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More than 750 million people are at risk of infection with food-borne liver flukes. Opisthorchis viverrini is considered among the most important of these parasites, due to its strong association with cholangiocarcinoma (CCA). O. viverrini infection results in a chronic inflammatory challenge to the host, which can lead to advanced, pathogen-specific disease sequelae including obstructive jaundice, hepatomegaly, cholecystitis, as well as CCA. However, before disease sequelae are apparent, important inflammatory changes to the liver can be detected early during O. viverrini infection. In a case-control study involving 328 men and women with O. viverrini infection, we determined the presence of advanced periductal fibrosis in asymptomatic, O. viverrini-infected individuals and then measured cytokine responses to O. viverrini excretory/secretory products (ES). In the 200 participants with advanced periductal fibrosis (cases), levels of Interleukin (IL)-6 to O. viverrini ES were 8 times higher than levels of the 128 O. viverrini-infected individuals without advanced periductal fibrosis (controls). Moreover, elevated IL-6 to parasite ES was associated with increased risk of advanced periductal fibrosis by 63% in a model adjusted for sex and age. The risk of advanced periductal fibrosis was also found to increase with higher levels of IL-6: individuals in the third quartile of IL-6-ES production had a 127% higher risk of developing advanced periductal fibrosis than individuals in the first quartile of IL-6 production. O. viverrini-infected individuals with advanced periductal fibrosis showed other hepatobiliary abnormalities, including reduced gallbladder contractility and the presence of gallbladder sludge. Conclusion These data strongly implicate a role for parasite specific IL-6 in the pathogenesis of advanced periductal fibrosis in opisthorchiasis, with possible links to other hepatobiliary abnormalities, including cholangiocarcinoma.

Opisthorchis viverrini is considered among the most important of the food-borne trematodes due to its strong association with advanced periductal fibrosis and bile duct cancer (cholangiocarcinoma). We investigated the relationship between plasma levels of Interleukin (IL)-6 and the risk of developing advanced fibrosis and bile duct cancer from chronic Opisthorchis infection. We show that IL-6 circulates in plasma at concentrations 58 times higher in individuals with advanced fibrosis than age, sex, and nearest-neighbor matched controls and 221 times higher in individuals with bile duct cancer than controls. We also observed a dose-response relationship between increasing levels of plasma IL-6 and increasing risk of advanced fibrosis and bile duct cancer; for example, in age and sex adjusted analyses, individuals with the highest quartiles of plasma IL-6 had a 19 times greater risk of developing advanced periductal fibrosis and a 150 times greater risk of developing of bile duct cancer than individuals with no detectable level of plasma IL-6. Finally, we show that a single plasma IL-6 measurement has excellent positive predictive value for the detection of both advanced bile duct fibrosis and bile duct cancer in regions with high O. viverrini transmission. These data support our hypothesis that common mechanisms drive bile duct fibrosis and bile duct tumorogenesis from chronic O. viverrini infection. Our study also adds a unique aspect to the literature on circulating levels of IL-6 as an immune marker of hepatobiliary pathology by showing that high levels of circulating IL-6 in plasma are not related to infection with O. viverrini, but to the development of the advanced and often lethal pathologies resulting from chronic O. viverrini infection.

SummaryBackgroundMelioidosis, an infectious disease caused by the Gram-negative bacillus Burkholderia pseudomallei, is difficult to cure. Antimicrobial treatment comprises intravenous drugs for at least 10 days, followed by oral drugs for at least 12 weeks. The standard oral regimen based on trial evidence is trimethoprim-sulfamethoxaxole (TMP-SMX) plus doxycycline. This regimen is used in Thailand but is associated with side-effects and poor adherence by patients, and TMP-SMX alone is recommended in Australia. We compared the efficacy and side-effects of TMP-SMX with TMP-SMX plus doxycycline for the oral phase of melioidosis treatment.MethodsFor this multi-centre, double-blind, non-inferiority, randomised placebo-controlled trial, we enrolled patients (aged ≥15 years) from five centres in northeast Thailand with culture-confirmed melioidosis who had received a course of parenteral antimicrobial drugs. Using a computer-generated sequence, we randomly assigned patients to receive TMP-SMX plus placebo or TMP-SMX plus doxycycline for 20 weeks (1:1; block size of ten, stratified by study site). We followed patients up every 4 months for 1 year and annually thereafter to the end of the study. The primary endpoint was culture-confirmed recurrent melioidosis, and the non-inferiority margin was a hazard ratio (HR) of 1·7. This study is registered with www.controlled-trials.com, number ISRCTN86140460.FindingsWe enrolled and randomly assigned 626 patients: 311 to TMP-SMX plus placebo and 315 to TMP-SMX plus doxycycline. 16 patients (5%) in the TMP-SMX plus placebo group and 21 patients (7%) in the TMP-SMX plus doxycycline group developed culture-confirmed recurrent melioidosis (HR 0·81; 95% CI 0·42–1·55). The criterion for non-inferiority was met (p=0.01). Adverse drug reactions were less common in the TMP-SMX plus placebo group than in the TMP-SMX plus doxycycline group (122 [39%] vs 167 [53%]).InterpretationOur findings suggest that TMP-SMX is not inferior to TMP-SMX plus doxycycline for the oral phase of melioidosis treatment, and is preferable on the basis of safety and tolerance by patients.FundingThailand Research Fund, the Melioidosis Research Center, the Center of Excellence in Specific Health Problems in Greater Mekong Sub-region cluster, and the Wellcome Trust.

BackgroundCholangiocarcinoma (CCA) is an extremely aggressive cancer that is usually fatal. Although globally morbidity and mortality are increasing, knowledge of the disease remains limited. The Mekong region of Southeast Asia, and particularly the northeast of Thailand, has by far the highest incidence of CCA worldwide with 135.4 per 100,000 among males and 43.0 per 100,000 among females being reported in Khon Kaen Province. Most patients are first seen during late stage disease with 5-year survival being less than 10 %. Starting in 1984, control and prevention strategies have been focused on health education. Although early detection can substantially increase 5-year survival, there are currently no strategies to increase early diagnosis.Methods/designThe Cholangiocarcinoma Screening and Care Program (CASCAP) is a prospective cohort study comprising two cohorts- the screening and the patient cohorts. For the screening cohort, ultrasound examination will be carried out regularly at least annually to determine whether there is current bile duct and/or liver pathology so that the optimal screening program for early diagnosis can be established. This cohort is expected to include at least 150,000 individuals coming from high-risk areas for CCA. For the patient cohort, it is estimated that about 25,000 CCA patients will be included during the 5-year recruitment period. All CCA patients will be treated according to routine clinical care and followed so that effective surgical treatment can be formulated. This cohort is indeed a conventional cancer registry. Thus, CASCAP is an ongoing project in which the number of participants changes dynamically.DiscussionsThis is the first project on CCA that involves screening the at risk population at the community level. At the time of preparing this report, a total of 85,927 individuals have been enrolled in the screening cohort, 55.0 % of whom have already undergone ultrasound screening, and 2661 CCA cases have been enrolled in the patient cohort. Among the participants of the screening, whose mean age was 53.8 ± 9.8 years, 55.6 % were female, 77.5 % attained primary school as the highest level of education, 79.9 % were farmers, 29.9 %, reported having relatives with CCA, 89.1 % had eaten uncooked fish, and 42.2 % of those who had been tested for liver fluke were found to be infected.

A cross sectional study on hepatobiliary abnormalities in opisthorchiasis was performed in 8,936 males and females aged from 20 to 60 years from 90 villages of Khon Kaen province, Northeast Thailand. All were stool-examined for Opisthorchis viverrini infection by standard quantitative formalin/ethyl acetate concentration technique. Of these, 3,359 participants with stool egg positive were underwent ultrasonography of the upper abdomen. The hepatobiliary abnormalities detected by ultrasound are described here. This study found a significantly higher frequency of advanced periductal fibrosis in persons with chronic opisthorchiasis (23.6%), particularly in males. Risks of the fibrosis included intensity of infection, and age younger than 30 years. Height of left lobe of the liver, cross-section of the gallbladder dimensions post fatty meal, sludge, and, interestingly, intrahepatic duct stones were significantly associated with the advanced periductal fibrosis. Eleven suspected cholangiocarcinoma (CCA) cases were observed. This study emphasizes the current status of high O. viverrini infection rate and the existence of hepatobiliary abnormalities including suspected CCA in opisthorchiasis endemic areas of Thailand.

Background: Mothers and their newborns are vulnerable to threats to their health and survival during the postnatal period. Full postnatal care (PNC) uptake decreases maternal deaths and is also essential for first 1,000 days of newborn’s life, but PNC usage is usually inadequate in rural areas. Little is known about the full PNC utilization among rural Myanmar women. This study, therefore, aimed to study the situation of the utilization of full PNC and examine its determinants. Methods: This community-based cross-sectional study was conducted in selected villages of the Magway Region, Myanmar. A total of 500 married women who had children aged under 2 years were selected using multistage cluster sampling and interviewed with semi-structured questionnaires. The determinants of full PNC usage were identified by generalized estimating equation (GEE) under a logistic regression framework. Results: Among 500 rural women, around a quarter (25.20%; 95% confidence interval (CI), 21.58-29.21%) utilized full PNC. Multivariable analysis revealed that factors associated with full PNC usage included mothers attaining educational level of secondary or higher (adjusted odds ratio (AOR), 2.16; 95% CI, 1.18-3.94), belonging to higher income level (AOR, 2.02; 95% CI, 1.11-3.68), having male involvement (AOR, 2.19; 95% CI, 1.02-4.69), being of low birth order (i.e. the first birth) (AOR, 3.26; 95% CI, 1.80-5.91), and having awareness of postnatal danger signs (AOR, 2.10; 95% CI, 1.15-3.83). Moreover, the presence of misconceptions on postnatal practice was identified as a strong barrier to adequate PNC usage (AOR, 0.12; 95% CI, 0.04-0.36). Conclusion: Most of the rural women practiced inadequate PNC in Myanmar. Maternal healthcare services at rural areas should be intensively promoted, particularly among women who had high birth order (greater number of births). Health education regarding perinatal misconceptions and danger signs, and benefits of full PNC services usage should be emphasized and urgently extended.

Mini-mental-State Examination (MMSE) is a widely used tool for dementia screening. However, several limitations are found and the Rowland Universal Dementia Assessment Scale (RUDAS) appears to be an alternative test. The objective in this study was to compare the performance of MMSE-Thai 2002 and RUDAS-Thai for dementia screening, and to determine their performances and identify their optimal cut-off points. The participants were older patients from a Geriatric and Neurology Outpatient Clinic, Srinagarind Hospital, Khon Kaen University. The RUDAS-Thai and the MMSE-Thai 2002 were administered to each participant. Subsequently, a specialist physician assessed each participant for dementia. Results showed the area under receiver operating characteristic curve for both RUDAS-Thai (81.0%; 95%CI, 74.8-87.2) and MMSE-Thai 2002 (81.2%; 95%CI, 74.9-87.4) were equal. A score of 24 or lower provided an optimal cut-off point. Our finding supports that the RUDAS-Thai can be an effective alternative test for dementia screening. For both test scores, a score of 24 or lower is an optimal cut-off point to provide an indication of developing dementia.