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Biomedical subjects

J P Bryan

Publications and source records attributed to J P Bryan.

At least 19 recordsLinked to original sources

A dose response study of hepatitis A vaccine in healthy adults who are > or = 30 years old and weigh > or = 77 kg.

The dose response relationship of 25-, 50-, and 100-U doses of an inactivated hepatitis A vaccine was examined in 358-seronegative volunteers in a 2-dose schedule. The 50-U and 100-U groups had statistically significantly higher seroconversion rates than the 25-U group at weeks 2, 4, 8, and 24. Seroconversion was statistically significantly greater for the 100-U compared with the 25- and 50-U doses 2 weeks after the first injection but was not significantly different by 4 weeks after the first injection in the 50- and 100-U dose groups. After 2 injections, all subjects in all groups seroconverted. The vaccine was well tolerated at all dosage levels.

Adult

Hepatitis B vaccine booster dose: low-dose recombinant hepatitis B vaccines as a booster dose.

BACKGROUND: The timing and best regimen for a booster dose of hepatitis B vaccine have not been determined. METHODS: Two studies were conducted to determine the response to a booster dose of 5 micrograms recombinant hepatitis B vaccine. In the first study, a 5 micrograms (0.5 ml) dose of Recombivax HB was administered intramuscularly 38 months after the initial dose to 71 volunteers. In a second study, we offered a 5 micrograms dose recombinant hepatitis B vaccine, either Recombivax HB (0.5 ml) or Engerix B (0.25 ml), to students who had previously been immunized with three doses of vaccine. RESULTS: In the first study, among the 44 persons for whom postbooster sera were available, the geometric mean concentration of anti-hepatitis B surface antigens increased from 42 to 2090 mIU/ml after the 5 micrograms (0.5 ml) dose of Recombivax. In the second study, after a 5 micrograms (0.5 ml) dose of Recombivax, the geometric mean concentration increased from 43 to 990 mIU/ml (n = 48), and in the group that received a 5 micrograms (0.25 ml) dose of Engerix B, the concentration increased from 83 to 2337 mIU/ml (n = 45) (p = 0.18 for postdose concentrations). CONCLUSION: A 5 micrograms dose of recombinant vaccine results in an excellent booster response at a cost one fourth to one half that of a full 1 ml dose of vaccine.

Adult

Clinical manifestations of Plasmodium falciparum malaria experimentally induced by mosquito challenge.

To determine the characteristics of clinical illness accompanying Plasmodium falciparum infection induced by controlled exposure to infected mosquitoes, records of 118 volunteers participating in studies conducted between 1985 and 1992 were reviewed. One hundred fourteen volunteers (97%) reported at least one symptom attributable to malaria, with fatigue, myalgias or arthralgias, headache, and chills most commonly reported. The median duration of symptoms was 3 days. Fever was recorded in 61% of volunteers; 4 volunteers had temperatures >40 degrees C. Neutropenia and thrombocytopenia were present in 9% and 12% of volunteers, respectively. Despite counts as low as 658/microL (neutrophils) or 73,000/microL (platelets), no secondary infectious or hemorrhagic complications occurred. In all cases, volunteers recovered completely and laboratory values returned to baseline after specific antimalarial therapy. Recrudescence did not occur in any volunteer. In this model, mosquito inoculation of P. falciparum is a reliable, safe, and well-tolerated method of experimental challenge.

Adolescent

Hepatitis B virus, human immunodeficiency virus type-1, and syphilis among women attending prenatal clinics in Belize, Central America.

Women and their infants may benefit from therapeutic interventions when hepatitis B, human immunodeficiency virus (HIV), or syphilis are detected during the prenatal period. We initiated hepatitis B and HIV screening of women attending prenatal clinics in Belize. Risk factor assessment information for hepatitis B infection and demographic data were determined by interview. Of 543 evaluable women, 81 (14.9%) were seropositive for hepatitis B core antibody (anti-HBc); one woman had asymptomatic hepatitis B surface antigenemia. Antibodies to HIV-1 were detected in one woman. Reactive syphilis serologies were detected in 15 (2.8%) women. Anti-HBc seroprevalence varied by district (range 3.1-43.5%) and by ethnicity (range 0.0-40.9%). Significant identified risks for anti-HBc seropositivity from univariate analyses included being of the Garifuna ethnic group, residence or birth in the Stann Creek or Toledo districts, a reactive syphilis serology, a household size of eight or greater, and five or more lifetime sexual partners. Multivariate analyses identified ethnicity and a reactive rapid plasma reagin as the best predictors of anti-HBc seropositivity. Highly variable differences in anti-HBc prevalence by district may permit the targeting of limited public health resources for education, screening, and prevention programs.

Adolescent

Prevalence of antibody to Trypanosoma cruzi in three populations in Belize.

Cross-sectional studies were conducted to determine the prevalence of antibody to Trypanosoma cruzi, the agent of Chagas' disease among three populations in Belize. Specimens were tested using a second-generation enzyme-linked immunoassay (EIA). Confirmatory testing with three single-antigen EIAs and a radioimmunoprecipitation assay (RIPA) were performed. Five (0.5%) of 962 blood donors at the Belize City Hospital were reactive including four (6%) of 65 donors from countries known to be endemic for Chagas' disease and one (0.1%) of 861 from Belize (P < 0.001). Among 467 healthy members of the Belize Defense Force, none were reactive. The third group included workers and families primarily from other Central American countries living on a banana plantation in a rural area of the country. Twenty-seven (6.1%) of 442 sera were reactive. The prevalence was 5.3% of 75 < 15 years of age, 4.2% of 236 15-34 years of age, and 9.7% of 124 > or = 35 years of age (P = 0.11, by chi-square for trend). The prevalence was similar in males (6.7% of 280) and females (5.8% of 154). The prevalence of those born in Belize (4 of 56, 7.1%) was similar with that of those born in El Salvador (9 of 110, 8.2%), Guatemala (6 of 117, 5.1%), and Honduras (8 of 129, 6.2%). Of the four persons with reactive sera who were born in Belize, the immigrant mother of one was also reactive, suggesting possible congenital transmission. Among 31 sera repeatedly reactive by EIA to T. cruzi that were further studied, 22 (71%) were reactive by at least two of three single-antigen confirmatory EIAs and 29 (94%) by RIPA. Additional studies should focus on the epidemiology of T. cruzi and ways to reduce risk of transfusion-related infections in Belize.

Adolescent

Epidemiology, preventive services, and illnesses of international travelers.

Medical preparation of travelers to overseas locations is an important part of military medical care. We reviewed pre-travel records of patients attending the travel clinic at the National Naval Medical Center (NNMC) and used a post-travel questionnaire to determine the most frequent medical problems associated with international travel. Among 1,416 individuals who received pre-travel care at NNMC, there were 760 (54%) males and 656 (46%) females, the median patient age was 48 years, the most common reason for travel was pleasure, and the median duration of travel was 21 days. The most common destinations were Asia (27%), Africa (15%), Europe (13%), Central America/Caribbean (12%), and South America (11%). The median number of immunizations prescribed was three. Malaria chemoprophylaxis was prescribed to 45%. The average cost of vaccines and medications to medically prepare a traveler was $67. Among 271 (82%) who returned the post-travel questionnaire, the most common illnesses reported were diarrhea (23%) and upper respiratory infections (19%); medical treatment was sought by 9%. Properly informed, military physicians can provide a valuable service at a reasonable cost to reduce the risk of travel-acquired medical problems and illnesses.

Adult

Seroprevalence of hepatitis B virus among school-age children in the Stann Creek District of Belize, Central America.

Adults in the Stann Creek District of Belize have a high prevalence of hepatitis B virus (HBV) infection, but the age of onset of these infections is unclear. We conducted a seroprevalence study of hepatitis B markers among Stann Creek school-age children to provide information for planning a hepatitis B vaccine program. The overall prevalence in 587 students was high for antibody to hepatitis B core antigen (anti-HBc) (43.3%) and hepatitis B surface antigen (HBsAg) (7.7%). There was marked variation of anti-HBc by school and by the predominant ethnic groups attending those schools. Maya had the highest prevalence (76%), followed by Mestizo (50%), Garifuna (37%), and Creole (25%). Children less than nine years of age attending the rural primary schools (mostly Mayan and Mestizo) had significantly higher prevalence of anti-HBc than did children attending the urban primary school (mostly Garifuna and Creole) (P < 0.05). Anti-HBc was found in 42% and 36% of students at the two high schools. Of the five schools tested, only at the urban primary school did anti-HBc positivity increase with age. Based on an analysis of the cost of serologic screening before immunization compared with mass vaccination, preimmunization serologic screening resulted in vaccine program cost savings in four of the five schools. Because most children in the rural areas contract hepatitis B before entering school, immunization against HBV should be integrated into the routine infant immunization program.

Adolescent

Prevalence of sand fly fever, West Nile, Crimean-Congo hemorrhagic fever, and leptospirosis antibodies in Pakistani military personnel.

To determine the prevalence of antibodies to viral diseases known or suspected to be present in Pakistan, we studied 570 sera from three groups of adults; two of the groups were involved in outbreaks of hepatitis, and the third included men admitted to a hospital for evaluation of febrile illnesses. Immunoglobulin G antileptospiral antibody was found in 1 to 6% of the subjects, with the highest rate in enlisted military personnel hospitalized for febrile illness. One man in the group with febrile illness had significantly elevated immunoglobulin M antileptospiral antibody titers. However, in a group of recruits experiencing suspected non-A, non-B hepatitis, 19 (11%) of 173 had a 4-fold rise in immunoglobulin M antibody to leptospirosis. Antibody to sand fly fever viruses was found in 27 to 70%. Antibody to West Nile virus was present in 33 to 41% of subjects. Antibody reactive with Japanese encephalitis virus was present in 25%, but plaque reduction neutralization tests suggested this to be cross-reaction with West Nile virus. All 212 specimens tested for antibody to Crimean-Congo hemorrhagic fever and Hantaan viruses were negative. This study indicates that diseases known to be prevalent in other areas of southwest Asia and the Middle East are also prevalent in northern Pakistan and may impact on those traveling or working in this area.

Adolescent

Randomized comparison of 5 and 10 microgram doses of two recombinant hepatitis B vaccines.

UNLABELLED: The high cost of hepatitis B vaccines remains an obstacle to their use. Since the recommended adult dose of Recombivax HB (MSD) is 10 micrograms and that of Engerix B (SKB) is 20 micrograms, we sought to determine if 10 microgram doses of each vaccine are equally immunogenic. Further, since 5 microgram doses of Recombivax are routinely used in those < or = 29 years of age in the US military, we sought to compare this dose with 5 microgram doses of Engerix B. Lower doses of Engerix would result in vaccine cost savings. METHODS: members of the Belize Defence Force who were > or = 18 years of age (median 24) without detectable anti-HBc were randomly assigned to receive Recombivax, 5 or 10 micrograms, or ENgerix, 5 or 10 micrograms IM at 0, 1, and 6 months. Randomization was weighted toward Engerix. RESULTS: after 3 doses, geometric mean concentrations (GMC) of anti-HBs were highest among those receiving Recombivax 10 micrograms (n=22) or 5 micrograms (n=46) with GMC anti-HBs of 744 and 570 mIU ml-1, respectively. Similar proportions in the two groups developed > or = 10 mIU m-1 anti-HBs (100 and 98%). Among the 91 people who received Engerix 10 micrograms, the GMC anti-HBs was 325 mIU ml-1 and 91% developed > or = 10 mIU ml-1. The 87 people who received Engerix 5 micrograms had the lowest GMC, 177 mIU ml-1 (p < 0.05 compared with either Recombivax group). Only 86% attained > or = 10 mIU ml-1 anti-HBs (p > 0.05 compared with other regimens). The proportion attaining > or = 100 mIU ml-1 was lower in the 5 microgram Engerix group (63%) compared with 80% in the 5 microgram or 95% in the 10 microgram Recombivax groups (p < 0.05). CONCLUSIONS: Engerix administered in 5 microgram doses is less immunogenic than 5 or 10 microgram doses of Recombivax. In healthy populations < 30 years of age, regimens of half the recommended adult dose (5 micrograms of Recombivax or 10 micrograms of Engerix) are highly immunogenic and may result in significant vaccine cost savings.

Adolescent

Prevalence of hepatitis B virus among health care workers in Belize, Central America.

A seroprevalence survey of hepatitis B virus (HBV) markers was conducted among health care workers in Belize to help determine the epidemiology of hepatitis B and to determine if screening before immunization might lower vaccine costs. Of the 330 workers tested, 94 (29%) were positive for antibody to HBV core antigen (anti-HBc) and three (1%) had HBV surface antigen. The presence of anti-HBc increased significantly with age from 12% in those 18-24 years old to 52% in those > or = 50 years old. The rate was 17% of 48 men compared with 30% of 282 women (P = 0.05). Rates increased with years of medical service and were higher among nurses (69 of 228; 30%) and nonprofessional staff (15 of 44; 34%) than among physicians (0 of 20). The presence of anti-HBc also differed significantly among ethnic groups: Mestizo, 4%; Creole, 33% and Garifuna, 57%. Rates differed by district ranging from 3% in a northern district (mostly Mestizo) to 67% in a southern district (mostly Garifuna). Parental exposure to hepatitis B through needle stick injuries and blood transfusions was not associated with anti-HBc. Multiple logistic regression analysis confirmed ethnicity, district of residence, and age as the best predictors of anti-HBc in health care workers. Cost analysis suggests that because of regional differences in exposure, testing of health care workers for anti-HBc in the Belize and Stann Creek districts in southern Belize before hepatitis B immunization would result in vaccine program cost savings.

Adolescent

Testing for antibody to hepatitis A to decrease the cost of hepatitis A prophylaxis with immune globulin or hepatitis A vaccines.

BACKGROUND: The introduction of new vaccines to prevent hepatitis A infection raises the question of the cost of these vaccines relative to immune globulin when short-term protection against hepatitis A is required. Since the prevalence of hepatitis A antibodies (anti-HAV) in the US population increases rapidly with age, testing for anti-HAV may decrease the cost of vaccination programs. METHODS: A cost-analysis model was developed that incorporates the cost of immune globulin or hepatitis A vaccine, the number of doses of vaccine, the cost of testing for anti-HAV in either commercial or public-sector laboratories, and the prevalence of anti-HAV in the general population by age. RESULTS: In comparison with hepatitis A vaccines, with expected costs between $10 and $25 per dose, use of immune globulin for postexposure prophylaxis or preexposure short-term (< or = 6 months) prophylaxis is much less expensive for all age groups. Testing for anti-HAV does not significantly diminish the cost of immune globulin regimens. In contrast, if anti-HAV testing is performed in a public-sector laboratory at $10 per test, and hepatitis A vaccine costs $10 per dose, testing reduces vaccination costs in those 40 years of age or older for a two-dose vaccine regimen and in those 30 years of age or older for a three-dose regimen. At the other end of the spectrum, if vaccine costs $35 per dose, commercial testing for anti-HAV at $25 per person reduces the costs in those 30 years of age or older if either a two- or three-dose regimen is elected. However, vaccine savings are realized in those 10 years and older if public-sector testing is performed and three doses of vaccine at $35 per dose are utilized. In an intermediate scenario of public-sector testing and vaccines costing $25 per dose, the cost would also be reduced in those 30 years old or older. CONCLUSIONS: Testing for anti-HAV in frequent travelers, international government, business, and volunteer workers, military personnel, etc, may be an effective means of decreasing costs of hepatitis A prevention.

Adolescent

Epidemic hepatitis E in Pakistan: patterns of serologic response and evidence that antibody to hepatitis E virus protects against disease.

IgM and IgG anti-hepatitis E virus (HEV) patterns were determined in sera collected during a hepatitis outbreak in Pakistan. HEV infection was detected serologically in 122 patients. IgM anti-HEV was detected in specimens collected up to 2 weeks before and 5-7 weeks after hospitalization in 91% and 100%, respectively, of 122 HEV-infected patients. IgG followed a similar pattern. Peak antibody titers appeared 2-4 weeks after hospitalization. At 20 months after hospitalization, IgM anti-HEV was not detected in any of 33 patients; IgG was found in all. IgG anti-HEV appeared to be protective in contracts of patients. This study confirms HEV as the cause of the outbreak, quantifies IgM and IgG anti-HEV responses, provides evidence that IgG anti-HEV protects against hepatitis E, and demonstrates that IgG anti-HEV persists, but at diminished titer, after infection. Hepatitis E in young adults is the result of primary infection with HEV and, if reinfection occurs, it does not commonly cause serious illness.

Antibodies, Viral

Safety, immunogenicity, and efficacy of a malaria sporozoite vaccine administered with monophosphoryl lipid A, cell wall skeleton of mycobacteria, and squalane as adjuvant.

A Plasmodium falciparum circumsporozoite protein (PfCSP) recombinant fusion protein, R32NS1(81), formulated with monophosphoryl lipid A, cell wall skeleton of mycobacteria, and squalane (Detox) was administered to 12 volunteers. One volunteer had malaise and self-limited painful induration at the injection site after the second dose and declined further immunization. The other 11 volunteers tolerated the three doses of 1,230 micrograms of vaccine, but most complained of sore arms; in five cases the pain or malaise was severe enough to interfere with work or sleep. Two weeks after the third dose of vaccine, four of the 11 immunized volunteers had > or = 14 micrograms/ml of antibodies to the repeat region of the PfCSP in their serum. Two of these four volunteers did not develop P. falciparum parasitemia when challenged by the bite of five mosquitoes carrying P. falciparum sporozoites. The seven volunteers with lower levels of antibodies and 11 of 11 controls developed parasitemia. These data are consistent with other studies, and indicate that vaccine-induced antibodies against the repeat region of PfCSP can prevent effective sporozoite infection of hepatocytes in humans. The challenge is to improve the immunogenicity of PfCSP-based vaccines, and to develop methods for including PfCSP peptides as components of multitarget malaria vaccines.

Adjuvants, Immunologic

Recombinant immunoblot assays for hepatitis C in human immunodeficiency virus type 1-infected US Navy personnel.

The prevalence of hepatitis A, B, C, and D viruses was studied in 467 military personnel with human immunodeficiency virus type 1 (HIV-1) infection. Antibody to hepatitis C virus (anti-HCV) by first-generation ELISA was found in 136 (29%). Of sera repeatedly reactive for anti-HCV by first-generation ELISA, two-antigen recombinant immunoblot assay (RIBA) was positive in 41 (32%) and four-antigen RIBA was positive in 55 (41%). Four-antigen RIBA was positive in 33 (30%) of the 109 with an OD on ELISA of < or = 2.0 compared with 22 (81%) of the 27 with an OD > 2.0 (P < .001). Anti-HCV detected by four-antigen RIBA was associated with increasing age, black or Hispanic race, and antibody to hepatitis B core antigen. When patients with hepatitis B surface antigen were excluded, elevated alanine aminotransferase was found in 5 (8%) of 63 with a negative RIBA and 13 (28%) of 47 with a positive RIBA (P = .006). While RIBA was negative in more than half of those with anti-HCV by ELISA, 55 (12%) of these HIV-1 infected personnel had anti-HCV detected by RIBA, which was associated with a strong reaction by ELISA, elevated liver enzymes, coinfection with hepatitis B, minority race, and older age.

AIDS-Related Opportunistic Infections

The prevalence of hepatitis A, B and C infection among different ethnic groups in Belize.

Little is known about the prevalence of infection with hepatitis viruses in Belize, Central America. We conducted a serologic survey among members of the Belize Defence Force (BDF), which is composed of the five major ethnic groups in Belize, to estimate prevalence rates of hepatitis A, B, and C among military-aged men and women in Belize. Of approximately 600 men and women in the BDF, 492 (82%) completed a questionnaire and blood collection. Antibody to hepatitis A was found in 94%, with similar rates by age, sex, rank, and ethnicity. Antibody to hepatitis B core antigen (anti-HBc) was found in 31%. Rates of anti-HBc varied significantly among the ethnic groups with the lowest rates in Mestizo (5%) and Mayan Indians (9%), and significantly higher rates among Creoles (30%) and Garifuna (56%). Rates increased with increasing age from 28% in those 18-24 years old to 35% in those > or = 35 years old (P = 0.07, by chi-square test for trend). Hepatitis B surface antigen was found in 21 (4%) overall. Antibody to hepatitis C was found in two (0.4%). In this young healthy population, exposure to hepatitis A before the age of 18 is almost universal, while exposure to hepatitis B is related to age and ethnic origin.

Adult

Association of hepatitis E virus with an outbreak of hepatitis in Pakistan: serologic responses and pattern of virus excretion.

Hepatitis E virus (HEV), a positive-strand RNA agent, has been associated with enterically transmitted non-A, non-B hepatitis in Asia, Africa, and Mexico. To evaluate the role of HEV in an outbreak of hepatitis in Pakistan, we used immune electron microscopy to detect 1) antibody to HEV, for evidence of infection, and 2) virus, to determine the pattern of HEV excretion. Paired sera from 2 patients were assayed for antibody by using reference HEV: one seroconverted, an atypical finding for HEV infections; the other had high levels of anti-HEV in both sera. Virus particles with the size (29 x 31 nm) and morphology of HEV were detected in feces from 10 of 85 patients and serologically identified as HEV by using reference antibodies from an HEV-infected chimpanzee. One of these HEV-containing specimens was collected 9 days before the onset of jaundice; it was among feces from 38 outpatients with nonspecific symptoms and biochemical hepatitis, 12 of whom subsequently developed jaundice. The other 9 feces with HEV were among 36 collected within 7 days of the onset of acute icteric hepatitis; all 11 feces from days 8 to 15 were negative for HEV. Fecal concentrations of HEV appeared to be lower than those of many enteric viruses: only one specimen contained as many as 5 particles per EM grid square. It is concluded that HEV was etiologically associated with the epidemic and was predominantly excreted at very low levels during the first week of jaundice.

Antibodies, Viral

Persistence of antibody to hepatitis B surface antigen after low-dose, intradermal hepatitis B immunization and response to a booster dose.

To determine the duration of antibody after low-dose, intradermal (i.d.), plasma-derived hepatitis B vaccination and the response to a booster dose, we studied two classes of medical students who were immunized with 2 micrograms doses i.d. In one class, 73/88 (85%) who had been immunized by skilled personnel at 0, 1 and 6 months, had protective concentrations (greater than or equal to 10 mIU ml-1) of anti-HBs at 20 months after the first dose. Twelve (92%) out of 13 students who received only two doses at 0 and 1 months also had protective concentrations at month 20. At month 27, 11/16 (69%) with antibody less than or equal to 10 mIU ml-1 responded to a fourth dose of 2 micrograms i.d. with protective concentrations of anti-HBs. In the second class, after three doses of vaccine at 0, 1, and 6 months, protective concentrations of anti-HBs were present in 90/93 (97%) at 14 months and in 71/80 (89%) at 25 months. In those who received only two doses, protective concentrations were found in 24/31 (74%) at 14 months and 9/16 (56%) at 25 months. After a booster dose of 2 micrograms i.d. at month 25, anti-HBs concentrations rose from a geometric mean of 78 to 1198 mIU ml-1 in 60 subjects previously immunized with three doses and from 18 to 1054 mIU ml-1 in 16 students previously immunized with only two doses. Overall, 73/76 (96%) of students in the second group had protective concentrations of antibody after the booster dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Low-dose intradermal and intramuscular vaccination against hepatitis B.

Hepatitis B and its sequelae are global problems preventable by immunization. Expense limits the use of hepatitis B vaccines, but low-dose intradermal immunization has been evaluated as a cost-saving strategy in numerous studies. With few exceptions, low-dose intradermal plasma-derived vaccines have elicited protective levels of antibody in 82%-100% of young healthy adults--a proportion similar to that noted with full-dose regimens; peak levels of antibody to hepatitis B surface antigen (HBsAg) are lower with reduced doses, however. Although children respond well to low-dose intradermal immunization, this procedure is technically difficult in neonates and should not be used for those born to HBsAg-positive mothers. For persons at high risk, antibody to HBsAg must be assessed after immunization to determine the need for a booster dose. A fourth dose 1-2 years after the initial series substantially increases antibody concentrations. In low intradermal doses, recombinant vaccine elicits lower rates of seroconversion than plasma-derived vaccine. However, low intramuscular doses of recombinant vaccine give favorable results. In short, low-dose intradermal or intramuscular immunization offers protection against hepatitis B at significant savings and may be useful for mass immunization of populations at high risk.

Hepatitis B