The evaluation of control measures against Schistosoma mekongi in Cambodia by a mathematical model

We constructed a mathematical model for the transmission of Schistosoma mekongi in Cambodia. The simulation of the model will be instrumental in planning schistosomiasis control measures. The model includes two definitive hosts, humans and dogs, as animal reservoirs. Dogs are recognized to play an important role in schistosomiasis transmission in Cambodia. For the purpose of dealing with age-specific prevalence and intensity of infection, the human population was classified into eight age categories in the model. To describe the seasonal fluctuation of the intermediate host population of S. mekongi, the "Post-Spate Survival" hypothesis was adopted for the population dynamics of Neotricula aperta present in the Mekong River. We carried out simulations to evaluate the effect of universal treatment (UT) and targeted mass treatment (TT) with praziquantel on the reduction in prevalence of S. mekongi. The simulations indicated that biyearly UT for 8 years or yearly TT for 5 years after three courses of yearly UT could reduce the prevalence to below 5% when a UT or TT coverage of 85% of inhabitants was achieved. The simulation suggested that the suppression of S. mekongi in Cambodia would be possible by UT or TT with a high coverage rate.</p

Liver Fluke Induces Cholangiocarcinoma

The authors discuss the molecular pathogenesis of opisthorchiasis and associated cholangiocarcinogenesis, particularly nitrative and oxidative DNA damage and the clinical manifestations of cholangiocarcinoma

Emerging Foodborne Trematodiasis

Foodborne trematodiasis is emerging because of increased aquaculture

Deployment of Early Diagnosis and Mefloquine- Artesunate Treatment of Falciparum Malaria in Thailand: The Tak Malaria Initiative

BACKGROUND: Early diagnosis and treatment with artesunate-mefloquine combination therapy (MAS) have reduced the transmission of falciparum malaria dramatically and halted the progression of mefloquine resistance in camps for displaced persons along the Thai-Burmese border, an area of low and seasonal transmission of multidrug-resistant Plasmodium falciparum. We extended the same combination drug strategy to all other communities (estimated population 450,000) living in five border districts of Tak province in northwestern Thailand. METHODS AND FINDINGS: Existing health structures were reinforced. Village volunteers were trained to use rapid diagnostic tests and to treat positive cases with MAS. Cases of malaria, hospitalizations, and malaria-related deaths were recorded in the 6 y before, during, and after the Tak Malaria Initiative (TMI) intervention. Cross-sectional surveys were conducted before and during the TMI period. P. falciparum malaria cases fell by 34% (95% confidence interval [CI], 33.5–34.4) and hospitalisations for falciparum malaria fell by 39% (95% CI, 37.0–39.9) during the TMI period, while hospitalisations for P. vivax malaria remained constant. There were 32 deaths attributed to malaria during, and 22 after the TMI, a 51.5% (95% CI, 39.0–63.9) reduction compared to the average of the previous 3 y. Cross-sectional surveys indicated that P. vivax had become the predominant species in Thai villages, but not in populations living on the Myanmar side of the border. In the displaced persons population, where the original deployment took place 7 y before the TMI, the transmission of P. falciparum continued to be suppressed, the incidence of falciparum malaria remained low, and the in vivo efficacy of the 3-d MAS remained high. CONCLUSIONS: In the remote malarious north western border area of Thailand, the early detection of malaria by trained village volunteers, using rapid diagnostic tests and treatment with mefloquine-artesunate was feasible and reduced the morbidity and mortality of multidrug-resistant P. falciparum

Cirrhosis: Morphologic dynamics for the nonmorphologist

Cirrhosis is an irreversible end-stage liver disease characterized by septate scars dividing a distorted liver into nodules. It generates through a sequence of dynamic changes and once it develops, it may alter its appearance through variations in secondary factors, such as injury and nutrition. The different classification schemes have, unfortunately, only served to make cirrhosis static in our thinking. Stationary morphologic characteristics are of value only if they can be correlated with etiology.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44380/1/10620_2005_Article_BF02231300.pd

Randomized Dose-Ranging Controlled Trial of AQ-13, a Candidate Antimalarial, and Chloroquine in Healthy Volunteers

OBJECTIVES: To determine: (1) the pharmacokinetics and safety of an investigational aminoquinoline active against multidrug–resistant malaria parasites (AQ-13), including its effects on the QT interval, and (2) whether it has pharmacokinetic and safety profiles similar to chloroquine (CQ) in humans. DESIGN: Phase I double-blind, randomized controlled trials to compare AQ-13 and CQ in healthy volunteers. Randomizations were performed at each step after completion of the previous dose. SETTING: Tulane–Louisiana State University–Charity Hospital General Clinical Research Center in New Orleans. PARTICIPANTS: 126 healthy adults 21–45 years of age. INTERVENTIONS: 10, 100, 300, 600, and 1,500 mg oral doses of CQ base in comparison with equivalent doses of AQ-13. OUTCOME MEASURES: Clinical and laboratory adverse events (AEs), pharmacokinetic parameters, and QT prolongation. RESULTS: No hematologic, hepatic, renal, or other organ toxicity was observed with AQ-13 or CQ at any dose tested. Headache, lightheadedness/dizziness, and gastrointestinal (GI) tract–related symptoms were the most common AEs. Although symptoms were more frequent with AQ-13, the numbers of volunteers who experienced symptoms with AQ-13 and CQ were similar (for AQ-13 and CQ, respectively: headache, 17/63 and 10/63, p = 0.2; lightheadedness/dizziness, 11/63 and 8/63, p = 0.6; GI symptoms, 14/63 and 13/63; p = 0.9). Both AQ-13 and CQ exhibited linear pharmacokinetics. However, AQ-13 was cleared more rapidly than CQ (respectively, median oral clearance 14.0–14.7 l/h versus 9.5–11.3 l/h; p ≤ 0.03). QTc prolongation was greater with CQ than AQ-13 (CQ: mean increase of 28 ms; 95% confidence interval [CI], 18 to 38 ms, versus AQ-13: mean increase of 10 ms; 95% CI, 2 to 17 ms; p = 0.01). There were no arrhythmias or other cardiac AEs with either AQ-13 or CQ. CONCLUSIONS: These studies revealed minimal differences in toxicity between AQ-13 and CQ, and similar linear pharmacokinetics

DNA-Sequence Variation Among Schistosoma mekongi Populations and Related Taxa; Phylogeography and the Current Distribution of Asian Schistosomiasis

Schistosomiasis is a disease caused by parasitic worms of the genus Schistosoma. In the lower Mekong river, schistosomiasis in humans is called Mekong schistosomiasis and is caused by Schistosoma mekongi. In the past, Mekong schistosomiasis was known only from the lower Mekong river. Here DNA-sequence variation is used to study the relationships and history of populations of S. mekongi. Populations from other rivers are compared and shown to be S. mekongi, thus confirming that this species is not restricted to only a small section of one river. The dates of divergence among populations are also estimated. Prior to this study it was assumed that S. mekongi originated in Yunnan, China, migrated southwards across Laos and into Cambodia, later becoming extinct in Laos (due to conditions unsuitable for transmission). In contrast, the dates estimated here indicate that S. mekongi entered Cambodia from Vietnam, 2.5–1 Ma. The pattern of genetic variation fits better with a more recent, and ongoing, northwards migration from Cambodia into Laos. The implications are that Mekong schistosomiasis is more widespread than once thought and that the human population at risk is up to 10 times greater than originally estimated. There is also an increased possibility of the spread of Mekong schistosomiasis across Laos

Unlocking the Transcriptomes of Two Carcinogenic Parasites, Clonorchis sinensis and Opisthorchis viverrini

The two parasitic trematodes, Clonorchis sinensis and Opisthorchis viverrini, have a major impact on the health of tens of millions of humans throughout Asia. The greatest impact is through the malignant cancer ( = cholangiocarcinoma) that these parasites induce in chronically infected people. Therefore, both C. sinensis and O. viverrini have been classified by the World Health Organization (WHO) as Group 1 carcinogens. Despite their impact, little is known about these parasites and their interplay with the host at the molecular level. Recent advances in genomics and bioinformatics provide unique opportunities to gain improved insights into the biology of parasites as well as their relationships with their hosts at the molecular level. The present study elucidates the transcriptomes of C. sinensis and O. viverrini using a platform based on next-generation (high throughput) sequencing and advanced in silico analyses. From 500,000 sequences, >50,000 sequences were assembled for each species and categorized as biologically relevant based on homology searches, gene ontology and/or pathway mapping. The results of the present study could assist in defining molecules that are essential for the development, reproduction and survival of liver flukes and/or that are linked to the development of cholangiocarcinoma. This study also lays a foundation for future genomic and proteomic research of C. sinensis and O. viverrini and the cancers that they are known to induce, as well as novel intervention strategies