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Pre-post effects of a tetanus care protocol implementation in a sub-Saharan African intensive care unit

30 August 2018 - 9:00pm

by Riaz Aziz, Soledad Colombe, Gibonce Mwakisambwe, Solomon Ndezi, Jim Todd, Samuel Kalluvya, Halinder S. Mangat, Reed Magleby, Arndt Koebler, Bernard Kenemo, Robert N. Peck, Jennifer A. Downs

Background

Tetanus is a vaccine-preventable, neglected disease that is life threatening if acquired and occurs most frequently in regions where vaccination coverage is incomplete. Challenges in vaccination coverage contribute to the occurrence of non-neonatal tetanus in sub-Saharan countries, with high case fatality rates. The current WHO recommendations for the management of tetanus include close patient monitoring, administration of immune globulin, sedation, analgesia, wound hygiene and airway support [1]. In response to these recommendations, our tertiary referral hospital in Tanzania implemented a standardized clinical protocol for care of patients with tetanus in 2006 and a subsequent modification in 2012. In this study we aimed to assess the impact of the protocol on clinical care of tetanus patients and their outcomes.

Methods and findings

We examined provision of care and outcomes among all patients admitted with non-neonatal tetanus to the ICU at Bugando Medical Centre between 2001 and 2016 in this retrospective cohort study. We compared three groups: the pre-protocol group (2001–2005), the Early protocol group (2006–2011), and the Late protocol group (2012–2016) and determined associations with mortality by univariable logistic regression.We observed a significant increase in provision of care as per protocol between the Early and Late groups. Patients in the Late group had a significantly higher utilization of mechanical ventilation (69.9% vs 22.0%, p< 0.0001), provision of surgical wound care (39.8% vs 20.3%, p = 0.011), and performance of tracheostomies (36.8% vs 6.7%, <0.0001) than patients in the Early group. Despite the increased provision of care, we found no significant decrease in overall mortality in the Early versus the Late groups (55.4% versus 40.3%, p = 0.069), or between the pre-protocol and post-protocol groups (60.7% versus 50.0%, p = 0.28). There was also no difference in 7-day ICU mortality (30.1% versus 27.8%, p = 0.70). Analysis of the causes of death revealed a decrease in deaths related to airway compromise (30.0% to 1.8%, p<0.001) but an increase in deaths due to presumed sepsis (15.0% to 44.6%, p = 0.018).

Conclusion

The overall mortality in patients suffering non-neonatal tetanus is high (>40%). Institution of a standardized tetanus management protocol, in accordance with WHO recommendations, decreased immediate mortality related to primary causes of death after tetanus. However, this was offset by an increase in death due to later ICU complications such as sepsis. Our results illustrate the complexity in achieving mortality reduction even in illnesses thought to require few critical care interventions. Improving basic ICU care and strengthening vaccination programs to prevent tetanus altogether are essential components of efforts to decrease the mortality caused by this lethal, neglected disease.

A long way from Laos

30 August 2018 - 9:00pm

by Jade Ramos-Poblete, Erica Kasper, Anandit Mu

Spinal cord hypometabolism associated with infection by human T-cell lymphotropic virus type 1(HTLV-1)

27 August 2018 - 9:00pm

by Luiz C. F. Romanelli, Débora M. Miranda, Anna B. F. Carneiro-Proietti, Marcelo Mamede, Herika M. M. Vasconcelos, Marina L Martins, Anísia S. D. Ferreira, Daniela V. F. Rosa, Jonas J. Paula, Marco A. Romano-Silva, Rodrigo Nicolato

Background

HTLV-1 infection is endemic in Brazil. About 1 to 2% of the Brazilian population is estimated to be infected, but most infected HTLV-1 individuals do not know about their own infection, which favors the continuity of sexual and vertical virus transmission. In addition, HTLV-1 associated central nervous system diseases and their pathophysiologic mechanisms are not fully understood. This study aimed to evaluate the correlation of spinal cord metabolism, viral and inflammatory profiles with features of neurological presentation in HTLV-1 infected individuals.

Methodology

This is a cross-sectional study of a cohort including 48 HTLV-1 infected individuals clinically classified as asymptomatic-AG (N = 21), symptomatic-SG (N = 11) and HAM/TSP-HG (N = 16) and a nested case-control study with HTLV-1 infected individuals-HIG (N = 48) and HTLV-1 non infected controls-CG (N = 30) that had their spinal cord analysed by Positron Emission Tomography with 18F-Fluordeoxyglucose (18F-FDG PET/CT). HTLV-1 infected individuals had 18F-FDG PET/CT results analyzed with clinical and demographic data, proviral load, cytokines and chemokines in the blood and cerebrospinal fluid (CSF).

Principal Findings

18F-FDG PET/CT showed hypometabolism in the thoracic spinal cord in HTLV-1 infected individuals. The method had an accuracy of 94.4% to identify HAM/TSP. A greater involvement of the thoracic spinal cord was observed, although hypometabolism was also observed in the cervical spinal cord segment in HTLV-1 infected individuals. Individuals with HAM/TSP showed a pro-inflammatory profile in comparison to asymptomatic and symptomatic groups, with a higher level of Interferon-inducible T-cell alpha chemoattractant (ITAC/CXCL11), IL-6, IL-12p70 in the plasma; and ITAC, IL-4, IL-5, IL-8 (CXCL8) and TNF-alpha in the CSF. Using regression, thoracic spinal cord SUV (standardized uptake value) and CSF ITAC level were identified as the HAM/TSP predictors in the multivariate model.

Conclusions

18F-FDG PET/CT imaging showed spinal cord hypometabolism in most HTLV-1 infected individuals, even in the asymptomatic HTLV-1 group. Thoracic spinal cord hypometabolism and CSF-ITAC levels were identified predictors of HAM/TSP.

Significance

Our findings suggested that in most HTLV-1 infected individuals there was compromise of central nervous system (CNS) structures despite of the lack of clinical symptoms. To explain the found hypometabolism, the role of microcirculatory and metabolic factors in the pathogenesis of neurological diseases associated with HTLV-1 infection must be further investigated. It is paramount to evaluate the central nervous function and to compare the performance among HTLV-1 infected individuals considered asymptomatic to the uninfected controls.

Community-directed vector control to supplement mass drug distribution for onchocerciasis elimination in the Madi mid-North focus of Northern Uganda

27 August 2018 - 9:00pm

by Benjamin G. Jacob, Denis Loum, Thomson L. Lakwo, Charles R. Katholi, Peace Habomugisha, Edson Byamukama, Edridah Tukahebwa, Eddie W. Cupp, Thomas R. Unnasch

Background

Onchocerciasis a neglected tropical disease that historically has been a major cause of morbidity and an obstacle to economic development in the developing world. It is caused by infection with Onchocerca volvulus, which is transmitted by black flies of the genus Simulium. The discovery of the potent effect of Mectizan (ivermectin) on O. volvulus microfilariae and the decision by its manufacturer to donate the drug for onchocerciasis spurred the implementation of international programs to control and, more recently, eliminate this scourge. These programs rely primarily on mass distribution of ivermectin (MDA) to the afflicted populations. However, MDA alone will not be sufficient to eliminate onchocerciasis where transmission is intense and where ivermectin MDA is precluded by co-endemicity with Loa loa. Vector control will likely be required as a supplemental intervention in these situations.

Methodology/Principal findings

Because biting by the black fly vectors is often a major nuisance in onchocerciasis afflicted communities, we hypothesized that community members might be mobilized to clear the breeding sites of the vegetation that represents the primary black fly larvae attachment point. We evaluated the effect of such a community based "slash and clear" intervention in multiple communities in Northern Uganda. Slash and Clear resulted in 89–99% declines in vector biting rates. The effect lasted up to 120 days post intervention.

Conclusions/Significance

Slash and clear might represent an effective, inexpensive, community- based tool to supplement ivermectin distribution as a contributory method to eliminate onchocerciasis and prevent recrudescence.

Evidence for transovarial transmission of tick-borne rickettsiae circulating in Northern Mongolia

27 August 2018 - 9:00pm

by Thomas C. Moore, Laura A. Pulscher, Luke Caddell, Michael E. von Fricken, Benjamin D. Anderson, Battsetseg Gonchigoo, Gregory C. Gray

Transstadial transmission of tick-borne rickettsiae has been well documented. Few studies, however, have evaluated the role of transovarial transmission of tick-borne rickettsiae, particularly in nature within the host-vector ecosystem. This cross-sectional study aimed to understand the role of transovarial transmission of tick-borne rickettsiae among feeding ticks at different life stages. Tick eggs laid by engorged wild-caught adult female ticks were pooled and tested for Rickettsia spp. and Anaplasma/Ehrlichia spp. using molecular techniques, while adult fed ticks were tested individually. Additionally, larval and nymphal ticks were collected in the wild from small mammals, pooled and tested for Rickettsia spp. and Anaplasma/Ehrlichia spp. There were 38 fed adult and 618 larvae/nymphs (60 pools total) Dermacentor spp. ticks collected from livestock and rodents. All individual adult ticks and tick pools were positive for Rickettsia spp. While none of the larvae/nymphs were positive for Anaplasma/Ehrlichia spp., two adult fed ticks were positive. Rickettsia spp. DNA was detected in 91% (30/33) of the pooled eggs tested, and one pool of eggs tested positive for Anaplasma/Ehrlichia spp. Sequencing data revealed Rickettsia spp. shared ≥99% identity with R. raoultii ompA. Anaplasma/Ehrlichia spp. shared ≥89% identity with A. ovis 16S ribosomal RNA. This study identified potential transovarial transmission of Rickettsia spp. and Anaplasma spp. among D. nuttalli ticks. Additional studies are needed to further assess the proportion of transovarial transmission occurring in nature to better understand the burden and disease ecology of tick-borne rickettsiae in Mongolia.

Field-collected <i>Triatoma sordida</i> from central Brazil display high microbiota diversity that varies with regard to developmental stage and intestinal segmentation

23 August 2018 - 9:00pm

by Joana L. Oliveira, Juliano C. Cury, Rodrigo Gurgel-Gonçalves, Ana C. Bahia, Fernando A. Monteiro

Background/Methodology

Triatomine bugs are the vectors of Trypanosoma cruzi, the agent of Chagas disease. Vector control has for decades relied upon insecticide spraying, but insecticide resistance has recently emerged in several triatomine populations. One alternative strategy to reduce T. cruzi transmission is paratransgenesis, whereby symbiotic bacteria are genetically engineered to produce T. cruzi-killing proteins in the vector’s gut. This approach requires in-depth knowledge of the vectors’ natural gut microbiota. Here, we use metagenomics (16S rRNA 454 pyrosequencing) to describe the gut microbiota of field-caught Triatoma sordida–likely the most common peridomestic triatomine in Brazil. For large nymphs (4th and 5th stage) and adults, we also studied separately the three main digestive-tract segments–anterior midgut, posterior midgut, and hindgut.

Principal findings

Bacteria of four phyla (12 genera) were present in both nymphs (all five stages) and adults, thus defining T. sordida’s ‘bacterial core’: Actinobacteria (Brevibacterium, Corynebacterium, Dietzia, Gordonia, Nitriliruptor, Nocardia, Nocardiopsis, Rhodococcus, and Williamsia), Proteobacteria (Pseudomonas and Sphingobium), and Firmicutes (Staphylococcus). We found some clear differences in bacterial composition and relative abundance among development stages; overall, Firmicutes and Proteobacteria increased, but Actinobacteria decreased, through development. Finally, the bacterial microbiotas of the bugs’ anterior midgut, posterior midgut, and hindgut were sharply distinct.

Conclusions/Significance

Our results identify the ‘bacterial core set’ of T. sordida and reveal important gut microbiota differences among development stages–particularly between 1st–3rd stage nymphs and adults. Further, we show that, within any given development stage, the vectors’ gut cannot be regarded as a single homogeneous environment. Cultivable, non-pathogenic ‘core’ bacterial species may now be tested as candidates for paratransgenic control of T. cruzi transmission by T. sordida.

Comparison of the dynamics of Japanese encephalitis virus circulation in sentinel pigs between a rural and a peri-urban setting in Cambodia

23 August 2018 - 9:00pm

by Juliette Di Francesco, Rithy Choeung, Borin Peng, Long Pring, Senglong Pang, Raphaël Duboz, Sivuth Ong, San Sorn, Arnaud Tarantola, Didier Fontenille, Veasna Duong, Philippe Dussart, Véronique Chevalier, Julien Cappelle

Japanese encephalitis is mainly considered a rural disease, but there is growing evidence of a peri-urban and urban transmission in several countries, including Cambodia. We, therefore, compared the epidemiologic dynamic of Japanese encephalitis between a rural and a peri-urban setting in Cambodia. We monitored two cohorts of 15 pigs and determined the force of infection–rate at which seronegative pigs become positive–in two study farms located in a peri-urban and rural area, respectively. We also studied the mosquito abundance and diversity in proximity of the pigs, as well as the host densities in both areas. All the pigs seroconverted before the age of 6 months. The force of infection was 0.061 per day (95% confidence interval = 0.034–0.098) in the peri-urban cohort and 0.069 per day (95% confidence interval = 0.047–0.099) in the rural cohort. Several differences in the epidemiologic dynamic of Japanese encephalitis between both study sites were highlighted. The later virus amplification in the rural cohort may be linked to the later waning of maternal antibodies, but also to the higher pig density in direct proximity of the studied pigs, which could have led to a dilution of mosquito bites at the farm level. The force of infection was almost identical in both the peri-urban and the rural farms studied, which shifts the classic epidemiologic cycle of the virus. This study is a first step in improving our understanding of Japanese encephalitis virus ecology in different environments with distinct landscapes, human and animal densities.

Risk factors for diagnosed noma in northwest Nigeria: A case-control study, 2017

23 August 2018 - 9:00pm

by Elise Farley, Annick Lenglet, Cono Ariti, Nma M. Jiya, Adeniyi Semiyu Adetunji, Saskia van der Kam, Karla Bil

Background

Noma (cancrum oris), a neglected tropical disease, rapidly disintegrates the hard and soft tissue of the face and leads to severe disfiguration and high mortality. The disease is poorly understood. We aimed to estimate risk factors for diagnosed noma to better guide existing prevention and treatment strategies using a case-control study design.

Methods

Cases were patients admitted between May 2015 and June 2016, who were under 15 years of age at reported onset of the disease. Controls were individuals matched to cases by village, age and sex. Caretakers answered the questionnaires. Risk factors for diagnosed noma were estimated by calculating unadjusted and adjusted odds ratios (ORs) and respective 95% confidence intervals (CI) using conditional logistic regression.

Findings

We included 74 cases and 222 controls (both median age 5 (IQR 3, 15)). Five cases (6.5%) and 36 (16.2%) controls had a vaccination card (p = 0.03). Vaccination coverage for polio and measles was below 7% in both groups. The two main reported water sources were a bore hole in the village (cases n = 27, 35.1%; controls n = 63, 28.4%; p = 0.08), and a well in the compound (cases n = 24, 31.2%; controls n = 102, 45.9%; p = 0.08). The adjusted analysis identified potential risk and protective factors for diagnosed noma which need further exploration. These include the potential risk factor of the child being fed pap every day (OR 9.8; CI 1.5, 62.7); and potential protective factors including the mother being the primary caretaker (OR 0.08; CI 0.01, 0.5); the caretaker being married (OR 0.006; CI 0.0006, 0.5) and colostrum being given to the baby (OR 0.4; CI 0.09, 2.09).

Interpretation

This study suggests that social conditions and infant feeding practices are potentially associated with being a diagnosed noma case in northwest Nigeria; these findings warrant further investigation into these factors.

Cysteine proteases in protozoan parasites

23 August 2018 - 9:00pm

by Jair L. Siqueira-Neto, Anjan Debnath, Laura-Isobel McCall, Jean A. Bernatchez, Momar Ndao, Sharon L. Reed, Philip J. Rosenthal

Cysteine proteases (CPs) play key roles in the pathogenesis of protozoan parasites, including cell/tissue penetration, hydrolysis of host or parasite proteins, autophagy, and evasion or modulation of the host immune response, making them attractive chemotherapeutic and vaccine targets. This review highlights current knowledge on clan CA cysteine proteases, the best-characterized group of cysteine proteases, from 7 protozoan organisms causing human diseases with significant impact: Entamoeba histolytica, Leishmania species (sp.), Trypanosoma brucei, T. cruzi, Cryptosporidium sp., Plasmodium sp., and Toxoplasma gondii. Clan CA proteases from three organisms (T. brucei, T. cruzi, and Plasmodium sp.) are well characterized as druggable targets based on in vitro and in vivo models. A number of candidate inhibitors are under development. CPs from these organisms and from other protozoan parasites should be further characterized to improve our understanding of their biological functions and identify novel targets for chemotherapy.

Cysteine proteases during larval migration and development of helminths in their final host

23 August 2018 - 9:00pm

by Alexandra Grote, Conor R. Caffrey, Karina M. Rebello, David Smith, John P. Dalton, Sara Lustigman

Neglected tropical diseases caused by metazoan parasites are major public health concerns, and therefore, new methods for their control and elimination are needed. Research over the last 25 years has revealed the vital contribution of cysteine proteases to invasion of and migration by (larval) helminth parasites through host tissues, in addition to their roles in embryogenesis, molting, egg hatching, and yolk degradation. Their central function to maintaining parasite survival in the host has made them prime intervention targets for novel drugs and vaccines. This review focuses on those helminth cysteine proteases that have been functionally characterized during the varied early stages of development in the human host and embryogenesis.

Cysteine proteases as digestive enzymes in parasitic helminths

23 August 2018 - 9:00pm

by Conor R. Caffrey, Louise Goupil, Karina M. Rebello, John P. Dalton, David Smith

We briefly review cysteine proteases (orthologs of mammalian cathepsins B, L, F, and C) that are expressed in flatworm and nematode parasites. Emphasis is placed on enzyme activities that have been functionally characterized, are associated with the parasite gut, and putatively contribute to degrading host proteins to absorbable nutrients [1–4]. Often, gut proteases are expressed as multigene families, as is the case with Fasciola [5] and Haemonchus [6], presumably expanding the range of substrates that can be degraded, not least during parasite migration through host tissues [5]. The application of the free-living planarian and Caenorhabditis elegans as investigative models for parasite cysteine proteases is discussed. Finally, because of their central nutritive contribution, targeting the component gut proteases with small-molecule chemical inhibitors and understanding their utility as vaccine candidates are active areas of research [7].

Estimating the effects of variation in viremia on mosquito susceptibility, infectiousness, and <i>R0</i> of Zika in <i>Aedes aegypti</i>

22 August 2018 - 9:00pm

by Blanka Tesla, Leah R. Demakovsky, Hannah S. Packiam, Erin A. Mordecai, Américo D. Rodríguez, Matthew H. Bonds, Melinda A. Brindley, Courtney C. Murdock

Zika virus (ZIKV) is an arbovirus primarily transmitted by Aedes mosquitoes. Like most viral infections, ZIKV viremia varies over several orders of magnitude, with unknown consequences for transmission. To determine the effect of viral concentration on ZIKV transmission risk, we exposed field-derived Ae. aegypti mosquitoes to four doses (103, 104, 105, 106 PFU/mL) representative of potential variation in the field. We demonstrate that increasing ZIKV dose in the blood-meal significantly increases the probability of mosquitoes becoming infected, and consequently disseminating virus and becoming infectious. Additionally, we observed significant interactions between dose and days post-infection on dissemination and overall transmission efficiency, suggesting that variation in ZIKV dose affects the rates of midgut escape and salivary gland invasion. We did not find significant effects of dose on mosquito mortality. We also demonstrate that detecting virus using RT-qPCR approaches rather than plaque assays potentially over-estimates key transmission parameters, including the time at which mosquitoes become infectious and viral burden. Finally, using these data to parameterize an R0 model, we showed that increasing viremia from 104 to 106 PFU/mL increased relative R0 3.8-fold, demonstrating that variation in viremia substantially affects transmission risk.

Therapeutic control of leishmaniasis by inhibitors of the mammalian target of rapamycin

22 August 2018 - 9:00pm

by Fatemeh Khadir, Christopher R. Shaler, Ahmad Oryan, Patrick T. Rudak, Delfina M. Mazzuca, Tahereh Taheri, Jimmy D. Dikeakos, S. M. Mansour Haeryfar, Sima Rafati

Leishmaniasis is a serious global health problem affecting many people worldwide. While patients with leishmaniasis can be treated with several agents, drug toxicicty and the emergence of resistant strains render available treatments ineffective in the long run. Inhibitors of the mammalian target of rapamycin (mTOR) have been demonstrated to exert anti-pathogen properties. In this study, we tested the therapeutic efficacy of several mTOR inhibitors in controlling infection with Leishmania major. Rapamycin, GSK-2126458 and KU-0063794 were administered to BALB/c mice, which had received an intrafootpad injection of the parasite. Footpad swelling and parasite burden were assessed, and cytokine production by mouse splenocytes and phenotypic changes in draining lymph node cells were evaluated. Treatment with a clinically relevant dose of rapamycin or with GSK-2126458, but not with KU-0063794, dramatically lowered both the footpad swelling and the parasite load in the draining lymph node. Importantly, the employed dose of rapamycin did not kill the promastigotes in vitro as judged by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays and electron microscopy. Moreover, the IL-4 production capacity of splenocytes harvested from infected mice that were treated with rapamycin was significantly reduced. Consequently, the IFN-γ:IL-4 production ratio was elevated, suggesting a T helper-type 1 (Th1)-skewed cytokine profile. Finally, the expression level of CD69, an early activation marker, on splenic and lymph node CD4+ and CD8+ T cells was enhanced in rapamycin-treated mice. Taken together, our findings suggest that select mTOR inhibitors may be used in therapeutic settings for the management of leishmaniasis. We propose that the beneficial effects of such inhibitors stem from their immunomodulatory properties. Therefore, the adjuvanticity of mTOR inhibitors may also be considered in vaccination strategies against Leishmania species.

Amiodarone for arrhythmia in patients with Chagas disease: A systematic review and individual patient data meta-analysis

20 August 2018 - 9:00pm

by Cinara Stein, Celina Borges Migliavaca, Verônica Colpani, Priscila Raupp da Rosa, Daniel Sganzerla, Natalia Elis Giordani, Sandro Renê Pinto de Sousa Miguel, Luciane Nascimento Cruz, Carisi Anne Polanczyk, Antonio Luiz P. Ribeiro, Maicon Falavigna

Background

Chagas disease is a neglected chronic condition caused by Trypanosoma cruzi, with high prevalence and burden in Latin America. Ventricular arrhythmias are common in patients with Chagas cardiomyopathy, and amiodarone has been widely used for this purpose. The aim of our study was to assess the effect of amiodarone in patients with Chagas cardiomyopathy.

Methodology

We searched MEDLINE, Embase and LILACS up to January 2018. Data from randomized and observational studies evaluating amiodarone use in Chagas cardiomyopathy were included. Two reviewers selected the studies, extracted data and assessed risk of bias. Overall quality of evidence was accessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE).

Principal findings

We included 9 studies (3 before-after studies, 5 case series and 1 randomized controlled trial). Two studies with a total of 38 patients had the full dataset, allowing individual patient data (IPD) analysis. In 24-hour Holter, amiodarone reduced the number of ventricular tachycardia episodes in 99.9% (95%CI 99.8%-100%), ventricular premature beats in 93.1% (95%CI 82%-97.4%) and the incidence of ventricular couplets in 79% (RR 0.21, 95%CI 0.11–0.39). Studies not included in the IPD analysis showed a reduction of ventricular premature beats (5 studies), ventricular tachycardia (6 studies) and ventricular couplets (1 study). We pooled the incidence of adverse side effects with random effects meta-analysis; amiodarone was associated with corneal microdeposits (61.1%, 95%CI 19.0–91.3, 5 studies), gastrointestinal events (16.1%, 95%CI 6.61–34.2, 3 studies), sinus bradycardia (12.7%, 95%CI 3.71–35.5, 6 studies), dermatological events (10.6%, 95%CI 4.77–21.9, 3 studies) and drug discontinuation (7.68%, 95%CI 4.17–13.7, 5 studies). Quality of evidence ranged from moderate to very low.

Conclusions

Amiodarone is effective in reducing ventricular arrhythmias, but there is no evidence for hard endpoints (sudden death, hospitalization). Although our findings support the use of amiodarone, it is important to balance the potential benefits and harms at the individual level for decision-making.

Laboratory selection of <i>Aedes aegypti</i> field populations with the organophosphate malathion: Negative impacts on resistance to deltamethrin and to the organophosphate temephos

20 August 2018 - 9:00pm

by Priscila Fernandes Viana Medeiros, Diogo Fernandes Bellinato, Denise Valle

Background

Resistance to pyrethroids and to the organophosphate temephos is widespread in Brazilian populations of the dengue vector, Aedes aegypti. Thereof, since 2009 Insect Growth Regulators are employed as larvicides, and malathion is used against adults.

Methodology/Principal findings

We performed laboratory selection with malathion of two A. aegypti field populations initially susceptible to this organophosphate but resistant to temephos and deltamethrin. A fixed malathion dose inducing at least 80% mortality in the first generation, was used throughout the selection process, interrupted after five generations, when the threshold of 20% mortality was reached. For each population, three experimental and two control groups, not exposed to insecticides, were kept independently. For both populations, quantitative bioassays revealed, in the selected groups, acquisition of resistance to malathion and negative impact of malathion selection on deltamethrin and temephos resistance levels. In the control groups resistance to all evaluated insecticides decreased except, unexpectedly, to deltamethrin. Analysis of the main resistance mechanisms employed routine methodologies: biochemical and molecular assays for, respectively, metabolic resistance and quantification of the NaV pyrethroid target main kdr mutations at positions 1016 and 1534. No diagnostic alteration could be specifically correlated with malathion selection, neither with the unusual deltamethrin increase in resistance levels observed in the control groups.

Conclusions/Significance

Our results confirm the multifactorial character of insecticide resistance and point to the need of high throughput methodologies and to the study of additional field vector populations in order to unravel resistance mechanisms.

The antiparasitic drug niclosamide inhibits dengue virus infection by interfering with endosomal acidification independent of mTOR

20 August 2018 - 9:00pm

by Jo-Chi Kao, Wei-Chun HuangFu, Tsung-Ting Tsai, Min-Ru Ho, Ming-Kai Jhan, Ting-Jing Shen, Po-Chun Tseng, Yung-Ting Wang, Chiou-Feng Lin

Background

The antiparasitic agent niclosamide has been demonstrated to inhibit the arthropod-borne Zika virus. Here, we investigated the antiviral capacity of niclosamide against dengue virus (DENV) serotype 2 infection in vitro and in vivo.

Principle Finding

Niclosamide effectively retarded DENV-induced infection in vitro in human adenocarcinoma cells (A549), mouse neuroblastoma cells (Neuro-2a), and baby hamster kidney fibroblasts (BHK-21). Treatment with niclosamide did not retard the endocytosis of DENV while niclosamide was unable to enhance the antiviral type I interferon response. Furthermore, niclosamide did not cause a direct effect on viral replicon-based expression. Niclosamide has been reported to competitively inhibit the mTOR (mammalian target of rapamycin), STAT3 (signal transducer and activator of transcription 3), and NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) signaling pathways; however, selective inhibitors of those pathways did not reduce DENV infection. Similar to the vacuolar-type H+-ATPase inhibitor bafilomycin A1, both niclosamide and other protonophores, such as CCCP (carbonyl cyanide m-chlorophenyl hydrazone), and FCCP (carbonyl cyanide-p-trifluoromethoxyphenylhydrazone), effectively reduced endosomal acidification and viral dsRNA replication. Co-administration of a single dose of niclosamide partially decreased viral replication, viral encephalitis, and mortality in DENV-infected ICR suckling mice.

Significance

These results demonstrate that niclosamide diminishes viral infection by hindering endosomal acidification.

<i>Echinococcus</i> in wild canids in Québec (Canada) and Maine (USA)

20 August 2018 - 9:00pm

by Janna M. Schurer, Emilie Bouchard, Ann Bryant, Sarah Revell, Grace Chavis, Anne Lichtenwalner, Emily J. Jenkins

Zoonotic Echinococcus spp. cestodes (E. canadensis and E. multilocularis) infect domestic animals, wildlife, and people in regions of Canada and the USA. We recovered and quantified Echinococcus spp. cestodes from 22 of 307 intestinal tracts of wild canids (23 wolves, 100 coyotes, 184 red and arctic foxes) in the state of Maine and the province of Québec. We identified the species and genotypes of three Echinococcus spp. cestodes per infected animal by sequencing mitochondrial DNA at two loci. We further confirmed the absence of E. multilocularis by extracting DNA from pools of all cestodes from each animal and running a duplex PCR capable of distinguishing the two species. We detected E. canadensis (G8 and G10), but not E. multilocularis, which is emerging as an important human and animal health concern in adjacent regions. Prevalence and median intensity of E. canadensis was higher in wolves (35%, 460) than coyotes (14%, 358). This parasite has historically been absent in Atlantic regions of North America, where suitable intermediate hosts, but not wolves, are present. Our study suggests that coyotes are serving as sylvatic definitive hosts for E. canadensis in Atlantic regions, and this may facilitate eastward range expansion of E. canadensis in the USA and Canada. As well, compared to wolves, coyotes are more likely to contaminate urban green spaces and peri-urban environments with zoonotic parasites.

Description of the first sleeping sickness case diagnosed in Burkina Faso since two decades

20 August 2018 - 9:00pm

by Emilie Dama, Aboubacar Drabo, Jacques Kaboré, Elie Ouédraogo, Bamoro Coulibaly, Hamidou Ilboudo, Justin Kaboré, Charlie Franck Compaoré, Hassane Sakandé, Micheline Ouédraogo, Jean-Baptiste Rayaissé, Fabrice Courtin, Philippe Solano, François Drabo, Vincent Jamonneau

Burkina Faso belongs to a group of countries in which human African trypanosomiasis (HAT), caused by Trypanosoma brucei gambiense, is no longer considered to be a public health problem. Although no native cases have been detected since 1993, there is still the risk of HAT re-emergence due to significant population movements between Burkina Faso and active HAT foci in Côte d’Ivoire. Since 2014, Burkina Faso receives support from the WHO to implement a passive surveillance program. This resulted in the detection in 2015 of the first putative native HAT case since two decades. However, epidemiological entomological and molecular biology investigations have not been able to identify with certainty the origin of this infection or to confirm that it was due to T. b. gambiense. This case emphasises the need to strengthen passive surveillance of the disease for sustained elimination of HAT as a public health problem in Burkina Faso.

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