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Preview: PLoS Neglected Tropical Diseases: New Articles

PLOS Neglected Tropical Diseases: New Articles



A Peer-Reviewed Open-Access Journal



Updated: 2017-12-16T16:50:51Z

 



(XML) Analysis of the efficacy of Taiwanese freeze-dried neurotoxic antivenom against Naja kaouthia, Naja siamensis and Ophiophagus hannah through proteomics and animal model approaches

2017-12-15T22:00:00Z

by Chien-Chun Liu, Chen-Hsien You, Po-Jung Wang, Jau-Song Yu, Guo-Jen Huang, Chien-Hsin Liu, Wen-Chin Hsieh, Chih-Chuan Lin

In Southeast Asia, envenoming resulting from cobra snakebites is an important public health issue in many regions, and antivenom therapy is the standard treatment for the snakebite. Because these cobras share a close evolutionary history, the amino acid sequences of major venom components in different snakes are very similar. Therefore, either monovalent or polyvalent antivenoms may offer paraspecific protection against envenomation of humans by several different snakes. In Taiwan, a bivalent antivenom—freeze-dried neurotoxic antivenom (FNAV)—against Bungarus multicinctus and Naja atra is available. However, whether this antivenom is also capable of neutralizing the venom of other species of snakes is not known. Here, to expand the clinical application of Taiwanese FNAV, we used an animal model to evaluate the neutralizing ability of FNAV against the venoms of three common snakes in Southeast Asia, including two ‘true’ cobras Naja kaouthia (Thailand) and Naja siamensis (Thailand), and the king cobra Ophiophagus hannah (Indonesia). We further applied mass spectrometry (MS)-based proteomic techniques to characterize venom proteomes and identify FNAV-recognizable antigens in the venoms of these Asian snakes. Neutralization assays in a mouse model showed that FNAV effectively neutralized the lethality of N. kaouthia and N. siamensis venoms, but not O. hannah venom. MS-based venom protein identification results further revealed that FNAV strongly recognized three-finger toxin and phospholipase A2, the major protein components of N. kaouthia and N. siamensis venoms. The characterization of venom proteomes and identification of FNAV-recognizable venom antigens may help researchers to further develop more effective antivenom designed to block the toxicity of dominant toxic proteins, with the ultimate goal of achieving broadly therapeutic effects against these cobra snakebites.(image)



(XML) Genotyping of Mycobacterium leprae for better understanding of leprosy transmission in Fortaleza, Northeastern Brazil

2017-12-15T22:00:00Z

by Amanda N. B. Fontes, Luana N. G. C. Lima, Rosa M. S. Mota, Rosa L. F. Almeida, Maria A. Pontes, Heitor de S. Gonçalves, Cristiane C. Frota, Varalakshmi D. Vissa, Patrick J. Brennan, Ricardo J. P. S. Guimaraes, Carl Kendall, Ligia R. F. S. Kerr, Philip N. Suffys

Leprosy is endemic in large part of Brazil with 28,761 new patients in 2015, the second largest number worldwide and reaches 9/10.000 in highly endemic regions and 2.7/10.000 in the city of Fortaleza, Ceará, Northeast Brazil. For better understanding of risk factors for leprosy transmission, we conducted an epidemiologic study supplemented by 17 locus VNTR and SNP 1–4 typing of Mycobacterium leprae in skin biopsy samples from new multibacillary (MB) patients diagnosed at a reference center in 2009 and 2010. Among the 1,519 new patients detected during the study period, 998 (65.7%) were MB and we performed DNA extraction and genotyping on 160 skin biopsy samples, resulting in 159 (16%) good multilocus VNTR types. Thirty-eight of these patients also provided VNTR types from M. leprae in nasal swabs. The SNP-Type was obtained for 157 patients and 87% were of type 4. Upon consideration all VNTR markers, 156 different genotypes and three pairs with identical genotypes were observed; no epidemiologic relation could be observed between individuals in these pairs. Considerable variability in differentiating index (DI) was observed between the different markers and the four with highest DI [(AT)15, (TA)18, (AT)17 and (GAA)21] frequently demonstrated differences in copy number when comparing genotypes from both type of samples. Excluding these markers from analysis resulted in 83 genotypes, 20 of which included 96 of the patients (60.3%). These clusters were composed of two (n = 8), three (n = 6), four (n = 1), five (n = 2), six (n = 1), 19 (n = 1) and 23 (n = 23) individuals and suggests that recent transmission is contributing to the maintenance of leprosy in Fortaleza. When comparing epidemiological and clinical variables among patients within clustered or with unique M. leprae genotypes, a positive bacterial index in skin biopsies and knowledge of working with someone with the disease were significantly associated with clustering. A tendency to belong to a cluster was observed with later notification of disease (mean value of 3.4 months) and having disability grade 2. A tendency for lack of clustering was observed for patients who reported to have lived with another leprosy case but this might be due to lack of inclusion of household contacts in the study. Although clusters were spread over the city, kernel analysis revealed that some of the patients belonging to the two major clusters were spatially related to some neighborhoods that report poverty and high disease incidence in children. Finally, inclusion of genotypes from nasal swabs might be warranted. A major limitation of the study is that sample size of 160 patients from a two year period represents only 15% of the new patients and this could have weakened statistical outcomes. This is the first molecular epidemiology study of leprosy in Brazil and although the high clustering level suggests that recent transmission is the major cause of disease in Fortaleza; the existence of two large clusters needs further investigation.(image)



(XML) Polypyridylruthenium(II) complexes exert anti-schistosome activity and inhibit parasite acetylcholinesterases

2017-12-14T22:00:00Z

by Madhu K. Sundaraneedi, Bemnet Tedla, Ramon M. Eichenberger, Luke Becker, Darren Pickering, Michael J. Smout, Siji Rajan, Phurpa Wangchuk, F. Richard Keene, Alex Loukas, J. Grant Collins, Mark S. Pearson

Background

Schistosomiasis affects over 200 million people and there are concerns whether the current chemotherapeutic control strategy (periodic mass drug administration with praziquantel (PZQ)—the only licenced anti-schistosome compound) is sustainable, necessitating the development of new drugs.

Methodology/Principal findings

We investigated the anti-schistosome efficacy of polypyridylruthenium(II) complexes and showed they were active against all intra-mammalian stages of S. mansoni. Two compounds, Rubb12-tri and Rubb7-tnl, which were among the most potent in their ability to kill schistosomula and adult worms and inhibit egg hatching in vitro, were assessed for their efficacy in a mouse model of schistosomiasis using 5 consecutive daily i.v. doses of 2 mg/kg (Rubb12-tri) and 10 mg/kg (Rubb7-tnl). Mice treated with Rubb12-tri showed an average 42% reduction (P = 0.009), over two independent trials, in adult worm burden. Liver egg burdens were not significantly decreased in either drug-treated group but ova from both of these groups showed significant decreases in hatching ability (Rubb12-tri—68%, Rubb7-tnl—56%) and were significantly morphologically altered (Rubb12-tri—62% abnormal, Rubb7-tnl—35% abnormal). We hypothesize that the drugs exerted their activity, at least partially, through inhibition of both neuronal and tegumental acetylcholinesterases (AChEs), as worms treated in vitro showed significant decreases in activity of these enzymes. Further, treated parasites exhibited a significantly decreased ability to uptake glucose, significantly depleted glycogen stores and withered tubercules (a site of glycogen storage), implying drug-mediated interference in this nutrient acquisition pathway.

Conclusions/Significance

Our data provide compelling evidence that ruthenium complexes are effective against all intra-mammalian stages of schistosomes, including schistosomula (refractory to PZQ) and eggs (agents of disease transmissibility). Further, the results of this study suggest that schistosome AChE is a target of ruthenium drugs, a finding that can inform modification of current compounds to identify analogues which are even more effective and selective against schistosomes.

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(XML) Virulence, pathology, and pathogenesis of Pteropine orthoreovirus (PRV) in BALB/c mice: Development of an animal infection model for PRV

2017-12-14T22:00:00Z

by Kazutaka Egawa, Masayuki Shimojima, Satoshi Taniguchi, Noriyo Nagata, Hideki Tani, Tomoki Yoshikawa, Takeshi Kurosu, Shumpei Watanabe, Shuetsu Fukushi, Masayuki Saijo

Background

Cases of acute respiratory tract infection caused by Pteropine orthoreovirus (PRV) of the genus Orthoreovirus (family: Reoviridae) have been reported in Southeast Asia, where it was isolated from humans and bats. It is possible that PRV-associated respiratory infections might be prevalent in Southeast Asia. The clinical course of PRV is not fully elucidated.

Methods

The virulence, pathology, and pathogenesis of two PRV strains, a human-borne PRV strain (isolated from a patient, who returned to Japan from Bali, Indonesia in 2007) and a bat-borne PRV (isolated from a bat [Eonycteris spelaea] in the Philippines in 2013) were investigated in BALB/c mice using virological, pathological, and immunological study methods.

Results

The intranasal inoculation of BALB/c mice with human-borne PRV caused respiratory infection. In addition, all mice with immunity induced by pre-inoculation with a non-lethal dose of PRV were completely protected against lethal PRV infection. Mice treated with antiserum with neutralizing antibody activity after inoculation with a lethal dose of PRV showed a reduced fatality rate. In this mouse model, bat-borne PRV caused respiratory infection similar to human-borne PRV. PRV caused lethal respiratory disease in an animal model of PRV infection, in which BALB/c mice were used.

Conclusions

The BALB/c mouse model might help to accelerate research on the virulence of PRV and be useful for evaluating the efficacy of therapeutic agents and vaccines for the treatment and prevention of PRV infection. PRV was shown for the first time to be a causative virus of respiratory disease on the basis of Koch’s postulations by the additional demonstration that PRV caused respiratory disease in mice through their intranasal inoculation with PRV.

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(XML) Drug resistance and treatment failure in leishmaniasis: A 21st century challenge

2017-12-14T22:00:00Z

by Alicia Ponte-Sucre, Francisco Gamarro, Jean-Claude Dujardin, Michael P. Barrett, Rogelio López-Vélez, Raquel García-Hernández, Andrew W. Pountain, Roy Mwenechanya, Barbara Papadopoulou

Reevaluation of treatment guidelines for Old and New World leishmaniasis is urgently needed on a global basis because treatment failure is an increasing problem. Drug resistance is a fundamental determinant of treatment failure, although other factors also contribute to this phenomenon, including the global HIV/AIDS epidemic with its accompanying impact on the immune system. Pentavalent antimonials have been used successfully worldwide for the treatment of leishmaniasis since the first half of the 20th century, but the last 10 to 20 years have witnessed an increase in clinical resistance, e.g., in North Bihar in India. In this review, we discuss the meaning of “resistance” related to leishmaniasis and discuss its molecular epidemiology, particularly for Leishmania donovani that causes visceral leishmaniasis. We also discuss how resistance can affect drug combination therapies. Molecular mechanisms known to contribute to resistance to antimonials, amphotericin B, and miltefosine are also outlined.(image)



(XML) Emergence of melioidosis in the Indian Ocean region: Two new cases and a literature review

2017-12-14T22:00:00Z

by Nicolas Allou, Olivier Martinet, Jérôme Allyn, Bruno Bouchet, Marie-Christine Jaffar-Bandjee, Thomas Galas, Nicolas Traversier, Olivier Belmonte

Author summary: Melioidosis is a disease caused by bacteria called B. pseudomallei. Infections can develop after contact with standing water. This disease can reach all the organs and especially the lungs. It is associated with a high mortality rate (up to 50%). Melioidosis is endemic in northern Australia and in Southeast Asia. Nevertheless, B. pseudomallei may be endemic in the Indian Ocean region and in Madagascar in particular, so clinicians and microbiologists should consider acute melioidosis as a differential diagnosis in the Indian Ocean region, in particular from Madagascar.(image)



(XML) RNA interference in Fasciola gigantica: Establishing and optimization of experimental RNAi in the newly excysted juveniles of the fluke

2017-12-12T22:00:00Z

by Arun Anandanarayanan, Opinder Krishen Raina, Hniang Lalrinkima, Ajayta Rialch, Muthu Sankar, Anju Varghese

Fasciolosis caused by Fasciola gigantica is a neglected tropical disease but a constraint on the growth and productivity of cattle, buffaloes and sheep in the tropical countries of Asia and Africa. Resistance to commonly used anthelmintics in Fasciola has increased the need to search for alternative therapeutic targets. RNA interference is the current tool of choice in the search for such targets in Fasciola. The susceptibility of juvenile Fasciola hepatica to double stranded (ds) RNA induced RNAi has been established but in F. gigantica a single preliminary report on RNAi induced mRNA transcript knockdown is available. Here we optimized conditions for RNAi in the liver fluke F.gigantica targeting six genes including superoxide dismutase (SOD), σ class of glutathione-s-transferase (GST), cathepsin (Cat) L1-D, Cat B1, Cat B2 and Cat B3 that showed robust transcriptional silencing of the targets following exposure of the newly excysted juveniles (NEJs) to long (170–223 nt) dsRNA. Knockdown was shown to be concentration dependent with significant mRNA transcript suppression occurring at 5 ng / μl that showed further suppression with the increase in the dsRNA concentration. The dsRNA induced persistent silencing of the mRNA transcript of SOD and σGST up to 15 days of observation. Delivery of the long dsRNA and siRNA to the newly excysted juveniles by soaking method was found to be efficient by tracking the uptake and diffusion of Cy3 labelled siRNA and long dsRNA in the flukes. Off-target effects of dsRNA trigger on some of the non-target genes were detected in the present investigation on RNAi in F. gigantica. The dsRNA induced superoxide dismutase protein suppression while impact of RNAi on other target proteins was not studied. There is no in vitro culture system for prolonged survival of the F. gigantica and in the present study in vitro maintenance of the NEJs is reported for a period of 3 weeks. The present study is the first attempt on optimization of RNAi protocols in F. gigantica where long dsRNA allowed for an efficient and persistent gene silencing, opening prospects for functional validation of putative vaccine and therapeutic targets in this neglected parasite.(image)



(XML) Elimination of trachoma as a public health problem in Ghana: Providing evidence through a pre-validation survey

2017-12-12T22:00:00Z

by Oscar Debrah, Ernest O. Mensah, Laura Senyonjo, Dziedzom K. de Souza, Tei E. Hervie, David Agyemang, Didier Bakajika, Benjamin Marfo, Felix Ahorsu, Seth Wanye, Robin Bailey, Joseph B. Koroma, Agatha Aboe, Nana-Kwadwo Biritwum

Background

In order to achieve elimination of trachoma, a country needs to demonstrate that the elimination prevalence thresholds have been achieved and then sustained for at least a two-year period. Ghana achieved the thresholds in 2008, and since 2011 has been implementing its trachoma surveillance strategy, which includes community and school screening for signs of follicular trachoma and trichiasis, in trachoma-endemic districts. In 2015–2016, the country conducted a district level population-based survey to validate elimination of trachoma as a public health problem.

Methods

As per WHO recommendations, a cross-sectional survey, employing a two-stage cluster random sampling methodology, was used across 18 previously trachoma endemic districts (evaluation units (EUs) in the Upper West and Northern Regions of Ghana. In each EU 24 villages were selected based on probability proportional to estimated size. A minimum of 40 households were targeted per village and all eligible residents were examined for clinical signs of trachoma, using the WHO simplified grading system. The number of trichiasis cases unknown to the health system was determined. Household environmental risk factors for trachoma were also assessed.

Results

Data from 45,660 individuals were examined from 11,099 households across 18 EUs, with 27,398 (60.0%) children aged 1–9 years and 16,610 (36.4%) individuals 15 years and above All EUs had shown to have maintained the WHO elimination threshold for Trachomatous inflammation-Follicular (TF) (<5.0% prevalence) in children aged 1–9 years old. The EU TF prevalence in children aged 1–9 years old ranged from between 0.09% to 1.20%. Only one EU (Yendi 0.36%; 95% CI: 0.0–1.01) failed to meet the WHO TT elimination threshold (< 0.2% prevalence in adults aged 15 and above). The EU prevalence of trichiasis (TT) unknown to the health system in adults aged ≥15 years, ranged from 0.00% to 0.36%. In this EU, the estimated TT backlog is 417 All TT patients identified in the study, as well as through on-going surveillance efforts will require further management. A total of 75.9% (95% CI 72.1–79.3, EU range 29.1–92.6) of households defecated in the open but many households had access to an improved water source 75.9% (95%CI: 71.5–79.8, EU range 47.4–90.1%), with 45.5% (95% CI 41.5–49.7%, EU range 28.4–61.8%) making a round trip of water collection < 30 minutes.

Conclusion

The findings from this survey indicate elimination thresholds have been maintained in Ghana in 17 of the 18 surveyed EUs. Only one EU, Yendi, did not achieve the TT elimination threshold. A scheduled house-by-house TT case search in this EU coupled with surgery to clear the backlog of cases is necessary in order for Ghana to request validation of elimination of trachoma as a public health problem.

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(XML) Trachomatous scarring among children in a formerly hyper-endemic district of Tanzania

2017-12-12T22:00:00Z

by Jacob T. Cox, Harran Mkocha, Beatriz Munoz, Sheila K. West

Background

Associations between repeated ocular infections with Chlamydia trachomatis in childhood and conjunctival scarring in adulthood are well established. Trachomatous scarring (TS) in children has also been observed in hyper-endemic areas, but data are scant regarding childhood scarring in areas where trachoma has been reduced to hypo-endemic levels.

Methods/Principle findings

In this cross-sectional study, a random sample of children, ages 1–9 years, were selected from 38 communities in the formerly hyper-endemic district of Kongwa, Tanzania. Each participant received an ocular examination and eye-swab test for C. trachomatis infection. Conjunctival photographs were taken and analyzed at 5x magnification to determine scarring presence and severity. Community-level case clustering was assessed using intra-class correlation coefficients, and associations between TS presence and demographic/clinical factors were assessed using contingency table analyses. 1,496 children (78% of eligible) participated in this study. The mean age was 5.5 years and 51% were female. Scarring prevalence was 2.1% (95% CI: 1.5%– 3.0%). The prevalence of follicular trachoma and ocular C. trachomatis infection were 3.2% and 6.5%, respectively. Most TS cases (68.7%) fell into the mildest category, grade S1. 18.7% were grade S2; 12.6% were grade S3. No significant associations were seen between TS presence and age, sex, follicular trachoma, or active ocular C. trachomatis infection (p-values: 0.14, 0.48, 0.27, 0.15, respectively). Thirty communities (78.9%) had 0–1 TS cases, and the most seen in any single community was four cases. Three years ago, follicular trachoma prevalence averaged 4.9% in communities with 0–1 TS cases, but 7.6% in communities with 2–4 TS cases (p-value: 0.08).

Conclusions

In this formerly hyper-endemic district of Tanzania, TS was rare in 1–9 year-olds and usually mild when present. Communities with higher rates of follicular trachoma in the past were more likely to have ≥2 cases of scarring, but the association was not statistically significant.

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(XML) Sustaining visceral leishmaniasis elimination in Bangladesh – Could a policy brief help?

2017-12-12T22:00:00Z

by Alyssa Fitzpatrick, Noor Saad M. S. Al-Kobaisi, Jessica Beitman Maya, Yu Ren Chung, Satyender Duhan, Erdene Elbegdorj, Sushant Jain, Edward Kuhn, Alexandra Nastase, Be-Nazir Ahmed, Piero Olliaro

Bangladesh has made significant progress towards elimination of visceral leishmaniasis, and is on track to achieve its target of less than one case per 10,000 inhabitants in each subdistrict in 2017. As the incidence of disease falls, it is likely that the political capital and financial resources dedicated towards the elimination of visceral leishmaniasis may decrease, raising the prospect of disease resurgence. Policy memos may play a crucial role during the transition of the elimination plan from the ‘attack’ to the ‘consolidation’ and ‘maintenance’ phases, highlighting key stakeholders and areas where ongoing investment is crucial. An example of a policy brief is outlined in this paper. The background to the current elimination efforts is highlighted, with emphasis on remaining uncertainties including the impact of disease reservoirs and sustainable surveillance strategies. A stakeholder map is provided outlining the current and projected future activities of key bodies. Identification of key stakeholders subsequently frames the discussion of three key policy recommendations in the Bangladeshi context for the transition to the consolidation and maintenance phases of the elimination program. Recommendations include determining optimal vector control and surveillance strategies, shifting the emphasis towards horizontal integration of disease programs, and prioritising remaining research questions with a focus on operational and technical capacity. Achieving elimination is as much a political as a scientific question. Integrating the discussion of key stakeholders with policy priorities and the research agenda provides a novel insight into potential pathways forwards in the elimination of visceral leishmaniasis in Bangladesh and in the rest of the Indian subcontinent.(image)



(XML) Characterization of the Giardia intestinalis secretome during interaction with human intestinal epithelial cells: The impact on host cells

2017-12-11T22:00:00Z

by Showgy Y. Ma’ayeh, Jingyi Liu, Dimitra Peirasmaki, Katarina Hörnaeus, Sara Bergström Lind, Manfred Grabherr, Jonas Bergquist, Staffan G. Svärd

Background

Giardia intestinalis is a non-invasive protozoan parasite that causes giardiasis in humans, the most common form of parasite-induced diarrhea. Disease mechanisms are not completely defined and very few virulence factors are known.

Methodology

To identify putative virulence factors and elucidate mechanistic pathways leading to disease, we have used proteomics to identify the major excretory-secretory products (ESPs) when Giardia trophozoites of WB and GS isolates (assemblages A and B, respectively) interact with intestinal epithelial cells (IECs) in vitro.

Findings

The main parts of the IEC and parasite secretomes are constitutively released proteins, the majority of which are associated with metabolism but several proteins are released in response to their interaction (87 and 41 WB and GS proteins, respectively, 76 and 45 human proteins in response to the respective isolates). In parasitized IECs, the secretome profile indicated effects on the actin cell cytoskeleton and the induction of immune responses whereas that of Giardia showed anti-oxidation, proteolysis (protease-associated) and induction of encystation responses. The Giardia secretome also contained immunodominant and glycosylated proteins as well as new candidate virulence factors and assemblage-specific differences were identified. A minor part of Giardia ESPs had signal peptides (29% for bot isolates) and extracellular vesicles were detected in the ESPs fractions, suggesting alternative secretory pathways. Microscopic analyses showed ESPs binding to IECs and partial internalization. Parasite ESPs reduced ERK1/2 and P38 phosphorylation and induced NF-κB nuclear translocation. Giardia ESPs altered gene expression in IECs, with a transcriptional profile indicating recruitment of immune cells via chemokines, disturbances in glucose homeostasis, cholesterol and lipid metabolism, cell cycle and induction of apoptosis.

Conclusions

This is the first study identifying Giardia ESPs and evaluating their effects on IECs. It highlights the importance of host and parasite ESPs during interactions and reveals the intricate cellular responses that can explain disease mechanisms and attenuated inflammatory responses during giardiasis.

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(XML) Longitudinal assessment of anti-PGL-I serology in contacts of leprosy patients in Bangladesh

2017-12-11T22:00:00Z

by Renate A. Richardus, Konrad van der Zwet, Anouk van Hooij, Louis Wilson, Linda Oskam, Roel Faber, Susan J. F. van den Eeden, David Pahan, Khorshed Alam, Jan Hendrik Richardus, Annemieke Geluk

Background

Despite elimination efforts, the number of Mycobacterium leprae (M. leprae) infected individuals who develop leprosy, is still substantial. Solid evidence exists that individuals living in close proximity to patients are at increased risk to develop leprosy. Early diagnosis of leprosy in endemic areas requires field-friendly tests that identify individuals at risk of developing the disease before clinical manifestation. Such assays will simultaneously contribute to reduction of current diagnostic delay as well as transmission. Antibody (Ab) levels directed against the M.leprae-specific phenolic glycolipid I (PGL-I) represents a surrogate marker for bacterial load. However, it is insufficiently defined whether anti-PGL-I antibodies can be utilized as prognostic biomarkers for disease in contacts. Particularly, in Bangladesh, where paucibacillary (PB) patients form the majority of leprosy cases, anti-PGL-I serology seems an inadequate method for leprosy screening in contacts as a directive for prophylactic treatment.

Methods

Between 2002 and 2009, fingerstick blood from leprosy patients’ contacts without clinical signs of disease from a field-trial in Bangladesh was collected on filter paper at three time points covering six years of follow-up per person. Analysis of anti-PGL-I Ab levels for 25 contacts who developed leprosy during follow-up and 199 contacts who were not diagnosed with leprosy, was performed by ELISA after elution of bloodspots from filter paper.

Results

Anti-PGL-I Ab levels at intake did not significantly differ between contacts who developed leprosy during the study and those who remained free of disease. Moreover, anti-PGL-I serology was not prognostic in this population as no significant correlation was identified between anti-PGL-I Ab levels at intake and the onset of leprosy.

Conclusion

In this highly endemic population in Bangladesh, no association was observed between anti-PGL-I Ab levels and onset of disease, urging the need for an extended, more specific biomarker signature for early detection of leprosy in this area.

Trial registration

ClinicalTrials.gov ISRCTN61223447

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(XML) Low cost, low tech SNP genotyping tools for resource-limited areas: Plague in Madagascar as a model

2017-12-11T22:00:00Z

by Cedar L. Mitchell, Voahangy Andrianaivoarimanana, Rebecca E. Colman, Joseph Busch, Heidie Hornstra-O’Neill, Paul S. Keim, David M. Wagner, Minoarisoa Rajerison, Dawn N. Birdsell

Background

Genetic analysis of pathogenic organisms is a useful tool for linking human cases together and/or to potential environmental sources. The resulting data can also provide information on evolutionary patterns within a targeted species and phenotypic traits. However, the instruments often used to generate genotyping data, such as single nucleotide polymorphisms (SNPs), can be expensive and sometimes require advanced technologies to implement. This places many genotyping tools out of reach for laboratories that do not specialize in genetic studies and/or lack the requisite financial and technological resources. To address this issue, we developed a low cost and low tech genotyping system, termed agarose-MAMA, which combines traditional PCR and agarose gel electrophoresis to target phylogenetically informative SNPs.

Methodology/Principal findings

To demonstrate the utility of this approach for generating genotype data in a resource-constrained area (Madagascar), we designed an agarose-MAMA system targeting previously characterized SNPs within Yersinia pestis, the causative agent of plague. We then used this system to genetically type pathogenic strains of Y. pestis in a Malagasy laboratory not specialized in genetic studies, the Institut Pasteur de Madagascar (IPM). We conducted rigorous assay performance validations to assess potential variation introduced by differing research facilities, reagents, and personnel and found no difference in SNP genotyping results. These agarose-MAMA PCR assays are currently employed as an investigative tool at IPM, providing Malagasy researchers a means to improve the value of their plague epidemiological investigations by linking outbreaks to potential sources through genetic characterization of isolates and to improve understanding of disease ecology that may contribute to a long-term control effort.

Conclusions

The success of our study demonstrates that the SNP-based genotyping capacity of laboratories in developing countries can be expanded with manageable financial cost for resource constraint laboratories. This is a practical formula that reduces resource-driven limitations to genetic research and promises to advance global collective knowledge of infectious diseases emanating from resource limited regions of the world.

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(XML) Interpreting ambiguous ‘trace’ results in Schistosoma mansoni CCA Tests: estimating sensitivity and specificity of ambiguous results with no gold standard

2017-12-08T22:00:00Z

by Michelle N. Clements, Christl A. Donnelly, Alan Fenwick, Narcis B. Kabatereine, Sarah C. L. Knowles, Aboulaye Meité, Eliézer K. N'Goran, Yolisa Nalule, Sarah Nogaro, Anna E. Phillips, Edridah Muheki Tukahebwa, Fiona M. Fleming

Background

The development of new diagnostics is an important tool in the fight against disease. Latent Class Analysis (LCA) is used to estimate the sensitivity and specificity of tests in the absence of a gold standard. The main field diagnostic for Schistosoma mansoni infection, Kato-Katz (KK), is not very sensitive at low infection intensities. A point-of-care circulating cathodic antigen (CCA) test has been shown to be more sensitive than KK. However, CCA can return an ambiguous ‘trace’ result between ‘positive’ and ‘negative’, and much debate has focused on interpretation of traces results.

Methodology/Principle findings

We show how LCA can be extended to include ambiguous trace results and analyse S. mansoni studies from both Côte d’Ivoire (CdI) and Uganda. We compare the diagnostic performance of KK and CCA and the observed results by each test to the estimated infection prevalence in the population.Prevalence by KK was higher in CdI (13.4%) than in Uganda (6.1%), but prevalence by CCA was similar between countries, both when trace was assumed to be negative (CCAtn: 11.7% in CdI and 9.7% in Uganda) and positive (CCAtp: 20.1% in CdI and 22.5% in Uganda). The estimated sensitivity of CCA was more consistent between countries than the estimated sensitivity of KK, and estimated infection prevalence did not significantly differ between CdI (20.5%) and Uganda (19.1%). The prevalence by CCA with trace as positive did not differ significantly from estimates of infection prevalence in either country, whereas both KK and CCA with trace as negative significantly underestimated infection prevalence in both countries.

Conclusions

Incorporation of ambiguous results into an LCA enables the effect of different treatment thresholds to be directly assessed and is applicable in many fields. Our results showed that CCA with trace as positive most accurately estimated infection prevalence.

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(XML) Assessing the benefits of five years of different approaches to treatment of urogenital schistosomiasis: A SCORE project in Northern Mozambique

2017-12-08T22:00:00Z

by Anna E. Phillips, Pedro H. Gazzinelli-Guimaraes, Herminio O. Aurelio, Josefo Ferro, Rassul Nala, Michelle Clements, Charles H. King, Alan Fenwick, Fiona M. Fleming, Neerav Dhanani Background In Mozambique, schistosomiasis is highly endemic across the whole country. The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) coordinates a five-year study that has been implemented in various African countries, including Mozambique. The overall goal of SCORE was to better understand how to best apply preventive chemotherapy with praziquantel (PZQ) for schistosomiasis control by evaluating the impact of alternative treatment approaches. Methods This was a cluster-randomised trial that compared the impact of different treatment strategies in study areas with prevalence among school children of ≥21% S. haematobium infection by urine dipstick. Each village was randomly allocated to one of six possible combinations of community-wide treatment (CWT), school-based treatment (SBT), and/or drug holidays over a period of four years, followed by final data collection in the fifth year. The most intense intervention arm involved four years of CWT, while the least intensive arm involved two years of SBT followed by two consecutive years of PZQ holiday. Each study arm included 25 villages randomly assigned to one of the six treatment arms. The primary outcome of interest was change in prevalence and intensity of S. haematobium among 100 children aged 9-to-12-years that were sampled each year in every village. In addition to children aged 9-to-12 years, 100 children aged 5–8 years in their first-year of school and 50 adults (aged 20–55 years) were tested in the first and final fifth year of the study. Prevalence and intensity of S. haematobium infection was evaluated by two filtrations, each of 10mL, from a single urine specimen. Principal findings In total, data was collected from 81,167 individuals across 149 villages in ten districts of Cabo Delgado province, Northern Mozambique. Overall PZQ treatment resulted in a significant reduction in the prevalence of S. haematobium infection from Year 1 to Year 5, where the average prevalence went from 60.5% to 38.8%, across all age groups and treatment arms. The proportion of those heavily infected also reduced from 17.6% to 11.9% over five years. There was a significantly higher likelihood of males being infected than females at baseline, but no significant difference between the sexes in their response to treatment. The only significant response based on a study arm was seen in both the 9-to-12-year-old and first-year cross sections, where two consecutive treatment holidays resulted in a significantly higher final prevalence of S. haematobium than no treatment holidays. When the arms were grouped together, four rounds of treatment (regardless of whether it was CWT or SBT), however, did result in a significantly greater reduction in S. haematobium prevalence than two rounds of treatment (i.e. with two intermittent or consecutive holiday years) over a five-year period. Conclusions Although PC was successful in reducing the burden of active infection, even among those heavily infected, annual CWT did not have a significantly greater impact on disease prevalence or intensity than less intense treatment arms. This may be due to extremely high starting prevalence and intensity in the study area, with frequent exposure to reinfection, or related to challenges in achieving high treatment coverage More frequent treatment had a greater impact on prevalence and intensity of infection when arms were grouped by number of treatments, however, cost efficiency was greater in arms only receiving two treatm[...]



(XML) Tracking the career development of scientists in low- and middle-income countries trained through TDR’s research capacity strengthening programmes: Learning from monitoring and impact evaluation

2017-12-07T22:00:00Z

by Béatrice Halpaap, Mahnaz Vahedi, Edith Certain, Tini Alvarado, Caroline Saint Martin, Corinne Merle, Michael Mihut, Pascal Launois

The Special Programme for Research and Training in Tropical Diseases (TDR) co-sponsored by UNICEF, UNDP, World Bank and WHO has been supporting research capacity strengthening in low- and middle-income countries for over 40 years. In order to assess and continuously optimize its capacity strengthening approaches, an evaluation of the influence of TDR training grants on research career development was undertaken. The assessment was part of a larger evaluation conducted by the European Science Foundation. A comprehensive survey questionnaire was developed and sent to a group of 117 trainees supported by TDR who had completed their degree (masters or PhD) between 2000 and 2012; of these, seventy seven (77) responded. Most of the respondents (80%) rated TDR support as a very important factor that influenced their professional career achievements. The “brain drain” phenomenon towards high-income countries was particularly low amongst TDR grantees: the rate of return to their region of origin upon completion of their degree was 96%. A vast majority of respondents are still working in research (89%), with 81% of respondents having participated in multidisciplinary research activities; women engaged in multidisciplinary collaboration to a higher extent than men. However, only a minority of all have engaged in intersectoral collaboration, an aspect that would require further study. The post-degree career choices made by the respondents were strongly influenced by academic considerations. At the time of the survey, 92% of all respondents hold full-time positions, mainly in the public sector. Almost 25% of the respondents reported that they had influenced policy and practice changes. Some of the challenges and opportunities faced by trainees at various stages of their research career have been identified. Modalities to overcome these will require further investigation. The survey evidenced how TDR’s research capacity grant programmes made a difference on researchers’ career development and on south-south collaborations, by strengthening and localizing research capacity in lower income regions, and also showed there is more that needs to be done. The factors involved, challenges and lessons learnt may help donors and policy makers improve their future interventions with regard to designing capacity strengthening programmes and setting funding priorities.(image)



(XML) A thermostable messenger RNA based vaccine against rabies

2017-12-07T22:00:00Z

by Lothar Stitz, Annette Vogel, Margit Schnee, Daniel Voss, Susanne Rauch, Thorsten Mutzke, Thomas Ketterer, Thomas Kramps, Benjamin Petsch

Although effective rabies virus vaccines have been existing for decades, each year, rabies virus infections still cause around 50.000 fatalities worldwide. Most of these cases occur in developing countries, where these vaccines are not available. The reasons for this are the prohibitive high costs of cell culture or egg grown rabies virus vaccines and the lack of a functional cold chain in many regions in which rabies virus is endemic. Here, we describe the excellent temperature resistance of a non-replicating mRNA based rabies virus vaccine encoding the rabies virus glycoprotein (RABV-G). Prolonged storage of the vaccine from -80°C to up to +70°C for several months did not impact the protective capacity of the mRNA vaccine. Efficacy after storage was demonstrated by the induction of rabies specific virus neutralizing antibodies and protection in mice against lethal rabies infection. Moreover, storing the vaccine at oscillating temperatures between +4° and +56°C for 20 cycles in order to simulate interruptions of the cold chain during vaccine transport, did not affect the vaccine’s immunogenicity and protective characteristics, indicating that maintenance of a cold chain is not essential for this vaccine.(image)



(XML) Presentation of life-threatening invasive nontyphoidal Salmonella disease in Malawian children: A prospective observational study

2017-12-07T22:00:00Z

by Calman A. MacLennan, Chisomo L. Msefula, Esther N. Gondwe, James J. Gilchrist, Paul Pensulo, Wilson L. Mandala, Grace Mwimaniwa, Meraby Banda, Julia Kenny, Lorna K. Wilson, Amos Phiri, Jenny M. MacLennan, Elizabeth M. Molyneux, Malcolm E. Molyneux, Stephen M. Graham

Nontyphoidal Salmonellae commonly cause invasive disease in African children that is often fatal. The clinical diagnosis of these infections is hampered by the absence of a clear clinical syndrome. Drug resistance means that empirical antibiotic therapy is often ineffective and currently no vaccine is available. The study objective was to identify risk factors for mortality among children presenting to hospital with invasive Salmonella disease in Africa. We conducted a prospective study enrolling consecutive children with microbiologically-confirmed invasive Salmonella disease admitted to Queen Elizabeth Central Hospital, Blantyre, in 2006. Data on clinical presentation, co-morbidities and outcome were used to identify children at risk of inpatient mortality through logistic-regression modeling. Over one calendar year, 263 consecutive children presented with invasive Salmonella disease. Median age was 16 months (range 0–15 years) and 52/256 children (20%; 95%CI 15–25%) died. Nontyphoidal serovars caused 248/263 (94%) of cases. 211/259 (81%) of isolates were multi-drug resistant. 251/263 children presented with bacteremia, 6 with meningitis and 6 with both. Respiratory symptoms were present in 184/240 (77%; 95%CI 71–82%), 123/240 (51%; 95%CI 45–58%) had gastrointestinal symptoms and 101/240 (42%; 95%CI 36–49%) had an overlapping clinical syndrome. Presentation at <7 months (OR 10.0; 95%CI 2.8–35.1), dyspnea (OR 4.2; 95%CI 1.5–12.0) and HIV infection (OR 3.3; 95%CI 1.1–10.2) were independent risk factors for inpatient mortality. Invasive Salmonella disease in Malawi is characterized by high mortality and prevalence of multi-drug resistant isolates, along with non-specific presentation. Young infants, children with dyspnea and HIV-infected children bear a disproportionate burden of the Salmonella-associated mortality in Malawi. Strategies to improve prevention, diagnosis and management of invasive Salmonella disease should be targeted at these children.(image)



(XML) Case report: A rare case of urinary myiasis induced by the fourth instar larvae of Telmatoscopus albipunctatus

2017-12-07T22:00:00Z

by Beibei Zhang, Lifu Wang, Jiahua Liu, Lian Xu, Langui Song, Xiaoying Wu, Xi Sun, Zhongdao Wu

Telmatoscopus albipunctatus, a cosmopolitan fly, is widely distributed throughout moist environments. It is one of the most medically important insects (especially in urban environments) that may potentially cause myiasis. Urinary myiasis and other sites of infestation, including the intestine, nasal passages, lung, and derma, have been reported. This is the first case report of a Chinese middlescent woman infected with T. albipunctatus in Guangzhou, China. In the present report, a 50-year-old woman came to The Third Affiliated Hospital of Southern Medical University, Guangzhou, China, because larvae were found when urinating in the morning; this had occurred every two days within the past two months. She complained of frequent micturition and urgency. Urine tests indicated that all indexes were normal except for slight urinary tract infection. Subsequently, the larvae were sent to the diagnostic section for parasitic infection in the Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China. The stereoscopic microscope and transmission electron microscope were used for morphological observation. On this basis, the cytochrome oxidase subunit 1 (COX1) gene was specifically amplified by PCR. Sequence analysis of the PCR product and phylogenetic analysis were used to identify the species. Morphological analysis combined with molecular biology methods indicated that the insect was the fourth instar larvae of T. albipunctatus. Our results show that this was a case of a 50-year-old woman infected with T. albipunctatus larvae in her urinary tract, and the findings suggest that clinicians should be vigilant for this infection.(image)



(XML) The physicochemical fingerprint of Necator americanus

2017-12-07T22:00:00Z

by Veeren M. Chauhan, David J. Scurr, Thomas Christie, Gary Telford, Jonathan W. Aylott, David I. Pritchard

Necator americanus, a haematophagous hookworm parasite, infects ~10% of the world’s population and is considered to be a significant public health risk. Its lifecycle has distinct stages, permitting its successful transit from the skin via the lungs (L3) to the intestinal tract (L4 maturing to adult). It has been hypothesised that the L3 larval sheath, which is shed during percutaneous infection (exsheathment), diverts the immune system to allow successful infection and reinfection in endemic areas. However, the physicochemical properties of the L3 larval cuticle and sheath, which are in direct contact with the skin and its immune defences, are unknown. In the present study, we controlled exsheathment, to characterise the sheath and underlying cuticle surfaces in situ, using atomic force microscopy (AFM) and time-of-flight secondary ion mass spectrometry (ToF-SIMS). AFM revealed previously unseen surface area enhancing nano-annuli exclusive to the sheath surface and confirmed greater adhesion forces exist between cationic surfaces and the sheath, when compared to the emergent L3 cuticle. Furthermore, ToF-SIMS elucidated different chemistries between the surfaces of the cuticle and sheath which could be of biological significance. For example, the phosphatidylglycerol rich cuticle surface may support the onward migration of a lubricated infective stage, while the anionic and potentially immunologically active heparan sulphate rich deposited sheath could result in the diversion of immune defences to an inanimate antigenic nidus. We propose that our initial studies into the surface analysis of this hookworm provides a timely insight into the physicochemical properties of a globally important human pathogen at its infective stage and anticipate that the development and application of this analytical methodology will support translation of these findings into a biological context.(image)



(XML) Correction: Underestimation of Leptospirosis Incidence in the French West Indies

2017-12-06T22:00:00Z

by Sylvie Cassadou, Jacques Rosine, Claude Flamand, Martina Escher, Martine Ledrans, Pascale Bourhy, Mathieu Picardeau, Philippe Quénel

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(XML) Correction: CD8+ T cells provide immune protection against murine disseminated endotheliotropic Orientia tsutsugamushi infection

2017-12-06T22:00:00Z

by Guang Xu, Nicole L. Mendell, Yuejin Liang, Thomas R. Shelite, Yenny Goez-Rivillas, Lynn Soong, Donald H. Bouyer, David H. Walker

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(XML) Body size and hosts of Triatoma infestans populations affect the size of bloodmeal contents and female fecundity in rural northwestern Argentina

2017-12-06T22:00:00Z

by Ricardo E. Gürtler, María del Pilar Fernández, María Carla Cecere, Joel E. Cohen

Human sleeping quarters (domiciles) and chicken coops are key source habitats of Triatoma infestans—the principal vector of the infection that causes Chagas disease—in rural communities in northern Argentina. Here we investigated the links among individual bug bloodmeal contents (BMC, mg), female fecundity, body length (L, mm), host blood sources and habitats. We tested whether L, habitat and host blood conferred relative fitness advantages using generalized linear mixed-effects models and a multimodel inference approach with model averaging. The data analyzed include 769 late-stage triatomines collected in 120 sites from six habitats in 87 houses in Figueroa, Santiago del Estero, during austral spring. L correlated positively with other body-size surrogates and was modified by habitat type, bug stage and recent feeding. Bugs from chicken coops were significantly larger than pig-corral and kitchen bugs. The best-fitting model of log BMC included habitat, a recent feeding, bug stage, log Lc (mean-centered log L) and all two-way interactions including log Lc. Human- and chicken-fed bugs had significantly larger BMC than bugs fed on other hosts whereas goat-fed bugs ranked last, in consistency with average blood-feeding rates. Fecundity was maximal in chicken-fed bugs from chicken coops, submaximal in human- and pig-fed bugs, and minimal in goat-fed bugs. This study is the first to reveal the allometric effects of body-size surrogates on BMC and female fecundity in a large set of triatomine populations occupying multiple habitats, and discloses the links between body size, microsite temperatures and various fitness components that affect the risks of transmission of Trypanosoma cruzi.(image)



(XML) Symptoms associated with adverse dengue fever prognoses at the time of reporting in the 2015 dengue outbreak in Taiwan

2017-12-06T22:00:00Z

by Chun-Yin Yeh, Po-Lin Chen, Kun-Ta Chuang, Yu-Chen Shu, Yu-Wen Chien, Guey Chuen Perng, Wen-Chien Ko, Nai-Ying Ko

Background

Tainan experienced the most severe dengue epidemic in Taiwan in 2015. This study investigates the association between the signs and symptoms at the time of reporting with the adverse dengue prognoses.

Methods

A descriptive study was conducted using secondary data from the Dengue Disease Reporting System in Tainan, Taiwan, between January 1 and December 31, 2015. A multivariate stepwise logistic regression was used to identify the risk factors for the adverse prognoses: ICU admissions and mortality.

Results

There were 22,777 laboratory-confirmed reported cases (mean age 45.6 ± 21.2 years), of which 3.7% were admitted to intensive care units (ICU), and 0.8% were fatal. The most common symptoms were fever (92.8%), myalgia (26.6%), and headache (22.4%). The prevalence of respiratory distress, altered consciousness, shock, bleeding, and thrombocytopenia increased with age. The multivariate analysis indicated that being in 65–89 years old age group [Adjusted Odds Ratio (aOR):4.95], or the 90 years old and above age group (aOR: 9.06), and presenting with shock (aOR: 8.90) and respiratory distress (aOR: 5.31) were significantly associated with the risk of ICU admission. While old age (aOR: 1.11), respiratory distress (aOR: 9.66), altered consciousness (aOR: 7.06), and thrombocytopenia (aOR: 2.55) were significantly associated with the risk of mortality.

Conclusions

Dengue patients older than 65 and those with severe and non-specific signs and symptoms at the time of reporting were at a higher risk of ICU admission and mortality. First-line healthcare providers need to be aware of the varied presentations between the different age groups to allow early diagnosis and in-time management, which would prevent ICU admissions and fatalities in dengue patients.

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(XML) Review of the factors influencing the motivation of community drug distributors towards the control and elimination of neglected tropical diseases (NTDs)

2017-12-06T22:00:00Z

by Alison Krentel, Margaret Gyapong, Shruti Mallya, Nana Yaa Boadu, Mary Amuyunzu-Nyamongo, Mariana Stephens, Deborah A. McFarland

Background

Community drug distributors or neglected tropical disease (NTD) volunteers have played a crucial role in ensuring the success of mass drug administration (MDA) programs using preventive chemotherapy (PC) for lymphatic filariasis, onchocerciasis, schistosomiasis, trachoma and soil transmitted helminths. In recent years however, a noticeable decline in motivation of some of these volunteers has been perceived, potentially negatively impacting the success of these programs. Potential hypotheses for this change in motivation include the long duration of many MDA programs, the change in sociocultural environments as well as the changes to the programs over time. This literature review identifies factors that affect NTD volunteer performance and motivation, which may be used to influence and improve future programming.

Methodology/Principal findings

A systematic search was conducted to identify studies published between January 1995 and September 2016 that investigate factors pertaining to volunteer motivation and performance in NTD drug distribution programs. Searches from several databases and grey literature yielded 400 records, of which 28 articles from 10 countries met the inclusion criteria. Quality assessment of studies was performed using the Critical Appraisal Skills Programme(CASP) checklist. Data pertaining to motivation, performance, retention and satisfaction was extracted and examined for themes. Recurring themes in the literature included monetary and material incentives, intrinsic motivation, gender, cost to participate, and health systems and community support. Of these, community support and the health system were found to be particularly impactful. Very few studies were found to explicitly look at novel incentives for volunteers and very few studies have considered the out of pocket and opportunity costs that NTD volunteers bear carrying out their tasks.

Conclusions/Significance

There is currently great interest in incorporating more attractive incentive schemes for NTD volunteers. However, our results show that the important challenges that volunteers face (cultural, health systems, financial and community related) may have less to do with financial incentives and may actually have a larger impact on their motivation than has previously been understood. Further integration of NTD programs into existing health systems is expected to improve the NTD volunteer working environment. Relevant community engagement related to the MDA program should also provide the supportive environment needed in the community to support NTD volunteers. Programs need to consider these issues to improve working conditions for NTD volunteers.

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(XML) A temporal comparison of sex-aggregation pheromone gland content and dynamics of release in three members of the Lutzomyia longipalpis (Diptera: Psychodidae) species complex

2017-12-01T22:00:00Z

by Mikel A. González, Krishna K. Bandi, Melissa J. Bell, Reginaldo P. Brazil, Erin Dilger, Angel Guerrero, Orin Courtenay, James G. C. Hamilton

Background

Lutzomyia longipalpis is the South American vector of Leishmania infantum, the etiologic agent of visceral leishmaniasis (VL). Male L. longipalpis produce a sex-aggregation pheromone that is critical in mating, yet very little is known about its accumulation over time or factors involved in release. This laboratory study aimed to compare accumulation of pheromone over time and determine factors that might influence release in three members of the L. longipalpis species complex.

Methodology/Principal findings

We investigated male sex-aggregation pheromone gland content at different ages and the release rate of pheromone in the presence or absence of females under different light conditions by gas chromatography-mass spectrometry (GC-MS). Pheromone gland content was determined by extraction of whole males and pheromone release rate was determined by collection of headspace volatiles. Pheromone gland content appeared age-related and pheromone began to accumulate between 6 to 12 h post eclosion and gradually increased until males were 7–9 days old. The greatest amount was detected in 9-day old Campo Grande males ((S)-9-methylgermacrene-B; X ± SE: 203.5 ± 57.4 ng/male) followed by Sobral 2S males (diterpene; 199.9 ± 34.3) and Jacobina males ((1S,3S,7R)-3-methyl-α-himachalene; 128.8 ± 30.3) at 7 days old. Pheromone release was not continuous over time. During a 4-hour period, the greatest quantities of pheromone were released during the first hour, when wing beating activity was most intense. It was then substantially diminished for the remainder of the time. During a 24 h period, 4–5 day old male sand flies released approximately 63 ± 11% of the pheromone content of their glands, depending on the chemotype. The presence of females significantly increased pheromone release rate. The light regime under which the sand flies were held had little influence on pheromone release except on Sobral 2S chemotype.

Conclusions/Significance

Accumulation of pheromone appears to occur at different rates in the different chemotypes examined and results in differing amounts being present in glands over time. Release of accumulated pheromone is not passive, but depends on biotic (presence of females) and abiotic (light) circumstances. There are marked differences in content and release between the members of the complex suggesting important behavioural, biosynthetic and ecological differences between them.

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(XML) Anthelminthic activity of glibenclamide on secondary cystic echinococcosis in mice

2017-11-30T22:00:00Z

by Julia A. Loos, María Sandra Churio, Andrea C. Cumino

Cystic echinococcosis (CE) is a worldwide parasitic zoonosis caused by the larval stage of Echinococcus granulosus. Current chemotherapy against this disease is based on the administration of benzimidazoles (BZMs). However, BZM treatment has a low cure rate and causes several side effects. Therefore, new treatment options are needed. The antidiabetic drug glibenclamide (Glb) is a second-generation sulfonylurea receptor inhibitor that has been shown to be active against protozoan parasites. Hence, we assessed the in vitro and in vivo pharmacological effects of Glb against the larval stage of E. granulosus. The in vitro activity was concentration dependent on both protoscoleces and metacestodes. Moreover, Glb combined with the minimum effective concentration of albendazole sulfoxide (ABZSO) was demonstrated to have a greater effect on metacestodes in comparison with each drug alone. Likewise, there was a reduction in the cyst weight after oral administration of Glb to infected mice (5 mg/kg of body weight administered daily for a period of 8 weeks). However, in contrast to in vitro assays, no differences in effectiveness were found between Glb + albendazole (ABZ) combined treatment and Glb monotherapy. Our results also revealed mitochondrial membrane depolarization and an increase in intracellular Ca2+ levels in Glb-treated protoscoleces. In addition, the intracystic drug accumulation and our bioinformatic analysis using the available E. granulosus genome suggest the presence of genes encoding sulfonylurea transporters in the parasite. Our data clearly demonstrated an anti-echinococcal effect of Glb on E. granulosus larval stage. Further studies are needed in order to thoroughly investigate the mechanism involved in the therapeutic response of the parasite to this sulfonylurea.(image)



(XML) Chagas disease vector control and Taylor's law

2017-11-30T22:00:00Z

by Joel E. Cohen, Lucía I. Rodríguez-Planes, María S. Gaspe, María C. Cecere, Marta V. Cardinal, Ricardo E. Gürtler

Background

Large spatial and temporal fluctuations in the population density of living organisms have profound consequences for biodiversity conservation, food production, pest control and disease control, especially vector-borne disease control. Chagas disease vector control based on insecticide spraying could benefit from improved concepts and methods to deal with spatial variations in vector population density.

Methodology/Principal findings

We show that Taylor's law (TL) of fluctuation scaling describes accurately the mean and variance over space of relative abundance, by habitat, of four insect vectors of Chagas disease (Triatoma infestans, Triatoma guasayana, Triatoma garciabesi and Triatoma sordida) in 33,908 searches of people's dwellings and associated habitats in 79 field surveys in four districts in the Argentine Chaco region, before and after insecticide spraying. As TL predicts, the logarithm of the sample variance of bug relative abundance closely approximates a linear function of the logarithm of the sample mean of abundance in different habitats. Slopes of TL indicate spatial aggregation or variation in habitat suitability. Predictions of new mathematical models of the effect of vector control measures on TL agree overall with field data before and after community-wide spraying of insecticide.

Conclusions/Significance

A spatial Taylor's law identifies key habitats with high average infestation and spatially highly variable infestation, providing a new instrument for the control and elimination of the vectors of a major human disease.

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(XML) TNF-α blockade suppresses pericystic inflammation following anthelmintic treatment in porcine neurocysticercosis

2017-11-30T22:00:00Z

by Siddhartha Mahanty, Miguel A. Orrego, Carla Cangalaya, M. Paz Adrianzen, Gianfranco Arroyo, Juan Calcina, Armando E. Gonzalez, Héctor H. García, Cristina Guerra-Giraldez, Theodore E. Nash, for the Cysticercosis Working Group in Peru Background Neurocysticercosis (NCC) is an infection of the brain with the larval cyst of the tapeworm, Taenia solium. Cysticidal treatment induces parasite killing resulting in a post inflammatory response and seizures, which generally requires corticosteroid treatment to control inflammation. The nature of this response and how to best control it is unclear. We investigated the anti-inflammatory effects of pretreatment with etanercept (ETN), an anti-tumor necrosis factor agent, or dexamethasone (DEX), a high potency corticosteroid, on the post treatment inflammatory response in naturally infected pigs with neurocysticercosis after a single dose of the cysticidal drug praziquantel (PZQ). Methodology/Principal findings We followed the methods from a previously developed treatment model of NCC in naturally infected swine. The four study groups of infected pigs included 3 groups treated with PZQ on day 0: PZQ-treated alone (100 mg/kg PO; n = 9), pretreated with dexamethasone (DEX, 0.2 mg/kg IM administered on days -1, +1 and +3; n = 6), and pretreated with etanercept (ETN, 25 mg IM per animal on days -7 and 0; n = 6). The fourth group remained untreated (n = 3). As measured by quantitative RT-PCR, ETN pretreatment depressed transcription of a wide range of proinflammatory, regulatory and matrix protease encoding genes at 120 hr post PZQ treatment in capsules of cysts that demonstrated extravasated Evans Blue (EB) (a measure of blood brain barrier dysfunction) compared to animals not receiving ETN. Transcription was significantly depressed for the proinflammatory genes tumor necrosis factor (TNF)-α, and interferon (IFN)-γ; the inflammation regulating genes cytotoxic T-lymphocyte-associated protein (CTLA)4, interleukin (IL)-13 and transforming growth factor (TGF)-β; the tissue remodeling genes matrix metalloprotease (MMP)1 and 9, tissue inhibitors of metalloproteases (TIMP)1 and 2, and the genes regulating endothelial function vascular endothelial growth factor (VEGF)1, angiopoietin (Ang)1, Ang 2, and platelet endothelial cell adhesion molecule (PECAM)-1. In contrast, transcription was only modestly decreased in the DEX pretreated pigs compared to PZQ alone, and only for TNF-α, IL-6, IFN-γ, TGF-β and Ang1. IL-10 was not affected by either ETN or DEX pretreatments. The degree of inflammation, assessed by semi-quantitative inflammatory scores, was modestly decreased in both ETN and DEX pretreated animals compared to PZQ treated pigs whereas cyst damage scores were moderately decreased only in cysts from DEX pretreated pigs. However, the proportion of cysts with EB extravasation was not significantly changed in ETN and DEX pretreated groups. Conclusions/Significance Overall, TNF-α blockade using ETN treatment modulated expression of a large variety of genes that play a role in induction and control of inflammation and structural changes. In contrast the number of inflammatory cells was only moderately decreased suggesting weaker effects on cell migration into the inflammatory capsules surrounding cysts than on release of modulatory molec[...]



(XML) The "F" in SAFE: Reliability of assessing clean faces for trachoma control in the field

2017-11-30T22:00:00Z

by Sheila K. West, Derick Ansah, Beatriz Munoz, Nicodemus Funga, Harran Mkocha

Background

Although facial cleanliness is part of the SAFE strategy for trachoma there is controversy over the reliability of measuring a clean face. A child’s face with no ocular and nasal discharge is clean and the endpoint of interest, regardless of the number of times it must be washed to achieve that endpoint. The issue of reliability rests on the reproducibility of graders to assess a clean face. We report the reproducibility of assessing a clean face in a field trial in Kongwa, Tanzania.

Methods/Findings

Seven graders were trained to assess the presence and absence of nasal and ocular discharge on children’s faces. Sixty children ages 1–7 years were recruited from a community and evaluated independently by seven graders, once and again about 50 minutes later. Intra-and inter-observer variation was calculated using unweighted kappa statistics. The average intra-observer agreement was kappa = 0.72, and the average inter-observer agreement was kappa = 0.78.

Conclusions

Intra-observer and inter-observer agreement was substantial for the assessment of clean faces using trained Tanzania staff who represent a variety of educational backgrounds. As long as training is provided, the estimate of clean faces in children should be reliable, and reflect the effort of families to keep ocular and nasal discharge off the faces. These data suggest assessment of clean faces could be added to trachoma surveys, which already measure environmental improvements, in districts.

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