Low antibody prevalence against <i>Bacillus cereus</i> biovar <i>anthracis</i> in Taï National Park, Côte d’Ivoire, indicates high rate of lethal infections in wildlife

by Fee Zimmermann, Susanne M. Köhler, Kathrin Nowak, Susann Dupke, Anne Barduhn, Ariane Düx, Alexander Lang, Hélène M. De Nys, Jan F. Gogarten, Roland Grunow, Emmanuel Couacy-Hymann, Roman M. Wittig, Silke R. Klee, Fabian H. Leendertz

Bacillus cereus biovar anthracis (Bcbva) is a member of the B. cereus group which carries both B. anthracis virulence plasmids, causes anthrax-like disease in various wildlife species and was described in several sub-Saharan African rainforests. Long-term monitoring of carcasses in Taï National Park, Côte d’Ivoire, revealed continuous wildlife mortality due to Bcbva in a broad range of mammalian species. While non-lethal anthrax infections in wildlife have been described for B. anthracis, nothing is known about the odds of survival following an anthrax infection caused by Bcbva. To address this gap, we present the results of a serological study of anthrax in five wildlife species known to succumb to Bcbva in this ecosystem. Specific antibodies were only detected in two out of 15 wild red colobus monkeys (Procolobus badius) and one out of 10 black-and-white colobus monkeys (Colobus polykomos), but in none of 16 sooty mangabeys (Cercocebus atys), 9 chimpanzees (Pan troglodytes verus) and 9 Maxwell’s duikers (Cephalophus maxwellii). The combination of high mortality and low antibody detection rates indicates high virulence of this disease across these different mammalian species.

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Evaluation of the pharmacokinetic-pharmacodynamic relationship of praziquantel in the <i>Schistosoma mansoni</i> mouse model

by Nada Abla, Jennifer Keiser, Mireille Vargas, Natalie Reimers, Helmut Haas, Thomas Spangenberg

After more than 40 years of use, Praziquantel (PZQ) still remains the drug of choice for the treatment of intestinal and urogenital schistosomiasis. Its anti-parasitic activity resides primarily in the (R)-enantiomer. Hitherto neither the molecular target nor the pharmacokinetic-pharmacodynamic relationship have been fully elucidated. Here we investigated the efficacy and pharmacokinetics of PZQ in the Schistosoma mansoni mouse model to determine the key factors that drive its efficacy. Dose-response studies with racemic PZQ with or without addition of an irreversible pan-cytochrome P450 (CYP) inhibitor, 1-aminobenzotriazole (ABT), were performed. In addition, efficacy of PZQ in the presence of the CYP inducer, dexamethasone (DEX), was determined. Plasma samples were obtained by tail vein bleeding at 4 time points. The (R)-PZQ levels were determined using a LC-MS/MS method. Non-compartmental pharmacokinetic analysis was performed using PKsolver. In addition, experiments using an enhanced in vitro assay were conducted. We found that the use of ABT increased (R)-PZQ plasma exposures in the systemic circulation by ~10 to 20 fold but the latter were not predictive of efficacy. The use of DEX decreased plasma exposures of (R)-PZQ in the systemic circulation by ~10 fold without reducing efficacy. We extrapolated the (R)-PZQ concentrations in mouse portal vein / mesenteric veins from the systemic exposures and found that a free exposure of (R)-PZQ of ~ 20 μM*h in the portal vein was needed to obtain a worm burden reduction >60%. It is suggested that the high (R)-PZQ concentrations available before the hepatic first pass metabolism drive the efficacy against S. mansoni adult worms residing in the mesenteric veins. It is then possible that the current dosing regimen of 40 mg/kg in preventive chemotherapy programs may provide suboptimal concentrations in low-weight patients such as children, due to smaller total amounts of drug administered, and may consequently result in lower cure rates.

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Estimating the prevalence and intensity of <i>Schistosoma mansoni</i> infection among rural communities in Western Tanzania: The influence of sampling strategy and statistical approach

by Jared S. Bakuza, Matthew J. Denwood, Gamba Nkwengulila, Barbara K. Mable

Background

Schistosoma mansoni is a parasite of major public health importance in developing countries, where it causes a neglected tropical disease known as intestinal schistosomiasis. However, the distribution of the parasite within many endemic regions is currently unknown, which hinders effective control. The purpose of this study was to characterize the prevalence and intensity of infection of S. mansoni in a remote area of western Tanzania.

Methodology/Principal findings

Stool samples were collected from 192 children and 147 adults residing in Gombe National Park and four nearby villages. Children were actively sampled in local schools, and adults were sampled passively by voluntary presentation at the local health clinics. The two datasets were therefore analysed separately. Faecal worm egg count (FWEC) data were analysed using negative binomial and zero-inflated negative binomial (ZINB) models with explanatory variables of site, sex, and age. The ZINB models indicated that a substantial proportion of the observed zero FWEC reflected a failure to detect eggs in truly infected individuals, meaning that the estimated true prevalence was much higher than the apparent prevalence as calculated based on the simple proportion of non-zero FWEC. For the passively sampled data from adults, the data were consistent with close to 100% true prevalence of infection. Both the prevalence and intensity of infection differed significantly between sites, but there were no significant associations with sex or age.

Conclusions/Significance

Overall, our data suggest a more widespread distribution of S. mansoni in this part of Tanzania than was previously thought. The apparent prevalence estimates substantially under-estimated the true prevalence as determined by the ZINB models, and the two types of sampling strategies also resulted in differing conclusions regarding prevalence of infection. We therefore recommend that future surveillance programmes designed to assess risk factors should use active sampling whenever possible, in order to avoid the self-selection bias associated with passive sampling.

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Platelet dysfunction contributes to bleeding complications in patients with probable leptospirosis

by Rahajeng N. Tunjungputri, Muhammad Hussein Gasem, Willemijn van der Does, Pandu H. Sasongko, Bambang Isbandrio, Rolf T. Urbanus, Philip G. de Groot, Andre van der Ven, Quirijn de Mast

Background

Severe leptospirosis is frequently complicated by a hemorrhagic diathesis, of which the pathogenesis is still largely unknown. Thrombocytopenia is common, but often not to the degree that spontaneous bleeding is expected. We hypothesized that the hemorrhagic complications are not only related to thrombocytopenia, but also to platelet dysfunction, and that increased binding of von Willebrand factor (VWF) to platelets is involved in both platelet dysfunction and increased platelet clearance.

Methodology/Principal findings

A prospective study was carried out in Semarang, Indonesia, enrolling 33 hospitalized patients with probable leptospirosis, of whom 15 developed clinical bleeding, and 25 healthy controls. Platelet activation and reactivity were determined using flow cytometry by measuring the expression of P-selectin and activation of the αIIbβ3 integrin by the binding of fibrinogen in unstimulated samples and after ex vivo stimulation by the platelet agonists adenosine-diphosphate (ADP) and thrombin-receptor activating peptide (TRAP). Platelet-VWF binding, before and after VWF stimulation by ristocetin, as well as plasma levels of VWF, active VWF, the VWF-inactivating enzyme ADAMTS13, thrombin-antithrombin complexes (TAT) and P-selectin were also measured. Bleeding complications were graded using the WHO bleeding scale. Our study revealed that platelet activation, with a secondary platelet dysfunction, is a feature of patients with probable leptospirosis, especially in those with bleeding manifestations. There was a significant inverse correlation of bleeding score with TRAP-stimulated P-selectin and platelet-fibrinogen binding (R = -0.72, P = 0.003 and R = -0.66, P = 0.01, respectively) but not with platelet count. Patients with bleeding also had a significantly higher platelet-VWF binding. Platelet counts were inversely correlated with platelet-VWF binding (R = -0.74; P = 0.0009. There were no correlations between platelet-VWF binding and the degree of platelet dysfunction, suggesting that increased platelet-VWF binding does not directly interfere with the platelet αIIbβ3 signaling pathway in patients with probable leptospirosis.

Conclusion/Significance

Platelet dysfunction is common in probable leptospirosis patients with manifest bleeding. Increased VWF-platelet binding may contribute to the activation and clearance of platelets.

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A scoring model for predicting prognosis of patients with severe fever with thrombocytopenia syndrome

by Bei Jia, Xiaomin Yan, Yuxin Chen, Guiyang Wang, Yong Liu, Biyun Xu, Peixin Song, Yang Li, Yali Xiong, Weihua Wu, Yingying Hao, Juan Xia, Zhaoping Zhang, Rui Huang, Chao Wu

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging epidemic infectious disease caused by the SFTS bunyavirus (SFTSV) with an estimated high case-fatality rate of 12.7% to 32.6%. Currently, the disease has been reported in mainland China, Japan, Korea, and the United States. At present, there is no specific antiviral therapy for SFTSV infection. Considering the higher mortality rate and rapid clinical progress of SFTS, supporting the appropriate treatment in time to SFTS patients is critical. Therefore, it is very important for clinicians to predict these SFTS cases who are more likely to have a poor prognosis or even more likely to decease. In the present study, we established a simple and feasible model for assessing the severity and predicting the prognosis of SFTS patients with high sensitivity and specificity. This model may aid the physicians to immediately initiate prompt treatment to block the rapid development of the illness and reduce the fatality of SFTS patients.

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Updated estimation of the impact of a Japanese encephalitis immunization program with live, attenuated SA 14-14-2 vaccine in Nepal

by Shyam Raj Upreti, Nicole P. Lindsey, Rajendra Bohara, Ganga Ram Choudhary, Sushil Shakya, Mukunda Gautam, Jagat Narain Giri, Marc Fischer, Susan L. Hills

Background

Japanese encephalitis (JE) is a mosquito-borne disease that is associated with considerable morbidity and mortality in many Asian countries. The objective of this study was to describe the impact of the JE immunization program using SA 14-14-2 JE vaccine implemented in Nepal during 2006 through 2011. A previous assessment after the initial program implementation phase described a significantly lower post-campaign JE incidence compared to expected incidence; however, the previous evaluation had limited post-campaign data for some districts.

Methodology/Principal findings

JE and acute encephalitis syndrome (AES) data gathered through Nepal’s routine surveillance system from 2004 through 2014 were analyzed to assess the impact of the JE immunization program implemented in 31 districts. Expected incidence rates were determined by calculating the incidence of cases per 100,000 person-years in each district before the vaccination campaigns. This rate was applied to the relevant population after the vaccination campaigns, which provided the expected number of cases had the campaign not occurred. The observed incidence rate was the number of reported cases per 100,000 person-years post-campaign. Expected and observed JE and AES cases and incidence rates were compared. The post-campaign JE incidence rate of 0.7 cases per 100,000 was 78% (95% CI 76%–79%) lower than expected had no campaign occurred and an estimated 3,011 (95% CI 2,941–3,057) JE cases were prevented. The post-vaccination AES incidence of 5.5 cases per 100,000 was 59% (58%–60%) lower than the expected and an estimated 9,497 (95% CI 9,268–9,584) AES cases were prevented.

Conclusions/Significance

This analysis strengthens previous findings of the substantial impact of Nepal’s JE immunization program using SA 14-14-2 JE vaccine.

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<i>“Koko et les lunettes magiques”</i>: An educational entertainment tool to prevent parasitic worms and diarrheal diseases in Côte d’Ivoire

by Clémence Essé, Véronique A. Koffi, Abel Kouamé, Kouassi Dongo, Richard B. Yapi, Honorine M. Moro, Christiane A. Kouakou, Marta S. Palmeirim, Bassirou Bonfoh, Eliézer K. N’Goran, Jürg Utzinger, Giovanna Raso

Background

Integrated control programs, emphasizing preventive chemotherapy along with health education, can reduce the incidence of soil-transmitted helminthiasis and schistosomiasis. The aim of this study was to develop an educational animated cartoon to improve school children’s awareness regarding soil-transmitted helminthiasis, diarrheal diseases, and related hygiene practices in Côte d’Ivoire. The key messages included in the cartoon were identified through prior formative research to specifically address local knowledge gaps.

Methodology

In a first step, preliminary research was conducted to assess the knowledge, attitudes, practices, and beliefs of school-aged children regarding parasitic worm infections and hygiene, to identify key health messages to be included in an animated cartoon. Second, an animated cartoon was produced, which included the drafting of the script and story board, and the production of the cartoon’s initial version. Finally, the animated cartoon was pilot tested in eight selected schools and further fine-tuned.

Principal findings

According to the questionnaire results, children believed that the consumption of sweet food, eating without washing their hands, sitting on the floor, and eating spoiled food were the main causes of parasitic worm infections. Abdominal pain, diarrhea, lack of appetite, failure to grow, and general fatigue were mentioned as symptoms of parasitic worm infections. Most of the children knew that they should go to the hospital for treatment if they experienced symptoms of parasitic worm diseases. The animated cartoon titled “Koko et les lunettes magiques” was produced by Afrika Toon, in collaboration with a scientific team composed of epidemiologists, civil engineers, and social scientists, and the local school children and teachers. Pilot testing of the animated cartoon revealed that, in the short term, children grasped and kept key messages. Most of the children who were shown the cartoon reported to like it.

Conclusion/Significances

Acceptance of the animated cartoon was high among children and teachers alike. The messaging was tailored to improve knowledge and practices for prevention of helminthiases and diarrheal diseases through prior identification of knowledge gaps. Integration of such education tools into the school curriculum, along with deworming campaigns, might improve sustainability of control and elimination efforts against helminthiases and diarrheal diseases.

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