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Comparison of serum humoral responses induced by oral immunization with the hepatitis B virus core antigen and the cholera toxin B subunit
The hepatitis B virus core (HBc) virus-like particle (VLP) is known as one of the most immunogenic antigens and carrier vehicles in different immunization strategies. Recent findings are suggesting the potential of the HBc VLPs as an oral immunogen. Here, we focus on the induction of serum humoral responses by oral administration of HBc VLPs in preparations substantially free of lipopolysaccharide and immunomodulating encapsidated RNA. The full-length HBc antigen was used, because the C-terminal arginine-rich tail may contribute to the immunogenicity of the antigen as the region is involved in cell surface heparan sulfate binding and internalization of the protein. Serum antibody levels and isotypes were determined following oral administration of the HBc VLPs with the perspective of using the HBc VLP as an immunostimulatory and carrier molecule for epitopes of blood-borne diseases in oral immunization vaccination strategies. Following oral administration of the HBc VLP preparations to mice, a strong serum humoral response was induced with mainly immunoglobulin G2a (IgG2a) antibodies, pointing toward a Th1 response which is essential in the control of intracellular pathogens. Intraperitoneal immunization with the HBc VLP induced a stronger, mixed Th1/Th2 response. Finally, a comparison was made with the induced serum humoral response following oral administration of the recombinant cholera toxin B pentamer, a commonly used oral immunogen. These immunizations, in contrast, induced predominantly antibodies of the IgG1 isotype, indicative of a Th2 response. These data suggest that the HBc VLP can be an interesting carrier molecule in oral vaccine development
Development of KABISA: a computer-based training program for clinical diagnosis in developing countries
Uses of first line emergency services in Cuba
OBJECTIVES: To rationalise the use of hospital emergency units, the Cuban health system developed from 1996 onwards an extra muros first line emergency system (FLES). We analyse the use of the FLES and its determinants, in order to develop proposals to channel inappropriate users to their family doctor. METHODS: In the FLES of an urban (Cerro) and a rural (Baracoa) municipality we collected, from July 1999 to June 2001, data on the moment of consultation, age and sex of the patient, referral status, motive of consultation, emergency classification, diagnosis and medical conduct. A variable "inappropriate use" was constructed. We used multivariate logistic regression to quantify the strength of the associations between patient characteristics, the night-time use, medical procedures, referral, and inappropriate use of the FLES. RESULTS: Over the 2 years observation period, 24879 and 59795 patient contacts were registered with the principal emergency policlinic in Baracoa and Cerro, respectively. In both municipalities the overall "inappropriate" use was almost 60%. There was no correlation with age and gender but inappropriate use was 50% more frequent during the day. Referred patients in both localities were up to 12 times more frequently hospitalized. CONCLUSION: Cuba's FLES attract patients that would be better attended by their family doctor. To strengthen his central position in the health system, one should strengthen the family doctor's technical platform, increase his permanence at the cabinet, and improve communication with the community on the rationale of the family doctor--FLES set up
Contribution du suivi scientifique du projet ASSRMKF aux travaux du comité de pilotage des réflexions autour de l'offre de soins chirurgicaux dans les districts sanitaires du Sénégal
Sputum smear microscopy: evaluation of impact of training, microscope distribution, and use of external quality assessment guidelines for resource-poor settings
Sputum smear microscopy is the main and often only laboratory technique used for the diagnosis of tuberculosis in resource-poor countries, making quality assurance (QA) of smear microscopy an important activity. We evaluated the effects of a 5-day refresher training course for laboratory technicians and the distribution of new microscopes on the quality of smear microscopy in 13 primary health care laboratories in Kinshasa, Democratic Republic of Congo. The 2002 external QA guidelines for acid-fast bacillus smear microscopy were implemented, and blinded rechecking of the slides was performed before and 9 months after the training course and microscope distribution. We observed that the on-site checklist was highly time-consuming but could be tailored to capture frequent problems. Random blinded rechecking by the lot QA system method decreased the number of slides to be reviewed. Most laboratories needed further investigation for possible unacceptable performance, even according to the least-stringent interpretation. We conclude that the 2002 external QA guidelines are feasible for implementation in resource-poor settings, that the efficiency of external QA can be increased by selecting sample size parameters and interpretation criteria that take into account the local working conditions, and that greater attention should be paid to the provision of timely feedback and correction of the causes of substandard performance at poorly performing laboratories
Risk factors for delay in the diagnosis and treatment of tuberculosis at a referral hospital in Rwanda
SETTING: Kigali University Hospital, the main referral centre for TB in Rwanda. OBJECTIVE: To evaluate delays in the diagnosis and treatment of tuberculosis (TB) and associated risk factors. DESIGN: Prospective data collection of patients treated for pulmonary TB (PTB) or extra-pulmonary TB (EPTB) between June and September 2006. RESULTS: Of 104 patients with a mean age of 35 years (range 17-84) recruited into the study, 62% were HIV-positive. EPTB was diagnosed in 60 cases. The median total, health care and patient delays were respectively 57, 28 and 25 days. The health system delay before referral was significantly longer than the delay at our institution (18 vs. 6 days, P<0.0001). Risk factors for a longer health system delay at our institution were smear-negative PTB or EPTB (OR 5.12) and a trial of antibiotics (OR 2.96). The latter was also found to significantly prolong total delay (OR 2.85), as did rural residence (OR 4.86). No significant association was found between patient delay and age, sex, profession or health insurance status. CONCLUSION: Smear-negative PTB and EPTB were associated with longer health system delays. A trial of antibiotics significantly increased the health system delay. Its use, recommended by the World Health Organization in case of smear-negative TB and EPTB in developing countries, needs validation at the tertiary health care level
Evaluation of the FluoreslenS and fluorescence microscopy blinded rechecking trial, Nairobi, Kenya
SETTING: Three busy laboratories in Nairobi, Kenya. OBJECTIVES: To determine the performance of an affordable fluorescence system (FluoreslenS) for tuberculosis microscopy, and to test an auramine-smear rechecking system. DESIGN: Alternating routine use of Ziehl-Neelsen (ZN) and fluorescence microscopy (FM) was performed to compare detection and errors found while rechecking. RESULTS: Overall, 19.5% of 25,250 ZN and 23% of 21,104 FM smears were positive (P < 10(-3)). The proportional increment of FM over ZN was 18% (range -6%-29%), with one centre detecting fewer positives (non-significant, NS). The average error frequencies were comparable (1.8% vs. 2.6% false-negative and 0.2% vs. 0.4% high false-positive for ZN and FM, respectively, NS). The superior performance of controllers and the overall equal ZN/FM quality in the laboratories could be demonstrated only after converting error percentages to relative sensitivity (RS). CONCLUSIONS: FM with the FluoreslenS system considerably improved sensitivity without loss of specificity in two of the busy routine laboratories, but the system is not sufficiently practical or user-friendly. Rechecking by FM can be done using guidelines for ZN smears, provided that routine ZN confirmation of positives is omitted. Calculation of RS allows an objective comparison of microscopy quality, independent of the variable prevalence of positives and sample size
Usefulness of Mycobacterium tuberculosis molecular typing in tuberculosis low-endemic agro-industrial setting of Brazil
To highlight the transmission and major phylogenetic clades of Mycobacterium tuberculosis, a retrospective study was carried out at two health facilities in a small agro-industrial area in Sao Paulo, Brazil, that has a low tuberculosis incidence rate. IS6110-RFLP and spoligotyping were performed on the isolates, with the former revealing that 31.3% (35/112) of strains were clustered. Epidemiological links were found in 16 of the 35 clustered patients and were associated with transmission among patients living in public housing. Spoligotyping grouped 62.8% of the strains. The T genetic family predominated among the isolates. Of interest is that five strains had a pattern characteristic of African or Asian origin (ST535), and two others were of the rare localized type ST1888 (BRA, VEN). In addition, three new types--1889, 1890, and 1891--were identified. Spoligotyping showed that some ST may be circulating to or from Brazil, and RFLP revealed ongoing transmission in inadequately ventilated public-housing buildings. This may point to a failure in tuberculosis control policy
Methods for evaluating effectiveness and cost-effectiveness of skilled care initiative in rural Burkina Faso
The definitive version is available at www3.interscience.wiley.comIntroduction This paper aims to describe the design, methods and approaches used to assess the effectiveness and cost-effectiveness of the Skilled Care Initiative in reducing pregnancy-related and perinatal mortality in Ouargaye district, Burkina Faso.
Methods The evaluation used a quasi-experimental design, mixed methods and a composite of tools to compare mortality and severe morbidity (near-miss) of women in reproductive age, perinatal mortality, facility functionality, perceived quality of care, utilisation of maternal health services, and costs borne by families and the health care system for maternal health care in Ouargaye and Diapaga districts. Structured questionnaires and interview guides were developed, pre-tested and piloted prior to the main survey. The evaluation was carried out from January to July 2006. A household census was used to retrospectively assess pregnancy-related and perinatal mortality over the previous 5 years, and causes of pregnancy-related death were identified using a newly developed and tested probabilistic model for interpreting verbal autopsy data. Data were directly entered into Personal Digital Assistant devices at the point of interview. Analyses included univariate and multivariate regressions and incremental cost-effectiveness ratios.
Results A population census covering over half a million people, three qualitative surveys and facility surveys in 47 health centres have been carried out.
Conclusion A partnership with key stakeholders and the use of mixed methods proved feasible for evaluating complex safe motherhood strategies, and the use of hand-held computers proved possible for direct data capture, even in this remote rural environment