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Aberrant plasma MMP and TIMP dynamics in Schistosoma - Immune reconstitution inflammatory syndrome (IRIS)

8 August 2018 - 9:00pm

by Odin Goovaerts, Pauline N. M. Mwinzi, Erick M. O. Muok, Ann Ceulemans, Robert Colebunders, Luc Kestens

Background

Among the different faces of immune reconstitution inflammatory syndrome (IRIS) developing in HIV-patients, no clinical definition has been reported for Schistosomiasis-IRIS (Schisto-IRIS). Although Schisto-IRIS remains largely uninvestigated, matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) have previously been associated with S. mansoni infection and tuberculosis-IRIS. Here, we aimed to investigate the relevance of these markers in Schisto-IRIS.

Methodology

Patients were diagnosed with IRIS related to S. mansoni within a cohort of patients with Schistosomiasis-HIV co-infection, using a clinical working definition of Schisto-IRIS. We compared 9 patients who developed Schisto-IRIS to 9 Schisto+HIV+ controls who did not, and 9 Schisto-HIV+ controls. Plasma levels of MMP-1, MMP-7, MMP-10, TIMP-1, TIMP-2, sCD14, intestinal fatty-acid binding protein, C-reactive protein, and 8 anti-nuclear antibodies (ANA) were analyzed prior to and during 3 months of ART.

Principal findings

Although no differences were observed for MMP-1 and -7, MMP-10 levels decreased significantly in Schisto+HIV+ controls during 3 months of ART (p = 0.005) while persisting in Schisto-IRIS patients at significantly higher levels compared to Schisto-HIV+ controls (p≤0.030). In contrast TIMP-1 levels only decreased significantly in Schisto-IRIS patients (p = 0.012), while TIMP-2 levels were lower compared to Schisto+HIV+ controls at 2 weeks (p = 0.007), 1 month (p = 0.005) and 3 months (p = 0.031) of ART. Five out of 8 ANAs studied decreased significantly in Schisto-IRIS patients after 1 month of ART(p≤0.039), whereas only 1 ANA decreased for Schisto+HIV+ controls (p = 0.027).

Conclusions/Significance

In this study, we propose a working definition for the diagnosis of Schisto-IRIS in resource limited settings. We report persistent plasma levels of MMP-10, along with a more pronounced decrease in TIMP-1 and ANA-levels, and low levels of TIMP-2 during 3 months of ART. Corresponding to the clinical symptoms, these data suggest that Schisto-IRIS is marked by unbalanced MMP/TIMP dynamics which favor inflammation.

Epidemiology and antimicrobial resistance of invasive non-typhoidal Salmonellosis in rural Thailand from 2006-2014

6 August 2018 - 9:00pm

by Toni Whistler, Patranuch Sapchookul, David W. McCormick, Ornuma Sangwichian, Possawat Jorakate, Sirirat Makprasert, Anchalee Jatapai, Sathapana Naorat, Uraiwan Surin, Surathinee Koosakunwat, Surachai Supcharassaeng, Barameht Piralam, Mathew Mikoleit, Henry C. Baggett, Julia Rhodes, Christopher J. Gregory

Introduction

Invasive salmonellosis is a common cause of bloodstream infection in Southeast Asia. Limited epidemiologic and antimicrobial resistance data are available from the region.

Methods

Blood cultures performed in all 20 hospitals in the northeastern province of Nakhon Phanom (NP) and eastern province of Sa Kaeo (SK), Thailand were captured in a bloodstream infection surveillance system. Cultures were performed as clinically indicated in hospitalized patients; patients with multiple positive cultures had only the first included. Bottles were incubated using the BacT/Alert system (bioMérieux, Thailand) and isolates were identified using standard microbiological techniques; all Salmonella isolates were classified to at least the serogroup level. Antimicrobial resistance was assessed using disk diffusion.

Results

Salmonella was the fifth most common pathogen identified in 147,535 cultures with 525 cases (211 in Nakhon Phanom (NP) and 314 in Sa Kaeo (SK)). The overall adjusted iNTS incidence rate in NP was 4.0 cases/100,000 person-years (95% CI 3.5–4.5) and in SK 6.4 cases/100,000 person-years (95% CI 5.7–7.1; p = 0.001). The most common serogroups were C (39.4%), D (35.0%) and B (9.9%). Serogroup D predominated in NP (103/211) with 59.2% of this serogroup being Salmonella serovar Enteritidis. Serogroup C predominated in SK (166/314) with 84.3% of this serogroup being Salmonella serovar Choleraesuis. Antibiotic resistance was 68.2% (343/503) for ampicillin, 1.2% (6/482) for ciprofloxacin (or 58.1% (280/482) if both intermediate and resistant phenotypes are considered), 17.0% (87/512) for trimethoprim-sulfamethoxazole, and 12.2% (59/484) for third-generation cephalosporins (cefotaxime or ceftazidime). Multidrug resistance was seen in 99/516 isolates (19.2%).

Conclusions

The NTS isolates causing bloodstream infections in rural Thailand are commonly resistant to ampicillin, cefotaxime, and TMP-SMX. Observed differences between NP and SK indicate that serogroup distribution and antibiotic resistance may substantially differ throughout Thailand and the region.

Improving clinical and epidemiological predictors of Buruli ulcer

6 August 2018 - 9:00pm

by Gilbert Adjimon Ayelo, Ghislain Emmanuel Sopoh, Jean-Gabin Houezo, René Fiodessihoue, Dissou Affolabi, Ange Dodji Dossou, Yves Thierry Barogui, Akpeedje Anita Carolle Wadagni, Didier Codjo Agossadou, Epco Hasker, Françoise Portaels, Bouke C. de Jong, Miriam Eddyani

Background

Buruli ulcer (BU) is a chronic necrotizing infectious skin disease caused by Mycobacterium ulcerans. The treatment with BU-specific antibiotics is initiated after clinical suspicion based on the WHO clinical and epidemiological criteria. This study aimed to estimate the predictive values of these criteria and how they could be improved.

Methodology/Principal findings

A total of 224 consecutive patients presenting with skin and soft tissue lesions that could be compatible with BU, including those recognized as unlikely BU by experienced clinicians, were recruited in two BU treatment centers in southern Benin between March 2012 and March 2015. For every participant, the WHO and four additional epidemiological and clinical diagnostic criteria were recorded. For microbiological confirmation, direct smear examination and IS2404 PCR were performed. We fitted a logistic regression model with PCR positivity for BU confirmation as outcome variable. On univariate analysis, most of the clinical and epidemiological WHO criteria were associated with a positive PCR result. However, lesions on the lower limbs and WHO category 3 lesions were rather associated with a negative PCR result (respectively OR: 0.4, 95%CI: 0.3–0.8; OR: 0.5, 95%IC: 0.3–0.9). Among the additional characteristics studied, the characteristic smell of BU was strongest associated with a positive PCR result (OR = 16.4; 95%CI = 7.5–35.6).

Conclusion/Significance

The WHO diagnostic criteria could be improved upon by differentiating between lesions on the upper and lower limbs and by including lesion size and the characteristic smell recognized by experienced clinicians.

Pharmacological characterization of crotamine effects on mice hind limb paralysis employing both <i>ex vivo</i> and <i>in vivo</i> assays: Insights into the involvement of voltage-gated ion channels in the crotamine action on skeletal muscles

6 August 2018 - 9:00pm

by Sunamita de Carvalho Lima, Lucas de Carvalho Porta, Álvaro da Costa Lima, Joana D’Arc Campeiro, Ywlliane Meurer, Nathália Bernardes Teixeira, Thiago Duarte, Eduardo Brandt Oliveira, Gisele Picolo, Rosely Oliveira Godinho, Regina Helena Silva, Mirian Akemi Furuie Hayashi

The high medical importance of Crotalus snakes is unquestionable, as this genus is the second in frequency of ophidian accidents in many countries, including Brazil. With a relative less complex composition compared to other genera venoms, as those from the Bothrops genus, the Crotalus genus venom from South America is composed basically by the neurotoxin crotoxin (a phospholipase A2), the thrombin-like gyroxin (a serinoprotease), a very potent aggregating protein convulxin, and a myotoxic polypeptide named crotamine. Interestingly not all Crotalus snakes express crotamine, which was first described in early 50s due to its ability to immobilize animal hind limbs, contributing therefore to the physical immobilization of preys and representing an important advantage for the envenoming efficacy, and consequently, for the feeding and survival of these snakes in nature. Representing about 10–25% of the dry weight of the crude venom of crotamine-positive rattlesnakes, the polypeptide crotamine is also suggested to be of importance for antivenom therapy, although the contribution of this toxin to the main symptoms of envenoming process remains far unknown until now. Herein, we concomitantly performed in vitro and in vivo assays to show for the first time the dose-dependent response of crotamine-triggered hind limbs paralysis syndrome, up to now believed to be observable only at high (sub-lethal) concentrations of crotamine. In addition, ex vivo assay performed with isolated skeletal muscles allowed us to suggest here that compounds active on voltage-sensitive sodium and/or potassium ion channels could both affect the positive inotropic effect elicited by crotamine in isolated diaphragm, besides also affecting the hind limbs paralysis syndrome imposed by crotamine in vivo. By identifying the potential molecular targets of this toxin, our data may contribute to open new roads for translational studies aiming to improve the snakebite envenoming treatment in human. Interestingly, we also demonstrate that the intraplantal or intraperitoneal (ip) injections of crotamine in mice do not promote pain. Therefore, this work may also suggest the profitable utility of non-toxic analogs of crotamine as a potential tool for targeting voltage-gated ion channels in skeletal muscles, aiming its potential use in the therapy of neuromuscular dysfunctions and envenoming therapy.

An exploratory study on rabies exposure through contact tracing in a rural area near Bengaluru, Karnataka, India

6 August 2018 - 9:00pm

by N. R. Ramesh Masthi, Pruthvi S.

Need for study

Rabies is a neglected zoonotic disease. Given the low incidence, apart from the existing reporting syst, there is a need to look for other means of case detection strategies for rabies. Contact tracing is one such method to efficiently capture information.

Objectives

To find out the rabid status of biting animal through contact tracing and to determine health seeking behavior of the bite victims.

Materials and methods

An exploratory study using contact tracing was conducted during the first quarter of 2017 in villages coming under three Public Health Centers. The households of the bite victims were visited and details of rabies exposure obtained from the bite victim/ adult responsible respondent using a standardized questionnaire.

Results

A total of 69 dog/cat bite cases were identified. 69.5% of bites were by stray dogs. 97.1% bite victims had Category III bites. Only 4.5% bite victims had taken PEP. 70.1% of animal bite cases were administered ARV. Only 7.2% bite victims had exposure to probable rabid animals. All dog bite victims were alive after 3 months of follow up.

Conclusion

Contact tracing was successful in case detection of probable rabid animal exposures and suitable for a period of one year.

Screening of the Pathogen Box for inhibitors with dual efficacy against <i>Giardia lamblia</i> and <i>Cryptosporidium parvum</i>

6 August 2018 - 9:00pm

by Kelly M. Hennessey, Ilse C. Rogiers, Han-Wei Shih, Matthew A. Hulverson, Ryan Choi, Molly C. McCloskey, Grant R. Whitman, Lynn K. Barrett, Ethan A. Merritt, Alexander R. Paredez, Kayode K. Ojo

There is need for a more efficient cell-based assay amenable to high-throughput drug screening against Giardia lamblia. Here, we report the development of a screening method utilizing G. lamblia engineered to express red-shifted firefly luciferase. Parasite growth and replication were quantified using D-luciferin as a substrate in a bioluminescent read-out platform. This assay was validated for reproducibility and reliability against the Medicines for Malaria Venture (MMV) Pathogen Box compounds. For G. lamblia, forty-three compounds showed ≥ 75% inhibition of parasite growth in the initial screen (16 μM), with fifteen showing ≥ 95% inhibition. The Pathogen Box was also screened against Nanoluciferase expressing (Nluc) C. parvum, yielding 85 compounds with ≥ 75% parasite growth inhibition at 10 μM, with six showing ≥ 95% inhibition. A representative set of seven compounds with activity against both parasites were further analyzed to determine the effective concentration that causes 50% growth inhibition (EC50) and cytotoxicity against mammalian HepG2 cells. Four of the seven compounds were previously known to be effective in treating either Giardia or Cryptosporidium. The remaining three shared no obvious chemical similarity with any previously characterized anti-parasite diarrheal drugs and offer new medicinal chemistry opportunities for therapeutic development. These results suggest that the bioluminescent assays are suitable for large-scale screening of chemical libraries against both C. parvum and G. lamblia.

<i>Schistosoma haematobium</i> effects on <i>Plasmodium falciparum</i> infection modified by soil-transmitted helminths in school-age children living in rural areas of Gabon

6 August 2018 - 9:00pm

by Jean Claude Dejon-Agobé, Jeannot Fréjus Zinsou, Yabo Josiane Honkpehedji, Ulysse Ateba-Ngoa, Jean-Ronald Edoa, Bayodé Roméo Adegbite, Ghyslain Mombo-Ngoma, Selidji Todagbe Agnandji, Michael Ramharter, Peter Gottfried Kremsner, Bertrand Lell, Martin Peter Grobusch, Ayôla Akim Adegnika

Background

Malaria burden remains high in the sub-Saharan region where helminths are prevalent and where children are often infected with both types of parasites. Although the effect of helminths on malaria infection is evident, the impact of these co-infections is not clearly elucidated yet and the scarce findings are conflicting. In this study, we investigated the effect of schistosomiasis, considering soil-transmitted helminths (STH), on prevalence and incidence of Plasmodium falciparum infection.

Methodology

This longitudinal survey was conducted in school-age children living in two rural communities in the vicinity of Lambaréné, Gabon. Thick blood smear light microscopy, urine filtration and the Kato-Katz technique were performed to detect malaria parasites, S. haematobium eggs and, STH eggs, respectively. P. falciparum carriage was assessed at inclusion, and incidence of malaria and time to the first malaria event were recorded in correlation with Schistosoma carriage status. Stratified multivariate analysis using generalized linear model was used to assess the risk of plasmodium infection considering interaction with STH, and survival analysis to assess time to malaria.

Main findings

The overall prevalence on subject enrolment was 30%, 23% and 9% for S. haematobium, P. falciparum infections and co-infection with both parasites, respectively. Our results showed that schistosomiasis in children tends to increase the risk of plasmodium infection but a combined effect with Trichuris trichiura or hookworm infection clearly increase the risk (aOR = 3.9 [95%CI: 1.7–9.2]). The incidence of malaria over time was 0.51[95%CI: 0.45–0.57] per person-year and was higher in the Schistosoma-infected group compared to the non-infected group (0.61 vs 0.43, p = 0.02), with a significant delay of time-to first-malaria event only in children aged from 6 to 10-years-old infected with Schistosoma haematobium.

Conclusions

Our results suggest that STH enhance the risk for P. falciparum infection in schistosomiasis-positive children, and when infected, that schistosomiasis enhances susceptibility to developing malaria in young children but not in older children.

Stratified sero-prevalence revealed overall high disease burden of dengue but suboptimal immunity in younger age groups in Pune, India

6 August 2018 - 9:00pm

by Akhilesh C. Mishra, Vidya A. Arankalle, Swapnil A. Gadhave, Pritam H. Mahadik, Shubham Shrivastava, Mandar Bhutkar, Varsha M. Vaidya

Background

In India, dengue disease is emerging as the most important vector borne public health problem due to rapid and unplanned urbanization, high human density and week management of the disease. Clinical cases are grossly underreported and not much information is available on prevalence and incidence of the disease.

Methodology

A cross sectional, stratified, facility based, multistage cluster sampling was conducted between May 4 and June 27, 2017 in Pune city. A total of 1,434 participants were enrolled. The serum samples were tested for detection of historical dengue IgG antibodies by ELISA using the commercial Panbio Dengue IgG Indirect ELISA kit. Anti-dengue IgG-capture Panbio ELISA was used for detection of high titered antibodies to detect recent secondary infection. We used this data to estimate key transmission parameters like force of infection and basic reproductive number. A subset of 120 indirect ELISA positive samples was also tested for Plaque Reduction Neutralizing Antibodies for determining serotype-specific prevalence.

Findings

Overall, 81% participants were infected with dengue virus (DENV) at least once if not more. The positivity was significantly different in different age groups. All the adults above 70 years were positive for DENV antibodies. Over 69% participants were positive for neutralizing antibodies against all 4 serotypes suggesting intense transmission of all DENV serotypes in Pune. Age-specific seroprevalence was consistent with long-term, endemic circulation of DENV. There was an increasing trend with age, from 21.6% among <36 months to 59.4% in age group 10–12 years. We estimate that 8.68% of the susceptible population gets infected by DENV each year resulting into more than 3,00,000 infections and about 47,000 to 59,000 cases per year. This transmission intensity is similar to that reported from other known hyper-endemic settings in Southeast Asia and the Americas but significantly lower than report from Chennai.

Conclusions

Our study suggests that Pune city has high disease burden, all 4 serotypes are circulating, significant spatial heterogeneity in seroprevalence and suboptimal immunity in younger age groups. This would allow informed decisions to be made on management of dengue and introduction of upcoming dengue vaccines in the city.

Estimating dengue under-reporting in Puerto Rico using a multiplier model

6 August 2018 - 9:00pm

by Manjunath B. Shankar, Rosa L. Rodríguez-Acosta, Tyler M. Sharp, Kay M. Tomashek, Harold S. Margolis, Martin I. Meltzer

Dengue is a mosquito-borne viral illness that causes a variety of health outcomes, from a mild acute febrile illness to potentially fatal severe dengue. Between 2005 and 2010, the annual number of suspected dengue cases reported to the Passive Dengue Surveillance System (PDSS) in Puerto Rico ranged from 2,346 in 2006 to 22,496 in 2010. Like other passive surveillance systems, PDSS is subject to under-reporting. To estimate the degree of under-reporting in Puerto Rico, we built separate inpatient and outpatient probability-based multiplier models, using data from two different surveillance systems—PDSS and the enhanced dengue surveillance system (EDSS). We adjusted reported cases to account for sensitivity of diagnostic tests, specimens with indeterminate results, and differences between PDSS and EDSS in numbers of reported dengue cases. In addition, for outpatients, we adjusted for the fact that less than 100% of medical providers submit diagnostic specimens from suspected cases. We estimated that a multiplication factor of between 5 (for 2010 data) to 9 (for 2006 data) must be used to correct for the under-reporting of the number of laboratory-positive dengue inpatients. Multiplication factors of between 21 (for 2010 data) to 115 (for 2008 data) must be used to correct for the under-reporting of laboratory-positive dengue outpatients. We also estimated that, after correcting for underreporting, the mean annual rate, for 2005–2010, of medically attended dengue in Puerto Rico to be between 2.1 (for dengue inpatients) to 7.8 (for dengue outpatients) per 1,000 population. These estimated rates compare to the reported rates of 0.4 (dengue outpatients) to 0.1 (dengue inpatients) per 1,000 population. The multipliers, while subject to limitations, will help public health officials correct for underreporting of dengue cases, and thus better evaluate the cost-and-benefits of possible interventions.

A systematic review of hepatitis B virus (HBV) drug and vaccine escape mutations in Africa: A call for urgent action

6 August 2018 - 9:00pm

by Jolynne Mokaya, Anna L. McNaughton, Martin J. Hadley, Apostolos Beloukas, Anna-Maria Geretti, Dominique Goedhals, Philippa C. Matthews

International sustainable development goals for the elimination of viral hepatitis as a public health problem by 2030 highlight the pressing need to optimize strategies for prevention, diagnosis and treatment. Selected or transmitted resistance associated mutations (RAMs) and vaccine escape mutations (VEMs) in hepatitis B virus (HBV) may reduce the success of existing treatment and prevention strategies. These issues are particularly pertinent for many settings in Africa where there is high HBV prevalence and co-endemic HIV infection, but lack of robust epidemiological data and limited education, diagnostics and clinical care. The prevalence, distribution and impact of RAMs and VEMs in these populations are neglected in the current literature. We therefore set out to assimilate data for sub-Saharan Africa through a systematic literature review and analysis of published sequence data, and present these in an on-line database (https://livedataoxford.shinyapps.io/1510659619-3Xkoe2NKkKJ7Drg/). The majority of the data were from HIV/HBV coinfected cohorts. The commonest RAM was rtM204I/V, either alone or in combination with compensatory mutations, and identified in both reportedly treatment-naïve and treatment-experienced adults. We also identified the suite of mutations rtM204V/I + rtL180M + rtV173L, that has been associated with vaccine escape, in over 1/3 of cohorts. Although tenofovir has a high genetic barrier to resistance, it is of concern that emerging data suggest polymorphisms that may be associated with resistance, although the precise clinical impact of these is unknown. Overall, there is an urgent need for improved diagnostic screening, enhanced laboratory assessment of HBV before and during therapy, and sustained roll out of tenofovir in preference to lamivudine alone. Further data are needed in order to inform population and individual approaches to HBV diagnosis, monitoring and therapy in these highly vulnerable settings.

Immunomodulatory drug methotrexate used to treat patients with chronic inflammatory rheumatisms post-chikungunya does not impair the synovial antiviral and bone repair responses

3 August 2018 - 9:00pm

by Yosra Bedoui, Claude Giry, Marie-Christine Jaffar-Bandjee, Jimmy Selambarom, Pascale Guiraud, Philippe Gasque

Chikungunya virus (CHIKV) is a mosquito-transmitted RNA alphavirus causing major outbreaks of infectious chronic inflammatory rheumatisms (CIR). Recently, methotrexate (MTX), a disease modifying anti-rheumatic drug has been used successfully to treat patients suffering from rheumatoid-like arthritis post-CHIK but its immunomodulatory activity in the context of viral persistence has been a matter of concerns. We herein used a model of primary human synovial fibroblasts (HSF) and the synthetic molecule polyriboinosinic:polyribocytidylic acid (PIC) to mimic chronic infectious settings in the joints of CHIKV infected patients. The innate antiviral immune and inflammatory responses were investigated in response to MTX used at the therapeutic concentration of 1 μM. We found that MTX did not affect cellular viability as indicated by the LDH release assay. By quantitative RT-PCR, we observed that HSF responded robustly to PIC by increasing ISG15 and IFNβ mRNA levels. Furthermore, PIC upregulated the mRNA expression of two of the major pattern recognition receptors, RIG-I and MDA5 involved in the innate immune detection of viral RNA. MTX did not impact the antiviral response of PIC on ISG15, IFNβ, RIG-I and MDA5 mRNA expressions. MTX alone or combined with PIC did not affect the expression of proinflammatory CCL2 and CXCL8 chemokines. PIC strongly upregulated the mRNA and protein expression of osteoclastogenic factors (IL-6, GM-CSF but not RANKL). Critically, MTX treatment alone or combined with PIC did not affect the expression of all three tested osteoclastogenic cytokines. We found that MTX alone did not increase the capacity of CHIKV to infect and replicate in HSF. In conclusion, our study argues for a beneficial effect of MTX to treat CIR post-CHIKV given that it does not critically impact the antiviral, the proinflammatory and the bone tissue remodeling responses of synovial cells.

Infection of epididymal epithelial cells and leukocytes drives seminal shedding of Zika virus in a mouse model

2 August 2018 - 9:00pm

by Erin M. McDonald, Nisha K. Duggal, Jana M. Ritter, Aaron C. Brault

While primarily a mosquito-borne virus, Zika virus (ZIKV; genus Flavivirus in the Flaviviridae family) is capable of being sexually transmitted. Thirty to fifty percent of men with confirmed ZIKV infection shed ZIKV RNA in their semen, and prolonged viral RNA shedding in semen can occur for more than 6 months. The cellular reservoir of ZIKV in semen is unknown, although spermatozoa have been shown to contain ZIKV RNA and antigen. Yet, spermatozoa are not a requisite for sexual transmission, as at least one case of ZIKV sexual transmission involved a vasectomized man. To determine the cellular reservoirs of ZIKV in semen, an established animal model of sexual transmission was used. The majority of virus detected in the seminal fluid of infected mice during the peak timing of sexual transmission was from the supernatant fraction, suggesting cell-free ZIKV may be largely responsible for sexual transmission. However, some ZIKV RNA was cell-associated. In the testes and epididymides of infected mice, intracellular staining of ZIKV RNA was more pronounced in spermatogenic precursors (spermatocytes and spermatogonia) than in spermatids. Visualization of intracellular negative strand ZIKV RNA demonstrated ZIKV replication intermediates in leukocytes, immature spermatids and epididymal epithelial cells in the male urogenital tract. Epididymal epithelial cells were the principal source of negative-strand ZIKV RNA during the peak timing of sexual transmission potential, indicating these cells may be the predominant source of infectious cell-free ZIKV in seminal fluid. These data promote a more complete understanding of sexual transmission of ZIKV and will inform further model development for future studies on persistent ZIKV RNA shedding.

Cs1, a <i>Clonorchis sinensis</i>-derived serodiagnostic antigen containing tandem repeats and a signal peptide

2 August 2018 - 9:00pm

by Na Cheng, Xue-Nian Xu, Yan Zhou, Yu-Ting Dong, Yi-Fang Bao, Bin Xu, Wei Hu, Zheng Feng

Background

Clonorchiasis, caused by the liver fluke Clonorchis sinensis, remains a serious public health issue in Asia, especially in China, and its relationship with cholangiocarcinoma has highlighted the importance of C. sinensis infection. Proteins containing tandem repeats (TRs) are found in a variety of parasites and, as targets of B-cell responses, are valuable for the serodiagnosis of parasite infections. Here, we identified a novel C. sinensis-specific antigen, Cs1, containing TRs, and investigated its diagnostic value, other immunological properties, and tissue distribution.

Methodology/Principal findings

A partial Cs1 cDNA sequence was cloned by screening an adult C. sinensis cDNA expression library. The full-length Cs1 cDNA was obtained by 5′ rapid amplification of cDNA ends. The deduced Cs1 protein consists of a signal peptide and five TRs of 21 amino acids. The recombinant Cs1 (rCs1) was constructed and purified. rCs1 showed higher sensitivity (94.3%) and specificity (94.4%) than the C. sinensis excretory–secretory products (ESPs) according to ELISA of 114 serum samples. Native Cs1 was identified in C. sinensis ESPs and crude antigens of adult C. sinensis by western blotting using an anti-rCs1 monoclonal antibody. ELISA of recombinant peptides of different Cs1 regions demonstrated that the TR region was immunodominant in Cs1. Immunohistochemistry and confocal microscopy revealed that Cs1 is located in a granule-like structure surrounding the acetabulum of C. sinensis adults that has not previously been described.

Conclusions/Significance

We identified a novel C. sinensis-specific TR protein, Cs1, which is an antigen of high serological significance, compared with C. sinensis ESPs. The deduced features of Cs1 show a unique structure containing TRs and a signal peptide and the TR region is immunodominant in Cs1. This provides a basis for targeted screens of other antigens. The novel structure in which Cs1 is located also deserves further investigation.

Simulation of population dynamics of <i>Bulinus globosus</i>: Effects of environmental temperature on production of <i>Schistosoma haematobium</i> cercariae

2 August 2018 - 9:00pm

by Chester Kalinda, Moses J. Chimbari, William E. Grant, Hsiao-Hsuan Wang, Julius N. Odhiambo, Samson Mukaratirwa

Background

Temperature is an important factor that influences the biology and ecology of intermediate host (IH) snails and the schistosome parasites they transmit. Although temperature shifts due to climate change has been predicted to affect the life history traits of IH snails and parasite production, the mechanisms of how this may affect parasite abundance and disease risks are still not clear.

Materials and methods

Using data from laboratory and field experiments, we developed a deterministic compartmental simulation model based on difference equations using a weekly time step that represented the life cycle of Bulinus globosus. We simulated snail population dynamics and the associated production of cercariae assuming current environmental temperatures as well as projected temperature increases of 1 °C and 2 °C.

Results

The model generated snail fecundity and survival rates similar to those observed in the laboratory and also produced reasonable snail population dynamics under seasonally varying temperatures representative of generally favorable environmental conditions. Simulated relative abundances of both snails and cercariae decreased with increasing environmental temperatures, with maximum snail abundances decreased by 14% and 27%, and maximum cercariae productions decreased by 8% and 17%, when temperatures were increased by 1 °C and 2 °C, respectively.

Conclusion

The results indicate that future rise in temperature due to climate change may alter the abundance of B. globosus and impact on the prevalence of schistosomiasis. Furthermore, increased temperatures may not linearly influence the abundance of S. haematobium. These results may have important implications for schistosomiasis control programmes in view of temperature driven changes in the life history traits of B. globosus and S. haematobium. Our study recommends that the use of deterministic models incorporating the effects of temperature on the life history traits of IH snails would be vital in understanding the potential impact of climate change on schistosomiasis incidences and prevalence.

Evaluation of the rSP03B sero-strip, a newly proposed rapid test for canine exposure to <i>Phlebotomus perniciosus</i>, vector of <i>Leishmania infantum</i>

2 August 2018 - 9:00pm

by Laura Willen, Pascal Mertens, Petr Volf

Background

Canine leishmaniasis (CanL) is a zoonotic disease, caused by Leishmania infantum and transmitted by Phlebotomus perniciosus in the Mediterranean basin. Previously, an ELISA based on the P. perniciosus salivary protein SP03B was proposed as a valid tool to screen for canine exposure to sand fly bites across regions endemic for CanL. Although this approach is useful in laboratory settings, a practical tool for immediate application in the field is needed. In this study we propose the rSP03B sero-strip, the first immunochromatographic test (ICT) in the field of vector exposure able to rapidly screen dogs living in endemic areas for the presence of P. perniciosus and to aid in the evaluation of vector control programs.

Methodology/Principal findings

The ICT was prepared using the bacterially expressed recombinant protein rSP03B as antigen. For test optimization, pre-immune sera from non-bitten laboratory-bred Beagles were used as negative controls. In order to validate the test, sera from laboratory-bred Beagles experimentally exposed to P. perniciosus bites were used as positive controls. Additionally, all samples were tested by ELISA using whole salivary gland homogenate (SGH) and the rSP03B protein as antigen. An almost perfect degree of agreement was found between the ICT and the SGH-ELISA. Furthermore, the newly proposed rSP03B sero-strip showed a sensitivity of 100% and a specificity of 86.79%.

Conclusions/Significance

We developed a simple and rapid ICT based on the P. perniciosus rSP03B salivary protein, able to replace the standard ELISA used in previous studies. Our rSP03B sero-strip showed to be highly sensitive and specific in the detection of antibodies (IgG) against P. perniciosus saliva. In the future, this test can be employed during large-scale epidemiological studies of CanL in the Mediterranean area to evaluate the efficacy of vector control programs.

The impact of the Ebola virus disease (EVD) epidemic on agricultural production and livelihoods in Liberia

2 August 2018 - 9:00pm

by Tsegaye T. Gatiso, Isabel Ordaz-Németh, Trokon Grimes, Menladi Lormie, Clement Tweh, Hjalmar S. Kühl, Jessica Junker

There is unequivocal evidence in the literature that epidemics adversely affect the livelihoods of individuals, households and communities. However, evidence in the literature is dominated by the socioeconomic impacts of HIV/AIDS and malaria, while evidence on the impact of the Ebola virus disease (EVD) on households’ livelihoods remains fragmented and scant. Our study investigates the effect of the EVD epidemic on the livelihoods of Liberian households using the Sustainable Livelihood Framework (SLF). The study also explores the effect of the EVD epidemic on agricultural production and productive efficiency of farm households using Spatial Stochastic Frontier Analysis (SSFA). We collected data from 623 households across Liberia in 2015, using a systematic random sampling design. Our results indicated that the annual income of sample households from communities where EVD occurred did not differ from the annual income of households from communities where EVD did not occur. Nonetheless, the majority of sample households reported a decrease in their income, compared to their income in the year before the survey. This suggests that the impact of the EVD epidemic might not only have been limited to communities directly affected by the epidemic, but also it may have indirectly affected communities in areas where EVD was not reported. We also found that the community-level incidence of EVD negatively affected crop production of farm households, which may have exacerbated the problem of food insecurity throughout the country. Moreover, we found that the EVD epidemic weakened the society’s trust in Liberian institutions. In a nutshell, our results highlight that epidemics, such as the recent EVD outbreak, may have long-lasting negative effects on the livelihoods of a society and their effect may extend beyond the communities directly affected by the epidemics. This means that the nation’s recovery from the impact of the epidemic would be more challenging, and the social and economic impacts of the epidemic may extend well beyond the end of the health crisis.

Precision mapping: An innovative tool and way forward to shrink the map, better target interventions, and accelerate toward the elimination of schistosomiasis

2 August 2018 - 9:00pm

by Louis-Albert Tchuem Tchuenté, J. Russell Stothard, David Rollinson, Jutta Reinhard-Rupp

Potential novel tick-borne Colpodella species parasite infection in patient with neurological symptoms

2 August 2018 - 9:00pm

by Jia-Fu Jiang, Rui-Ruo Jiang, Qiao-Cheng Chang, Yuan-Chun Zheng, Bao-Gui Jiang, Yi Sun, Na Jia, Ran Wei, Hong-Bo Liu, Qiu-Bo Huo, Hong Wang, Michael E. von Fricken, Wu-Chun Cao

The importance of dog population contact network structures in rabies transmission

1 August 2018 - 9:00pm

by Mirjam Laager, Céline Mbilo, Enos Abdelaziz Madaye, Abakar Naminou, Monique Léchenne, Aurélie Tschopp, Service Kemdongarti Naïssengar, Timo Smieszek, Jakob Zinsstag, Nakul Chitnis

Canine rabies transmission was interrupted in N’Djaména, Chad, following two mass vaccination campaigns. However, after nine months cases resurged with re-establishment of endemic rabies transmission to pre-intervention levels. Previous analyses investigated district level spatial heterogeneity of vaccination coverage, and dog density; and importation, identifying the latter as the primary factor for rabies resurgence. Here we assess the impact of individual level heterogeneity on outbreak probability, effectiveness of vaccination campaigns and likely time to resurgence after a campaign. Geo-located contact sensors recorded the location and contacts of 237 domestic dogs in N’Djaména over a period of 3.5 days. The contact network data showed that urban dogs are socially related to larger communities and constrained by the urban architecture. We developed a network generation algorithm that extrapolates this empirical contact network to networks of large dog populations and applied it to simulate rabies transmission in N’Djaména. The model predictions aligned well with the rabies incidence data. Using the model we demonstrated, that major outbreaks are prevented when at least 70% of dogs are vaccinated. The probability of a minor outbreak also decreased with increasing vaccination coverage, but reached zero only when coverage was near total. Our results suggest that endemic rabies in N’Djaména may be explained by a series of importations with subsequent minor outbreaks. We show that highly connected dogs hold a critical role in transmission and that targeted vaccination of such dogs would lead to more efficient vaccination campaigns.

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