The effect of iron on metronidazole activity against Trichomonas vaginalis in vitro.

Metronidazole is administered in an inactive form then activated to its cytotoxic form within the hydrogenosome of trichomonads. Two hydrogenosomal proteins, pyruvate ferredoxin oxidoreductase (PFOR) and ferredoxin, play a critical role in the reductive activation of metronidazole. The expression of these proteins and other hydrogenosomal proteins are likewise positively regulated by iron. In the present study, the effect of iron on minimal lethal concentration (MLC) of metronidazole on in vitro cultured Trichomonas vaginalis(T. vaginalis) isolates was investigated. Interestingly, Addition of Ferrous ammonium sulphate (FAS) to T. vaginalis culture led to decrease in the MLC of metronidazole. On using aerobic assay, MLC of metronidazole on untreated T. vaginalis of both isolates was 12.5 µg/ml that decreased to 0.38 µg/ml on FAS treated trichomonads. Also anaerobic assay revealed that MLC on untreated parasites was 3.12 µg/ml that decreased to 0.097 µg/ml and 0.19 µg/ml for isolate 1 and isolate 2 respectively after iron addition. It was concluded that, addition of iron to in vitro cultured T. vaginalis decreases metronidazole MLC that was detected by both aerobic and anaerobic assays.

Human Schistosomiasis mansoni associated with hepatocellular carcinoma in Egypt: current perspective.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. It was reported to account for about 4.7 % of chronic liver disease in Egyptian patients. The present study aimed at studying the different factors that may be implicated in the relationship of schistosomiasis mansoni with HCC in Egypt. A total of 75 Egyptian patients with primary liver tumours (HCC) were enrolled in this study. They were subjected to full history taking and indirect hemagglutination assay (IHA) for the diagnosis of schistosomiasis. According to the results, the patients were categorized into two groups: Group I: 29 patients with negative IHA for schistosomiasis and hepatitis C virus (HCV) positive with no history or laboratory evidence of previous or current Schistosoma mansoni infection. Group II: 46 patients with positive IHA for schistosomiasis and HCV positive. The significant higher proportion of HCC patients in the present study had concomitant HCV and schistosomiasis (61.3 %) compared to HCC patients with HCV alone (38.7 %) suggesting that the co-infection had increased the incidence of HCC among these patients. Analysis of the age distribution among HCC patients revealed that patients in Group II were younger in age at time of diagnosis of HCC with mean age 57.1 years, as compared to patients in Group I with mean age 64.3 years with a highly significant statistical difference between the 2 groups. HCC in Group II was more common in rural residents while it was more common in urban areas in Group I with a significant statistical difference between the 2 groups. Analysis of the sex distribution among the studied groups showed that HCC was more common in males than females in both groups. As regards the aggression of HCC, it was more commonly multifocal and larger in size in patients with concomitant infection than in patients with HCV alone.

Schistosoma mansoni infection: is it a risk factor for development of hepatocellular carcinoma?

The burden of hepatocellular carcinoma (HCC) in Egypt has been increasing with a doubling in the incidence rate in the past 10 years, which necessitates the investigation of the possible risk factors to its development. The present study aimed at investigating the role of Schistosoma mansoni infection as a risk factor for development of HCC. Five hundred parasite free mice were categorized into four groups: Group I (induction of carcinoma by diethylnitrosamine (DEN)), Group II (DEN+Infection), Group III (Infection) and Group IV (Control). Groups I and II were further subdivided into 4 subgroups according to the dose of DEN given. Serum samples from each group were examined for levels of tumor markers alpha fetoprotein (AFP) and ferritin by ELISA, then mice were sacrificed and subjected to histopathological examination of their livers. These were repeated every week till the end of the experiment. The results of the histopathological examination clarified the role of S. mansoni in enhancing and aggravating the carcinogenic effect of DEN; dysplastic changes appeared earlier, with a higher grade and with a smaller dose of DEN in Group II compared to Group I. Serum levels of tumor markers showed earlier statistically significant differences in Group II than in Group I when compared to Group IV. We conclude that S. mansoni accelerates hepatic dysplastic changes in the presence of other risk factors making cancer appear early and with a more aggressive nature, compared to the same risk in absence of schistosomiasis.

Experimental study for early diagnosis of prepatent schistosomiasis mansoni by detection of free circulating DNA in serum.

Sensitive and specific diagnostic methods of schistosomiasis at an early stage of infection are crucial to avoid irreversible pathological reactions induced by eggs. This study aimed to evaluate the PCR technique for detection of free circulating Schistosoma mansoni DNA in serum in the early prepatent period in experimentally infected mice, in comparison to the commonly used indirect hemagglutination assay (IHA) for the detection of bilharzial antibody and stool examination. Sixty-four mice were experimentally infected with S. mansoni, and every 3 or 4 days through the 8 weeks postinfection (p.i.), serum samples were collected from randomly chosen four infected mice, then pooled and examined for circulating DNA and bilharzial antibody. The results showed that the earliest deposition of eggs in the small intestine was observed at the fifth week p.i., and the eggs were detected in feces in the seventh week p.i. PCR detected free circulating DNA of S. mansoni starting from the third day p.i., while IHA failed to detect infection up to the eighth week p.i. It is concluded that detection of free circulating DNA by PCR can be used as a valuable test for early diagnosis of prepatent S. mansoni infection.