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The introduction of dengue follows transportation infrastructure changes in the state of Acre, Brazil: A network-based analysis

PLoS Neglected Tropical Diseases News - 17 November 2017 - 10:00pm

by Raquel Martins Lana, Marcelo Ferreira da Costa Gomes, Tiago França Melo de Lima, Nildimar Alves Honório, Cláudia Torres Codeço

Human mobility, presence and passive transportation of Aedes aegypti mosquito, and environmental characteristics are a group of factors which contribute to the success of dengue spread and establishment. To understand this process, we assess data from dengue national and municipal basins regarding population and demographics, transportation network, human mobility, and Ae. aegypti monitoring for the Brazilian state of Acre since the first recorded dengue case in the year 2000 to the year 2015. During this period, several changes in Acre’s transport infrastructure and urbanization have been started. To reconstruct the process of dengue introduction in Acre, we propose an analytic framework based on concepts used in malaria literature, namely vulnerability and receptivity, to inform risk assessments in dengue-free regions as well as network theory concepts for disease invasion and propagation. We calculate the probability of dengue importation to Acre from other Brazilian states, the evolution of dengue spread between Acrean municipalities and dengue establishment in the state. Our findings suggest that the landscape changes associated with human mobility have created favorable conditions for the establishment of dengue virus transmission in Acre. The revitalization of its major roads, as well as the increased accessibility by air to and within the state, have increased dengue vulnerability. Unplanned urbanization and population growth, as observed in Acre during the period of study, contribute to ideal conditions for Ae. aegypti mosquito establishment, increase the difficulty in mosquito control and consequently its local receptivity.

Mycolactone displays anti-inflammatory effects on the nervous system

PLoS Neglected Tropical Diseases News - 17 November 2017 - 10:00pm

by Caroline Isaac, Annie Mauborgne, Alfonso Grimaldi, Kemy Ade, Michel Pohl, Cristina Limatola, Yves Boucher, Caroline Demangel, Laure Guenin-Macé

Background

Mycolactone is a macrolide produced by the skin pathogen Mycobacterium ulcerans, with cytotoxic, analgesic and immunomodulatory properties. The latter were recently shown to result from mycolactone blocking the Sec61-dependent production of pro-inflammatory mediators by immune cells. Here we investigated whether mycolactone similarly affects the inflammatory responses of the nervous cell subsets involved in pain perception, transmission and maintenance. We also investigated the effects of mycolactone on the neuroinflammation that is associated with chronic pain in vivo.

Methodology/ Principle findings

Sensory neurons, Schwann cells and microglia were isolated from mice for ex vivo assessment of mycolactone cytotoxicity and immunomodulatory activity by measuring the production of proalgesic cytokines and chemokines. In all cell types studied, prolonged (>48h) exposure to mycolactone induced significant cell death at concentrations >10 ng/ml. Within the first 24h treatment, nanomolar concentrations of mycolactone efficiently suppressed the cell production of pro-inflammatory mediators, without affecting their viability. Notably, mycolactone also prevented the pro-inflammatory polarization of cortical microglia. Since these cells critically contribute to neuroinflammation, we next tested if mycolactone impacts this pathogenic process in vivo. We used a rat model of neuropathic pain induced by chronic constriction of the sciatic nerve. Here, mycolactone was injected daily for 3 days in the spinal canal, to ensure its proper delivery to spinal cord. While this treatment failed to prevent injury-induced neuroinflammation, it decreased significantly the local production of inflammatory cytokines without inducing detectable cytotoxicity.

Conclusion/ Significance

The present study provides in vitro and in vivo evidence that mycolactone suppresses the inflammatory responses of sensory neurons, Schwann cells and microglia, without affecting the cell viability. Together with previous studies using peripheral blood leukocytes, our work implies that mycolactone-mediated analgesia may, at least partially, be explained by its anti-inflammatory properties.

Longitudinal survey of two serotine bat (<i>Eptesicus serotinus</i>) maternity colonies exposed to EBLV-1 (European Bat Lyssavirus type 1): Assessment of survival and serological status variations using capture-recapture models

PLoS Neglected Tropical Diseases News - 17 November 2017 - 10:00pm

by Emmanuelle Robardet, Christophe Borel, Marie Moinet, Dorothée Jouan, Marine Wasniewski, Jacques Barrat, Franck Boué, Elodie Montchâtre-Leroy, Alexandre Servat, Olivier Gimenez, Florence Cliquet, Evelyne Picard-Meyer

This study describes two longitudinal serological surveys of European Bat Lyssavirus type 1 (EBLV-1) antibodies in serotine bat (Eptesicus serotinus) maternity colonies located in the North-East of France. This species is currently considered as the main EBLV-1 reservoir. Multievent capture-recapture models were used to determine the factors influencing bat rabies transmission as this method accounts for imperfect detection and uncertainty in disease states. Considering the period of study, analyses revealed that survival and recapture probabilities were not affected by the serological status of individuals, confirming the capacity of bats to be exposed to lyssaviruses without dying. Five bats have been found with EBLV-1 RNA in the saliva at the start of the study, suggesting they were caught during virus excretion period. Among these bats, one was interestingly recaptured one year later and harbored a seropositive status. Along the survey, some others bats have been observed to both seroconvert (i.e. move from a negative to a positive serological status) and serorevert (i.e. move from a positive to a negative serological status). Peak of seroprevalence reached 34% and 70% in site A and B respectively. On one of the 2 sites, global decrease of seroprevalence was observed all along the study period nuanced by oscillation intervals of approximately 2–3 years supporting the oscillation infection dynamics hypothesized during a previous EBLV-1 study in a Myotis myotis colony. Seroprevalence were affected by significantly higher seroprevalence in summer than in spring. The maximum time observed between successive positive serological statuses of a bat demonstrated the potential persistence of neutralizing antibodies for at least 4 years. At last, EBLV-1 serological status transitions have been shown driven by age category with higher seroreversion frequencies in adults than in juvenile. Juveniles and female adults seemed indeed acting as distinct drivers of the rabies virus dynamics, hypothesis have been addressed but their exact role in the EBLV-1 transmission still need to be specified.

Detection of relapsing fever <i>Borrelia</i> spp., <i>Bartonella</i> spp. and Anaplasmataceae bacteria in argasid ticks in Algeria

PLoS Neglected Tropical Diseases News - 16 November 2017 - 10:00pm

by Ismail Lafri, Basma El Hamzaoui, Idir Bitam, Hamza Leulmi, Reda Lalout, Oleg Mediannikov, Mohamed Chergui, Mohamed Karakellah, Didier Raoult, Philippe Parola

Background

Argasid ticks (soft ticks) are blood-feeding arthropods that can parasitize rodents, birds, humans, livestock and companion animals. Ticks of the Ornithodoros genus are known to be vectors of relapsing fever borreliosis in humans. In Algeria, little is known about relapsing fever borreliosis and other bacterial pathogens transmitted by argasid ticks.

Methodology/Principal findings

Between May 2013 and October 2015, we investigated the presence of soft ticks in 20 rodent burrows, 10 yellow-legged gull (Larus michahellis) nests and animal shelters in six locations in two different bioclimatic zones in Algeria. Six species of argasid ticks were identified morphologically and through 16S rRNA gene sequencing. The presence and prevalence of Borrelia spp., Bartonella spp., Rickettsia spp. and Anaplasmataceae was assessed by qPCR template assays in each specimen. All qPCR-positive samples were confirmed by standard PCR, followed by sequencing the amplified fragments. Two Borrelia species were identified: Borrelia hispanica in Ornithodoros occidentalis in Mostaganem, and Borrelia cf. turicatae in Carios capensis in Algiers. One new Bartonella genotype and one new Anaplasmataceae genotype were also identified in Argas persicus.

Conclusions

The present study highlights the presence of relapsing fever borreliosis agents, although this disease is rarely diagnosed in Algeria. Other bacteria of unknown pathogenicity detected in argasid ticks which may bite humans deserve further investigation.

Conservation of a microRNA cluster in parasitic nematodes and profiling of miRNAs in excretory-secretory products and microvesicles of <i>Haemonchus contortus</i>

PLoS Neglected Tropical Diseases News - 16 November 2017 - 10:00pm

by Henry Y. Gu, Neil D. Marks, Alan D. Winter, William Weir, Thomas Tzelos, Tom N. McNeilly, Collette Britton, Eileen Devaney

microRNAs are small non-coding RNAs that are important regulators of gene expression in a range of animals, including nematodes. We have analysed a cluster of four miRNAs from the pathogenic nematode species Haemonchus contortus that are closely linked in the genome. We find that the cluster is conserved only in clade V parasitic nematodes and in some ascarids, but not in other clade III species nor in clade V free-living nematodes. Members of the cluster are present in parasite excretory-secretory products and can be detected in the abomasum and draining lymph nodes of infected sheep, indicating their release in vitro and in vivo. As observed for other parasitic nematodes, H. contortus adult worms release extracellular vesicles (EV). Small RNA libraries were prepared from vesicle-enriched and vesicle-depleted supernatants from both adult worms and L4 stage larvae. Comparison of the miRNA species in the different fractions indicated that specific miRNAs are packaged within vesicles, while others are more abundant in vesicle-depleted supernatant. Hierarchical clustering analysis indicated that the gut is the likely source of vesicle-associated miRNAs in the L4 stage, but not in the adult worm. These findings add to the growing body of work demonstrating that miRNAs released from parasitic helminths may play an important role in host-parasite interactions.

Drivers of house invasion by sylvatic Chagas disease vectors in the Amazon-Cerrado transition: A multi-year, state-wide assessment of municipality-aggregated surveillance data

PLoS Neglected Tropical Diseases News - 16 November 2017 - 10:00pm

by Raíssa N. Brito, David E. Gorla, Liléia Diotaiuti, Anália C. F. Gomes, Rita C. M. Souza, Fernando Abad-Franch

Background

Insecticide spraying efficiently controls house infestation by triatomine bugs, the vectors of Trypanosoma cruzi. The strategy, however, is ineffective against sylvatic triatomines, which can transmit Chagas disease by invading (without colonizing) man-made structures. Despite growing awareness of the relevance of these transmission dynamics, the drivers of house invasion by sylvatic triatomines remain poorly understood.

Methods/Findings

About 12,000 sylvatic triatomines were caught during routine surveillance in houses of Tocantins state, Brazil, in 2005–2013. Using negative binomial regression, information-theoretic model evaluation/averaging, and external model validation, we investigated the effects of regional (Amazon/Cerrado), landscape (preservation/disturbance), and climate covariates (temperature, rainfall) on the municipality-aggregated numbers of house-invading Rhodnius pictipes, R. robustus, R. neglectus, and Panstrongylus geniculatus. House invasion by R. pictipes and R. robustus was overall more frequent in the Amazon biome, tended to increase in municipalities with more well-preserved land, and decreased in rainier municipalities. Across species, invasion decreased with higher landscape-disturbance levels and in hotter-day municipalities. Invasion by R. neglectus and P. geniculatus increased somewhat with more land at intermediate disturbance and peaked in average-rainfall municipalities. Temperature effects were more pronounced on P. geniculatus than on Rhodnius spp.

Conclusions

We report widespread, frequent house invasion by sylvatic triatomines in the Amazon–Cerrado transition. Our analyses indicate that readily available environmental metrics may help predict the risk of contact between sylvatic triatomines and humans at coarse geographic scales, and hint at specific hypotheses about climate and deforestation effects on those vectors–with some taxon-specific responses and some seemingly general trends. Thus, our focal species appear to be quite sensitive to higher temperatures, and might be less common in more heavily-disturbed than in better-preserved environments. This study illustrates, in sum, how entomological routine-surveillance data can be efficiently used for Chagas disease risk prediction and stratification when house-colonizing vectors are absent.

Zika virus: An updated review of competent or naturally infected mosquitoes

PLoS Neglected Tropical Diseases News - 16 November 2017 - 10:00pm

by Yanouk Epelboin, Stanislas Talaga, Loïc Epelboin, Isabelle Dusfour

Zika virus (ZIKV) is an arthropod-borne virus (arbovirus) that recently caused outbreaks in the Americas. Over the past 60 years, this virus has been observed circulating among African, Asian, and Pacific Island populations, but little attention has been paid by the scientific community until the discovery that large-scale urban ZIKV outbreaks were associated with neurological complications such as microcephaly and several other neurological malformations in fetuses and newborns. This paper is a systematic review intended to list all mosquito species studied for ZIKV infection or for their vector competence. We discuss whether studies on ZIKV vectors have brought enough evidence to formally exclude other mosquitoes than Aedes species (and particularly Aedes aegypti) to be ZIKV vectors. From 1952 to August 15, 2017, ZIKV has been studied in 53 mosquito species, including 6 Anopheles, 26 Aedes, 11 Culex, 2 Lutzia, 3 Coquillettidia, 2 Mansonia, 2 Eretmapodites, and 1 Uranotaenia. Among those, ZIKV was isolated from 16 different Aedes species. The only species other than Aedes genus for which ZIKV was isolated were Anopheles coustani, Anopheles gambiae, Culex perfuscus, and Mansonia uniformis. Vector competence assays were performed on 22 different mosquito species, including 13 Aedes, 7 Culex, and 2 Anopheles species with, as a result, the discovery that A. aegypti and Aedes albopictus were competent for ZIKV, as well as some other Aedes species, and that there was a controversy surrounding Culex quinquefasciatus competence. Although Culex, Anopheles, and most of Aedes species were generally observed to be refractory to ZIKV infection, other potential vectors transmitting ZIKV should be explored.

Post-kala-azar dermal leishmaniasis in the Indian subcontinent: A threat to the South-East Asia Region Kala-azar Elimination Programme.

PLoS Neglected Tropical Diseases News - 16 November 2017 - 10:00pm

by Eduard E. Zijlstra, Fabiana Alves, Suman Rijal, Byron Arana, Jorge Alvar

Background

The South-East Asia Region Kala-azar Elimination Programme (KAEP) is expected to enter the consolidation phase in 2017, which focuses on case detection, vector control, and identifying potential sources of infection. Post-kala-azar dermal leishmaniasis (PKDL) is thought to play a role in the recurrence of visceral leishmaniasis (VL)/kala-azar outbreaks, and control of PKDL is among the priorities of the KAEP.

Methodology and principal finding

We reviewed the literature with regard to PKDL in Asia and interpreted the findings in relation to current intervention methods in the KAEP in order to make recommendations. There is a considerable knowledge gap regarding the pathophysiology of VL and PKDL, especially the underlying immune responses. Risk factors (of which previous VL treatments may be most important) are poorly understood and need to be better defined. The role of PKDL patients in transmission is largely unknown, and there is insufficient information about the importance of duration, distribution and severity of the rash, time of onset, and self-healing. Current intervention methods focus on active case detection and treatment of all PKDL cases with miltefosine while there is increasing drug resistance. The prevention of PKDL by improved VL treatment currently receives insufficient attention.

Conclusion and significance

PKDL is a heterogeneous and dynamic condition, and patients differ with regard to time of onset after VL, chronicity, and distribution and appearance of the rash, as well as immune responses (including tendency to self-heal), all of which may vary over time. It is essential to fully describe the pathophysiology in order to make informed decisions on the most cost-effective approach. Emphasis should be on early detection of those who contribute to transmission and those who are in need of treatment, for whom short-course, effective, and safe drug regimens should be available. The prevention of PKDL should be emphasised by innovative and improved treatment for VL, which may include immunomodulation.

Correction: The microbiome in urogenital schistosomiasis and induced bladder pathologies

PLoS Neglected Tropical Diseases News - 15 November 2017 - 10:00pm

by Adewale S. Adebayo, Mangesh Survayanshi, Shrikanth Bhute, Atinuke M. Agunloye, Raphael D. Isokpehi, Chiaka I. Anumudu, Yogesh S. Shouche

Development and validation of an immunoperoxidase antigen detection test for improved diagnosis of rabies in Indonesia

PLoS Neglected Tropical Diseases News - 13 November 2017 - 10:00pm

by Ibnu Rahmadane, Andrea F. Certoma, Grantley R. Peck, Yul Fitria, Jean Payne, Axel Colling, Brian J. Shiell, Gary Beddome, Susanne Wilson, Meng Yu, Chris Morrissy, Wojtek P. Michalski, John Bingham, Ian A. Gardner, John D. Allen

Rabies continues to pose a significant threat to human and animal health in regions of Indonesia. Indonesia has an extensive network of veterinary diagnostic laboratories and the 8 National laboratories are equipped to undertake diagnostic testing for rabies using the commercially-procured direct fluorescent antibody test (FAT), which is considered the reference (gold standard) test. However, many of the Indonesian Provincial diagnostic laboratories do not have a fluorescence microscope required to undertake the FAT. Instead, certain Provincial laboratories continue to screen samples using a chemical stain-based test (Seller’s stain test, SST). This test has low diagnostic sensitivity, with negative SST-tested samples being forwarded to the nearest National laboratory resulting in significant delays for completion of testing and considerable additional costs. This study sought to develop a cost-effective and diagnostically-accurate immunoperoxidase antigen detection (RIAD) test for rabies that can be readily and quickly performed by the resource-constrained Provincial laboratories. This would reduce the burden on the National laboratories and allow more rapid diagnoses and implementation of post-exposure prophylaxis. The RIAD test was evaluated using brain smears fixed with acetone or formalin and its performance was validated by comparison with established rabies diagnostic tests used in Indonesia, including the SST and FAT. A proficiency testing panel was distributed between Provincial laboratories to assess the reproducibility of the test. The performance of the RIAD test was improved by using acetone fixation of brain smears rather than formalin fixation such that it was of equivalent accuracy to that of the World Organisation for Animal Health (OIE)-recommended FAT, with both tests returning median diagnostic sensitivity and specificity values of 0.989 and 0.993, respectively. The RIAD test and FAT had higher diagnostic sensitivity than the SST (median = 0.562). Proficiency testing using a panel of 6 coded samples distributed to 16 laboratories showed that the RIAD test had good reproducibility with an overall agreement of 97%. This study describes the successful development, characterisation and use of a novel RIAD test and its fitness for purpose as a screening test for use in provincial Indonesian veterinary laboratories.

Impact of the Ebola outbreak on <i>Trypanosoma brucei gambiense</i> infection medical activities in coastal Guinea, 2014-2015: A retrospective analysis from the Guinean national Human African Trypanosomiasis control program

PLoS Neglected Tropical Diseases News - 13 November 2017 - 10:00pm

by Mariame Camara, Eric Ouattara, Alexandre Duvignaud, René Migliani, Oumou Camara, Mamadou Leno, Philippe Solano, Bruno Bucheton, Mamadou Camara, Denis Malvy

Background

The 2014–2015 Ebola outbreak massively hit Guinea. The coastal districts of Boffa, Dubreka and Forecariah, three major foci of Human African Trypanosomiasis (HAT), were particularly affected. We aimed to assess the impact of this epidemic on sleeping sickness screening and caring activities.

Methodology/Principal findings

We used preexisting data from the Guinean sleeping sickness control program, collected between 2012 and 2015. We described monthly: the number of persons (i) screened actively; (ii) or passively; (iii) treated for HAT; (iv) attending post-treatment follow-up visits. We compared clinical data, treatment characteristics and Disability Adjusted Life-Years (DALYs) before (February 2012 to December 2013) and during (January 2014 to October 2015) the Ebola outbreak period according to available data. Whereas 32,221 persons were actively screened from February 2012 to December 2013, before the official declaration of the first Ebola case in Guinea, no active screening campaigns could be performed during the Ebola outbreak. Following the reinforcement and extension of HAT passive surveillance system early in 2014, the number of persons tested passively by month increased from 7 to 286 between April and September 2014 and then abruptly decreased to 180 until January 2015 and to none after March 2015. 213 patients initiated HAT treatment, 154 (73%) before Ebola and 59 (28%) during the Ebola outbreak. Those initiating HAT therapy during Ebola outbreak were recruited through passive screening and diagnosed at a later stage 2 of the disease (96% vs. 55% before Ebola, p<0.0001). The proportion of patients attending the 3 months and 6 months post-treatment follow-up visits decreased from 44% to 10% (p <0.0001) and from 16% to 3% (p = 0.017) respectively. The DALYs generated before the Ebola outbreak were estimated to 48.7 (46.7–51.5) and increased up to 168.7 (162.7–174.7), 284.9 (277.1–292.8) and 466.3 (455.7–477.0) during Ebola assuming case fatality rates of 2%, 5% and 10% respectively among under-reported HAT cases.

Conclusions/Significance

The 2014–2015 Ebola outbreak deeply impacted HAT screening activities in Guinea. Active screening campaigns were stopped. Passive screening dramatically decreased during the Ebola period, but trends could not be compared with pre-Ebola period (data not available). Few patients were diagnosed with more advanced HAT during the Ebola period and retention rates in follow-up were lowered. The drop in newly diagnosed HAT cases during Ebola epidemic is unlikely due to a fall in HAT incidence. Even if we were unable to demonstrate it directly, it is much more probably the consequence of hampered screening activities and of the fear of the population on subsequent confirmation and linkage to care. Reinforced program monitoring, alternative control strategies and sustainable financial and human resources allocation are mandatory during post Ebola period to reduce HAT burden in Guinea.

Rapid clearance of <i>Schistosoma mansoni</i> circulating cathodic antigen after treatment shown by urine strip tests in a Ugandan fishing community – Relevance for monitoring treatment efficacy and re-infection

PLoS Neglected Tropical Diseases News - 13 November 2017 - 10:00pm

by Anna O. Kildemoes, Birgitte J. Vennervald, Edridah M. Tukahebwa, Narcis B. Kabatereine, Pascal Magnussen, Claudia J. de Dood, André M. Deelder, Shona Wilson, Govert J. van Dam

Trial registration

ClinicalTrials.gov NCT00215267

Effect of water, sanitation and hygiene interventions on active trachoma in North and South Wollo zones of Amhara Region, Ethiopia: A Quasi-experimental study

PLoS Neglected Tropical Diseases News - 10 November 2017 - 10:00pm

by Beselam Tadesse, Alemayehu Worku, Abera Kumie, Solomon Abebe Yimer

Background

Trachoma is chronic kerato conjunctivitis, which is caused by repeated infection with Chlamydia trachomatis bacterium. It is hyper endemic in many rural areas of Ethiopia. The objective of this study was to measure the effect of water, sanitation and hygiene interventions on active trachoma in selected woredas of North and South Wollo zones of Amhara Region, Ethiopia.

Methodology

A community based quasi-experimental study was conducted from October 2014 to December 2015 among children aged 1–8 years at baseline and among one year older same children after intervention. A four-stage random cluster-sampling technique was employed to select study participants. From each selected household, one child was clinically assessed for active trachoma. Structured questionnaire was used to collect socio demographic and behavioral data. MacNemar test was applied to compare the prevalence of active trachoma between baseline and after the intervention period at both intervention and non-intervention study areas.

Results

The prevalence of active trachoma was reduced from baseline prevalence of 26% to 18% after one-year intervention period in the intervention woredas (P≤0.001). MacNemar test result showed significant reduction of active trachoma prevalence after the intervention period in the intervention woredas compared to the non-intervention woredas (P≤0.001). Water, sanitation and hygiene related activities were significantly improved after the intervention period in the intervention woredas (P<0.05).

Conclusions

There was a significant reduction of active trachoma prevalence between the baseline and after the intervention period in the intervention woredas, but not in the non-intervention ones. Improved water, sanitation and hygiene interventions contributed to the reduction of active trachoma. However, the magnitude of active trachoma prevalence observed after the intervention is still very high in the studied areas of North and South Wollo Zones communities. To achieve the global trachoma elimination target by the year 2020 as set by the WHO, continued WaSH interventions and periodic monitoring, evaluation and reporting of the impact of WaSH on active trachoma is warranted.

<i>Cs</i>severin inhibits apoptosis through mitochondria-mediated pathways triggered by Ca<sup>2 +</sup> dyshomeostasis in hepatocarcinoma PLC cells

PLoS Neglected Tropical Diseases News - 10 November 2017 - 10:00pm

by Mengchen Shi, Lina Zhou, Lu Zhao, Mei Shang, Tongtong He, Zeli Tang, Hengchang Sun, Pengli Ren, Zhipeng Lin, Tingjin Chen, Jinyun Yu, Jin Xu, Xinbing Yu, Yan Huang

Background

Numerous experimental and epidemiological studies have demonstrated a link between Clonorchis sinensis (C. sinensis) infestation and cholangiocarcinoma (CCA) as well as hepatocellular carcinoma (HCC). The underlying molecular mechanism involved in the malignancy of CCA and HCC has not yet been addressed. Csseverin, a component of the excretory/secretory products of C. sinensis (CsESPs), was confirmed to cause obvious apoptotic inhibition in the human HCC cell line PLC. However, the antiapoptotic mechanism is unclear. In the present study, we investigated the cellular features of the antiapoptotic mechanism upon transfection of the Csseverin gene.

Methods

In the present study, we evaluated the effects of Csseverin gene overexpression on the apoptosis of PLC cells using an Annexin PE/7-AAD assay. Western blotting was applied to quantify the activation of caspase-3 and caspase-9, the mitochondrial translocation of Bax and the release of Cyt c upon Csseverin overexpression in PLC cells. Laser scanning confocal microscopy was used to analyze the changes of intracellular calcium. Fluorescence assay and immunofluorescence assays were performed to observe the changes of the mitochondrial permeability transition pore (MPTP).

Results

The overexpression of Csseverin in PLC cells showed apoptosis resistance after the induction of apoptosis. Additionally, the activation of caspase-3 and caspase-9 was specifically weakened in Csseverin overexpression PLC cells. The overexpression of Csseverin reduced the increase in intracellular free Ca2+, thereby inhibiting MPTP opening in PLC cells. Moreover, Bax mitochondrial translocation and the subsequent release of Cyt c were downregulated in apoptotic Csseverin overexpression PLC cells.

Conclusions

The present findings suggest that Csseverin, a component of CsESPs, confers protection from human HCC cell apoptosis via the inactivation of membranous Ca2+ channels. Csseverin might be involved in the process of HCC through C. sinensis infestation in affected patients.

Polyclonal antibodies for the detection of <i>Trypanosoma cruzi</i> circulating antigens

PLoS Neglected Tropical Diseases News - 9 November 2017 - 10:00pm

by Edith S. Málaga-Machaca, Alessandra Romero-Ramirez, Robert H. Gilman, Sofía Astupiña-Figueroa, Noelia Angulo, Alejandro Florentini, Cinthya J. Lovon-Luque, Remo A. Gonza, Ada del Carpio-Sanz, Inés Cabello, Rosina Camargo, Fernando Recuenco, Liliam A. Barrueta-Soria, Manuela R. Verastegui, Maritza Calderon, Holger Mayta

Background

Detection of Trypanosoma cruzi antigens in clinical samples is considered an important diagnostic tool for Chagas disease. The production and use of polyclonal antibodies may contribute to an increase in the sensitivity of immunodiagnosis of Chagas disease.

Methodology/Principal findings

Polyclonal antibodies were raised in alpacas, rabbits, and hens immunized with trypomastigote excreted-secreted antigen, membrane proteins, trypomastigote lysate antigen and recombinant 1F8 to produce polyclonal antibodies. Western blot analysis was performed to determine specificity of the developed antibodies. An antigen capture ELISA of circulating antigens in serum, plasma and urine samples was developed using IgY polyclonal antibodies against T. cruzi membrane antigens (capture antibody) and IgG from alpaca raised against TESA. A total of 33 serum, 23 plasma and 9 urine samples were analyzed using the developed test. Among serum samples, compared to serology, the antigen capture ELISA tested positive in 55% of samples. All plasma samples from serology positive subjects were positive in the antigen capture ELISA. All urine positive samples had corresponding plasma samples that were also positive when tested by the antigen capture ELISA.

Conclusions

Polyclonal antibodies are useful for detection of circulating antigens in both the plasma and urine of infected individuals. Detection of antigens is direct evidence of the presence of the parasite, and could be a better surrogate of current infection status.

Biological and phylogenetic characteristics of West African lineages of West Nile virus

PLoS Neglected Tropical Diseases News - 8 November 2017 - 10:00pm

by Gamou Fall, Nicholas Di Paola, Martin Faye, Moussa Dia, Caio César de Melo Freire, Cheikh Loucoubar, Paolo Marinho de Andrade Zanotto, Ousmane Faye, Amadou Alpha Sall

The West Nile virus (WNV), isolated in 1937, is an arbovirus (arthropod-borne virus) that infects thousands of people each year. Despite its burden on global health, little is known about the virus’ biological and evolutionary dynamics. As several lineages are endemic in West Africa, we obtained the complete polyprotein sequence from three isolates from the early 1990s, each representing a different lineage. We then investigated differences in growth behavior and pathogenicity for four distinct West African lineages in arthropod (Ap61) and primate (Vero) cell lines, and in mice. We found that genetic differences, as well as viral-host interactions, could play a role in the biological properties in different WNV isolates in vitro, such as: (i) genome replication, (ii) protein translation, (iii) particle release, and (iv) virulence. Our findings demonstrate the endemic diversity of West African WNV strains and support future investigations into (i) the nature of WNV emergence, (ii) neurological tropism, and (iii) host adaptation.

Quantitative label-free proteomic analysis of human urine to identify novel candidate protein biomarkers for schistosomiasis

PLoS Neglected Tropical Diseases News - 8 November 2017 - 10:00pm

by Olugbenga Samson Onile, Bridget Calder, Nelson C. Soares, Chiaka I. Anumudu, Jonathan M. Blackburn

Background

Schistosomiasis is a chronic neglected tropical disease that is characterized by continued inflammatory challenges to the exposed population and it has been established as a possible risk factor in the aetiology of bladder cancer. Improved diagnosis of schistosomiasis and its associated pathology is possible through mass spectrometry to identify biomarkers among the infected population, which will influence early detection of the disease and its subtle morbidity.

Methodology

A high-throughput proteomic approach was used to analyse human urine samples for 49 volunteers from Eggua, a schistosomiasis endemic community in South-West, Nigeria. The individuals were previously screened for Schistosoma haematobium and structural bladder pathologies via microscopy and ultrasonography respectively. Samples were categorised into schistosomiasis, schistosomiasis with bladder pathology, bladder pathology, and a normal healthy control group. These samples were analysed to identify potential protein biomarkers.

Results

A total of 1306 proteins and 9701 unique peptides were observed in this study (FDR = 0.01). Fifty-four human proteins were found to be potential biomarkers for schistosomiasis and bladder pathologies due to schistosomiasis by label-free quantitative comparison between groups. Thirty-six (36) parasite-derived potential biomarkers were also identified, which include some existing putative schistosomiasis biomarkers that have been previously reported. Some of these proteins include Elongation factor 1 alpha, phosphopyruvate hydratase, histone H4 and heat shock proteins (HSP 60, HSP 70).

Conclusion

These findings provide an in-depth analysis of potential schistosoma and human host protein biomarkers for diagnosis of chronic schistosomiasis caused by Schistosoma haematobium and its pathogenesis.

The additional benefit of residual spraying and insecticide-treated curtains for dengue control over current best practice in Cuba: Evaluation of disease incidence in a cluster randomized trial in a low burden setting with intensive routine control

PLoS Neglected Tropical Diseases News - 8 November 2017 - 10:00pm

by Maria Eugenia Toledo, Veerle Vanlerberghe, Julio Popa Rosales, Mayelin Mirabal, Pedro Cabrera, Viviana Fonseca, Tania Gómez Padrón, Mirtha Pérez Menzies, Domingo Montada, Patrick Van der Stuyft

Background

Aedes control interventions are considered the cornerstone of dengue control programmes, but there is scarce evidence on their effect on disease. We set-up a cluster randomized controlled trial in Santiago de Cuba to evaluate the entomological and epidemiological effectiveness of periodical intra- and peri-domiciliary residual insecticide (deltamethrin) treatment (RIT) and long lasting insecticide treated curtains (ITC).

Methodology/Principal findings

Sixty three clusters (around 250 households each) were randomly allocated to two intervention (RIT and ITC) and one control arm. Routine Aedes control activities (entomological surveillance, source reduction, selective adulticiding, health education) were applied in the whole study area. The outcome measures were clinical dengue case incidence and immature Aedes infestation. Effectiveness of tools was evaluated using a generalized linear regression model with a negative binomial link function.Despite significant reduction in Aedes indices (Rate Ratio (RR) 0.54 (95%CI 0.32–0.89) in the first month after RIT, the effect faded out over time and dengue incidence was not reduced. Overall, in this setting there was no protective effect of RIT or ITC over routine in the 17months intervention period, with for house index RR of 1.16 (95%CI 0.96–1.40) and 1.25 (95%CI 1.03–1.50) and for dengue incidence 1.43 (95%CI 1.08–1.90) and RR of 0.96 (95%CI 0.72–1.28) respectively. The monthly dengue incidence rate (IR) at cluster level was best explained by epidemic periods (Incidence Rate Ratio (IRR) 5.50 (95%CI 4.14–7.31)), the IR in bordering houseblocks (IRR 1.03 (95%CI 1.02–1.04)) and the IR pre-intervention (IRR 1.02 (95%CI 1.00–1.04)).

Conclusions

Adding RIT to an intensive routine Aedes control programme has a transient effect on the already moderate low entomological infestation levels, while ITC did not have any effect. For both interventions, we didn’t evidence impact on disease incidence. Further studies are needed to evaluate impact in settings with high Aedes infestation and arbovirus case load.

Health seeking behavior following snakebites in Sri Lanka: Results of an island wide community based survey

PLoS Neglected Tropical Diseases News - 6 November 2017 - 10:00pm

by Dileepa Senajith Ediriweera, Anuradhani Kasturiratne, Arunasalam Pathmeswaran, Nipul Kithsiri Gunawardena, Shaluka Francis Jayamanne, David Griffiths Lalloo, Hithanadura Janaka de Silva

Introduction

Sri Lanka has a population of 21 million and about 80,000 snakebites occur annually. However, there are limited data on health seeking behavior following bites. We investigated the effects of snakebite and envenoming on health seeking behavior in Sri Lanka.

Methods

In a community-based island-wide survey conducted in Sri Lanka 44,136 households were sampled using a multistage cluster sampling method. An individual who reported experiencing a snakebite within the preceding 12 months was considered a case. An interviewer-administered questionnaire was used to obtain details of the bite and health seeking behavior among cases.

Results

Among 165,665 individuals surveyed, there were 695 snakebite victims. 682 (98.1%) had sought health care after the bite; 381 (54.8%) sought allopathic treatment and 301 (43.3%) sought traditional treatment. 323 (46.5%) had evidence of probable envenoming, among them 227 (70.3%) sought allopathic treatment, 94 (29.1%) sought traditional treatment and 2 did not seek treatment. There was wide geographic variation in the proportion of seeking allopathic treatment from <20% in the Western province to > 90% in the Northern province. Multiple logistic regression analysis showed that seeking allopathic treatment was independently associated with being systemically envenomed (Odds Ratio = 1.99, 95% CI: 1.36–2.90, P < 0.001), distance to the healthcare facility (OR = 1.13 per kilometer, 95% CI: 1.09 to 1.17, P < 0.001), time duration from the bite (OR = 0.49 per day, 95% CI: 0.29–0.74, P = 0.002), and the local incidence of envenoming (OR = 1.31 for each 50 per 100,000, 95% CI: 1.19–1.46, P < 0.001) and snakebite (OR = 0.90 for each 50 per 100,000, 95% CI: 0.85–0.94, P < 0.001) in the relevant geographic area.

Conclusions

In Sri Lanka, both allopathic and traditional treatments are sought following snakebite. The presence of probable envenoming was a major contribution to seeking allopathic treatment.

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