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Biomedical subjects

W H Bancroft

Publications and source records attributed to W H Bancroft.

At least 37 records · Page 2Linked to original sources

Subcutaneous administration of inactivated hepatitis B vaccine by automatic jet injection.

To assess the feasibility of jet injection for mass immunization against hepatitis B virus, inactivated, alum-adsorbed hepatitis B vaccine (Merck, Sharp, and Dohme Research Laboratories, West Point, PA) was administered subcutaneously by automatic jet injection to 19 volunteers lacking antibody to hepatitis B surface antigen (anti-HBs). Three 20-microgram doses were given at 0, 1, and 6 months. Of 19 volunteers, 5 (26%) developed anti-HBs by 1 month after the first injection, and 15 of 19 (79%) were anti-HBs-positive 6 to 8 weeks after the first booster administration. Following the second booster, 16 of 19 (84%) recipients had detectable anti-HBs. Possible systemic reactions were limited to low-grade fever (37.8 degrees C) in one volunteer following one injection, and mild lethargy in a second recipient. Local reactions to jet injection of vaccine occurred more frequently, with indurated, nodular lesions 3-10 mm in diameter developing at the site of 19 of 57 (33%) vaccine injections, compared with 2 of 57 (3%) saline placebo injections. Such nodules were generally painless. Sore arms were noted in 11 of 57 (19%) vaccine injections. With the exception of frequent but minor local reactions, subcutaneous administration of inactivated hepatitis B vaccine by automatic jet injection is safe, and results in vaccine immunogenicity approximating that associated with intramuscular needle injection.

Adult↗

Dengue 2 vaccine: dose response in volunteers in relation to yellow fever immune status.

A live dengue 2 vaccine was tested in 38 volunteers in an evaluation of the safety, infectivity, and immunogenicity of doses of 10(1.8)-10(5.5) plaque-forming units. Twenty yellow fever-immune and 18 yellow fever-nonimmune individuals received 0.5 ml of vaccine sc. Immunization was dose related in yellow fever-immune volunteers, with a 50% immunizing dose of 10(3.3) plaque-forming units. In the group not immune to yellow fever, some but not all recipients of each vaccine dilution were immunized, and no 50% immunizing dose could be estimated. Volunteers immune to yellow fever developed adequate titers of neutralizing antibody to dengue 2 virus and maintained them for at least three years; those not immune to yellow fever developed lower antibody titers that disappeared within six months in half of the cases. More than 40 isolates of dengue 2 virus from 12 volunteers retained the in vitro growth characteristics of the vaccine virus; this result affirmed the genetic stability of the virus. Common clinical signs in immunized individuals were leukopenia (55%), macular rash (15%), and fever (10%).

Adolescent↗

Etiology of viral hepatitis in American soldiers.

To define better which types of hepatitis are prevalent among American soldiers, the authors studied 413 separate episodes of acute viral hepatitis among 412 soldiers admitted to US Army hospitals during 1978-1979. Most soldiers (68.8%) had acute hepatitis B (estimated annual hospitalization rate: 5.41/1000 soldiers in West Germany, 2.51/1000 in South Korea, less than 1/1000 in the United States). Subtype ayw was predominant in Germany, whereas adr was predominant in South Korea. Hepatitis B was more often associated with contact history or parenteral use of drugs in West Germany than in South Korea (p less than 0.001). Non-A, non-B hepatitis accounted for 27% of cases in West Germany (2.16/1000), but only 3% in South Korea (0.11/1000); hepatitis A only 15% in South Korea (0.48/1000) and 1% in West Germany (0.08/1000). These findings indicate that hepatitis B is the most prevalent form of viral hepatitis among US soldiers worldwide but also suggest substantial differences in the epidemiology of this infection in South Korea and West Germany. Such data will be useful in developing hepatitis B immunization policy within the military.

Adult↗

Dengue-2 vaccine: infection of Aedes aegypti mosquitoes by feeding on viremic recipients.

Colonized Aedes aegypti mosquitoes were fed on voluntary recipients of an experimental, live, attenuated, dengue type 2 (PR 159/S-1) vaccine to estimate the frequency of vector infection and the stability of the virus in mosquitoes. Two volunteers were viremic at the time of mosquito feeding, but only two of 114 mosquitoes that took a viremic blood meal became infected with the vaccine virus. Strains of virus recovered from the bodies of the mosquitoes and the volunteer's blood retained the temperature sensitivity and small plaque growth characteristics of the vaccine virus. Dengue viral antigen was not detectable in any of the mosquito heads by direct immunofluorescence and in vitro virus transmission by droplet feeding was not observed. This experiment showed that vector mosquitoes can be infected with vaccine virus by feeding on viremic vaccinees. Furthermore, the virus is sufficiently stable to retain the in vitro growth characteristics associated with the vaccine virus.

Aedes↗

IgM antibody to hepatitis B core antigen as a diagnostic parameter of acute infection with hepatitis B virus.

Because many patients with acute hepatitis B lack detectable hepatitis B surface antigen (HBsAg), a radioimmunoassay for IgM antibody to hepatitis B core antigen (anti-HBc) was developed and evaluated as a diagnostic test. IgM anti-HBc was detected in each of 47 patients with acute hepatitis and transient HBsAg (geometric mean titer, greater than or equal to 1:191,000), but also in five of 12 HBsAg carriers (geometric mean titer, 1:459) and one of 46 healthy individuals positive for anti-HBc. However, it was not present in one patient during the first six months of a persistent infection. Of 255 patients with acute hepatitis and HBsAg and/or anti-HBc, 210 were HBsAg-positive whereas 230 had IgM anti-HBc. The latter was the only specific marker in 12.3% of all cases of acute hepatitis B. Thus, IgM anti-HBc is a valuable marker for the diagnosis of acute infection with hepatitis B virus.

Acute Disease↗

Dengue-2 vaccine: virological, immunological, and clinical responses of six yellow fever-immune recipients.

Six male volunteers, previously immunized with yellow fever vaccine, were inoculated subcutaneously with a live, attenuated dengue-2 virus (PR-159/S-1) candidate vaccine. Five recipients developed viremia 8 or 9 days after vaccination, which lasted 1 to 10 days. The onset of viremia was followed by fever in three people, transient leukopenia in four, and an erythematous rash in one. One volunteer developed an oral temperature of 38.8 degrees C with headache, myalgia, fatigue, and photophobia suggestive of mild dengue fever. All five viremic volunteers developed fourfold or greater rises in serum neutralizing antibody. The sixth volunteer, who had a low titer of preexisting dengue-2 neutralizing antibody, had no viremia, no symptoms, and a modest rise in hemagglutination inhibiting antibody. Virus isolates obtained from plasma retained the small-plaque and temperature-sensitive growth characteristics of the vaccine virus in vitro. In this study, the vaccine virus genetically stable and immunogenic and seemed sufficiently attenuated for additional testing in humans.

Adult↗

Dengue in Jamaica.

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Dengue Virus↗

Experimental transmission of hepatitis B virus by semen and saliva.

The ability of human semen and saliva to transmit hepatitis B virus (HBV) by parenteral and nonparenteral routes was studied. Semen, donated by a hepatitis B surface antigen (HBsAg)- and hepatitis B e antigen (HBeAg)-positive carrier, was administered to one gibbon by subcutaneous inoculation and to another by intravaginal instillation. Both developed HBsAg, followed by the development of antibody to HBsAg (anti-HBs) and antibody to hepatitis B core antigen (anti-HBc). Saliva from two donors who were HBsAg- and HBeAg-positive was pooled and administered subcutaneously to two gibbons and orally to five others. The animals inoculated subcutaneously developed HBsAg followed by anti-HBs, but none of the gibbons exposed orally developed evidence of HBV infection. Thus, semen and saliva of HBsAg carriers can be infectious, and venereal transmission of HBV by semen can occur. Transmission of HBV in saliva can also occur through breaks in the skin, but experimental transmission of HBV by saliva administered orally has not been accomplished.

Administration, Oral↗

A military community outbreak of hepatitis type A related to transmission in a child care facility.

An outbreak of hepatitis type A occurred among military personnel and dependents on a military post in Anchorage, Alaska, August 1976-April 1977. One hundred sixteen clinical cases of hepatitis were identified over a nine-month-period. Ninety-six per cent of those cases that were tested demonstrated IgM antibody to hepatitis A virus. A large child care facility was implicated as a major focus of hepatitis virus transmission. Sixty-four (55%) of the cases were directly or indirectly linked to the child care facility. The length of time that a child spent at the facility appeared to increase the child's risk of developing hepatitis and the risk of his transmitting the hepatitis A virus to other members of the immediate household.

Adolescent↗

Specific immunoglobulin M response to hepatitis A virus determined by solid-phase radioimmunoassay.

Immunoglobulin M antibody to hepatitis A virus (IgM anti-HAV) is found in most patients with acute type A hepatitis. To determine the duration of this IgM response as well as to confirm that IgM anti-HAV is a specific marker for acute infection, we developed a solid-phase radioimmunoassay for IgM anti-HAV. This new assay is 25-fold more sensitive than a conventional blocking radioimmunoassay for anti-HAV, and interference due to rheumatoid factor was eliminated by simultaneously testing sera against virus-free control antigen. Maximum IgM anti-HAV titers (1:6,400 to greater than or equal to 1:51,200) were detected during the first 30 days after the onset of illness. Although the IgM anti-HAV titer subsequently declined 64-fold over the ensuing 90 days, low-titer IgM anti-HAV (1:100 to 1:400) persisted in many sera for 90 to 150 days. Acute sera having an IgM anti-HAV titer of greater than or equal to 1:25,600 possessed a significantly higher mean IgM concentration (492 mg/dl) than acute sera with an IgM anti-HAV titer of less than or equal to 1:12,800 (344 mg/dl; P < 0.05). IgM anti-HAV titers did not correlate with other clinical or laboratory measures of disease severity. Detection of IgM anti-HAV proved to be both a highly specific (>99%) and a sensitive (>99%) method for the diagnosis of type A hepatitis.

Animals↗

Seroimmunity to polioviruses in U.S. Army recruits.

Titers of neutralizing antibody to poliovirus types 1, 2, and 3 were determined for serum specimens obtained from 268 U.S. Army recruits. Among those tested, 20.9% lacked neutralizing antibody to one or more types of poliovirus, and 1.1% lacked antibody to all three types. An analysis of demographic data showed that age of less than 18 years, schooling for less than 10 years, and residence in the northeastern United States were associated with higher percentages of recruits lacking neutralizing antibodies to polioviruses in serum.

Adolescent↗

Lack of specific effect of adenine arabinoside, human interferon, and ribavirin on in vitro production of hepatitis B surface antigen.

PLC/PRF/5 hepatoma cells continue to produce hepatitis B surface antigen (HBsAg) after greater than 80 passages in vitro, but they do not express other markers of heaptitis B virus (HBV) replication. In this respect, they resemble most liver cells that are persistently infected with HBV. PLC/PRF/5 cells were cultured in the presence of adenine arabinoside, human fibroblast interferon, and ribavirin to determine whether production of HBsAg was sensitive to these antiviral agents. HBsAg released into culture media was detected by radioimmunoassay, and cellular protein synthesis was assessed by [3H]amino acid incorporation studies. A dose-related inhibition of HBsAg occurred with each antiviral agent that was tested, but in each case, this inhibition was matched by a reduction of cellular protein synthesis to a similar degree. Thus, no specific effect on the production of HBsAg was found with any of the antiviral agents tested.

Amino Acids↗

Effect of immune status on dengue 2 virus replication in cultured leukocytes from infants and children.

Cord blood leukocytes from neonates with maternal dengue antibody supported dengue 2 virus replication in vitro; those from neonates without maternal antibody did not. Cord bloods of infants born to dengue-immune mothers contained a potent enhancing factor which gradually decayed with age and which was absent from neonates born to nonimmune mothers. Permissiveness of cultures of washed peripheral blood leukocytes from infants with maternal antibody declined steadily with increasing age in parallel with the decay of maternal antibody, and the leukocytes were no longer permissive after 10 to 12 months. The demonstration of a dengue maternal infection-enhancing factor in human cord blood from dengue-immune mothers supports the hypothesis that severe primary dengue hemorrhagic fever with shock seen in Bangkok infants is related to maternal immune status.

Age Factors↗

Effect of passage history on dengue-2 virus replication in subpopulations of human leukocytes.

Three passage levels of dengue-2 virus strain PR-159, obtained during the course of deriving the attenuated S-1 vaccine, were tested for their ability to replicate in subpopulations of human peripheral blood leukocytes: (i) 6th primary African green monkey kidney (PGMK) cell passage (parent virus); (ii) 19th PGMK cell passage of a small-plaque-forming clone derived from the parent virus (S-1 PGMK virus); and (iii) virus derived by four additional passages of the S-1 PGMK virus in diploid fetal rhesus lung cells (S-1 vaccine virus). Replication of these PR-159 viruses and another strain of dengue-2 virus adapted to Raji cells (16681-Raji virus) was measured in adherent and nonadherent mononuclear cells. All viruses except the S-1 PGMK virus replicated in monocytes. Occasional replication of the S-1 PGMK virus was associated with reversion to parent virus. The addition to the monocyte cultures of low concentrations of homologous dengue-2 antibody or non-neutralizing heterologous antibody increased the yield of the parent virus as much as 400-fold. This phenomenon of immune enhancement usually enabled the S-1 PGMK virus to replicate slowly in monocytes, but the progeny virus produced large plaques similar to the parent virus. Replication of the S-1 vaccine virus in cultured monocytes did not result in the appearance of large plaques. We could not recover S-1 vaccine virus from monocytes harvested from infected volunteers in the same manner that monocytes from natural human infections yield wild virus. The three passage levels of PR-159 virus were tested for replication in lymphocytes in comparison with the 16681-Raji virus. Only the 16681-Raji virus replicated in human lymphocytes cultured with or without enhancing antibody.

Animals↗

Absence of leukocytes permissive to dengue 2 virus in the acute phase of dengue hemorrhagic fever.

Patients with primary dengue infection developed dengue 2 virus (D2V) permissive peripheral blood leukocytes (PBL) 2--3 weeks after infection. PBL from healthy individuals with dengue antibody were permissive to D2V in vitro, suggesting that immunologically mediated in vitro D2V permissiveness persists for a relatively long time after recovery from dengue infection. However, PBL obtained from second infection dengue hemorrhagic fever patients did not support D2V growth during the acute phase of illness but did so during convalescence. Leukocytes from dengue-immune patients with typhoid fever or non-dengue viral illness were permissive throughout both acute and convalescent phases of illness although there was tendency for increased permissiveness during convalescence. Acute phase PBL from DHF patients synthesized and secreted dengue neutralizing antibody in culture. Absence of D2V replication in these cultures was strongly, but not completely, correlated with antibody production. Other immunological mechanisms, in addition to antibody, may be operating in vitro or in vivo during acute phase dengue hemorrhagic fever to alter the permissiveness of PBL to D2V infection.

Adolescent↗

Dimethyl sulfoxide enhancement of phlebotomus fever virus plaque formation.

Dimethyl sulfoxide (DMSO)incorporated into an agar overlay containing DEAE-dextran enhanced plaque formation in Vero cells by Naples sandfly fever virus passaged in mouse brain or Vero cell cultures. No plaques were visible when DMSO was used without the DEAE-dextran, some plaques were rarely visible (less than 0.5mm) when DEAE-dextran was used without the DMSO, and up to 10-fold more plaques were clearly visible (0.5-1.5 mm) when both chemicals were used. The combined enhancing effect of DMSO and DEAE-dextran was also observed with mouse brain passaged, but not Vero passaged Sicilian sandfly fever virus. Other Phlebotomus group viruses produced a bit plaques (3-5 mm) and did not require DMSO for plaque formation, although an increase in plaque clarity was obtained with DMSO for some of them. Plaque reduction neutralization tests were assayed successfully under agar containing DMSO. The alphavirus Sindbis produced slightly larger plaques under agar containing DMSO, but there was no effect on clarity or size of plaques produced by the flavivirus dengue-2.

Arboviruses↗