Liver morbidity due to Schistosoma mekongi in Cambodia after seven rounds of mass drug administration

Severe liver disease due to Schistosoma mekongi was frequent in northern Cambodia. Between 1995 and 2002, seven rounds of mass chemotherapy (praziquantel) reduced infection from 50% to below 3%. In 2002, we assessed hepatosplenic morbidity by historical, clinical and ultrasonographic investigations in adults (older than 14 years) from endemic (n = 342) and non-endemic (n = 103) areas (Kratie province). Clinical hepatomegaly (25 vs. 0%), splenomegaly (55 vs. 0%), reported blood in stool (41 vs. 20%) and abdominal pain (78 vs. 57%) were significantly higher in the endemic area. In this area, significantly more subjects reported a family history of death due to schistosomiasis (12 vs. 0%); 63% (vs. 0%) reported having at least three treatments of praziquantel in previous years; and only 11% (vs. 99%) had normal liver ultrasonographic examination. Periportal fibrosis with portal hypertension was diagnosed in 46% (vs. 0%) of people in this area; 18% (vs. 0%) and 5% (vs. 0%) of portal hypertension was classified as moderate and severe, respectively. People aged between 24 and 35 years were mostly affected. There was no gender difference. The pathology in the endemic district is most probably residual morbidity of S. mekongi infections. Contributions of co-infections (hepatitis) cannot be excluded. Careful monitoring of the affected communities is require

Helminth and Intestinal Protozoa Infections, Multiparasitism and Risk Factors in Champasack Province, Lao People's Democratic Republic

Multiparsitism is a general public health concern in tropical countries, and is of particular importance in the Mekong River basin of Southeast Asia. Here, we report results obtained from an in-depth study of hepato-biliary and intestinal multiparasitism and associated risk factors in three settings of the most southern province of Lao People's Democratic Republic. Multiple species intestinal parasite infections were very common: more than 80% of the study participants harbored at least two and up to seven different intestinal parasites concurrently. Of particular concerns are the high prevalence of the liver fluke Opisthorchis viverrini (64.1%) and the moderate prevalence of the blood fluke Schistosoma mekongi (24.2%), as these fluke infections are responsible for severe hepato-biliary morbidity, including the bile duct cancer cholangiocarcinoma. Hookworm was the most common nematode infection (76.8%). We conclude that given the very high prevalence rates of parasite infections and the extent of multiparasitism, regular deworming is warranted and that this intervention should be coupled with health education and improved assess to clean water and adequate sanitation to consolidate morbidity control and ensure long-term sustainability

Contribution of Metabolites to P450 Inhibition-Based Drug-Drug Interactions: Scholarship from the IQ DMLG Metabolite Group

The 2012 EMA drug interaction guidance and the FDA draft drug interaction guidance proposed that human circulating metabolites should be investigated in vitro for their drug-drug interaction (DDI) potential if present at ≥ 25% of parent AUC (FDA) or >25% & >10% of total drug-related AUC (EMA). To examine the application of these regulatory recommendations, a group of scientists, representing 18 pharmaceutical companies of the Drug Metabolism Leadership Group (DMLG) of the Innovation and Quality Consortium (IQ), conducted a scholarship over a 2.5-year period to assess the contributions of metabolites to P450 inhibition-based DDI. The group assessed the risk of having a metabolite as the sole contributor to a DDI based on literature and analysis of 140 most frequently prescribed drugs (as of 2012), defined structural alerts associated with P450 inhibition and inactivation by metabolites, and analyzed the current approaches to trigger in vitro DDI studies for metabolites. The group concluded that the risk of P450 inhibition caused by a metabolite alone is relatively low. Only 8 drugs out of the 140 most frequently prescribed drugs (6%) showed in vivo DDI which were not predicted based on the in vitro P450 inhibition properties of the parent drug. The group recommended two main considerations when assessing the need to conduct in vitro P450 inhibition studies for metabolites: 1. Consider key structural alerts that suggest P450 inhibition potential (e.g. alkylamines for mechanism-based inhibition); and 2. Use multiple approaches, including the two literature approaches by Yu & Tweedie (2013) and Callegari et al. (2013), which involved a metabolite cut-off value of approximately 100% of AUC of parent, and consideration of metabolite Cmax/Ki, to minimize surprises in P450 inhibition-based DDI in the clinic