Neutralizing antibody response to booster vaccination with the 17d yellow fever vaccine.

A retrospective review was conducted of yellow fever vaccination among laboratory workers receiving annual serologic assessment to determine the initial and long-term response after boosting. Patients were divided into three groups based on pre-vaccination serology: Group 1, 1:10; Group 2, 1:20-1:40 and Group 3, >1:40. The percent with > or = four-fold increase in titers after booster vaccination were: 78% (646/829, Group 1), 65% (79/121, Group 2) and 10% (8/79, Group 3) (p<0.0001). The median times to titer failure (<1:40) were 798 days (Group 1), 3340 days (Group 2) and 7709 days (Group 3) (p<0.0001). Pre-vaccination serology influenced the initial and long-term response to yellow fever booster vaccination.

Anthrax vaccine: short-term safety experience in humans.

Bacillus anthracis is the major terrorist and biological warfare agent of concern to civilian and military medical planners. The licensed anthrax vaccine, adsorbed (AVA) is believed to be an effective prophylactic medical countermeasure against this threat. Our objective in this report was to expand the safety database for this vaccine by assessing data on self-reported, short-term safety of AVA during more than 25 years of use, measured by local and systemic adverse events temporally associated with the administration of AVA. A minority of AVA recipients reported systemic and injection site reactions. Females reported a higher incidence of injection site and systemic adverse events than males. Data show a difference in incidence of local reactions between lots. A prospective, randomized, placebo-controlled study to actively examine reactogenicity is needed to more completely define the extent and nature of reactions associated with receipt of AVA in humans as well as to confirm the gender lot differences in local reaction rates.

Anthrax vaccine: evidence for safety and efficacy against inhalational Anthrax

It reviews the evidence of the safety and efficacy of the vaccine (anthrax vaccine adsorbed [AVA]), presenting information on its history, safety, efficacy in humans and animals, and efficacy against geographically diverse strains of B. anthracis.

An evaluation of Health Workers for Change in seven settings: a useful management and health system development tool.

This paper presents the findings of a multi-centre study assessing the impact of Health Workers for Change (HWFC) workshops in seven different primary care sites, based on the common core protocol described in this paper. The paper discusses a common methodology used by the studies, consisting of a triangulation of qualitative and quantitative methods. Such methodologies are inherently complex as they require comparisons across systems, sites and procedures. The studies were conducted in six sites in Africa and one site in Argentina. Generally, the intervention resulted either in positive change or in no change, except in the area of staff relationships where conflicts were more frequent after the intervention than before. This may reflect a willingness to confront problems or contentious issues. Implementing the HWFC workshops improved provider-client relations, facility level functioning and aspects of staff interrelationships, and had some impact at the system level. All studies indicated that overall health system development is essential for improved service provision including quality of care. The findings also indicated that this intervention complemented and could assist health sector reform efforts and can play a role in sensitizing health workers to gender issues. The paper concludes with a discussion of the robustness of the methodology used in the studies.

An assessment of the impact of Health Workers for Change in Avellaneda, province of Buenos Aires, Argentina.

This paper describes the evaluation of the Health Workers for Change (HWFC) workshop series in a primary health care clinic in Avellaneda, Argentina. The study found that there was an important impact at the facility level 2 months after the intervention (T2). Health workers were motivated and willing to examine their own practices critically in an effort to improve quality of care. Informants from the community also perceived that patients were being treated more kindly. Eleven months later (T3), however, the impact at the facility level had receded significantly. At the system level the main benefit of the workshops was to focus attention on the health workers themselves, particularly their perception that there was little communication with the authorities. As a result, the number of system level supervisors increased and they were urged to spend more time in the clinics. Reasons for the limited impact at T3 are discussed and suggestions are made for improving the intervention.

Anthrax vaccine: increasing intervals between the first two doses enhances antibody response in humans.

The influence of dosing interval on the human antibody response to anthrax vaccine adsorbed (AVA) was evaluated in two retrospective serological studies. In both studies, the interval between the first two doses was 2, 3 or 4 weeks. In the first study, banked sera were selected from 89 at-risk individuals at a mean time of 13 days after the second dose of vaccine. In the second study, banked sera were selected from 51 at-risk individuals at a mean time of 48 days following the first dose of AVA. In both studies, the geometric mean anti-protective antigen IgG antibody titer increased significantly as the interval between the two doses increased from 2 to 4 weeks (p=0.0005-0.029). In the first study, the seroconversion rate also increased as the interval between the first two doses increased (p=0. 0034). A prospective, randomized study has been completed and is being analyzed to confirm these findings.

Gendered experiences of health care.

OBJECTIVE: To develop a method capable of bringing to light gender specific problems in the social interaction between providers and clients, and in so doing, contribute to improving quality of care for both sexes in five primary health care centers in Argentina. DESIGN: A qualitative study using semi-structured interviews. Texts were processed in a database and analyzed using a formal method of discourse called Semiotics of Statements. Male and female clients' ideas on perceived causes of illnesses and health care needs were compared, following which providers' perceptions on the same issues were then contrasted. Problems in quality of care were suggested when: (i) differences in perceptions and/or values between providers and either male or female clients were observed; and (ii) similarities in values revealed reinforcement of traditional gender roles. SETTING: Public sector care provided to urban poor with hypertension and diabetes mellitus type 2 in five clinics in Avellaneda, Argentina. Participants were clients identified through community organizations (n = 27), and all physicians from these clinics (n = 10), 60% of nurses (n = 6) and 80% of receptionists (n = 4) were interviewed. RESULTS: Providers' views differed from women's in regard to: (i) the degree of individual responsibility (risky behavior) in disease causation; (ii) legitimacy of the reasons many women seek care; (iii) function of talk in the consultation; (iv) effects of chastisement; and (v) relevance of domestic violence. In addition, a series of shared values were identified that reinforce traditional gender roles, including situations detrimental to men's health. CONCLUSION: The method permitted identification of subjective issues relating to social interaction that could not have been accessed with other approaches, and that had practical implications for providers, as well as managers, policy-makers, educators and patient advocates.

Immunogenicity of an inactivated Rift Valley fever vaccine in humans: a 12-year experience.

Rift Valley fever (RVF) virus causes serious and fatal disease in animals and man. To protect personnel who work with RVF virus in the laboratory, or troops who may be exposed to this virus, the US Army successfully developed an improved version of inactivated RVF vaccine, TSI-GSD-200. From early 1986 to late 1997, 598 at-risk workers at the US Army Medical Research Institute of Infectious Diseases (USAMRIID) were vaccinated as part of an occupational safety and health program. The subjects of this study received three subcutaneous doses (0, 7 and 28 days) of 0.5 ml of TSI-GSD-200. A total of 540 vaccinees (90.3%) initially responded (group A) with an 80% plaque-reduction neutralization antibody titer (PRNT80) of > or =1:40; whereas 58 subjects (9.7%) were initial nonresponders (group B) failing to achieve this titer. Volunteers who either failed to respond or who achieved a titer of > or =1:40 but whose titer waned below 1:40 were boosted 1-4 times with the same vaccine. Among 247 group A subjects who received the first recall injection, 242 (98%) were successfully boosted, achieving a PRNT80 > or =1:40. Thirty-three of 44 (75%) initial nonresponders were converted to responder status after the first booster, which is a lower rate than that of group A (P < 0.001). After the primary series and the first booster, Kaplan-Meier analysis showed 50% probability of group A members maintaining a titer of > or =1:40 for approximately eight years; whereas group B had a 50% probability of maintaining a titer for only 204 days. Group A immune response rates to boosts 1-4 ranged from 87 to 100% with geometric mean titers (GMTs) ranging from 80 to 916. Boosts 1-4 immune response rates of group B volunteers ranged from 67 to 79% with GMTs ranging from 90 to 177. Minor side effects to TSI-GSD-200 were noted in 2.7% of all vaccinees after primaries and 3.5% of all vaccinees who had primaries and up to four boosters. We conclude that the use of TSI-GSD-200 is safe and provides good long-term immunity in humans when the primary series and one boost are administered.

An accelerated schedule for tick-borne encephalitis vaccine: the American Military experience in Bosnia.

Tick-borne encephalitis (TBE) is a viral illness endemic to the Balkan region. United States military forces were deployed to Bosnia in early 1996 as part of Operation Joint Endeavor, a U.S.-led multinational peace-keeping operation. To counteract the TBE threat, an inactivated, parenteral vaccine (FSME-Immun Inject; Immuno AG, Vienna, Austria) was offered to soldiers at high risk on a volunteer basis in an accelerated, 3-dose schedule (0, 7, and 28 days). Passive adverse reaction surveillance was conducted on 3,981 vaccinated personnel. Paired sera from a randomly selected group of 1,913 deployed personnel (954 who received vaccine and 959 who were unvaccinated) were tested for antibodies to TBE by an ELISA. Three-dose recipients demonstrated an 80% seroconversion rate (4-fold or greater increase in anti-TBE titers). By comparison, the TBE infection rate in the unvaccinated cohort was found to be only 0.42% (4 of 959). Only 0.18% of vaccinees reported self-limited symptoms. An accelerated immunization schedule appears to be an acceptable option for military personnel or travelers on short-term notice to TBE-endemic areas.

The Deaf Mentor Experimental Project for young children who are deaf and their families.

The Deaf Mentor Experimental Project investigated the efficacy of deaf mentor services to young deaf children and their families. These services focused on deaf adults (mentors), who made regular home visits to the children and their families; shared their language (American Sign Language), culture, and personal knowledge of deafness with the families; and served as role models for the children. The children also received regular home visits from a hearing parent adviser who helped the family promote the child's early listening, English, and literacy skills. The result was a bilingual-bicultural home environment for these children. The children who received deaf mentor services were compared to matched children who did not receive these services but who received parent adviser services. Children receiving this early bilingual-bicultural programming made greater language gains during treatment time, had considerably larger vocabularies, and scored higher on measures of communication, language, and English syntax than the matched children.

Immunologic interference from sequential administration of live attenuated alphavirus vaccines.

Two different human vaccine trials examined interference arising from sequential administration of vaccines against heterologous alphaviruses. The first trial indicated that persons previously vaccinated against Venezuelan equine encephalitis virus (VEEV) exhibited poor neutralizing antibody responses to a live attenuated chikungunya virus (CHIKV) vaccine (46% response rate). The second trial prospectively examined neutralizing antibody responses to live attenuated VEEV vaccine in persons previously inoculated with either CHIKV vaccine or placebo. Following seroconversion to CHIKV, CHIKV vaccine recipients' geometric mean titers (GMTs) to VEEV by 80% plaque-reduction neutralization titration never exceeded 10, compared with a peak GMT of 95 after VEEV vaccination for alphavirus-naive volunteers who initially received placebo (P < .003). ELISA antibody responses demonstrated cross-reactive IgG to VEEV after primary CHIKV immunization and then an anamnestic response upon subsequent VEEV vaccination. These data indicate that preexisting alphavirus immunity in humans interferes with subsequent neutralizing antibody response to a live attenuated, heterologous vaccine.

Gender inequity: an issue for quality assessment researchers and managers.

This article explores the question of whether the issue of gender inequity can and should be included in the different models of quality assessment gaining ground internationally. The discussion is divided into three parts: reflections on some of the conceptual issues that justify research on gender equity in health services; a brief review of the literature that provides empirical data in this area; and comments on the challenges faced by researchers in this field, and possible ways to incorporate gender indicators into quality assessment research and management.

PIP: The Pan American Health Organization has recently emphasized the importance of equity in health services in a document which outlines priorities and strategies for health sector reform in the Americas. The proposal to consider together gender and quality assessment research comes in the wake of a growing international quality assessment and assurance movement, the Total Quality Management (TQM) Movement. The authors explore whether gender equity concerns with regard to the distribution of health services should be included in this growing international movement. The authors first consider some of the conceptual issues which justify research into gender equity in health services. They then review some research on gender equity. The final section of the paper comments upon the challenges faced by researchers in the field, and possible ways to incorporate gender indicators into quality assessment research and management.

Heart rate response during handball singles match-play and selected physical fitness components of experienced male handball players.

Limited information is available concerning the exercise response during handball (HB) singles match-play. Also, few studies exist that have examined VO2 peak and body composition of HB players. The purpose of this study was to examine the heart rate (HR) response during match play and peak physiologic responses and relative fat in twelve experienced HB players. Peak physiologic responses were measured during treadmill running and body composition was assessed via hydrodensiotometry. During HB match-play, HR was measured and stored every five seconds using a Polar Vantage XL heart watch. Physical characteristics and peak physiologic responses included the following: Age (yrs) 47.2; BW (kg) 78.0; height (cm) 178.9; % fat 18.9; VO2 peak (ml.kg-1.min-1) 48.0; RER peak 1.03; HR peak (bpm) 183.1 and lactic acid peak (mmol.l-1) 10.3. During HB match-play, HR averaged 85% of peak during one hour of play. Moreover, 67% of match-play time, HR was > 80% of peak. When HR responses were examined over one hour of match-play (twelve, five minute blocks) only the first five minutes were significantly different (lower) than the other 55 minutes. The exercise intensity and the relatively stable HR response observed during HB suggests that this activity appears to be appropriate for meeting the American College of Sports Medicine guidelines to develop and maintain cardiorespiratory fitness.

Long-term duration of detectable neutralizing antibodies after administration of live-attenuated VEE vaccine and following booster vaccination with inactivated VEE vaccine.

The US Army successfully developed a live-attenuated Venezuelan Equine Encephalitis (VEE) vaccine, TC-83, in 1961, and subsequently developed a formalin-inactivated vaccine, C-84, in 1974. Initial evaluation of both vaccines was promising, but no long-term safety and immunogenicity data have been reported. This study is the first analysis of the long-term safety and immunogenicity of TC-83 and C-84. From January 1976 to December 1990, 821 laboratory workers at the USAMRIID were vaccinated with a single 0.5 ml subcutaneous (s.c.) dose of TC-83; 128 were boosted with a single 0.5 ml s.c. dose of C-84. Eighty-two per cent of vaccinees responded to TC-83 with an 80% plaque reduction neutralization titer (PRNT80) of > or = 1:20. Minor side-effects were noted in 23% of vaccinees. No long-term sequelae were recorded. Kaplan-Meier analysis showed a 60% probability of vaccinees maintaining a PRNT80 of > or = 1:20 for 5.5-8 years. C-84 was given to two groups: 76 initial nonresponders to TC-83, Group A, and 52 initial responders to TC-83 whose PRNT80 became < 1:20 over time, Group B. C-84 successfully boosted 76% of Group A and 100% of Group B to a PRNT80 > or = 1:20 Kaplan-Meier analysis showed 100% probability of Group B members maintaining a titer of > or = 1:20 for the duration of follow-up, which, in some cases, exceeded 10 years; while Group A had only a 60% probability of maintaining a titer for 1-2 years. Only minor local reactions to C-84 were noted in 6.3% of vaccinees. We conclude that, although TC-83 is reactogenic, when administered as the primary vaccine and C-84 is administered as a boost, these vaccines provide good long-term immunity and are safe in humans. However, a single dose vaccine that is more immunogenic and less reactogenic is needed.

Increased xylose reductase activity in the xylose-fermenting yeast Pichia stipitis by overexpression of XYL1.

The Pichia stipitis xylose reductase gene (XYL1) was inserted into an autonomous plasmid that P. stipitis maintains in multicopy. The plasmid pXOR with the XYL1 insert or a control plasmid pJM6 without XYL1 was introduced into P. stipitis. When grown on xylose under aerobic conditions, the strain with pXOR had up to 1.8-fold higher xylose reductase (XOR) activity than the control strain. Oxygen limitation led to higher XOR activity in both experimental and control strains grown on xylose. However, the XOR activities of the two strains grown on xylose were similar under oxygen limitation. When grown on glucose under aerobic or oxygen-limited conditions, the experimental strain had XOR activity up to 10 times higher than that of the control strain. Ethanol production was not improved, but rather it decreased with the introduction of pXOR compared to the control, and this was attributed to nonspecific effects of the plasmid.

An approach to determining the kinematic parameters of biomechanical systems with applications to the wrist.

This paper presents an accurate and robust approach for determining the kinematic parameters of biomechanical systems. A computationally efficient algorithm is given for estimating the translation vector and rotation matrix of a moving body from measurements of the position of at least four spatially distributed points on the body. This algorithm provides an estimation of the spatial location and orientation of the body which is less sensitive to measurement error than other methods. It is indicated how the kinematic parameters can be used to determine the linear translation and angular rotation of the moving body in terms of an anatomically relevant coordinate system. The design, fabrication and calibration of an inexpensive, serial-link, three-dimensional mechanical digitizer for use in data acquisition is described. This device is kinematically optimized and is easy to use for accurate data collection. An implementation of this approach to quantifying certain aspects of the kinematics of the human wrist is discussed.

Release of benzalkonium chloride from a heparin-bonded umbilical catheter with resultant factitious hypernatremia and hyperkalemia.

Elevated serum sodium and potassium levels were recently observed when sampled through a heparin-bonded umbilical catheter and measured with certain ion-selective electrodes. The cationic surfactant, benzalkonium chloride (BZC), is known to falsely elevate those cations in serum. Inasmuch as most heparin-bonded umbilical catheters use BZC during the bonding process, an in vitro study was performed to estimate the quantity of BZC released and the duration of sodium and potassium elevations during pooled sera infusion. Three heparin-bonded umbilical catheters and 3 silastic umbilical catheters were first flushed with 0.3 mL of normal saline and then perfused with pooled sera (sodium, 142 mEq/L; potassium, 4.6 mEq/L) at 2.5 microL/h. Effluent samples were collected from 0 to 8 hours and analyzed by ion-selective electrodes. Elevated serum sodium concentrations from 160 to greater than or equal to 250 mEq/L and potassium concentrations from 6.0 to greater than or equal to 9.6 mEq/L were observed. The BZC concentration in the catheter effluent was measured by mass spectrometry, with peak values of 10 micrograms/mL detected by this method. When varying concentrations of BZC (1 to 100 micrograms/mL) were added directly to pooled serum, a dose-dependent increase in serum sodium was observed. These data demonstrate that BZC released from heparin-bonded umbilical catheters elevates serum electrolyte values measured with some ion-selective electrodes. The observed increase in sodium and potassium concentrations may lead to clinical errors in management. Benzalkonium chloride is associated with myriad of linical symptomatology. Whether this amount of BZC is toxic in the small premature neonate is presently unknown.