Thesis (M.D.)--University of Hong Kong, 1991. / Also available in print.

Thesis (Ph. D.)--University of Hong Kong, 2005. / Title proper from title frame. Also available in printed format.

Bochum, Universiẗat, Diss., 2004.

No description available.

Globally, policy recommendations on vaccines as provided by the Strategic Group of Experts on Immunization (SAGE) rely on a number of factors including burden of disease. In the scope of this thesis, two studies were conducted in order to inform the World Health Organization Hepatitis E Virus (HEV) working group and ultimately the SAGE: 1) a systematic review and meta-analysis of the global incidence, prevalence and mortality associated with all genotypes of HEV; and 2) a global subgroup analysis of incidence, prevalence and mortality on special populations and high risk populations. Circulation of HEV was documented in all global regions. Severe disease was observed among pregnant women and fulminant hepatic failure patients in both studies conducted. Poor data quality was observed in both studies, this poses a serious challenge for estimating the burden of disease. Countries should consider the implementation of an HEV surveillance system to improve data quality and ultimately to inform decision-making.

Isoniazid (INH), one of the most effective agents in the treatment and prophylaxis of tuberculosis associated with a mild increase in liver transaminases in up to 20% of treated patients and severe hepatotoxicity in up to 2% of treated patients. Since the 1970's, a number of studies have been reported on the mechanism of INH-induced hepatotoxicity. The original studies in rats suggested that the hepatotoxic effect of INH was due to the microsomal metabolism of acetylhydrazine (AcHz, a metabolite of INH) to a reactive intermediate. More recently other workers have been unable to reproduce the original results in the rat, or other mechanistic models have been proposed. Therefore, it is necessary to establish a reproducible animal model which resembles INH hepatotoxicity in the human being. In these experiments,, male New Zealand white rabbits were used, and divided into 12 treatment groups of 6-8 rabbits each. Serum argininosuccinate lyase (ASAL) levels and histological changes in liver slides were chosen as indices of hepatotoxicity. After the determination of acetylator phenotype for each rabbit, INH and its metabolites, acetylisoniazid (AcINH), hydrazine (Hz) and AcHz were administered in a two-day regimen orally or subcutaneously. The results showed that the serum ASAL level in rabbits is a sensitive and specific enzyme marker which parallels the incidence of hepatic necrosis seen on histology. The serum ASAL control values 4.3±2.6 (SD) Takahara units were maintained until about 24 hrs after the first challenge of INH in the two-day regimen (0.36+3x0.26 mmol/kg/dx2d, s.c.); peak values of up to 2674 Takahara units occurred at about 72 hrs. No significant difference between the toxicity of INH given orally and subcutaneously was detected. Phenobarbital (PB) (0.1 mg/kgx3d, i.p.) pretreatment increased the elevation of serum ASAL level caused by INH (0.36+3x0.26 mmol/kg/dx2d, p.o.) significantly (p<0.05, F test) compared with the group without PB pretreatment. The 65 experimental rabbits were classified into populations of acetylator phenotype by measuring their acetylation rate of sulfamethazine (SMZ): fast acetylators with a SMZ t[formula omitted] of 12.8±4.4 (SD) (n=54) and slow acetylators with a SMZ t[formula omitted] of 50.3±10.4 (SD) (n=ll). Among the rabbits challenged with INH (0.36+3x0.26 mmol/kg/dx2d, p.o. or s.c.) with or without PB pretreatment, no correlation was found between the peak serum ASAL values and acetylation rate represented by SMZ t[formula omitted (r=0.05, n=18). This lack of this correlation was also present in rabbits challenged with AcINH and Hz. Among INH and its metabolites, AcINH, Hz and AcHz, Hz is the most potent hepatotoxin. Its effect is dose-dependent over the dose range (0.10+3x0.07, 0.14+3x0.10 and 0.19+3x0.14 mmol/kg/dx2d, p.o.). AcHz (0.36+3x0.26 mmol/kg/dx2d, s.c.), produced no significant hepatotoxic effect, which is contradictory to the results reported by other authors. AcINH (0.28+3x0.20 mmol/kg/dx2d, s.c, 0.42+3x0.30 mmol/kg/dx2d, s.c. or p.o.) had a intermediate hepatotoxic effect which is similar to that of INH. The results showed that (1) the rabbit is a reproducible animal model for studying INH hepatotoxicity; (2) the release of ASAL to serum and pathological changes resemble that seen in human beings; (3) the hepatotoxicity of INH is potentiated by PB pretreatment which is in accordance with the evidence in human beings of an increased risk in the presence of microsomal enzyme inducers; (4) the acetylation rate does not affect the hepatotoxicity of INH; (5) among the metabolites tested, Hz was most potent. These data indicate that the hypothesis that INH hepatotoxicity is due to microsomal metabolism of AcHz is probably incorrect. We think that it is more likely that Hz is responsible. Further studies are required to elucidate the exact mechanism in the rabbit model. / Medicine, Faculty of / Anesthesiology, Pharmacology and Therapeutics, Department of / Graduate

published_or_final_version / Public Health / Master / Master of Public Health

Cryptosporidium is a protozoan parasite that causes gastroenteritis in man and animals. One mode of transmission of cryptosporidiosis is by the fecal-oral route. A method was developed for the concentration and detection of Cryptosporidium oocysts in water to study this organism's occurrence in the environment and its potential for waterborne disease transmission. Oocysts from an infected calf were used in experiments and monoclonal antibody labeled with fluorescein isothiocyanate was used for oocyst detection. A concentration method was developed using spun polypropylene cartridge filters. Optimal conditions for concentration, filter elution, filter porosity, and detection were determined by passage of 20-L volumes of tapwater seeded with 10⁵-10⁶ oocysts through the filters. The best method incorporated a 1-μm filter; 2 L eluent containing 0.1% Tween 80; backflush of eluent through filter; cutting the filter; mechanically shaking filter and eluate; and for 378-L volumes, three successive washings of filter material. Modifications were made when attempting to recover 10²-10³ oocysts in 378-L volurnes. These included addition of 1% Tween 80 and 1% sodium dodecyl sulfate (both made in distilled water) to the pellet, followed by homogenization, sonication, Sheather's flotation, and examination of the entire final preparation using a slide antibody test. To distinguish oocysts from other organisms such as yeast which may cross-react with the antibody, crystal violet and acid-fast stains were used. Cryptosporidium oocysts were isolated from secondarily treated sewage and identified on the basis of size, shape, reaction with antibody, acid-fastness, and inability to take up crystal violet. Limited studies with hepatitis A virus (HAV), a cause of waterborne disease, were performed using the HAS-15 strain of HAV and the FRhk-4 cell line. Four procedures used for concentration and detection of HAV in water were developed. They were radioimmunoassay for detection of viral antigen, production of HAV stocks, radioimmunofocus assay for quantitation of infective virus, and inhibition of certain strains of enteroviruses other than HAV, by guanidine.

No description available.

No description available.