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Attenuation and efficacy of live-attenuated Rift Valley fever virus vaccine candidates in non-human primates

9 May 2018 - 9:00pm

by Darci R. Smith, Sara C. Johnston, Ashley Piper, Miriam Botto, Ginger Donnelly, Joshua Shamblin, César G. Albariño, Lisa E. Hensley, Connie Schmaljohn, Stuart T. Nichol, Brian H. Bird

Rift Valley fever virus (RVFV) is an important mosquito-borne veterinary and human pathogen that has caused large outbreaks of severe disease throughout Africa and the Arabian Peninsula. Currently, no licensed vaccine or therapeutics exists to treat this potentially deadly disease. The explosive nature of RVFV outbreaks and the severe consequences of its accidental or intentional introduction into RVFV-free areas provide the impetus for the development of novel vaccine candidates for use in both livestock and humans. Rationally designed vaccine candidates using reverse genetics have been used to develop deletion mutants of two known RVFV virulence factors, the NSs and NSm genes. These recombinant viruses were demonstrated to be protective and immunogenic in rats, mice, and sheep, without producing clinical illness in these animals. Here, we expand upon those findings and evaluate the single deletion mutant (ΔNSs rRVFV) and double deletion mutant (ΔNSs-ΔNSm rRVFV) vaccine candidates in the common marmoset (Callithrix jacchus), a non-human primate (NHP) model resembling severe human RVF disease. We demonstrate that both the ΔNSs and ΔNSs-ΔNSm rRVFV vaccine candidates were found to be safe and immunogenic in the current study. The vaccinated animals received a single dose of vaccine that led to the development of a robust antibody response. No vaccine-induced adverse reactions, signs of clinical illness or infectious virus were detected in the vaccinated marmosets. All vaccinated animals that were subsequently challenged with RVFV were protected against viremia and liver disease. In summary, our results provide the basis for further development of the ΔNSs and ΔNSs-ΔNSm rRVFV as safe and effective human RVFV vaccines for this significant public health threat.

Prevalence and risk factors for <i>Taenia solium</i> cysticercosis in school-aged children: A school based study in western Sichuan, People’s Republic of China

8 May 2018 - 9:00pm

by John J. Openshaw, Alexis Medina, Stephen A. Felt, Tiaoying Li, Zhou Huan, Scott Rozelle, Stephen P. Luby

Background

Taenia solium cysticercosis affects millions of impoverished people worldwide and can cause neurocysticercosis, an infection of the central nervous system which is potentially fatal. Children may represent an especially vulnerable population to neurocysticercosis, due to the risk of cognitive impairment during formative school years. While previous epidemiologic studies have suggested high prevalence in rural China, the prevalence in children as well as risk factors and impact of disease in low-resource areas remain poorly characterized.

Methodology/Principal findings

Utilizing school based sampling, we conducted a cross-sectional study, administering a questionnaire and collecting blood for T. solium cysticercosis antibodies in 2867 fifth and sixth grade students across 27 schools in west Sichuan. We used mixed-effects logistic regression models controlling for school-level clustering to study associations between risk factors and to characterize factors influencing the administration of deworming medication. Overall prevalence of cysticercosis antibodies was 6%, but prevalence was significantly higher in three schools which all had prevalences of 15% or higher. Students from households owning pigs (adjusted odds ratio [OR] 1.81, 95% CI 1.08–3.03), from households reporting feeding their pigs human feces (adjusted OR 1.49, 95% CI 1.03–2.16), and self-reporting worms in their feces (adjusted OR 1.85, 95% CI 1.18–2.91) were more likely to have cysticercosis IgG antibodies. Students attending high prevalence schools were more likely to come from households allowing pigs to freely forage for food (OR 2.26, 95% CI 1.72–2.98) and lacking a toilet (OR 1.84, 95% CI 1.38–2.46). Children who were boarding at school were less likely to have received treatment for gastrointestinal worms (adjusted OR 0.58, 95% CI 0.42–0.80).

Conclusions/Significance

Our study indicates high prevalences of cysticercosis antibodies in young school aged children in rural China. While further studies to assess potential for school-based transmission are needed, school-based disease control may be an important intervention to ensure the health of vulnerable pediatric populations in T. solium endemic areas.

Correction: Participation of women and children in hunting activities in Sierra Leone and implications for control of zoonotic infections

7 May 2018 - 9:00pm

by Jesse Bonwitt, Martin Kandeh, Michael Dawson, Rashid Ansumana, Foday Sahr, Ann H. Kelly, Hannah Brown

Knowledge, attitudes and practices (KAP) regarding leptospirosis among residents of riverside settlements of Santa Fe, Argentina

7 May 2018 - 9:00pm

by Tamara Ricardo, Laura C. Bergero, Esteban P. Bulgarella, M. Andrea Previtali

Background

Leptospirosis is a global and re-emerging zoonotic disease caused by Leptospira spirochetes that are shed into the environment by infected animals. Humans can get infected via contact with animal hosts or contaminated environment. In Argentina, the highest annual incidences were reported in the province of Santa Fe, where epidemic outbreaks occurred during flooding events. This study examined the knowledge, attitudes and practices (KAP) regarding leptospirosis among residents of riverside slum settlements from Santa Fe after a major flood.

Methods and findings

A cross-sectional questionnaire was administered to 113 residents of 3 riverside settlements from Santa Fe. The influence of knowledge and attitudes regarding leptospirosis on the likelihood that an individual will use preventive practices were evaluated using linear mixed-effects models. The majority of respondents (83.2%) had previously heard about leptospirosis; however specific knowledge about leptospirosis was limited. The results of the modeling efforts, show that the likelihood of using preventive practices was associated with having greater knowledge score, but not with more positive attitudes. We also found that females were more likely to use safer practices than males.

Conclusions

Even though the majority of respondents had heard about leptospirosis, a high percentage of them had limited knowledge regarding the severity of the disease and its prevalence in the region. Our results suggest that public health interventions in these riverside communities should focus on educating the public on the multiple dimensions of leptospirosis in order to attain greater adherence to preventive practices instead of intending to change the perceptions or attitudes towards the disease, which did not have a significant influence. The key challenge lies in identifying effective strategies to reach the high risk group for leptospirosis here that is male fishermen, who spend most of the time in precarious campsites on the river islands.

Highly targeted cholera vaccination campaigns in urban setting are feasible: The experience in Kalemie, Democratic Republic of Congo

7 May 2018 - 9:00pm

by Louis Albert Massing, Soumah Aboubakar, Alexandre Blake, Anne-Laure Page, Sandra Cohuet, Adalbert Ngandwe, Eric Mukomena Sompwe, Romain Ramazani, Marcela Allheimen, Philippe Levaillant, Pauline Lechevalier, Marie Kashimi, Axelle de la Motte, Arielle Calmejane, Malika Bouhenia, Ernest Dabire, Didier Bompangue, Benoit Kebela, Klaudia Porten, Francisco Luquero

Introduction

Oral cholera vaccines are primarily recommended by the World Health Organization for cholera control in endemic countries. However, the number of cholera vaccines currently produced is very limited and examples of OCV use in endemic countries, and especially in urban settings, are scarce. A vaccination campaign was organized by Médecins Sans Frontières and the Ministry of Health in a highly endemic area in the Democratic Republic of Congo. This study aims to describe the vaccine coverage achieved with this highly targeted vaccination campaign and the acceptability among the vaccinated communities.

Methods and findings

We performed a cross-sectional survey using random spatial sampling. The study population included individuals one year old and above, eligible for vaccination, and residing in the areas targeted for vaccination in the city of Kalemie. Data sources were household interviews with verification by vaccination card. In total 2,488 people were included in the survey. Overall, 81.9% (95%CI: 77.9–85.3) of the target population received at least one dose of vaccine. The vaccine coverage with two doses was 67.2% (95%CI: 61.9–72.0) among the target population. The vaccine coverage was higher during the first round (74.0, 95%CI: 69.3–78.3) than during the second round of vaccination (69.1%, 95%CI: 63.9–74.0). Vaccination coverage was lower in male adults. The main reason for non-vaccination was to be absent during the campaign. No severe adverse events were notified during the interviews.

Conclusions

Cholera vaccination campaigns using highly targeted strategies are feasible in urban settings. High vaccination coverage can be obtained using door to door vaccination. However, alternative strategies should be considered to reach non-vaccinated populations like male adults and also in order to improve the efficiency of the interventions.

The protein family TcTASV-C is a novel <i>Trypanosoma cruzi</i> virulence factor secreted in extracellular vesicles by trypomastigotes and highly expressed in bloodstream forms

4 May 2018 - 9:00pm

by Lucas D. Caeiro, Catalina D. Alba-Soto, Mariana Rizzi, María Elisa Solana, Giselle Rodriguez, Agustina M. Chidichimo, Matías E. Rodriguez, Daniel O. Sánchez, Gabriela V. Levy, Valeria Tekiel

TcTASV-C is a protein family of about 15 members that is expressed only in the trypomastigote stage of Trypanosoma cruzi. We have previously shown that TcTASV-C is located at the parasite surface and secreted to the medium. Here we report that the expression of different TcTASV-C genes occurs simultaneously at the trypomastigote stage and while some secreted and parasite-associated products are found in both fractions, others are different. Secreted TcTASV-C are mainly shedded through trypomastigote extracellular vesicles, of which they are an abundant constituent, despite its scarce expression on culture-derived trypomastigotes. In contrast, TcTASV-C is highly expressed in bloodstream trypomastigotes; its upregulation in bloodstream parasites was observed in different T. cruzi strains and was specific for TcTASV-C, suggesting that some host-molecules trigger TcTASV-C expression. TcTASV-C is also strongly secreted by bloodstream parasites. A DNA prime—protein boost immunization scheme with TcTASV-C was only partially effective to control the infection in mice challenged with a highly virulent T. cruzi strain. Vaccination triggered a strong humoral response that delayed the appearance of bloodstream trypomastigotes at the early phase of the infection. Linear epitopes recognized by vaccinated mice were mapped within the TcTASV-C family motif, suggesting that blockade of secreted TcTASV-C impacts on the settlement of infection. Furthermore, although experimental and naturally T. cruzi-infected hosts did not react with antigens from extracellular vesicles, vaccinated and challenged mice recognized not only TcTASV-C but also other vesicle-antigens. We hypothesize that TcTASV-C is involved in the establishment of the initial T. cruzi infection in the mammalian host. Altogether, these results point towards TcTASV-C as a novel secreted virulence factor of T. cruzi trypomastigotes.

Antigen B from <i>Echinococcus granulosus</i> enters mammalian cells by endocytic pathways

4 May 2018 - 9:00pm

by Edileuza Danieli da Silva, Martin Cancela, Karina Mariante Monteiro, Henrique Bunselmeyer Ferreira, Arnaldo Zaha

Background

Cystic hydatid disease is a zoonosis caused by the larval stage (hydatid) of Echinococcus granulosus (Cestoda, Taeniidae). The hydatid develops in the viscera of intermediate host as a unilocular structure filled by the hydatid fluid, which contains parasitic excretory/secretory products. The lipoprotein Antigen B (AgB) is the major component of E. granulosus metacestode hydatid fluid. Functionally, AgB has been implicated in immunomodulation and lipid transport. However, the mechanisms underlying AgB functions are not completely known.

Methodology/Principal findings

In this study, we investigated AgB interactions with different mammalian cell types and the pathways involved in its internalization. AgB uptake was observed in four different cell lines, NIH-3T3, A549, J774 and RH. Inhibition of caveolae/raft-mediated endocytosis causes about 50 and 69% decrease in AgB internalization by RH and A549 cells, respectively. Interestingly, AgB colocalized with the raft endocytic marker, but also showed a partial colocalization with the clathrin endocytic marker. Finally, AgB colocalized with an endolysosomal tracker, providing evidence for a possible AgB destination after endocytosis.

Conclusions/Significance

The results indicate that caveolae/raft-mediated endocytosis is the main route to AgB internalization, and that a clathrin-mediated entry may also occur at a lower frequency. A possible fate for AgB after endocytosis seems to be the endolysosomal system. Cellular internalization and further access to subcellular compartments could be a requirement for AgB functions as a lipid carrier and/or immunomodulatory molecule, contributing to create a more permissive microenvironment to metacestode development and survival.

Rift valley fever viral load correlates with the human inflammatory response and coagulation pathway abnormalities in humans with hemorrhagic manifestations

4 May 2018 - 9:00pm

by Annabelle de St. Maurice, Jessica Harmon, Luke Nyakarahuka, Stephen Balinandi, Alex Tumusiime, Jackson Kyondo, Sophia Mulei, Annemarion Namutebi, Barbara Knust, Trevor Shoemaker, Stuart T. Nichol, Anita K. McElroy, Christina F. Spiropoulou

Rift Valley fever virus is an arbovirus that affects both livestock and humans throughout Africa and in the Middle East. Despite its endemicity throughout Africa, it is a rare event to identify an infected individual during the acute phase of the disease and an even rarer event to collect serial blood samples from the affected patient. Severely affected patients can present with hemorrhagic manifestations of disease. In this study we identified three Ugandan men with RVFV disease that was accompanied by hemorrhagic manifestations. Serial blood samples from these men were analyzed for a series of biomarkers specific for various aspects of human pathophysiology including inflammation, endothelial function and coagulopathy. There were significant differences between biomarker levels in controls and cases both early during the illness and after clearance of viremia. Positive correlation of viral load with markers of inflammation (IP-10, CRP, Eotaxin, MCP-2 and Granzyme B), markers of fibrinolysis (tPA and D-dimer), and markers of endothelial function (sICAM-1) were all noted. However, and perhaps most interesting given the fact that these individuals exhibited hemorrhagic manifestations of disease, was the finding of a negative correlation between viral load and P-selectin, ADAMTS13, and fibrinogen all of which are associated with coagulation pathways occurring on the endothelial surface.

A research agenda to reinforce rabies control: A qualitative and quantitative prioritization

4 May 2018 - 9:00pm

by Anne M. G. Neevel, Tessa Hemrika, Eric Claassen, Linda H. M. van de Burgwal

Background

Despite the existence of safe and effective vaccines, rabies disease still causes an estimated 59,000 human deaths a year in the endemic areas in Asia and Africa. These numbers reflect severe drawbacks regarding the implementation of PrEP and PEP in endemic settings, such as lack of political will and low priority given to rabies. Since these contextual factors have proven to be persistent, there is an urgency to improve current strategies or develop novel approaches in order to control rabies disease in the future.

Methods/Findings

This study aimed to identify and systematically prioritize the research needs, through interviews and questionnaires with key-opinion-leaders (KOLs). A total of 46 research needs were identified and prioritized. The top research needs are considered very high priority based on both importance for rabies control and need for improvement. KOLs agree that animal rabies control remains most important for rabies control, while research on human host, agent (rabies virus) and the environment should be prioritized in terms of need for improvement. A wide variety in perceptions is observed between and within the disciplines of virology, public health and veterinary health and between KOLs with more versus those with less experience in the field.

Conclusion/Significance

The results of this study give well-defined, prioritized issues that stress the drawbacks that are experienced by KOLs in daily practice. The most important research domains are: 1) cheap and scalable production system for RIG 2) efficacy of dog mass vaccination programs and 3) cheap human vaccines. Addressing these research needs should exist next to and may reinforce current awareness and mass vaccination campaigns. The differences in perspectives between actors revealed in this study are informative for effective execution of the One Health research agenda.

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.

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