Prolonged ischemia elicits acute allograft rejection involved in CXCR3 activation in rat kidney transplants.

BACKGROUND: Acute rejection is a major obstacle in patients with prolonged ischemia in deceased-donor renal transplantation. Chemokines and their receptors play a critical role in leukocyte trafficking, resulting in allograft rejection; therefore, the role of chemokine receptor CXCR3 in acute rejection induced by prolonged ischemia in rat kidney transplantation models was evaluated. METHODS: Syngeneic and allogeneic renal transplantations were performed. For cold ischemia, grafts were stored in 4.0°C University of Wisconsin solution for 12 or 16 h. Serum and renal tissues were harvested 7.0 d after surgery and serum TNF-α, IL-6, and renal function were measured. Graft histology was stained with periodic acid-Schiff and immunohistochemical staining and further evaluated for signs of acute rejection. CXCR3 proteins were quantified by Western blot. The transplanted rats were divided into 4 groups as follows: iso-12-h = isogeneic transplant with 12-h CIT graft; iso-16-h = isogeneic kidney transplant with 16-h CIT graft; allo-12-h = allogeneic renal transplant with 12-h CIT graft; allo-16 h = allogeneic renal transplant with 16-h CIT graft; and 16 h+T = allogeneic 16-h CIT graft received tacrolimus. RESULTS: Prolonged cold ischemia time (CIT; 16 h) enhanced acute glomerular damage, interstitial inflammation, and tubulointerstitial cellular infiltration in allografts with and without immunosuppressant tacrolimus; but it was not apparent in the isografts. The expression of CXCR3 protein and the proportion of CXCR3-positive cells were significantly higher in the allo-16 h and 16 h +T groups than that in the allo-12 h group 7d post-surgery. CONCLUSIONS: CIT triggered acute rejection in allogeneic, but not in isogeneic, kidney transplants, accompanied by an elevation of leukocyte recruitment and damaged graft function. The upregulated expression of chemokine receptor CXCR3 promoted inflammatory infiltration and acute allograft rejection.

Efficacy and safety of praziquantel, tribendimidine and mebendazole in patients with co-infection of Clonorchis sinensis and other helminths.

BACKGROUND: Both tribendimidine and mebendazole are broad-spectrum drugs for anti-intestinal nematodes. We aim to assess the efficacy and safety of tribendimidine and mebendazole in patients with co-infection of Clonorchis sinensis and other helminths. METHOD: We performed a randomized open-label trial in Qiyang, People's Republic of China. Eligible participants were randomly assigned to one of four groups: (i) a single dose of 400 mg tribendimidine, (ii) 200 mg tribendimidine twice daily, (iii) 75 mg/kg praziquantel divided in four doses within 2 days, and (iv) a single dose of 400 mg mebendazole. Cure rates and egg reduction rates were assessed, and adverse events were monitored after treatments. Uncured patients accepted the second treatment with the same drugs after the first treatment. RESULTS: 156 patients were eligible for the study. Results from the first treatment showed that the cure rates of single-dose tribendimidine and praziquantel against C. sinensis were 50% and 56.8%, respectively; the single-dose tribendimidine achieved the cure rate of 77.8% in the treatment for hookworm, which was significantly higher than that of praziquantel; Low cure rates were obtained in the treatment of single-dose tribendimidine against Ascaris lumbricoides and Trichuris trichiura (28.6% and 23.1%). Results of the second treatment illustrated the cure rates of tribendimidine and praziquantel against C. sinensis were 78.1% and 75%, respectively. Most adverse events were mild and transient. Adverse events caused by tribendimidine were significantly less than praziquantel. CONCLUSION: Single-dose tribendimidine showed similar efficacy against C. sinensis as praziquantel with less adverse events, and achieved significantly higher cure rate in the treatment for hookworm than those of praziquantel and mebendazole. Low cure rates, which were still higher than other drugs, were obtained in the treatment of single-dose tribendimidine against Ascaris lumbricoides and Trichuris trichiura. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN55086560.

[How to establish the monitoring and evaluation system in elimination stage of malaria in China: the experience from Malaria Indicator Survey system].

Malaria is one of the most important public health problems around the world. Most region of China has embarked a transition from interruption of malaria transmission to elimination. This paper summarizes the main function and construction, the key parts, and the advantages in national field work of Malaria Indicator Survey (MIS) system, indicates the difficulties of establishing a Monitoring and Evaluation (M&E) System in malaria elimination in China and draws lessons from the MIS.

[Epidemiological survey on clonorchiasis sinensis in an endemic area of South Hunan Province].

OBJECTIVE: To make an epidemiological investigation on clonorchiasis sinensis and relevant factors in the south of Hunan Province. METHODS: One village from each of Lengshuitan District and Qiyang County was selected for the survey from November to December in 2006. Stool samples from villagers were collected and examined by modified Kato-Katz method. Questionnairing was performed for relevant knowledge and attitude among residents. The infection rate in animal reservoirs and intermediate hosts were detected. RESULTS: A total of 586 cases with Clonorchis sinensis infection were found from 777 people with a prevalence of 75.4%. The average egg density was 451 eggs per gram (EPG) feces. Light, moderate and heavy infections occupied 85.5% (501/586), 14.0% (82/586), and 0.5% (3/586) respectively. Prevalence in males and females was 76.9% (316/411) and 73.8% (270/366) respectively with no significant difference (chi2 = 1.013, P > 0.05). Infections were found in all age groups, with the highest prevalence in the group of 70 to 79 years (85.7%, 30/35). By occupations, the prevalence was 82.5% (447/542) in peasants, 79.3% (42/53) in doctors, 73.7% (28/38) in teachers, and 73.5% (25/34) in local cadres. The infection rate was 17.4% (29/167) and 7.4% (2/27) in Parafossarulus seriatulus and Alocinma longicornis, and 69.2% (9/13) and 5.3% (1/19) in Carassius auratus and Cyprinus carpios respectively. Adult worms were found in all 3 dogs dissected. Over 80% inhabitants did not know that this disease can be acquired by eating raw fish. 95.6% (153/160) of the farmers and 56.7% (349/616) of the students had a history of eating raw fish. The water was contaminated with C. sinensis eggs by using untreated feces as fertilizer for farming and by scrubbing pail latrines in the ponds. CONCLUSION: The prevalence of clonorchiasis in human population is high in Lengshuitan District and Qiyang County of Hunan Province. Eating raw fish and using untreated feces as fertilizer are the most important epidemiological factors of the disease.

[Density fluctuation of microfilariae and the role of residual infection source in filariasis transmission after its interruption].

OBJECTIVE: To investigate the density fluctuation of microfilariae, persistence of microfilaremia and possible new infection due to residual microfilaremia in areas with filariasis transmission interrupted. METHODS: The observation site was made in a village of Jishou City, Hunan Province. Inhabitants were regularly examined by thick blood smear and the density fluctuation of residual microfilaremia in known and newly-found cases were followed up. With a consent from the cases with residual microfilaremia, no treatment was given until they naturally turned negative. Antifilarial antibody level was detected by IFAT and a test kit for filariasis-special IgG4. Culex quinquefociatus was dissected to determine the natural infection rate and density of III stage filarial larvae in transmission season. The identified cases were followed-up by interviews and physical examinations to see if clinical manifestations appeared. RESULTS: Blood examination was carried out for all inhabitants for 10 times, 4 cases with microfilaremia, including 3 cases found at the beginning of the project and one newly infected case, were discovered after the interruption of filariasis transmission in the 19-year period. Among the 4 cases followed up, one case naturally turned negative within 7 years, one case became negative in the 9th year but returned positive in the 12th year, and then naturally turned negative in the 13th year. The 3rd case turned negative in the 14th year and was again positive in the 19th and the 20th years, and became negative through diethylcarbamazine (DEC) treatment in the 21st year. The new case was found to have microfilaremia in the 16th year and kept positive for 5 years until DEC treatment. Serological tests (IFAT and special IgG4) revealed no new positive cases. The natural infection rate and larvae density in Culex quinquefasciatus decreased annually. Conclusion The persistence period of residual microfilaremia in individual cases might last for more than 20 years after filariasis transmission has been interrupted.