral hepatitis that had previously included some stimulation of reporting. The active surveillance system covered all primary sources of medical care, including all private physicians who were most likely to see persons with hepatitis. Secondary sources, those that did not provide direct medical care but might be aware of new cases, were also surveyed. The results of active surveillance showed that passive reporting was about 65% complete in Pierce County. No change occurred in the number of hepatitis A cases reported, but hepatitis B cases increased by 50%, and non-A, non-B hepatitis cases increased by 138%. Most of the increase was a result of enhanced reporting from private physicians. The two risk groups most affected by underreporting were homosexual men with hepatitis B and blood transfusion recipients with non-A, non-B hepatitis. During active surveillance, the proportion of persons with hepatitis B who reported homosexual activity was 52% compared with 20% from passive surveillance. Transfusion recipients represented 24% of the non-A, non-B hepatitis reported from active surveillance compared with 9% reported from passive surveillance. Although Pierce County may not be representative of all counties in the United States, persons responsible for public health prevention programs should recognize that data acquired through passive surveillance may not accurately reflect the magnitude of the risk for specific populations or the amount of disease that can be prevented.