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Interruption of onchocerciasis transmission in Bioko Island: Accelerating the movement from control to elimination in Equatorial Guinea

3 May 2018 - 9:00pm

by Zaida Herrador, Belén Garcia, Policarpo Ncogo, Maria Jesus Perteguer, Jose Miguel Rubio, Eva Rivas, Marta Cimas, Guillermo Ordoñez, Silvia de Pablos, Ana Hernández-González, Rufino Nguema, Laura Moya, María Romay-Barja, Teresa Garate, Kira Barbre, Agustín Benito

Background

Onchocerciasis, also known as river blindness, is a parasitic disease. More than 99 percent of all cases occur in Africa. Bioko Island (Equatorial Guinea) is the only island endemic for onchocerciasis in the world. Since 2005, when vector Simulium yahense was eliminated, there have not been any reported cases of infection. This study aimed to demonstrate that updated WHO criteria for stopping mass drug administration (MDA) have been met.

Methodology/Principal findings

A cross-sectional study was conducted from September 2016 to January 2017. Participants were 5- to 9-year-old school children. Onchocerciasis/lymphatic Filariasis (LF, only in endemic districts) rapid diagnostic tests (RDTs) were performed. Blood spots were collected from RDT positive children and 10 percent of the RDT negatives to determine Ov16 and Wb123 IgG4 antibodies through enzyme-linked immunosorbent assay (ELISA). Skin snips were collected from RDT positives. Filarial detection was performed by PCR in positives and indeterminate sera. Black fly collection was carried out in traditional breeding sites. A total of 7,052 children, ranging from 5 to 9 years of age, were included in the study. Four children (0.06%) were Ov16 IgG4 RDT positives, but negative by ELISA Ov16, while 6 RDT negative children tested positive by ELISA. A total of 1,230 children from the Riaba and Baney districts were tested for LF. One child was Wb123 RDT positive (0.08%), but ELISA negative, while 3 RDT negative children were positive by Wb123 ELISA. All positive samples were negative by PCR for onchocerciasis and LF (in blood spot and skin snip). All fly collections and larval prospections in the traditional catching and prospection sites were negative.

Conclusions/Significance

WHO criteria have been met, therefore MDA in Bioko Island can be stopped. Three years of post-treatment surveillance should be implemented to identify any new occurrences of exposure or infection.

Prevalence and risk factors of Rift Valley fever in humans and animals from Kabale district in Southwestern Uganda, 2016

3 May 2018 - 9:00pm

by Luke Nyakarahuka, Annabelle de St. Maurice, Lawrence Purpura, Elizabeth Ervin, Stephen Balinandi, Alex Tumusiime, Jackson Kyondo, Sophia Mulei, Patrick Tusiime, Julius Lutwama, John Klena, Shelley Brown, Barbara Knust, Pierre E. Rollin, Stuart T. Nichol, Trevor R. Shoemaker

Background

Rift Valley fever (RVF) is a zoonotic disease caused by Rift Valley fever virus (RVFV) found in Africa and the Middle East. Outbreaks can cause extensive morbidity and mortality in humans and livestock. Following the diagnosis of two acute human RVF cases in Kabale district, Uganda, we conducted a serosurvey to estimate RVFV seroprevalence in humans and livestock and to identify associated risk factors.

Methods

Humans and animals at abattoirs and villages in Kabale district were sampled. Persons were interviewed about RVFV exposure risk factors. Human blood was tested for anti-RVFV IgM and IgG, and animal blood for anti-RVFV IgG.

Principal findings

655 human and 1051 animal blood samples were collected. Anti-RVFV IgG was detected in 78 (12%) human samples; 3 human samples (0.5%) had detectable IgM only, and 7 (1%) had both IgM and IgG. Of the 10 IgM-positive persons, 2 samples were positive for RVFV by PCR, confirming recent infection. Odds of RVFV seropositivity were greater in participants who were butchers (odds ratio [OR] 5.1; 95% confidence interval [95% CI]: 1.7–15.1) and those who reported handling raw meat (OR 3.4; 95% CI 1.2–9.8). No persons under age 20 were RVFV seropositive. The overall animal seropositivity was 13%, with 27% of cattle, 7% of goats, and 4% of sheep seropositive.In a multivariate logistic regression, cattle species (OR 9.1; 95% CI 4.1–20.5), adult age (OR 3.0; 95% CI 1.6–5.6), and female sex (OR 2.1; 95%CI 1.0–4.3) were significantly associated with animal seropositivity. Individual human seropositivity was significantly associated with animal seropositivity by subcounty after adjusting for sex, age, and occupation (p < 0.05).

Conclusions

Although no RVF cases had been detected in Uganda from 1968 to March 2016, our study suggests that RVFV has been circulating undetected in both humans and animals living in and around Kabale district. RVFV seropositivity in humans was associated with occupation, suggesting that the primary mode of RVFV transmission to humans in Kabale district could be through contact with animal blood or body fluids.

(S)WASH-D for Worms: A pilot study investigating the differential impact of school- versus community-based integrated control programs for soil-transmitted helminths

3 May 2018 - 9:00pm

by Naomi E. Clarke, Archie C. A. Clements, Salvador Amaral, Alice Richardson, James S. McCarthy, John McGown, Stuart Bryan, Darren J. Gray, Susana V. Nery

Background

Soil-transmitted helminths (STH) infect nearly 1.5 billion individuals globally, and contribute to poor physical and cognitive development in children. STH control programs typically consist of regular delivery of anthelminthic drugs, targeting school-aged children. Expanding STH control programs community-wide may improve STH control among school-aged children, and combining deworming with improvements to water, sanitation and hygiene (WASH) may further reduce transmission. The (S)WASH-D for Worms pilot study aims to compare the differential impact of integrated WASH and deworming programs when implemented at primary schools only versus when additionally implemented community-wide.

Methodology/Principal findings

A two-arm, non-randomized cluster intervention study was conducted. Six communities were identified by partner WASH agencies and enrolled in the study. All communities received a school-based WASH and deworming program, while three additionally received a community-based WASH and deworming program. STH infections were measured in school-aged children at baseline and six months after deworming. Over 90% of eligible children were recruited for the study, of whom 92.3% provided stool samples at baseline and 88.9% at follow-up. The school WASH intervention improved school sanitation, while the community WASH intervention reduced open defecation from 50.4% (95% CI 41.8–59.0) to 23.5% (95% CI 16.7–32.0). There was a trend towards reduced odds of N. americanus infection among children who received the community-wide intervention (OR 0.42, 95% CI 0.07–2.36, p = 0.32).

Conclusions

This pilot study provides proof of principle for testing the hypothesis that community-wide STH control programs have a greater impact on STH infections among children than school-based programs, and supports the rationale for conducting a full-scale cluster randomized controlled trial. High recruitment and participation rates and successful implementation of school WASH programs demonstrate study feasibility and acceptability. However, eliminating open defecation remains a challenge; ongoing work is required to develop community sanitation programs that achieve high and sustainable latrine coverage.

Trial registration

Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12615001012561

Ebolaviruses: New roles for old proteins

3 May 2018 - 9:00pm

by Diego Cantoni, Jeremy S. Rossman

In 2014, the world witnessed the largest Ebolavirus outbreak in recorded history. The subsequent humanitarian effort spurred extensive research, significantly enhancing our understanding of ebolavirus replication and pathogenicity. The main functions of each ebolavirus protein have been studied extensively since the discovery of the virus in 1976; however, the recent expansion of ebolavirus research has led to the discovery of new protein functions. These newly discovered roles are revealing new mechanisms of virus replication and pathogenicity, whilst enhancing our understanding of the broad functions of each ebolavirus viral protein (VP). Many of these new functions appear to be unrelated to the protein’s primary function during virus replication. Such new functions range from bystander T-lymphocyte death caused by VP40-secreted exosomes to new roles for VP24 in viral particle formation. This review highlights the newly discovered roles of ebolavirus proteins in order to provide a more encompassing view of ebolavirus replication and pathogenicity.

Correction: Dengue seroprevalence and force of primary infection in a representative population of urban dwelling Indonesian children

2 May 2018 - 9:00pm

by Ari Prayitno, Anne-Frieda Taurel, Joshua Nealon, Hindra Irawan Satari, Mulya Rahma Karyanti, Rini Sekartini, Soedjatmiko Soedjatmiko, Hartono Gunardi, Bernie Endyarni Medise, R. Tedjo Sasmono, James Mark Simmerman, Alain Bouckenooghe, Sri Rezeki Hadinegoro

microRNA profiles and functions in mosquitoes

2 May 2018 - 9:00pm

by Xinyu Feng, Shuisen Zhou, Jingwen Wang, Wei Hu

Mosquitoes are incriminated as vectors for many crippling diseases, including malaria, West Nile fever, Dengue fever, and other neglected tropical diseases (NTDs). microRNAs (miRNAs) can interact with multiple target genes to elicit biological functions in the mosquitoes. However, characterization and function of individual miRNAs and their potential targets have not been fully determined to date. We conducted a systematic review of published literature following PRISMA guidelines. We summarize the information about miRNAs in mosquitoes to better understand their metabolism, development, and responses to microorganisms. Depending on the study, we found that miRNAs were dysregulated in a species-, sex-, stage-, and tissue/organ-specific manner. Aberrant miRNA expressions were observed in development, metabolism, host-pathogen interactions, and insecticide resistance. Of note, many miRNAs were down-regulated upon pathogen infection. The experimental studies have expanded the identification of miRNA target from the 3′ untranslated regions (UTRs) of mRNAs of mosquitoes to the 5′ UTRs of mRNAs of the virus. In addition, we discuss current trends in mosquito miRNA research and offer suggestions for future studies.

Patients’ costs, socio-economic and health system aspects associated with malaria in pregnancy in an endemic area of Colombia

2 May 2018 - 9:00pm

by Elisa Sicuri, Azucena Bardají, Sergi Sanz, Sergi Alonso, Silke Fernandes, Kara Hanson, Myriam Arevalo-Herrera, Clara Menendez

Malaria in pregnancy threatens birth outcomes and the health of women and their newborns. This is also the case in low transmission areas, such as Colombia, where Plasmodium vivax is the dominant parasite species. Within the Colombian health system, which underwent major reforms in the ‘90s, malaria treatment is provided free of charge to patients. However, patients still incur costs, such as transportation and value of time lost due to the disease. We estimated such costs among 40 pregnant women with clinical malaria (30% Plasmodium falciparum, 70% Plasmodium vivax) in the municipality of Tierralta, Northern Colombia. In a cross-sectional study, women were interviewed after an outpatient or inpatient laboratory confirmed malaria episode. Women were asked to report all types of cost incurred before (including prevention), during and immediately after the contact with the health facility. Median total cost was over 16US$ for an outpatient visit, rising to nearly 30US$ if other treatments were sought before reaching the health facility. Median total inpatient cost was 26US$ or 54US$ depending on whether costs incurred prior to admission were excluded or included. For both outpatients and inpatients, direct costs were largely due to transportation and indirect costs constituted the largest share of total costs. Estimated costs are likely to represent only one of the constraints that women face when seeking treatment in an area characterized, at the time of the study, by armed conflict, displacement, and high vulnerability of indigenous women, the group at highest risk of malaria. Importantly, the Colombian peace process, which culminated with the cease-fire in August 2016, may have a positive impact on achieving universal access to healthcare in conflict areas. The current study can inform malaria elimination initiatives in Colombia.

Metabolite profiling for biomarkers in <i>Schistosoma haematobium</i> infection and associated bladder pathologies

30 April 2018 - 9:00pm

by Adewale S. Adebayo, Swapnil D. Mundhe, Henrietta O. Awobode, Olugbenga S. Onile, Atinuke M. Agunloye, Raphael D. Isokpehi, Yogesh S. Shouche, Bayatigeri Santhakumari, Chiaka I. Anumudu

Background

Metabolic fingerprinting analysis can offer insights into underlying reactions in a biological system; hence it is crucial to the understanding of disease pathogenesis and could provide useful tools for discovering biomarkers. We sought to examine the urine and plasma metabolome in individuals affected by urogenital schistosomiasis and its associated-bladder pathologies.

Methodology

Blood and midstream urine were obtained from volunteers who matched our inclusion criteria among residents from Eggua, southwestern Nigeria. Samples were screened by urinalysis, microscopy, PCR and ultrasonography, and categorised as advanced (urogenital schistosomiasis associated-bladder pathologies), infection-only (urogenital schistosomiasis alone) and controls (no infection and no pathology). Metabolites were extracted and data acquired with ultra high-performance liquid chromatography coupled with Thermo Q-Exactive orbitrap HRMS. Data was analysed with MetaboAnalyst, Workflow4Metabolomics, HMDB, LipidMaps and other bioinformatics tools, with univariate and multivariate statistics for metabolite selection.

Principal findings

There were low levels of host sex steroids, and high levels of several benzenoids, catechols and lipids (including ganglioside, phosphatidylcholine and phosphatidylethanolamine), in infection-only and advanced cases (FDR<0.05, VIP>2, delta>2.0). Metabolites involved in biochemical pathways related to chorismate production were abundant in controls, while those related to choline and sphingolipid metabolism were upregulated in advanced cases (FDR<0.05). Some of these human host and Schistosoma haematobium molecules, including catechol estrogens, were good markers to distinguish infection-only and advanced cases.

Conclusions

Altered glycerophospholipid and sphingolipid metabolism could be key factors promoting the development of bladder pathologies and tumours during urogenital schistosomiasis.

Microdeletion on chromosome 8p23.1 in a familial form of severe Buruli ulcer

30 April 2018 - 9:00pm

by Quentin B. Vincent, Aziz Belkadi, Cindy Fayard, Estelle Marion, Ambroise Adeye, Marie-Françoise Ardant, Christian R. Johnson, Didier Agossadou, Lazaro Lorenzo, Julien Guergnon, Christine Bole-Feysot, Jeremy Manry, Patrick Nitschké, Ioannis Theodorou, Jean-Laurent Casanova, Laurent Marsollier, Annick Chauty, Laurent Abel, Alexandre Alcaïs, Franco-Beninese Buruli Research Group

Buruli ulcer (BU), the third most frequent mycobacteriosis worldwide, is a neglected tropical disease caused by Mycobacterium ulcerans. We report the clinical description and extensive genetic analysis of a consanguineous family from Benin comprising two cases of unusually severe non-ulcerative BU. The index case was the most severe of over 2,000 BU cases treated at the Centre de Dépistage et de Traitement de la Lèpre et de l’Ulcère de Buruli, Pobe, Benin, since its opening in 2003. The infection spread to all limbs with PCR-confirmed skin, bone and joint infections. Genome-wide linkage analysis of seven family members was performed and whole-exome sequencing of both patients was obtained. A 37 kilobases homozygous deletion confirmed by targeted resequencing and located within a linkage region on chromosome 8 was identified in both patients but was absent from unaffected siblings. We further assessed the presence of this deletion on genotyping data from 803 independent local individuals (402 BU cases and 401 BU-free controls). Two BU cases were predicted to be homozygous carriers while none was identified in the control group. The deleted region is located close to a cluster of beta-defensin coding genes and contains a long non-coding (linc) RNA gene previously shown to display highest expression values in the skin. This first report of a microdeletion co-segregating with severe BU in a large family supports the view of a key role of human genetics in the natural history of the disease.

Characterization of a novel organic solute transporter homologue from <i>Clonorchis sinensis</i>

27 April 2018 - 9:00pm

by Yanyan Lu, Won Gi Yoo, Fuhong Dai, Ji-Yun Lee, Jhang Ho Pak, Woon-Mok Sohn, Sung-Jong Hong

Clonorchis sinensis is a liver fluke that can dwell in the bile ducts of mammals. Bile acid transporters function to maintain the homeostasis of bile acids in C. sinensis, as they induce physiological changes or have harmful effects on C. sinensis survival. The organic solute transporter (OST) transports mainly bile acid and belongs to the SLC51 subfamily of solute carrier transporters. OST plays a critical role in the recirculation of bile acids in higher animals. In this study, we cloned full-length cDNA of the 480- amino acid OST from C. sinensis (CsOST). Genomic analysis revealed 11 exons and nine introns. The CsOST protein had a ‘Solute_trans_a’ domain with 67% homology to Schistosoma japonicum OST. For further analysis, the CsOST protein sequence was split into the ordered domain (CsOST-N) at the N-terminus and disordered domain (CsOST-C) at the C-terminus. The tertiary structure of each domain was built using a threading-based method and determined by manual comparison. In a phylogenetic tree, the CsOST-N domain belonged to the OSTα and CsOST-C to the OSTβ clade. These two domains were more highly conserved with the OST α- and β-subunits at the structure level than at sequence level. These findings suggested that CsOST comprised the OSTα- and β-subunits. CsOST was localized in the oral and ventral suckers and in the mesenchymal tissues abundant around the intestine, vitelline glands, uterus, and testes. This study provides fundamental data for the further understanding of homologues in other flukes.

Efficacy and safety of co-administered ivermectin plus albendazole for treating soil-transmitted helminths: A systematic review meta-analysis and individual patient data analysis

27 April 2018 - 9:00pm

by Marta S. Palmeirim, Eveline Hürlimann, Stefanie Knopp, Benjamin Speich, Vicente Belizario Jr., Serene A. Joseph, Michel Vaillant, Piero Olliaro, Jennifer Keiser

Background

The soil-transmitted helminths (STH), Ascaris lumbricoides, Trichuris trichiura and hookworms infect 1.5 billion people worldwide and cause an estimated burden of 3.3 million disability-adjusted life years (DALYs). Current control strategies focus on morbidity reduction through preventive chemotherapy (PC) but the most commonly used recommended drugs (albendazole and mebendazole) are particularly inefficacious against T. trichiura. This, together with the threat of emerging drug resistance, calls for new control strategies, including co-administration with other anthelminthics. Ivermectin plus albendazole is widely used against lymphatic filariasis, but its efficacy and safety against STH infections has not yet been fully understood.

Methods and findings

We conducted a systematic literature review and meta-analysis on the efficacy and safety of ivermectin-albendazole co-administration in five different databases (i.e. PubMed, ISI Web of Science, ScienceDirect, CENTRAL and clinicaltrials.gov) from 1960 to January 2018. Four studies reporting efficacy of ivermectin-albendazole against STH infections and five studies on its safety met the selection criteria and were included for quantitative analysis. Ivermectin-albendazole was significantly associated with lower risk (RR = 0.44, 95% confidence interval (CI) = 0.31–0.62) for T. trichiura infection after treatment compared to albendazole alone. The co-administration revealed no or only marginal benefit on cure and egg reduction rates over albendazole alone for A. lumbricoides and hookworm infections. Adverse events (AEs) occurring after ivermectin-albendazole co-administration were mostly mild and transient. Overall, the number of individuals reporting any AE was not different (RR = 1.09, 95% CI = 0.87–1.36) in co-treated and albendazole-treated patients. However, although not statistically significant, sub-group analysis showed a tendency for slightly more AEs in patients with filariasis treated with ivermectin-albendazole compared to those treated with albendazole alone (RR = 1.29, 95% CI = 0.81–2.05).

Conclusions

Our findings suggest a good tolerability and higher efficacy of ivermectin-albendazole against T. trichiura compared to the current standard single-dose albendazole treatment, which supports the use of this co-administration in PC programs. Large-scale definitive randomized controlled trials are required to confirm our results.

Impact of lower challenge doses of enterotoxigenic <i>Escherichia coli</i> on clinical outcome, intestinal colonization and immune responses in adult volunteers

27 April 2018 - 9:00pm

by Subhra Chakraborty, Clayton Harro, Barbara DeNearing, Jessica Brubaker, Sean Connor, Nicole Maier, Len Dally, Jorge Flores, A. Louis Bourgeois, Richard Walker, David A. Sack

A reliable and effective human challenge model is needed to help down-select the most promising ETEC vaccines currently under development. Such a model would need to reliably induce diarrhea in a high proportion of volunteers using the lowest possible inoculum to maximize safety and sensitivity. Previously we validated a challenge model that utilized a dose of 2x107 CFU of ETEC strain H10407 (LT+, ST+, CFA/I+ and O78+) to induce attack rates for moderate to severe diarrhea (MSD) of ~60–70%. Here we detail efforts to further refine the model in an attempt to determine if a lower challenge dose of H10407 can be used. Thirty subjects were randomized 1:1 to receive an oral administration of H10407 at doses of 106 or 105 CFU in bicarbonate buffer. After challenge, subjects were monitored for signs and symptoms of enteric illness and stool samples were collected to detect shedding of the challenge strain. Systemic and mucosal immune responses were measured using serum, antibody in lymphocyte supernatant and fecal samples. The attack rate was 13.3% (2/15) and 26.7% (4/15) for MSD in the 105 and 106 groups, respectively. Four MSD cases met criteria for early antibiotic treatment. All subjects but one shed the challenge strain in fecal samples. The frequency and magnitude of anti-LT toxin, CFA/I and LPS O78 immune responses were antigen, dose, severity of diarrhea and shedding levels dependent. Notably, although of lower magnitude, there were considerable immune responses in the subjects with no diarrhea. This may indicate that immune responses to asymptomatic infections of ETEC in children in the endemic countries may contribute to protection. Based on this and our prior studies, we conclude that a dose of 2x107 H10407 remains the lowest practical dose for use in future volunteer studies evaluating candidate vaccines and other preventive or therapeutic ETEC interventions. Trial registration: ClinicalTrials.gov NCT00844493.

Identification and characterization of the <i>Fasciola hepatica</i> sodium- and chloride-dependent taurine transporter

27 April 2018 - 9:00pm

by Bulut Hamali, Sandra Pichler, Elisabeth Wischnitzki, Klaus Schicker, Melanie Burger, Marion Holy, Kathrin Jaentsch, Martina Molin, Eva Maria Sehr, Oliver Kudlacek, Michael Freissmuth

The parasitic liver fluke Fasciola hepatica infests mainly ruminants, but it can also cause fasciolosis in people, who ingest the metacercariae encysted on plants. The drug of choice to treat fasciolosis is triclabendazole (TBZ), which has been on the market for several decades. This is also true for the other available drugs. Accordingly, drug-resistant flukes have been emerging at an increasing rate making it desirable to identify alternative drug targets. Here, we focused on the fact that adult F. hepatica persists in the hostile environment of the bile ducts of infected organisms. A common way to render bile acids less toxic is to conjugate them to taurine (2-aminoethanesulfonic acid). We cloned a transporter from the solute carrier-6 (SLC6) family, which was most closely related to the GABA-transporter-2 of other organisms. When heterologously expressed, this F. hepatica transporter supported the high-affinity cellular uptake of taurine (KM = 12.0 ± 0.5 μM) but not of GABA. Substrate uptake was dependent on Na+- and Cl- (calculated stoichiometry 2:1). Consistent with the low chloride concentration in mammalian bile, the F. hepatica transporter had a higher apparent affinity for Cl- (EC50 = 14±3 mM) than the human taurine transporter (EC50 = 55±7 mM). We incubated flukes with unconjugated bile acids in the presence and absence of taurine: taurine promoted survival of flukes; the taurine transporter inhibitor guanidinoethansulfonic acid abolished this protective effect of taurine. Based on these observations, we conclude that the taurine transporter is critical for the survival of liver flukes in the bile. Thus, the taurine transporter represents a candidate drug target.

Addressing the most neglected diseases through an open research model: The discovery of fenarimols as novel drug candidates for eumycetoma

26 April 2018 - 9:00pm

by Wilson Lim, Youri Melse, Mickey Konings, Hung Phat Duong, Kimberly Eadie, Benoît Laleu, Ben Perry, Matthew H. Todd, Jean-Robert Ioset, Wendy W. J. van de Sande

Eumycetoma is a chronic infectious disease characterized by a large subcutaneous mass, often caused by the fungus Madurella mycetomatis. A combination of surgery and prolonged medication is needed to treat this infection with a success rate of only 30%. There is, therefore, an urgent need to find more effective drugs for the treatment of this disease. In this study, we screened 800 diverse drug-like molecules and identified 215 molecules that were active in vitro. Minimal inhibitory concentrations were determined for the 13 most active compounds. One of the most potent compounds, a fenarimol analogue for which a large analogue library is available, led to the screening of an additional 35 compounds for their in vitro activity against M. mycetomatis hyphae, rendering four further hit compounds. To assess the in vivo potency of these hit compounds, a Galleria mellonella larvae model infected with M. mycetomatis was used. Several of the compounds identified in vitro demonstrated promising efficacy in vivo in terms of prolonged larval survival and/or reduced fungal burden. The results presented in this paper are the starting point of an Open Source Mycetoma (MycetOS) approach in which members of the global scientific community are invited to participate and contribute as equal partners. We hope that this initiative, coupled with the promising new hits we have reported, will lead to progress in drug discovery for this most neglected of neglected tropical diseases.

Viewpoint on the review by Savioli and colleagues on the 2017 WHO guideline on soil-transmitted helminth infections in at-risk population groups

26 April 2018 - 9:00pm

by Antonio Montresor, Juan Pablo Peña-Rosas, Pura Rayco-Solon, Francesco Branca, Susan L. Norris, Gautam Biswas

Hepatitis B and hepatitis D virus infections in the Central African Republic, twenty-five years after a fulminant hepatitis outbreak, indicate continuing spread in asymptomatic young adults

26 April 2018 - 9:00pm

by Narcisse Patrice Komas, Sumantra Ghosh, Mariama Abdou-Chekaraou, Pierre Pradat, Nasser Al Hawajri, Alexandre Manirakiza, Gina Laure Laghoe, Claudine Bekondi, Ségolène Brichler, Jean-Omer Ouavéné, Abdoulaye Sépou, Brice Martial Yambiyo, Jean Chrysostome Gody, Valentin Fikouma, Athénais Gerber, Natali Abeywickrama Samarakoon, Dulce Alfaiate, Caroline Scholtès, Nora Martel, Frédéric Le Gal, Hugo Lo Pinto, Ikram Amri, Olivier Hantz, David Durantel, Jean-Louis Lesbordes, Emmanuel Gordien, Philippe Merle, Tudor Drugan, Christian Trépo, Fabien Zoulim, Jean-Claude Cortay, Alan Campbell Kay, Paul Dény

Hepatitis delta virus (HDV) increases morbidity in Hepatitis B virus (HBV)-infected patients. In the mid-eighties, an outbreak of HDV fulminant hepatitis (FH) in the Central African Republic (CAR) killed 88% of patients hospitalized in Bangui. We evaluated infections with HBV and HDV among students and pregnant women, 25 years after the fulminant hepatitis (FH) outbreak to determine (i) the prevalence of HBV and HDV infection in this population, (ii) the clinical risk factors for HBV and/or HDV infections, and (iii) to characterize and compare the strains from the FH outbreak in the 1980s to the 2010 HBV–HDV strains. We performed a cross sectional study with historical comparison on FH-stored samples (n = 179) from 159 patients and dried blood-spots from volunteer students and pregnant women groups (n = 2172). We analyzed risk factors potentially associated with HBV and HDV. Previous HBV infection (presence of anti-HBc) occurred in 345/1290 students (26.7%) and 186/870 pregnant women (21.4%)(p = 0.005), including 110 students (8.8%) and 71 pregnant women (8.2%), who were also HBsAg-positive (p = 0.824). HDV infection occurred more frequently in pregnant women (n = 13; 18.8%) than students (n = 6; 5.4%) (p = 0.010). Infection in childhood was probably the main HBV risk factor. The risk factors for HDV infection were age (p = 0.040), transfusion (p = 0.039), and a tendency for tattooing (p = 0.055) and absence of condom use (p = 0.049). HBV-E and HDV-1 were highly prevalent during both the FH outbreak and the 2010 screening project. For historical samples, due to storage conditions and despite several attempts, we could only obtain partial HDV amplification representing 25% of the full-length genome. The HDV-1 mid-eighties FH-strains did not form a specific clade and were affiliated to two different HDV-1 African subgenotypes, one of which also includes the 2010 HDV-1 strains. In the Central African Republic, these findings indicate a high prevalence of previous and current HBV-E and HDV-1 infections both in the mid-eighties fulminant hepatitis outbreak and among asymptomatic young adults in 2010, and reinforce the need for universal HBV vaccination and the prevention of HDV transmission among HBsAg-positive patients through blood or sexual routes.

Enhanced surveillance for Rift Valley Fever in livestock during El Niño rains and threat of RVF outbreak, Kenya, 2015-2016

26 April 2018 - 9:00pm

by Harry Oyas, Lindsey Holmstrom, Naomi P. Kemunto, Matthew Muturi, Athman Mwatondo, Eric Osoro, Austine Bitek, Bernard Bett, Jane W. Githinji, Samuel M. Thumbi, Marc-Alain Widdowson, Peninah M. Munyua, M. Kariuki Njenga

Background

In mid-2015, the United States’ Pandemic Prediction and Forecasting Science and Technical Working Group of the National Science and Technology Council, Food and Agriculture Organization Emergency Prevention Systems, and Kenya Meteorological Department issued an alert predicting a high possibility of El-Niño rainfall and Rift Valley Fever (RVF) epidemic in Eastern Africa.

Methodology/Principal findings

In response to the alert, the Kenya Directorate of Veterinary Services (KDVS) carried out an enhanced syndromic surveillance system between November 2015 and February 2016, targeting 22 RVF high-risk counties in the country as identified previously through risk mapping. The surveillance collected data on RVF-associated syndromes in cattle, sheep, goats, and camels from >1100 farmers through 66 surveillance officers. During the 14-week surveillance period, the KDVS received 10,958 reports from participating farmers and surveillance officers, of which 362 (3.3%) had at least one syndrome. The reported syndromes included 196 (54.1%) deaths in young livestock, 133 (36.7%) abortions, and 33 (9.1%) hemorrhagic diseases, with most occurring in November and December, the period of heaviest rainfall. Of the 69 herds that met the suspect RVF herd definition (abortion in flooded area), 24 (34.8%) were defined as probable (abortions, mortalities in the young ones, and/or hemorrhagic signs) but none were confirmed.

Conclusion/Significance

This surveillance activity served as an early warning system that could detect RVF disease in animals before spillover to humans. It was also an excellent pilot for designing and implementing syndromic surveillance in animals in the country, which is now being rolled out using a mobile phone-based data reporting technology as part of the global health security system.

Review of the 2017 WHO Guideline: Preventive chemotherapy to control soil-transmitted helminth infections in at-risk population groups. An opportunity lost in translation

26 April 2018 - 9:00pm

by Lorenzo Savioli, Marco Albonico, Denis Daumerie, Nathan C. Lo, J. Russell Stothard, Samuel Asaolu, Louis Albert Tchuem Tchuenté, Roy M. Anderson

Aminopeptidase secreted by <i>Chromobacterium sp</i>. Panama inhibits dengue virus infection by degrading the E protein

25 April 2018 - 9:00pm

by Raúl G. Saraiva, Jingru Fang, Seokyoung Kang, Yesseinia I. Angleró-Rodríguez, Yuemei Dong, George Dimopoulos

Dengue virus (DENV) is the most prevalent and burdensome arbovirus transmitted by Aedes mosquitoes, against which there is only a limited licensed vaccine and no approved drug treatment. A Chromobacterium species, C. sp. Panama, isolated from the midgut of A. aegypti is able to inhibit DENV replication within the mosquito and in vitro. Here we show that C. sp. Panama mediates its anti-DENV activity through secreted factors that are proteinous in nature. The inhibitory effect occurs prior to virus attachment to cells, and is attributed to a factor that destabilizes the virion by promoting the degradation of the viral envelope protein. Bioassay-guided fractionation, coupled with mass spectrometry, allowed for the identification of a C. sp. Panama-secreted neutral protease and an aminopeptidase that are co-expressed and appear to act synergistically to degrade the viral envelope (E) protein and thus prevent viral attachment and subsequent infection of cells. This is the first study characterizing the anti-DENV activity of a common soil and mosquito-associated bacterium, thereby contributing towards understanding how such bacteria may limit disease transmission, and providing new tools for dengue prevention and therapeutics.

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