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Biomedical subjects

P L Perine

Publications and source records attributed to P L Perine.

At least 19 recordsLinked to original sources

Randomized controlled trial of concurrent hepatitis A and B vaccination.

Hepatitis A and B viruses are threats to deployed military forces. The objective of this study was to determine the feasibility of concurrent vaccination against hepatitis A and B viruses. One hundred five healthy persons, 20 to 49 years of age and without serologic markers to hepatitis A or B viruses, were randomized to receive an inactivated hepatitis A vaccine (HEP A; 25 units in 0.5 mL), recombinant hepatitis B vaccine (HEP B; 10 micrograms in 1.0 mL), or both (HEP A & B) concurrently in separate arms. Vaccines were administered intramuscularly at 0, 1, and 6 months. Sera obtained at 1, 2, 6, 7, and 12 months after the first dose were tested for quantitative antibody to hepatitis A virus (anti-HAV) and antibody to hepatitis B surface antigen. Local reactions (e.g., pain) were reported by less than half of the volunteers and were similar at the site of HEP A, whether given alone or concurrently. However, more persons complained of pain (usually mild) at the HEP B site when HEP B was given concurrently with HEP A compared with HEP B alone (43% vs. 15%, 34% vs. 9%, and 42% vs. 15% for doses 1, 2, and 3, respectively; p < 0.05 for each dose). Among persons immunized with HEP A alone or HEP A & B, the proportion with > or = 10 mIU/mL anti-HAV was 83% in both groups 1 month after dose 1 and 100% at months 2, 7, and 12. The geometric mean concentrations of anti-HAV increased from 21 mIU/mL at month 1 to 2,649 and 2,312 mIU/mL in the HEP A and HEP A & B groups, respectively, at month 7. The response to HEP B was similar whether administered alone or concurrently. Antibody responses were similar in those receiving HEP A or HEP B concurrently or alone, but more subjects reported pain (usually mild) at the HEP B site after concurrent vaccination than after HEP B alone. Further work should be conducted to approve HEP A for patients younger than 2 years of age and to develop combined HEP A and HEP B vaccines in the United States.

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↗

STDS in women attending family planning clinics: a case study in Addis Ababa.

For cultural reasons modern contraception has been slow to gain acceptance in Ethiopia. Knowledge about contraception and abortion is still limited in many family and community settings in which it is socially disapproved. By 1990 only 4% of Ethiopian females aged 15-49 used contraception. Little is known of sexually transmitted disease (STD) prevalence in family planning (FP) attenders in Africa in general and Ethiopia in particular, even though attenders of family planning clinics (FPCs) are appropriate target groups for epidemiological studies and control programmes. A study of 2111 women of whom 542 (25.7%) attended FPCs in Addis Ababa showed utilisation rates to be highest in women who were: Tigre (33%) or Amhara (31%), aged 20-34 years (30%), age 16 or older at first marriage/coitus (28%:38% in those first married after 25 years); who had a monthly family income of 10 Ethiopian Birr (EB) or more (33%:36% for those with income 100-500 EB), three or more children (37%), more than five lifetime husbands/sexual partners (39%); or were bargirls (73%) or prostitutes (43%). The seroprevalence rates for all STDs, higher in FPC attenders compared with other women, were syphilis (TPHA) 39%, Neisseria gonorrhoeae 66%, genital chlamydia 64%, HSV-2 41%, HBV 40% and Haemophilus ducreyi 20%. Only 4% of FPC attenders had no serological evidence of STD: 64% were seropositive for 3 or more different STD. Clinical evidence of pelvic inflammatory disease (PID) was also more common in the FPC attenders (54%), 37% having evidence of salpingitis. The FPC provides a favourable setting for screening women likely to have high seroprevalence of STD, who for lack of symptoms will not attend either an STD clinic nor a hospital for routine check up. We recommend that measures be taken to adequately screen, treat and educate FPC attenders, their partners, and as appropriate and when possible their clients, in an attempt to control STDs and ultimately HIV in the community. Social, economic and cultural factors in the occurrence of STDs, prostitution, family planning and modern contraception coverage in Ethiopia are identified and deficiencies of current programmes briefly discussed with the objective of targeting services more effectively.

Cultural Characteristics↗

Molecular epidemiology, in 1994, of Neisseria gonorrhoeae in Manila and Cebu City, Republic of the Philippines.

BACKGROUND AND OBJECTIVES: Failure of gonococcal infections to respond to 500 mg of ciprofloxacin or 400 mg of ofloxacin has been reported from Australia, the United Kingdom, and the United States. Recently, high rates of decreased susceptibility to the fluoroquinolones have been detected in penicillinase-producing Neisseria gonorrhoeae in the Republic of the Philippines. GOALS: To assess the diversity of antimicrobial-resistant gonococcal strains isolated from female sex workers in Manila and Cebu City in the Republic of the Philippines in 1994. STUDY DESIGN: Isolates of N. gonorrhoeae isolated from 92 female sex workers in Manila (n = 28) and Cebu City (n = 64), respectively, were characterized by plasmid profile, auxotype/serovar class, and antimicrobial susceptibility profile. RESULTS: Plasmid-mediated resistance to penicillin or tetracycline was identified in 79.3% (73/92) of the isolates: penicillinase-producing N. gonorrhoeae (65/92; 70.7%), tetracycline-resistant N. gonorrhoeae (6/92; 6.5%), and penicillinase-producing/tetracycline-resistant N. gonorrhoeae (1/92; 1.1%). A beta-lactamase plasmid of 3.9 megadaltons was discovered. Of 54.3% (50/92) of strains resistant to nalidixic acid, 84% (42/50) of strains had minimum inhibitory concentrations of > or = 0.125 microgram/ml ciprofloxacin; penicillinase-producing N. gonorrhoeae (possessing the 3.05-, 3.2-, 3.9-, and 4.4-megadalton beta-lactamase plasmids, respectively) accounted for 68% (34/50) of these strains. CONCLUSIONS: In the Republic of the Philippines, gonococcal isolates resistant to penicillin or tetracycline accounted for 85.9% (79/92) of the isolates examined and included strains exhibiting resistance to fluoroquinolones. All gonococcal infections should be treated with antimicrobial therapies known to be active against all gonococcal strains to reduce the spread of strains exhibiting decreased susceptibilities to fluoroquinolones.

Drug Resistance, Microbial↗

Sexually transmitted diseases in the tropics.

Several sexually transmitted diseases are endemic in the tropics. The morbidity and mortality from the human immunodeficiency viruses (HIV-1 and HIV-2) alone now rival that caused by Plasmodium falciparum malaria in several African and Asian nations. The genital ulcers of chancroid and syphilis facilitate the sexual transmission of HIV. Within the last two decades, the bacteria causing chancroid and gonorrhoea throughout the world have acquired plasmids that mediate bacterial resistance to penicillins and other antibiotics. This has significantly increased the costs of treatment. There is little prospect that the prevalence of gonorrhoea, chancroid, syphilis and HIV will decrease in the tropics in the near future without a global change in sexual behaviours and practices.

Female↗

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↗

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↗

A clinico-epidemiological study of epidemic typhus in Africa.

Epidemic, louse-borne typhus persists in the rugged, mountainous areas of Ethiopia and much of northeastern and central Africa as well as in the rural highlands of Central and South America, where the conditions of living favor the harboring of body lice and where antibiotic treatment and effective louse-control measures are unavailable. The historical significance and current epidemiology of typhus, including the reservoir of Rickettsia prowazekii in flying squirrels in the United States, are reviewed, and the clinical presentation, laboratory findings, and hospital course in the cases of 60 patients admitted with epidemic, louse-borne typhus to the St. Paul's Hospital in Addis Ababa, Ethiopia, are described. Treatment of this disease with oral doxycycline, tetracycline, or chloramphenicol prevents complications and results in prompt resolution of symptoms.

Adolescent↗

Genetic analysis of HIV-1 isolates from Zambia and an expanded phylogenetic tree for HIV-1.

Geographic variation in the HIV-1 virus is extensive but incompletely documented. We herein report the first genetic characterization of HIV-1 isolates from Zambia. The genomic region encoding the GAG polyprotein has been compared among 22 Zambian isolates and 14 North American isolates using a combination of polymerase chain reaction (PCR) and DNA sequencing methods. The Zambian isolates were similar to one another but distinct from other HIV-1 isolates. They exhibited a characteristic PCR "fingerprint" wherein certain primer combinations were unable to amplify because of mispairing. The sequence of the complete gag gene of three isolates from Zambia has been determined, and phylogenetic tree analysis placed them in a branch distinct from other African isolates and North American isolates. The PCR procedure used here may be widely applicable for genetic characterization of HIV-1.

Base Sequence↗

IgG subclass responses to human immunodeficiency virus-1 antigens: lack of IgG2 response to gp41 correlates with clinical manifestation of disease.

To analyze differential antibody responsiveness of potential pathogenetic significance, sera from 66 patients with human immunodeficiency virus-1 (HIV-1) infections at various Walter Reed (WR) stages of the disease were analyzed to determine the subclass distribution of HIV antibodies. Although all IgG subclasses were involved in the HIV antibody response, the frequency was highest for IgG1 and the lowest for IgG4. When IgG subclass responses to different HIV antigens were compared qualitatively, IgG1 was the major subclass reactive with env, pol, and gag antigens; IgG2 and IgG3 were almost equally represented in response to gag gene products; and IgG4 showed minimal reactivity to p24 antigen in all HIV-infected patients regardless of their clinical presentation. In contrast, significantly lower levels of IgG2 anti-gp41 were observed in patients at WR 5 and 6 (5%) when compared to those at stage WR 1 and 2 (88%). The IgG2 response to a recombinant gp 120/41 antigen, however, remained unchanged, suggesting that the lack of IgG2 response may be associated with lack of responsiveness to the carbohydrate epitope on gp41. Indeed, parallel measurements of IgG antibody responses to group A carbohydrate were also lower in patients at WR 5 and 6 stages, without affecting antibody responses to polyribosyl ribitol phosphate and phosphocholine. As antibody responses to group A carbohydrate with its N-acetyl D-glucosamine (GlcNAc) determinant were lower at the WR 5 and 6 stage of HIV disease, GlcNAc may be one of the antigenic determinants on gp41 that plays a critical role in some of the pathologic events of HIV infection.

Acquired Immunodeficiency Syndrome↗

Genetic comparison of human immunodeficiency virus (HIV-1) isolates by polymerase chain reaction.

Amplification of DNA by polymerase chain reaction (PCR) is influenced by the homology of oligonucleotide primers with the DNA template. We have developed a procedure, termed anchored PCR, whereby nucleotide sequence alterations in the template can be directly related to the quantity of amplified product. Genetic variation in the human immunodeficiency virus HIV-1 has been studied using anchored PCR. In four field isolates of the virus, the 3'LTR was compared both by PCR analysis of DNA from virus cultures and DNA sequencing. DNA templates that matched the primers varied less than threefold in PCR product yield, whereas significant 3' end primer-template mispairing decreased PCR product 10- to 100-fold. Using these guidelines for genetic variability manifested through PCR, 40 PCR primers encompassing the GAG, ENV, and 3' LTR segments of the genome were used to compare sequential HIV-1 isolates form six patients. Some primers were apparently located in genomic regions without significant interisolate variability, as they yielded equivalent amounts of amplified DNA from all the isolates. The quantity of amplified DNA obtained with other primers varied 10- to 100-fold among patients, but was consistent for sequential isolates from an individual patient. Two African HIV-1 isolates were readily distinguished from a panel of North American isolates by the same method. Systematic classification of HIV-1 genetic variants may be possible by anchored PCR.

Acquired Immunodeficiency Syndrome↗

In vitro activities of tosufloxacin, temafloxacin, and A-56620 against pathogens of diarrhea.

Tosufloxacin (A-60969 HCl), a new quinolone with broad activity against gram-positive and anaerobic organisms, was compared in vitro with other quinolones against bacterial pathogens of diarrhea. Tosufloxacin was the most active agent against Salmonella spp., Shigella spp., Campylobacter spp., Aeromonas hydrophila, and Vibrio spp. Temafloxacin (A-62254) also demonstrated good activity against these organisms.

Anti-Bacterial Agents↗

Syphilis intervention in pregnancy: Zambian demonstration project.

Despite availability of simpler serologic tests for syphilis and near cure with penicillin, unacceptably high prevalence of infectious maternal syphilis exist in many developing countries, including Zambia. It is the foremost risk factor for mid-trimester abortions, stillbirths, prematurity and morbidity and mortality among infants born with congenital syphilis in Zambia. An intervention project was conducted in Lusaka aimed at demonstrating the effectiveness of new health education methods and prenatal screening for syphilis in reducing the adverse outcomes during pregnancy. During pre-intervention phase, approximately 150 consecutive pregnant women from each of the three study and the three control centres were recruited when they presented in labour at the University Teaching Hospital. The intervention phase lasted for one year at the three study centres during which new methods of health education were introduced to improve early attendances during pregnancy. Also, on-site syphilis screening was performed twice during pregnancy and seroreactive women, and in many cases their sexual partners, were treated by the existing prenatal clinic staff. During the post-intervention phase the steps of pre-intervention phase were repeated to evaluate the impact of intervention. Overall, 8.0% of women were confirmed seroreactive for syphilis; there was no difference between the study and the control centres (p greater than 0.05). Fifty seven percent (132/230) of syphilitic pregnancies ended with an adverse outcome, that is, abortion (RR 5.0), stillbirth (RR 3.6), prematurity (RR 2.6) and low birth weight (RR 7.8). The overall risk of adverse outcomes due to syphilis was 8.29 (95% confidence interval 6.53, 10.53). The new methods of health education were effective and the percentage of women who had their first prenatal visit under 16 weeks of gestation improved from 9.4 to 42.5. Although screening and treatment during intervention was suboptimal, the adverse outcomes attributable to syphilis were reduced to 28.3%; this is almost a two-third reduction when compared with 72.4% of adverse outcomes at control centres (p < less than 0.001). The intervention is culturally and politically acceptable in Zambia. The cost of each prenatal screening is US$0.60 and of averting each adverse outcome US$12. In countries with high rates of syphilis, there is an urgent need for STD control and Maternal and Child Health (MCH) programmes to pool their resources together to revitalise the prenatal care.

Adult↗

Long-term preservation of whole blood samples for flow cytometry analysis in normal and HIV-infected individuals from Africa.

A whole blood method requiring less than 4 ml of heparinized blood was developed to assess the practicality of preparing whole blood samples that could be easily stored, transported and readily used to determine the lymphocyte phenotypes and proliferation responses of individuals from remote areas who are infected with the human immunodeficiency virus. Minor modifications in standard whole blood procedure for lymphocyte phenotyping have significantly increased the stability of light scatter and fluorescence intensity of the cells for subsequent flow cytometry (FC) analysis. These changes include removal of lysis solution prior to fixation, fixation of monoclonal antibody-stained cells in 1% paraformaldehyde for 30 minutes and storage of fixed samples in medium containing 1% bovine serum albumin. Lymphocyte subsets and their functional subsets could reliably be determined on samples stored for up to 4 weeks. Further, blood samples could be kept at room temperature for up to 96 hours or at ambient temperature during transportation from Africa before staining for FC without affecting their quantitation. While samples could be processed for FC analysis under field-laboratory conditions, proliferation assays could only be performed on samples that were transported within 48 hours of their collection. The whole blood method saves time and expense and decreases the volumes of blood required to perform phenotypic analysis and functional assays on specimens collected in remote areas.

Adult↗