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Integration of Multiplex Bead Assays for Parasitic Diseases into a National, Population-Based Serosurvey of Women 15-39 Years of Age in Cambodia

by Jeffrey W. Priest, M. Harley Jenks, Delynn M. Moss, Bunsoth Mao, Sokhal Buth, Kathleen Wannemuehler, Sann Chan Soeung, Naomi W. Lucchi, Venkatachalam Udhayakumar, Christopher J. Gregory, Rekol Huy, Sinuon Muth, Patrick J. Lammie

Collection of surveillance data is essential for monitoring and evaluation of public health programs. Integrated collection of household-based health data, now routinely carried out in many countries through demographic health surveys and multiple indicator surveys, provides critical measures of progress in health delivery. In contrast, biomarker surveys typically focus on single or related measures of malaria infection, HIV status, vaccination coverage, or immunity status for vaccine-preventable diseases (VPD). Here we describe an integrated biomarker survey based on use of a multiplex bead assay (MBA) to simultaneously measure antibody responses to multiple parasitic diseases of public health importance as part of a VPD serological survey in Cambodia. A nationally-representative cluster-based survey was used to collect serum samples from women of child-bearing age. Samples were tested by MBA for immunoglobulin G antibodies recognizing recombinant antigens from Plasmodium falciparum and P. vivax, Wuchereria bancrofti, Toxoplasma gondii, Taenia solium, and Strongyloides stercoralis. Serologic IgG antibody results were useful both for generating national prevalence estimates for the parasitic diseases of interest and for confirming the highly focal distributions of some of these infections. Integrated surveys offer an opportunity to systematically assess the status of multiple public health programs and measure progress toward Millennium Development Goals.

Tegument Glycoproteins and Cathepsins of Newly Excysted Juvenile <i>Fasciola hepatica</i> Carry Mannosidic and Paucimannosidic <i>N</i>-glycans

by Andres Garcia-Campos, Alessandra Ravidà, D. Linh Nguyen, Krystyna Cwiklinski, John P. Dalton, Cornelis H. Hokke, Sandra O’Neill, Grace Mulcahy

Recently, the prevalence of Fasciola hepatica in some areas has increased considerably and the availability of a vaccine to protect livestock from infection would represent a major advance in tools available for controlling this disease. To date, most vaccine-target discovery research on this parasite has concentrated on proteomic and transcriptomic approaches whereas little work has been carried out on glycosylation. As the F. hepatica tegument (Teg) may contain glycans potentially relevant to vaccine development and the Newly Excysted Juvenile (NEJ) is the first lifecycle stage in contact with the definitive host, our work has focused on assessing the glycosylation of the NEJTeg and identifying the NEJTeg glycoprotein repertoire. After in vitro excystation, NEJ were fixed and NEJTeg was extracted. Matrix-assisted laser desorption ionisation-time of flight-mass spectrometry (MALDI-TOF-MS) analysis of released N-glycans revealed that oligomannose and core-fucosylated truncated N-glycans were the most dominant glycan types. By lectin binding studies these glycans were identified mainly on the NEJ surface, together with the oral and ventral suckers. NEJTeg glycoproteins were affinity purified after targeted biotinylation of the glycans and identified using liquid chromatography and tandem mass spectrometry (LC-MS/MS). From the total set of proteins previously identified in NEJTeg, eighteen were also detected in the glycosylated fraction, including the F. hepatica Cathepsin B3 (FhCB3) and two of the Cathepsin L3 (FhCL3) proteins, among others. To confirm glycosylation of cathepsins, analysis at the glycopeptide level by LC-ESI-ion-trap-MS/MS with collision-induced dissociation (CID) and electron-transfer dissociation (ETD) was carried out. We established that cathepsin B1 (FhCB1) on position N80, and FhCL3 (BN1106_s10139B000014, scaffold10139) on position N153, carry unusual paucimannosidic Man2GlcNAc2 glycans. To our knowledge, this is the first description of F. hepatica NEJ glycosylation and the first report of N-glycosylation of F. hepatica cathepsins. The significance of these findings for immunological studies and vaccine development is discussed.

Low Protective Efficacy of the Current Japanese Encephalitis Vaccine against the Emerging Genotype 5 Japanese Encephalitis Virus

by Lei Cao, Shihong Fu, Xiaoyan Gao, Minghua Li, Shiheng Cui, Xiaolong Li, Yuxi Cao, Wenwen Lei, Zhi Lu, Ying He, Huanyu Wang, Jinghua Yan, George Fu Gao, Guodong Liang

Background

The current Japanese encephalitis (JE) vaccine derived from G3 JE virus (JEV) can induce protective immunity against G1–G4 JEV genotypes. However, protective efficacy against the emerging G5 genotype has not been reported.

Methods/Principal Findings

Using in vitro and in vivo tests, biological phenotype and cross-immunoreactions were compared between G3 JEV and G5 JEV (wild strains). The PRNT90 method was used to detect neutralizing antibodies against different genotypes of JEV in JE vaccine-immunized subjects and JE patients. In JE vaccine-immunized mice, the lethal challenge protection rates against G3 and G5 JEV wild strains were 100% and 50%, respectively. The seroconversion rates (SCRs) of virus antibodies against G3 and G5 JEV among vaccinated healthy subjects were 100% and 35%, respectively. All clinically identified JE patients showed high levels of G3 JEV neutralizing antibodies (≥1:10–1280) with positive serum geometric mean titers (GMTs) of 43.2, while for G5 JEV, neutralizing antibody conversion rates were only 64% with positive serum GMTs of 11.14. Moreover, the positive rate of JEV neutralizing antibodies against G5 JEV in pediatric patients was lower than in adults.

Conclusions/Significance

Low levels of neutralizing/protective antibodies induced by the current JE vaccine, based on the G3 genotype, were observed against the emerging G5 JEV genotype. Our results demonstrate the need for more detailed studies to reevaluate whether or not the apparent emergence of G5 JEV can be attributed to failure of the current vaccine to induce appropriate immune protectivity against this genotype of JEV.

The Accuracy of Praziquantel Dose Poles for Mass Treatment of Schistosomiasis in School Girls in KwaZulu-Natal, South Africa

by Marije Baan, Hashini Nilushika Galappaththi-Arachchige, Silindile Gagai, Christine G. Aurlund, Birgitte J. Vennervald, Myra Taylor, Lisette van Lieshout, Eyrun F. Kjetland

Background

More than 260 million people live with schistosomiasis and regular mass-treatment should be implemented to prevent morbidity. Praziquantel, dosed at 40 milligrams per kilogram bodyweight, is the drug of choice. During the last decades the WHO Tablet Pole–which estimates tablet need by height as representing weight–has been used as a practical and cheap tool in mass treatment. In South Africa this method could be inaccurate given the prevalence of overweight and obesity. In this study in female pupils in KwaZulu-Natal, South Africa, we explored the accuracy of the WHO Tablet Pole and the recently developed Modified Dose Pole for adults with two additional intervals and correction for body mass index (BMI).

Methodology

In randomly selected primary and secondary schools of schistosomiasis-endemic areas, height and weight of female pupils were measured. The WHO Tablet Pole and Modified Dose Pole were used to indicate the amount of praziquantel according to height and the dose in milligrams per kilogram bodyweight was calculated. The BMI correction was performed by adding 600 milligrams (1 tablet) to the indicated dose if a person was overweight/obese.

Principal Findings

3157 female students were investigated and 35% were found to be overweight/obese. Using the WHO Tablet Pole, 73% would have received an adequate dose (range 30–60 mg/kg). When correcting for BMI, this would have been 94%. Using the Modified Dose Pole with BMI correction, 97% would have been adequately treated.

Conclusions

This study shows that the WHO Tablet Pole will be inaccurate in estimating the dose of praziquantel in South African girls due to high prevalence of overweight/obesity. Under-dosing of individuals who appear overweight/obese could be largely prevented by adding an extra praziquantel tablet to the recommended dose. Further research must be done to explore if subjective weight estimates are reliable.

Prevalence of River Epilepsy in the Orientale Province in the Democratic Republic of the Congo

by Robert Colebunders, Floribert Tepage, Ente Rood, Michel Mandro, Emmanuel Nji Abatih, Gisele Musinya, Germain Mambandu, José Kabeya, Michel Komba, Bethany Levick, John L Mokili, Anne Laudisoit

Background

An increased prevalence of epilepsy has been reported in many onchocerciasis endemic areas.

Objective

To determine the prevalence and distribution of epilepsy in an onchocerciasis endemic region in the Democratic Republic of the Congo (DRC).

Design/Methods

An epilepsy prevalence study was carried out in 2014, in two localities of the Bas-Uélé district, an onchocerciasis endemic region in the Orientale Province of the DRC. Risk factors for epilepsy were identified using a random effects logistic regression model and the distribution of epilepsy cases was investigated using the Moran’s I statistic of spatial auto-correlation.

Results

Among the 12,776 individuals of Dingila, 373 (2.9%) individuals with epilepsy were identified. In a house-to-house survey in Titule, 68 (2.3%) of the 2,908 people who participated in the survey were found to present episodes of epilepsy. Epilepsy showed a marked spatial pattern with clustering of cases occurring within and between adjacent households. Individual risk of epilepsy was found to be associated with living close to the nearest fast flowing river where blackflies (Diptera: Simuliidae)–the vector of Onchocerca volvulus–oviposit and breed.

Conclusions

The prevalence of epilepsy in villages in the Bas-Uélé district in the DRC was higher than in non-onchocerciasis endemic regions in Africa. Living close to a blackflies infested river was found to be a risk factor for epilepsy.

Toxoplasmic Retinochoroiditis: Clinical Characteristics and Visual Outcome in a Prospective Study

by Ana Luisa Quintella do Couto Aleixo, André Luiz Land Curi, Eliezer Israel Benchimol, Maria Regina Reis Amendoeira

Purpose

To ascertain the clinical features and visual outcome of toxoplasma retinochoroiditis in a large series of cases.

Subjects and Methods

Two hundred and thirty subjects diagnosed with active toxoplasma retinochoroiditis were prospectively followed for periods ranging from 269 to 1976 days. All patients presented with active retinochoroiditis and positive IgG T. gondii serology at the beginning of the study and received a standardized drug treatment for toxoplasmosis, both in the first episode and in the subsequent recurrences.

Results

The group involved 118 (51.3%) men and 112 (48.7%) women, with ages ranging from 14 to 77 years, mean of 32.4 years (SD = 11.38). Primary retinochoroidal lesions were observed in 52 (22.6%) cases and active retinochoroiditis combined with old scars in 178 (77.4%) subjects at the beginning of the study. A hundred sixty-two recurrent episodes in 104 (45.2%) patients were observed during follow-up. New subclinical retinochoroidal lesions were detected in 23 of 162 (14.2%) recurrences episodes during the follow-up. Posterior segment complications were observed in 73 (31.7%) subjects. Retinochoroidal lesions adjacent to the optic nerve and in the macular area were observed in 27 of 40 (67.5%) cases of severe visual impairment (VA = 20/200 or worse).

Conclusion

Toxoplasma retinochoroiditis in this population had a high recurrence rate after an active episode. Severe visual impairment was associated with location of the retinochoroidal scar, recurrences and posterior segment complications. It is crucial to consider the location of the lesion in studies analyzing visual prognosis as a measure for treatment effectiveness and prevention strategies.

Potential Impact of Sexual Transmission on Ebola Virus Epidemiology: Sierra Leone as a Case Study

by Jessica L. Abbate, Carmen Lia Murall, Heinz Richner, Christian L. Althaus

Background

Sexual transmission of Ebola virus disease (EVD) 6 months after onset of symptoms has been recently documented, and Ebola virus RNA has been detected in semen of survivors up to 9 months after onset of symptoms. As countries affected by the 2013–2015 epidemic in West Africa, by far the largest to date, are declared free of Ebola virus disease (EVD), it remains unclear what threat is posed by rare sexual transmission events that could arise from survivors.

Methodology/Principal Findings

We devised a compartmental mathematical model that includes sexual transmission from convalescent survivors: a SEICR (susceptible-exposed-infectious-convalescent-recovered) transmission model. We fitted the model to weekly incidence of EVD cases from the 2014–2015 epidemic in Sierra Leone. Sensitivity analyses and Monte Carlo simulations showed that a 0.1% per sex act transmission probability and a 3-month convalescent period (the two key unknown parameters of sexual transmission) create very few additional cases, but would extend the epidemic by 83 days [95% CI: 68–98 days] (p < 0.0001) on average. Strikingly, a 6-month convalescent period extended the average epidemic by 540 days (95% CI: 508–572 days), doubling the current length, despite an insignificant rise in the number of new cases generated.

Conclusions/Significance

Our results show that reductions in the per sex act transmission probability via abstinence and condom use should reduce the number of sporadic sexual transmission events, but will not significantly reduce the epidemic size and may only minimally shorten the length of time the public health community must maintain response preparedness. While the number of infectious survivors is expected to greatly decline over the coming months, our results show that transmission events may still be expected for quite some time as each event results in a new potential cluster of non-sexual transmission. Precise measurement of the convalescent period is thus important for planning ongoing surveillance efforts.

Correction: Environmental Mapping of Paracoccidioides spp. in Brazil Reveals New Clues into Genetic Diversity, Biogeography and Wild Host Association

PLoS Neglected Tropical Diseases News - 29 April 2016 - 9:00pm

by Thales Domingos Arantes, Raquel Cordeiro Theodoro, Marcus de Melo Teixeira, Sandra de Moraes Gimenes Bosco, Eduardo Bagagli

Comprehensive Transcriptome Analysis of Sex-Biased Expressed Genes Reveals Discrete Biological and Physiological Features of Male and Female <i>Schistosoma japonicum</i>

PLoS Neglected Tropical Diseases News - 29 April 2016 - 9:00pm

by Pengfei Cai, Shuai Liu, Xianyu Piao, Nan Hou, Geoffrey N. Gobert, Donald P. McManus, Qijun Chen

Schistosomiasis is a chronic and debilitating disease caused by blood flukes (digenetic trematodes) of the genus Schistosoma. Schistosomes are sexually dimorphic and exhibit dramatic morphological changes during a complex lifecycle which requires subtle gene regulatory mechanisms to fulfil these complex biological processes. In the current study, a 41,982 features custom DNA microarray, which represents the most comprehensive probe coverage for any schistosome transcriptome study, was designed based on public domain and local databases to explore differential gene expression in S. japonicum. We found that approximately 1/10 of the total annotated genes in the S. japonicum genome are differentially expressed between adult males and females. In general, genes associated with the cytoskeleton, and motor and neuronal activities were readily expressed in male adult worms, whereas genes involved in amino acid metabolism, nucleotide biosynthesis, gluconeogenesis, glycosylation, cell cycle processes, DNA synthesis and genome fidelity and stability were enriched in females. Further, miRNAs target sites within these gene sets were predicted, which provides a scenario whereby the miRNAs potentially regulate these sex-biased expressed genes. The study significantly expands the expressional and regulatory characteristics of gender-biased expressed genes in schistosomes with high accuracy. The data provide a better appreciation of the biological and physiological features of male and female schistosome parasites, which may lead to novel vaccine targets and the development of new therapeutic interventions.

Predicting Dengue Fever Outbreaks in French Guiana Using Climate Indicators

PLoS Neglected Tropical Diseases News - 29 April 2016 - 9:00pm

by Antoine Adde, Pascal Roucou, Morgan Mangeas, Vanessa Ardillon, Jean-Claude Desenclos, Dominique Rousset, Romain Girod, Sébastien Briolant, Philippe Quenel, Claude Flamand

Background

Dengue fever epidemic dynamics are driven by complex interactions between hosts, vectors and viruses. Associations between climate and dengue have been studied around the world, but the results have shown that the impact of the climate can vary widely from one study site to another. In French Guiana, climate-based models are not available to assist in developing an early warning system. This study aims to evaluate the potential of using oceanic and atmospheric conditions to help predict dengue fever outbreaks in French Guiana.

Methodology/Principal Findings

Lagged correlations and composite analyses were performed to identify the climatic conditions that characterized a typical epidemic year and to define the best indices for predicting dengue fever outbreaks during the period 1991–2013. A logistic regression was then performed to build a forecast model. We demonstrate that a model based on summer Equatorial Pacific Ocean sea surface temperatures and Azores High sea-level pressure had predictive value and was able to predict 80% of the outbreaks while incorrectly predicting only 15% of the non-epidemic years. Predictions for 2014–2015 were consistent with the observed non-epidemic conditions, and an outbreak in early 2016 was predicted.

Conclusions/Significance

These findings indicate that outbreak resurgence can be modeled using a simple combination of climate indicators. This might be useful for anticipating public health actions to mitigate the effects of major outbreaks, particularly in areas where resources are limited and medical infrastructures are generally insufficient.

Local Cellular Immune Responses and Pathogenesis of Buruli Ulcer Lesions in the Experimental <i>Mycobacterium Ulcerans</i> Pig Infection Model

PLoS Neglected Tropical Diseases News - 29 April 2016 - 9:00pm

by Miriam Bolz, Nicolas Ruggli, Nicole Borel, Gerd Pluschke, Marie-Thérèse Ruf

Background

Buruli ulcer is a neglected tropical disease of the skin that is caused by infection with Mycobacterium ulcerans. We recently established an experimental pig (Sus scrofa) infection model for Buruli ulcer to investigate host-pathogen interactions, the efficacy of candidate vaccines and of new treatment options.

Methodology/Principal Findings

Here we have used the model to study pathogenesis and early host-pathogen interactions in the affected porcine skin upon infection with mycolactone-producing and non-producing M. ulcerans strains. Histopathological analyses of nodular lesions in the porcine skin revealed that six weeks after infection with wild-type M. ulcerans bacteria extracellular acid fast bacilli were surrounded by distinct layers of neutrophils, macrophages and lymphocytes. Upon ulceration, the necrotic tissue containing the major bacterial burden was sloughing off, leading to the loss of most of the mycobacteria. Compared to wild-type M. ulcerans bacteria, toxin-deficient mutants caused an increased granulomatous cellular infiltration without massive tissue necrosis, and only smaller clusters of acid fast bacilli.

Conclusions/Significance

In summary, the present study shows that the pathogenesis and early immune response to M. ulcerans infection in the pig is very well reflecting BU disease in humans, making the pig infection model an excellent tool for the profiling of new therapeutic and prophylactic interventions.

The Effect of Intestinal Parasitic Infection on the Clinical Outcome of Malaria in Coinfected Children in Cameroon

PLoS Neglected Tropical Diseases News - 29 April 2016 - 9:00pm

by Tebit E. Kwenti, Franklin A. Nkume, Ajime T. Tanjeko, Tayong D. B. Kwenti

Background

The interaction between intestinal parasites and malaria is still not clear. Data in published literature are conflicting. We studied the effect of intestinal parasitic infection (IPI) on the clinical outcome of malaria in coinfected children.

Methods

In a cross sectional study performed between October 2014 and September 2015, children infected with malaria, as demonstrated by the presence of asexual parasites in Giemsa stained blood films, were enrolled. Stool samples were obtained from participants and subjected to the formol-ether concentration technique for the detection of intestinal parasites. The Complete blood count was performed using an automated haematology analyser (Mindray, BC-2800). The risk ratio, Pearson’s chi-square and the student T test were all performed as part of the statistical analyses. Statistical significance was set at p < 0.05.

Results

In all, 405 children successfully took part in the study. The children were between 1 week and 120 months of age (mean ± SD = 41.5 ± 33.5). Coinfection with intestinal parasites was observed in 11.6%. The rate of severe malaria (SM) attack in this study was 10.9%. SM was not observed to be associated with age (p = 0.377) or gender (p = 0.387), meanwhile coinfection with intestinal parasites was associated with age (p = 0.003). Among SM cases, IPI prevalence was higher in children with mild (WHO group 3) severe malaria (p = 0.027). Overall, IPI was not observed to be associated with SM (p = 0.656) or malaria parasite density (p = 0.185) or haemoglobin concentration (p = 0.205). The main clinical features of SM observed were hyperpyrexia (68.2%), severe malarial anaemia (61.4%), and multiple convulsion (52.3%).

Conclusion

IPI was not observed to be associated with the severity of malaria, the malaria parasite density, and the haemoglobin concentration in coinfected children in Cameroon. The clinical outcome of malaria in children coinfected with intestinal parasites may depend on the geographical setting after all.

Vestibular Evoked Myogenic Potential (VEMP) Triggered by Galvanic Vestibular Stimulation (GVS): A Promising Tool to Assess Spinal Cord Function in Schistosomal Myeloradiculopathy

PLoS Neglected Tropical Diseases News - 29 April 2016 - 9:00pm

by Júlia Fonseca de Morais Caporali, Denise Utsch Gonçalves, Ludimila Labanca, Leonardo Dornas de Oliveira, Guilherme Vaz de Melo Trindade, Thiago de Almeida Pereira, Pedro Henrique Diniz Cunha, Marina Santos Falci Mourão, José Roberto Lambertucci

Background

Schistosomal myeloradiculopathy (SMR), the most severe and disabling ectopic form of Schistosoma mansoni infection, is caused by embolized ova eliciting local inflammation in the spinal cord and nerve roots. The treatment involves the use of praziquantel and long-term corticotherapy. The assessment of therapeutic response relies on neurological examination. Supplementary electrophysiological exams may improve prediction and monitoring of functional outcome. Vestibular evoked myogenic potential (VEMP) triggered by galvanic vestibular stimulation (GVS) is a simple, safe, low-cost and noninvasive electrophysiological technique that has been used to test the vestibulospinal tract in motor myelopathies. This paper reports the results of VEMP with GVS in patients with SMR.

Methods

A cross-sectional comparative study enrolled 22 patients with definite SMR and 22 healthy controls that were submitted to clinical, neurological examination and GVS. Galvanic stimulus was applied in the mastoid bones in a transcranial configuration for testing VEMP, which was recorded by electromyography (EMG) in the gastrocnemii muscles. The VEMP variables of interest were blindly measured by two independent examiners. They were the short-latency (SL) and the medium-latency (ML) components of the biphasic EMG wave.

Results

VEMP showed the components SL (p = 0.001) and ML (p<0.001) delayed in SMR compared to controls. The delay of SL (p = 0.010) and of ML (p = 0.020) was associated with gait dysfunction.

Conclusion

VEMP triggered by GVS identified alterations in patients with SMR and provided additional functional information that justifies its use as a supplementary test in motor myelopathies.

Genetic Variation in Autophagy-Related Genes Influences the Risk and Phenotype of Buruli Ulcer

PLoS Neglected Tropical Diseases News - 29 April 2016 - 9:00pm

by Carlos Capela, Ange Dodji Dossou, Rita Silva-Gomes, Ghislain Emmanuel Sopoh, Michel Makoutode, João Filipe Menino, Alexandra Gabriel Fraga, Cristina Cunha, Agostinho Carvalho, Fernando Rodrigues, Jorge Pedrosa

Introduction

Buruli ulcer (BU) is a severe necrotizing human skin disease caused by Mycobacterium ulcerans. Clinically, presentation is a sum of these diverse pathogenic hits subjected to critical immune-regulatory mechanisms. Among them, autophagy has been demonstrated as a cellular process of critical importance. Since microtubules and dynein are affected by mycolactone, the critical pathogenic exotoxin produced by M. ulcerans, cytoskeleton-related changes might potentially impair the autophagic process and impact the risk and progression of infection.

Objective

Genetic variants in the autophagy-related genes NOD2, PARK2 and ATG16L1 has been associated with susceptibility to mycobacterial diseases. Here, we investigated their association with BU risk, its severe phenotypes and its progression to an ulcerative form.

Methods

Genetic variants were genotyped using KASPar chemistry in 208 BU patients (70.2% with an ulcerative form and 28% in severe WHO category 3 phenotype) and 300 healthy endemic controls.

Results

The rs1333955 SNP in PARK2 was significantly associated with increased susceptibility to BU [odds ratio (OR), 1.43; P = 0.05]. In addition, both the rs9302752 and rs2066842 SNPs in NOD2 gee significantly increased the predisposition of patients to develop category 3 (OR, 2.23; P = 0.02; and OR 12.7; P = 0.03, respectively, whereas the rs2241880 SNP in ATG16L1 was found to significantly protect patients from presenting the ulcer phenotype (OR, 0.35; P = 0.02).

Conclusion

Our findings indicate that specific genetic variants in autophagy-related genes influence susceptibility to the development of BU and its progression to severe phenotypes.

Underestimation of Leptospirosis Incidence in the French West Indies

PLoS Neglected Tropical Diseases News - 29 April 2016 - 9:00pm

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

Background

Leptospirosis is a neglected zoonosis affecting mainly tropical and subtropical regions worldwide, particularly South America and the Caribbean. As in many other countries, under-reporting of cases was suspected in the French West Indies because of inadequate access to diagnostic tests for the general population.

Methodology/Principal findings

In order to estimate the real incidence of leptospirosis in Guadeloupe and Martinique, a study was performed in 2011 using the three prevailing available biological tests for diagnosis: Microscopic Agglutination Test (MAT), IgM ELISA and PCR. The study investigated inpatients and outpatients and used active case ascertainment from data provided by a general practitioners’ sentinel network. The epidemiology of the disease was also described in terms of severity and demographic characteristics. Leptospirosis incidence was estimated at 69.4 (95%CI 47.6–91.1) and 60.6 (95%CI 36.3–85.0) annual cases per 100 000 inhabitants in Guadeloupe and Martinique, respectively, which was 3 and 4 times higher than previous estimations.

Conclusion/Significance

Inclusion of PCR and IgM ELISA tests for diagnosis of leptospirosis resulted in improved sensitivity in comparison with MAT alone. Our results highlighted the substantial health burden of the disease in these two territories and the importance of access to appropriate laboratory tests. Based on our results, PCR and IgM ELISA tests have now been included in the list of tests reimbursed by the national system of social security insurance in France. Our results also underline the relevance of implementing an integrated strategy for the surveillance, prevention and control of leptospirosis in the French West Indies.

High Throughput Screening Identifies Novel Lead Compounds with Activity against Larval, Juvenile and Adult <i>Schistosoma mansoni</i>

PLoS Neglected Tropical Diseases News - 29 April 2016 - 9:00pm

by Nuha R. Mansour, Ross Paveley, J. Mark F. Gardner, Andrew S. Bell, Tanya Parkinson, Quentin Bickle

An estimated 600 million people are affected by the helminth disease schistosomiasis caused by parasites of the genus Schistosoma. There is currently only one drug recommended for treating schistosomiasis, praziquantel (PZQ), which is effective against adult worms but not against the juvenile stage. In an attempt to identify improved drugs for treating the disease, we have carried out high throughput screening of a number of small molecule libraries with the aim of identifying lead compounds with balanced activity against all life stages of Schistosoma. A total of almost 300,000 compounds were screened using a high throughput assay based on motility of worm larvae and image analysis of assay plates. Hits were screened against juvenile and adult worms to identify broadly active compounds and against a mammalian cell line to assess cytotoxicity. A number of compounds were identified as promising leads for further chemical optimization.

Treatment Success in <i>Trypanosoma cruzi</i> Infection Is Predicted by Early Changes in Serially Monitored Parasite-Specific T and B Cell Responses

PLoS Neglected Tropical Diseases News - 29 April 2016 - 9:00pm

by María G. Alvarez, Graciela L. Bertocchi, Gretchen Cooley, María C. Albareda, Rodolfo Viotti, Damián E. Perez-Mazliah, Bruno Lococo, Melisa Castro Eiro, Susana A. Laucella, Rick L. Tarleton

Background

Chagas disease is the highest impact parasitic disease in Latin America. We have proposed that changes in Trypanosoma cruzi-specific immune responses might serve as surrogate indicators of treatment success. Herein, we addressed in a long-term follow-up study whether cure achieved after treatment can be predicted by changes in non-conventional indexes of anti-parasite serological and T cell activities.

Methodology/Principal Findings

T. cruzi-specific T cell responses, as measured by interferon-γ ELISPOT and T. cruzi-specific antibodies assessed by ELISA, hemagglutination and immunofluorescence tests as well as by a multiplex assay incorporating 14 recombinant T. cruzi proteins were measured in 33 patients at 48–150 months post-benznidazole treatment. Cure — as assessed by conventional serological tests — was associated with an early decline in T. cruzi-specific IFN-γ-producing T cells and in antibody titers measured by the multiplex serological assay. Changes in the functional status and potential of T. cruzi-specific T cells, indicative of reduced antigen stimulation, provided further evidence of parasitological cure following benznidazole treatment. Patients showing a significant reduction in T. cruzi-specific antibodies had higher pre-therapy levels of T. cruzi-specific IFN-γ- producing T cells compared to those with unaltered humoral responses post-treatment.

Conclusions/Significance

Monitoring of appropriate immunological responses can provide earlier and robust measures of treatment success in T. cruzi infection.

Symptoms and Immune Markers in <i>Plasmodium</i>/Dengue Virus Co-infection Compared with Mono-infection with Either in Peru

PLoS Neglected Tropical Diseases News - 29 April 2016 - 9:00pm

by Eric S. Halsey, G. Christian Baldeviano, Kimberly A. Edgel, Stalin Vilcarromero, Moises Sihuincha, Andres G. Lescano

Background

Malaria and dengue are two of the most common vector-borne diseases in the world, but co-infection is rarely described, and immunologic comparisons of co-infection with mono-infection are lacking.

Methodology and Principal Findings

We collected symptom histories and blood specimens from subjects in a febrile illness surveillance study conducted in Iquitos and Puerto Maldonado, Peru, between 2002–2011. Nineteen symptoms and 18 immune markers at presentation were compared among those with co-infection with Plasmodium/dengue virus (DENV), Plasmodium mono-infection, and DENV mono-infection. Seventeen subjects were identified as having Plasmodium/DENV co-infection and were retrospectively matched with 51 DENV mono-infected and 44 Plasmodium mono-infected subjects. Those with Plasmodium mono-infection had higher levels of IL-4, IL-6, IL-10, IL-12, IL-13, IL-17A, IFN-γ, and MIP1-α/CCL3 compared with DENV mono-infection or co-infection; those with Plasmodium mono-infection had more cough than those with DENV mono-infection. Subjects with DENV mono-infection had higher levels of TGF-β1 and more myalgia than those with Plasmodium mono-infection. No symptom was more common and no immune marker level was higher in the co-infected group, which had similar findings to the DENV mono-infected subjects.

Conclusions/Significance

Compared with mono-infection with either pathogen, Plasmodium/DENV co-infection was not associated with worse disease and resembled DENV mono-infection in both symptom frequency and immune marker level.

Bayesian Spatiotemporal Pattern and Eco-climatological Drivers of Striped Skunk Rabies in the North Central Plains

PLoS Neglected Tropical Diseases News - 29 April 2016 - 9:00pm

by Ram K. Raghavan, Cathleen A. Hanlon, Douglas G. Goodin, Rolan Davis, Michael Moore, Susan Moore, Gary A. Anderson

Striped skunks are one of the most important terrestrial reservoirs of rabies virus in North America, and yet the prevalence of rabies among this host is only passively monitored and the disease among this host remains largely unmanaged. Oral vaccination campaigns have not efficiently targeted striped skunks, while periodic spillovers of striped skunk variant viruses to other animals, including some domestic animals, are routinely recorded. In this study we evaluated the spatial and spatio-temporal patterns of infection status among striped skunk cases submitted for rabies testing in the North Central Plains of US in a Bayesian hierarchical framework, and also evaluated potential eco-climatological drivers of such patterns. Two Bayesian hierarchical models were fitted to point-referenced striped skunk rabies cases [n = 656 (negative), and n = 310 (positive)] received at a leading rabies diagnostic facility between the years 2007–2013. The first model included only spatial and temporal terms and a second covariate model included additional covariates representing eco-climatic conditions within a 4km2 home-range area for striped skunks. The better performing covariate model indicated the presence of significant spatial and temporal trends in the dataset and identified higher amounts of land covered by low-intensity developed areas [Odds ratio (OR) = 3.41; 95% Bayesian Credible Intervals (CrI) = 2.08, 3.85], higher level of patch fragmentation (OR = 1.70; 95% CrI = 1.25, 2.89), and diurnal temperature range (OR = 0.54; 95% CrI = 0.27, 0.91) to be important drivers of striped skunk rabies incidence in the study area. Model validation statistics indicated satisfactory performance for both models; however, the covariate model fared better. The findings of this study are important in the context of rabies management among striped skunks in North America, and the relevance of physical and climatological factors as risk factors for skunk to human rabies transmission and the space-time patterns of striped skunk rabies are discussed.

A Deep Insight into the Sialome of <i>Rhodnius neglectus</i>, a Vector of Chagas Disease

PLoS Neglected Tropical Diseases News - 29 April 2016 - 9:00pm

by Paula Beatriz Santiago, Teresa C. F. Assumpção, Carla Nunes de Araújo, Izabela Marques Dourado Bastos, David Neves, Ionizete Garcia da Silva, Sébastien Charneau, Rayner Myr L. Queiroz, Tainá Raiol, João Victor de Araújo Oliveira, Marcelo Valle de Sousa, Eric Calvo, José M. C. Ribeiro, Jaime M. Santana

Background

Triatomines are hematophagous insects that act as vectors of Chagas disease. Rhodnius neglectus is one of these kissing bugs found, contributing to the transmission of this American trypanosomiasis. The saliva of hematophagous arthropods contains bioactive molecules responsible for counteracting host haemostatic, inflammatory, and immune responses.

Methods/Principal Findings

Next generation sequencing and mass spectrometry-based protein identification were performed to investigate the content of triatomine R. neglectus saliva. We deposited 4,230 coding DNA sequences (CDS) in GenBank. A set of 636 CDS of proteins of putative secretory nature was extracted from the assembled reads, 73 of them confirmed by proteomic analysis. The sialome of R. neglectus was characterized and serine protease transcripts detected. The presence of ubiquitous protein families was revealed, including lipocalins, serine protease inhibitors, and antigen-5. Metalloproteases, disintegrins, and odorant binding protein families were less abundant.

Conclusions/Significance

The data presented improve our understanding of hematophagous arthropod sialomes, and aid in understanding hematophagy and the complex interplay among vectors and their vertebrate hosts.

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