PLoS Neglected Tropical Diseases News

Subscribe to PLoS Neglected Tropical Diseases News feed PLoS Neglected Tropical Diseases News
A Peer-Reviewed Open-Access Journal
Updated: 1 hour 36 min ago

Systematic review of clinical trials assessing the therapeutic efficacy of visceral leishmaniasis treatments: A first step to assess the feasibility of establishing an individual patient data sharing platform

5 September 2017 - 9:00pm

by Jacob T. Bush, Monique Wasunna, Fabiana Alves, Jorge Alvar, Piero L. Olliaro, Michael Otieno, Carol Hopkins Sibley, Nathalie Strub Wourgaft, Philippe J. Guerin

Background

There are an estimated 200,000 to 400,000 cases of visceral leishmaniasis (VL) annually. A variety of factors are taken into account when considering the best therapeutic options to cure a patient and reduce the risk of resistance, including geographical area, malnourishment and HIV coinfection. Pooled analyses combine data from many studies to answer specific scientific questions that cannot be answered with individual studies alone. However, the heterogeneity of study design, data collection, and analysis often makes direct comparison difficult. Individual Participant Data (IPD) files can be standardised and analysed, allowing detailed analysis of this merged larger pool, but only a small fraction of systematic reviews and meta-analyses currently employ pooled analysis of IPD. We conducted a systematic literature review to identify published studies and studies reported in clinical trial registries to assess the feasibility of developing a VL data sharing platform to facilitate an IPD-based analysis of clinical trial data. Studies conducted between 1983 to 2015 that reported treatment outcome were eligible.

Principal findings

From the 2,271 documents screened, 145 published VL clinical trials were identified, with data from 26,986 patients. Methodologies varied for diagnosis and treatment outcomes, but overall the volume of data potentially available on different drugs and dose regimens identified hundreds or possibly thousands of patients per arm suitable for IPD pooled meta-analyses.

Conclusions

A VL data sharing platform would provide an opportunity to maximise scientific use of available data to enable assessment of treatment efficacy, contribute to evidence-based clinical management and guide optimal prospective data collection.

"We need people to collaborate together against this disease": A qualitative exploration of perceptions of dengue fever control in caregivers' of children under 5 years, in the Peruvian Amazon

5 September 2017 - 9:00pm

by Amy L. Frank, Emily R. Beales, Gilles de Wildt, Graciela Meza Sanchez, Laura L. Jones

Background

Dengue Fever presents a significant and growing burden of disease to endemic countries, where children are at particular risk. Worldwide, no effective anti-viral treatment has been identified, thus vector control is key for disease prevention, particularly in Peru where no vaccine is currently available. This qualitative study aimed to explore the perceptions of dengue control in caregivers’ of children under 5 years in Peru, to help direct future mosquito control programmes and strategy.

Methods

Eighteen semi-structured interviews were conducted in one health centre in Iquitos, Peru. Interviews were audio-recorded, transcribed and translated by an independent translator. Data were analysed using an inductive thematic approach.

Findings

Three core analytic themes were interpreted: (1) awareness of dengue and its control, (2) perceived susceptibility of children, rural riverside communities and city inhabitants, and (3) perceived responsibility of vector control. Participants were aware of dengue symptoms, transmission and larvae eradication strategies. Misconceptions about the day-time biting behaviour of the Aedes aegypti mosquito and confusion with other mosquito-borne diseases influenced preventative practice. Community-wide lack of cooperation was recognised as a key barrier. This was strengthened by attitudes that the government or health centre were responsible for dengue control and a belief that the disease cannot be prevented through individual actions. Participants felt powerless to prevent dengue due to assumed inevitability of infection and lack of faith in preventative practices. However, children and rural communities were believed to be most vulnerable.

Conclusions

Perceptions of dengue control amongst caregivers to under 5’s were important in shaping their likelihood to participate in preventative practices. There is a need to address the perceived lack of community cooperation through strategies creating a sense of ownership of community control and enhancing social responsibility. The belief that dengue cannot be prevented by individual actions in a community also warrants attention. Specific misconceptions about dengue should be addressed through the community health worker system and further research directed to identify the needs of certain vulnerable groups.

Genotypic characterization directly applied to sputum improves the detection of <i>Mycobacterium africanum</i> West African 1, under-represented in positive cultures

1 September 2017 - 9:00pm

by C. N’Dira Sanoussi, Dissou Affolabi, Leen Rigouts, Séverin Anagonou, Bouke de Jong

Background

This study aimed to compare the prevalence of Mycobacterium tuberculosis complex (MTBc) lineages between direct genotyping (on sputum) and indirect genotyping (on culture), to characterize potential culture bias against difficult growers.

Methodology/Principal findings

Smear-positive sputa from consecutive new tuberculosis patients diagnosed in Cotonou, (Benin) were included, before patients had started treatment. An aliquot of decontaminated sputum was used for direct spoligotyping, and another aliquot was cultured on Löwenstein Jensen (LJ) medium (90 days), for indirect spoligotyping. After DNA extraction, spoligotyping was done according to the standard method for all specimens, and patterns obtained from sputa were compared versus those from the derived culture isolates. From 199 patient’s sputa, 146 (73.4%) yielded a positive culture. In total, direct spoligotyping yielded a pattern in 98.5% (196/199) of the specimens, versus 73.4% (146/199) for indirect spoligotyping on cultures. There was good agreement between sputum- and isolate derived patterns: 94.4% (135/143) at spoligotype level and 96.5% (138/143) at (sub)lineage level. Two of the 8 pairs with discrepant pattern were suggestive of mixed infection in sputum. Ancestral lineages (Lineage 1, and M. africanum Lineages 5 and 6) were less likely to grow in culture (OR = 0.30, 95%CI (0.14 to 0.64), p = 0.0016); especially Lineage 5 (OR = 0.37 95%CI (0.17 to 0.79), p = 0.010). Among modern lineages, Lineage 4 was over-represented in positive-culture specimens (OR = 3.01, 95%CI (1.4 to 6.51), p = 0.005).

Conclusions/ Significance

Ancestral lineages, especially M. africanum West African 1 (Lineage 5), are less likely to grow in culture relative to modern lineages, especially M. tuberculosis Euro-American (Lineage 4). Direct spoligotyping on smear positive sputum is effective and efficient compared to indirect spoligotyping of cultures. It allows for a more accurate unbiased determination of the population structure of the M. tuberculosis complex.

Trial registration

ClinicalTrials.gov NCT02744469

Spatial distribution and risk factors of <i>Schistosoma haematobium</i> and hookworm infections among schoolchildren in Kwale, Kenya

1 September 2017 - 9:00pm

by Evans Asena Chadeka, Sachiyo Nagi, Toshihiko Sunahara, Ngetich Benard Cheruiyot, Felix Bahati, Yuriko Ozeki, Manabu Inoue, Mayuko Osada-Oka, Mayuko Okabe, Yukio Hirayama, Mwatasa Changoma, Keishi Adachi, Faith Mwende, Mihoko Kikuchi, Risa Nakamura, Yombo Dan Justin Kalenda, Satoshi Kaneko, Kenji Hirayama, Masaaki Shimada, Yoshio Ichinose, Sammy M. Njenga, Sohkichi Matsumoto, Shinjiro Hamano

Background

Large-scale schistosomiasis control programs are implemented in regions with diverse social and economic environments. A key epidemiological feature of schistosomiasis is its small-scale heterogeneity. Locally profiling disease dynamics including risk factors associated with its transmission is essential for designing appropriate control programs. To determine spatial distribution of schistosomiasis and its drivers, we examined schoolchildren in Kwale, Kenya.

Methodology/Principal findings

We conducted a cross-sectional study of 368 schoolchildren from six primary schools. Soil-transmitted helminths and Schistosoma mansoni eggs in stool were evaluated by the Kato-Katz method. We measured the intensity of Schistosoma haematobium infection by urine filtration. The geometrical mean intensity of S. haematobium was 3.1 eggs/10 ml urine (school range, 1.4–9.2). The hookworm geometric mean intensity was 3.2 eggs/g feces (school range, 0–17.4). Heterogeneity in the intensity of S. haematobium and hookworm infections was evident in the study area. To identify factors associated with the intensity of helminth infections, we utilized negative binomial generalized linear mixed models. The intensity of S. haematobium infection was associated with religion and socioeconomic status (SES), while that of hookworm infection was related to SES, sex, distance to river and history of anthelmintic treatment.

Conclusions/Significance

Both S. haematobium and hookworm infections showed micro-geographical heterogeneities in this Kwale community. To confirm and explain our observation of high S. haematobium risk among Muslims, further extensive investigations are necessary. The observed small scale clustering of the S. haematobium and hookworm infections might imply less uniform strategies even at finer scale for efficient utilization of limited resources.

Neurosyphilis in Africa: A systematic review

31 August 2017 - 9:00pm

by Michael Marks, Joseph N. Jarvis, William Howlett, David C. W. Mabey

Introduction

Neurological involvement is one of the most important clinical manifestations of syphilis and neurological disease occurs in both early and late syphilis. The impact of HIV co-infection on clinical neurosyphilis remains unclear. The highest prevalence of both syphilis and HIV is in Africa. Therefore it might be expected that neurosyphilis would be an important and not uncommon manifestation of syphilis in Africa and frequently occur in association with HIV co-infection; yet few data are available on neurosyphilis in Africa. The aim of this study is to review data on neurosyphilis in Africa since the onset of the HIV epidemic.

Methods

We searched the literature for references on neurosyphilis in Africa for studies published between the 1st of January 1990 and 15th February 2017. We included case reports, case series, and retrospective and prospective cohort and case-control studies. We did not limit inclusion based on the diagnostic criteria used for neurosyphilis. For retrospective and prospective cohorts, we calculated the proportion of study participants who were diagnosed with neurosyphilis according to the individual study criteria. Depending on the study, we assessed the proportion of patients with syphilis found to have neurosyphilis, and the proportion of patients with neurological syndromes who had neurosyphilis. Due to heterogeneity of data no formal pooling of the data or meta-analysis was undertaken.

Results

Amongst patients presenting with a neurological syndrome, three studies of patients with meningitis were identified; neurosyphilis was consistently reported to cause approximately 3% of all cases. Three studies on stroke reported mixed findings but were limited due to the small number of patients undergoing CSF examination, whilst neurosyphilis continued to be reported as a common cause of dementia in studies from North Africa. Ten studies reported on cases of neurosyphilis amongst patients known to have syphilis. Studies from both North and Southern Africa continue to report cases of late stage syphilis, including tabes dorsalis and neurosyphilis, in association with ocular disease.

Discussion

This is the first systematic review of the literature on neurosyphilis in Africa since the beginning of the HIV epidemic. Neurosyphilis continues to be reported as a manifestation of both early and late syphilis, but the methodological quality of the majority of the included studies was poor. Future well-designed prospective studies are needed to better delineate the incidence and clinical spectrum of neurosyphilis in Africa and to better define interactions with HIV in this setting.

Community effectiveness of indoor spraying as a dengue vector control method: A systematic review

31 August 2017 - 9:00pm

by Moody Samuel, Dorit Maoz, Pablo Manrique, Tara Ward, Silvia Runge-Ranzinger, Joao Toledo, Ross Boyce, Olaf Horstick

Background

The prevention and control of dengue rely mainly on vector control methods, including indoor residual spraying (IRS) and indoor space spraying (ISS). This study aimed to systematically review the available evidence on community effectiveness of indoor spraying.

Methods

A systematic review was conducted using seven databases (PubMed, EMBASE, LILACS, Web of Science, WHOLIS, Cochrane, and Google Scholar) and a manual search of the reference lists of the identified studies. Data from included studies were extracted, analysed and reported.

Results

The review generated seven studies only, three IRS and four ISS (two/three controlled studies respectively). Two IRS studies measuring human transmission showed a decline. One IRS and all four ISS studies measuring adult mosquitoes showed a very good effect, up to 100%, but not sustained. Two IRS studies and one ISS measuring immature mosquitoes, showed mixed results.

Conclusions

It is evident that IRS and also ISS are effective adulticidal interventions against Aedes mosquitoes. However, evidence to suggest effectiveness of IRS as a larvicidal intervention and to reduce human dengue cases is limited–and even more so for ISS. Overall, there is a paucity of studies available on these two interventions that may be promising for dengue vector control, particularly for IRS with its residual effect.

The francophone network on neglected tropical diseases

31 August 2017 - 9:00pm

by Jean Jannin, Philippe Solano, Isadora Quick, Patrice Debre

Dengue, West Nile virus, chikungunya, Zika—and now Mayaro?

31 August 2017 - 9:00pm

by Peter J. Hotez, Kristy O. Murray

Exploring virulence and immunogenicity in the emerging pathogen <i>Sporothrix brasiliensis</i>

30 August 2017 - 9:00pm

by Paula Portella Della Terra, Anderson Messias Rodrigues, Geisa Ferreira Fernandes, Angela Satie Nishikaku, Eva Burger, Zoilo Pires de Camargo

Sporotrichosis is a polymorphic chronic infection of humans and animals classically acquired after traumatic inoculation with soil and plant material contaminated with Sporothrix spp. propagules. An alternative and successful route of transmission is bites and scratches from diseased cats, through which Sporothrix yeasts are inoculated into mammalian tissue. The development of a murine model of subcutaneous sporotrichosis mimicking the alternative route of transmission is essential to understanding disease pathogenesis and the development of novel therapeutic strategies. To explore the impact of horizontal transmission in animals (e.g., cat-cat) and zoonotic transmission on Sporothrix fitness, the left hind footpads of BALB/c mice were inoculated with 5×106 yeasts (n = 11 S. brasiliensis, n = 2 S. schenckii, or n = 1 S. globosa). Twenty days post-infection, our model reproduced both the pathophysiology and symptomology of sporotrichosis with suppurating subcutaneous nodules that progressed proximally along lymphatic channels. Across the main pathogenic members of the S. schenckii clade, S. brasiliensis was usually more virulent than S. schenckii and S. globosa. However, the virulence in S. brasiliensis was strain-dependent, and we demonstrated that highly virulent isolates disseminate from the left hind footpad to the liver, spleen, kidneys, lungs, heart, and brain of infected animals, inducing significant and chronic weight loss (losing up to 15% of their body weight). The weight loss correlated with host death between 2 and 16 weeks post-infection. Histopathological features included necrosis, suppurative inflammation, and polymorphonuclear and mononuclear inflammatory infiltrates. Immunoblot using specific antisera and homologous exoantigen investigated the humoral response. Antigenic profiles were isolate-specific, supporting the hypothesis that different Sporothrix species can elicit a heterogeneous humoral response over time, but cross reaction was observed between S. brasiliensis and S. schenckii proteomes. Despite great diversity in the immunoblot profiles, antibodies were mainly derived against 3-carboxymuconate cyclase, a glycoprotein oscillating between 60 and 70 kDa (gp60-gp70) and a 100-kDa molecule in nearly 100% of the assays. Thus, our data broaden the current view of virulence and immunogenicity in the Sporothrix-sporotrichosis system, substantially expanding the possibilities for comparative genomic with isolates bearing divergent virulence traits and helping uncover the molecular mechanisms and evolutionary pressures underpinning the emergence of Sporothrix virulence.

Decoding the similarities and differences among mycobacterial species

30 August 2017 - 9:00pm

by Sony Malhotra, Sundeep Chaitanya Vedithi, Tom L. Blundell

Mycobacteriaceae comprises pathogenic species such as Mycobacterium tuberculosis, M. leprae and M. abscessus, as well as non-pathogenic species, for example, M. smegmatis and M. thermoresistibile. Genome comparison and annotation studies provide insights into genome evolutionary relatedness, identify unique and pathogenicity-related genes in each species, and explore new targets that could be used for developing new diagnostics and therapeutics. Here, we present a comparative analysis of ten-mycobacterial genomes with the objective of identifying similarities and differences between pathogenic and non-pathogenic species. We identified 1080 core orthologous clusters that were enriched in proteins involved in amino acid and purine/pyrimidine biosynthetic pathways, DNA-related processes (replication, transcription, recombination and repair), RNA-methylation and modification, and cell-wall polysaccharide biosynthetic pathways. For their pathogenicity and survival in the host cell, pathogenic species have gained specific sets of genes involved in repair and protection of their genomic DNA. M. leprae is of special interest owing to its having the smallest genome (1600 genes and ~1300 psuedogenes), yet poor genome annotation. More than 75% of the pseudogenes were found to have a functional ortholog in the other mycobacterial genomes and belong to protein families such as transferases, oxidoreductases and hydrolases.

Increased rates of Guillain-Barré syndrome associated with Zika virus outbreak in the Salvador metropolitan area, Brazil

30 August 2017 - 9:00pm

by Ashley R. Styczynski, Juliane M. A. S. Malta, Elisabeth R. Krow-Lucal, Jadher Percio, Martha E. Nóbrega, Alexander Vargas, Tatiana M. Lanzieri, Priscila L. Leite, J. Erin Staples, Marc X. Fischer, Ann M. Powers, Gwong-Jen J. Chang, P. L. Burns, Erin M. Borland, Jeremy P. Ledermann, Eric C. Mossel, Lawrence B. Schonberger, Ermias B. Belay, Jorge L. Salinas, Roberto D. Badaro, James J. Sejvar, Giovanini E. Coelho

In mid-2015, Salvador, Brazil, reported an outbreak of Guillain-Barré syndrome (GBS), coinciding with the introduction and spread of Zika virus (ZIKV). We found that GBS incidence during April–July 2015 among those ≥12 years of age was 5.6 cases/100,000 population/year and increased markedly with increasing age to 14.7 among those ≥60 years of age. We conducted interviews with 41 case-patients and 85 neighborhood controls and found no differences in demographics or exposures prior to GBS-symptom onset. A higher proportion of case-patients (83%) compared to controls (21%) reported an antecedent illness (OR 18.1, CI 6.9–47.5), most commonly characterized by rash, headache, fever, and myalgias, within a median of 8 days prior to GBS onset. Our investigation confirmed an outbreak of GBS, particularly in older adults, that was strongly associated with Zika-like illness and geo-temporally associated with ZIKV transmission, suggesting that ZIKV may result in severe neurologic complications.

A dynamic model for estimating adult female mortality from ovarian dissection data for the tsetse fly <i>Glossina pallidipes</i> Austen sampled in Zimbabwe

30 August 2017 - 9:00pm

by Sarah F. Ackley, John W. Hargrove

Human and animal trypanosomiasis, spread by tsetse flies (Glossina spp), is a major public health concern in much of sub-Saharan Africa. The basic reproduction number of vector-borne diseases, such as trypanosomiasis, is a function of vector mortality rate. Robust methods for estimating tsetse mortality are thus of interest for understanding population and disease dynamics and for optimal control. Existing methods for estimating mortality in adult tsetse, from ovarian dissection data, often use invalid assumptions of the existence of a stable age distribution, and age-invariant mortality and capture probability. We develop a dynamic model to estimate tsetse mortality from ovarian dissection data in populations where the age distribution is not necessarily stable. The models correspond to several hypotheses about how temperature affects mortality: no temperature dependence (model 1), identical temperature dependence for mature adults and immature stages, i.e., pupae and newly emerged adults (model 2), and differential temperature dependence for mature adults and immature stages (model 3). We fit our models to ovarian dissection data for G. pallidipes collected at Rekomitjie Research Station in the Zambezi Valley in Zimbabwe. We compare model fits to determine the most probable model, given the data, by calculating the Akaike Information Criterion (AIC) for each model. The model that allows for a differential dependence of temperature on mortality for immature stages and mature adults (model 3) performs significantly better than models 1 and 2. All models produce mortality estimates, for mature adults, of approximately 3% per day for mean daily temperatures below 25°C, consistent with those of mark-recapture studies performed in other settings. For temperatures greater than 25°C, mortality among immature classes of tsetse increases substantially, whereas mortality remains roughly constant for mature adults. As a sensitivity analysis, model 3 was simultaneously fit to both the ovarian dissection and trap data; while this fit also produces comparable mortality at temperatures below 25°C, it is not possible to obtain good fits to both data sources simultaneously, highlighting the uncertain correspondence between trap catches and population levels and/or the need for further improvements to our model. The modelling approach employed here could be applied to any substantial time series of age distribution data.

Spatial distribution, <i>Leishmania</i> species and clinical traits of Cutaneous Leishmaniasis cases in the Colombian army

29 August 2017 - 9:00pm

by Luz H. Patino, Claudia Mendez, Omaira Rodriguez, Yanira Romero, Daniel Velandia, Maria Alvarado, Julie Pérez, Maria Clara Duque, Juan David Ramírez

In Colombia, the cutaneous leishmaniasis (CL) is the most common manifestation across the army personnel. Hence, it is mandatory to determine the species associated with the disease as well as the association with the clinical traits. A total of 273 samples of male patients with CL were included in the study and clinical data of the patients was studied. PCR and sequencing analyses (Cytb and HSP70 genes) was performed to identify the species and the intra-specific genetic variability. A georeferenced database was constructed to identify the spatial distribution of Leishmania species isolated. The identification of five species of Leishmania that circulate in the areas where army personnel are deployed is described. Predominant infecting Leishmania species corresponds to L. braziliensis (61.1%), followed by Leishmania panamensis (33.5%), with a high distribution of both species at geographical and municipal level. The species L. guyanensis, L. mexicana and L. lainsoni were also detected at lower frequency. We also showed the identification of different genotypes within L. braziliensis and L. panamensis. In conclusion, we identified the Leishmania species circulating in the areas where Colombian army personnel are deployed, as well as the high intra-specific genetic variability of L. braziliensis and L. panamensis and how these genotypes are distributed at the geographic level.

The elimination of the dengue vector, <i>Aedes aegypti</i>, from Brisbane, Australia: The role of surveillance, larval habitat removal and policy

28 August 2017 - 9:00pm

by Brendan J. Trewin, Jonathan M. Darbro, Cassie C. Jansen, Nancy A. Schellhorn, Myron P. Zalucki, Tim P. Hurst, Gregor J. Devine

Aedes aegypti (L.) (Diptera: Culicidae) is a highly invasive mosquito whose global distribution has fluctuated dramatically over the last 100 years. In Australia the distribution of Ae. aegypti once spanned the eastern seaboard, for 3,000 km north to south. However, during the 1900s this distribution markedly reduced and the mosquito disappeared from its southern range. Numerous hypotheses have been proffered for this retraction, however quantitative evidence of the mechanisms driving the disappearance are lacking. We examine historical records during the period when Ae. aegypti disappeared from Brisbane, the largest population centre in Queensland, Australia. In particular, we focus on the targeted management of Ae. aegypti by government authorities, that led to local elimination, something rarely observed in large cities. Numerous factors are likely to be responsible including the removal of larval habitat, especially domestic rainwater tanks, in combination with increased mosquito surveillance and regulatory enforcement. This account of historical events as they pertain to the elimination of Ae. aegypti from Brisbane, will inform assessments of the risks posed by recent human responses to climate change and the reintroduction of 300,000 rainwater tanks into the State over the past decade.

Human leptospirosis in Seychelles: A prospective study confirms the heavy burden of the disease but suggests that rats are not the main reservoir

28 August 2017 - 9:00pm

by Leon Biscornet, Koussay Dellagi, Frédéric Pagès, Jastin Bibi, Jeanine de Comarmond, Julien Mélade, Graham Govinden, Maria Tirant, Yann Gomard, Vanina Guernier, Erwan Lagadec, Jimmy Mélanie, Gérard Rocamora, Gildas Le Minter, Julien Jaubert, Patrick Mavingui, Pablo Tortosa

Background

Leptospirosis is a bacterial zoonosis caused by pathogenic Leptospira for which rats are considered as the main reservoir. Disease incidence is higher in tropical countries, especially in insular ecosystems. Our objectives were to determine the current burden of leptospirosis in Seychelles, a country ranking first worldwide according to historical data, to establish epidemiological links between animal reservoirs and human disease, and to identify drivers of transmission.

Methods

A total of 223 patients with acute febrile symptoms of unknown origin were enrolled in a 12-months prospective study and tested for leptospirosis through real-time PCR, IgM ELISA and MAT. In addition, 739 rats trapped throughout the main island were investigated for Leptospira renal carriage. All molecularly confirmed positive samples were further genotyped.

Results

A total of 51 patients fulfilled the biological criteria of acute leptospirosis, corresponding to an annual incidence of 54.6 (95% CI 40.7–71.8) per 100,000 inhabitants. Leptospira carriage in Rattus spp. was overall low (7.7%) but dramatically higher in Rattus norvegicus (52.9%) than in Rattus rattus (4.4%). Leptospira interrogans was the only detected species in both humans and rats, and was represented by three distinct Sequence Types (STs). Two were novel STs identified in two thirds of acute human cases while noteworthily absent from rats.

Conclusions

This study shows that human leptospirosis still represents a heavy disease burden in Seychelles. Genotype data suggests that rats are actually not the main reservoir for human disease. We highlight a rather limited efficacy of preventive measures so far implemented in Seychelles. This could result from ineffective control measures of excreting animal populations, possibly due to a misidentification of the main contaminating reservoir(s). Altogether, presented data stimulate the exploration of alternative reservoir animal hosts.

Pre-treatment with <i>Lactobacillus plantarum</i> prevents severe pathogenesis in mice infected with <i>Leptospira interrogans</i> and may be associated with recruitment of myeloid cells

25 August 2017 - 9:00pm

by Hari-Hara Potula, Luciana Richer, Catherine Werts, Maria Gomes-Solecki

Recent estimates on global morbidity and mortality caused by Leptospirosis point to one million cases and almost 60,000 deaths a year worldwide, especially in resource poor countries. We analyzed how a commensal probiotic immunomodulator, Lactobacillus plantarum, affects Leptospira interrogans pathogenesis in a murine model of sub-lethal leptospirosis. We found that repeated oral pre-treatment of mice with live L. plantarum restored body weight to normal levels in mice infected with L. interrogans. Pre-treatment did not prevent L. interrogans access to the kidney but it affected the inflammatory response and it reduced histopathological signs of disease. Analysis of the immune cell profiles in lymphoid tissues of mice pre-treated with L. plantarum showed increased numbers of B cells as well as naïve and memory CD4+ helper T cell populations in uninfected mice that shifted towards increased numbers of effector CD4+ helper T in infected mice. CD8+ cytotoxic T cell profiles in pre-treated uninfected and infected mice mirrored the switch observed for CD4+ except that CD8+ memory T cells were not affected. In addition, pre-treatment led to increased populations of monocytes in lymphoid tissues of uninfected mice and to increased populations of macrophages in the same tissues of infected mice. Immunohistochemistry of kidney sections of pre-treated infected mice showed an enrichment of neutrophils and macrophages and a reduction of total leucocytes and T cells. Our results suggest that complex myeloid and T cell responses orchestrate the deployment of monocytes and other cells from lymphoid tissue and the recruitment of neutrophils and macrophages to the kidney, and that, the presence of these cells in the target organ may be associated with reductions in pathogenesis observed in infected mice treated with L. plantarum.

Treatment of <i>Schistosoma mansoni</i> with miltefosine <i>in vitro</i> enhances serological recognition of defined worm surface antigens

25 August 2017 - 9:00pm

by Marwa H. El-Faham, Maha M. Eissa, Joseph E. Igetei, Eglal I. Amer, Susan Liddell, Mervat Z. El-Azzouni, Michael J. Doenhoff

Background

Miltefosine, an anti-cancer drug that has been successfully repositioned for treatment of Leishmania infections, has recently also shown promising effects against Schistosoma spp targeting all life cycle stages of the parasite. The current study examined the effect of treating Schistosoma mansoni adult worms with miltefosine on exposure of worm surface antigens in vitro.

Methodology/Principal findings

In an indirect immunofluorescence assay, rabbit anti-S.mansoni adult worm homogenate and anti-S. mansoni infection antisera gave strong immunofluorescence of the S. mansoni adult worm surface after treatment with miltefosine, the latter antiserum having previously been shown to synergistically enhance the schistosomicidal activity of praziquantel. Rabbit antibodies that recognised surface antigens exposed on miltefosine-treated worms were recovered by elution off the worm surface in low pH buffer and were used in a western immunoblotting assay to identify antigenic targets in a homogenate extract of adult worms (SmWH). Four proteins reacting with the antibodies in immunoblots were purified and proteomic analysis (MS/MS) combined with specific immunoblotting indicated they were the S. mansoni proteins: fructose-1,6 bisphosphate aldolase (SmFBPA), Sm22.6, alkaline phosphatase and malate dehydrogenase. These antibodies were also found to bind to the surface of 3-hour schistosomula and induce immune agglutination of the parasites, suggesting they may have a role in immune protection.

Conclusion/Significance

This study reveals a novel mode of action of miltefosine as an anti-schistosome agent. The immune-dependent hypothesis we investigated has previously been lent credence with praziquantel (PZQ), whereby treatment unmasks parasite surface antigens not normally exposed to the host during infection. Antigens involved in this molecular mechanism could have potential as intervention targets and antibodies against these antigens may act to increase the drug’s anti-parasite efficacy and be involved in the development of resistance to re-infection.

Modeling zoonotic cutaneous leishmaniasis incidence in central Tunisia from 2009-2015: Forecasting models using climate variables as predictors

25 August 2017 - 9:00pm

by Khouloud Talmoudi, Hedia Bellali, Nissaf Ben-Alaya, Marc Saez, Dhafer Malouche, Mohamed Kouni Chahed

Transmission of zoonotic cutaneous leishmaniasis (ZCL) depends on the presence, density and distribution of Leishmania major rodent reservoir and the development of these rodents is known to have a significant dependence onenvironmental and climate factors. ZCL in Tunisia is one of the most common forms of leishmaniasis. The aim of this paper was to build a regression model of ZCL cases to identify the relationship between ZCL occurrence and possible risk factors, and to develop a predicting model for ZCL's control and prevention purposes. Monthly reported ZCL cases, environmental and bioclimatic data were collected over 6 years (2009–2015). Three rural areas in the governorate of Sidi Bouzid were selected as the study area. Cross-correlation analysis was used to identify the relevant lagged effects of possible risk factors, associated with ZCL cases. Non-parametric modeling techniques known as generalized additive model (GAM) and generalized additive mixed models (GAMM) were applied in this work. These techniques have the ability to approximate the relationship between the predictors (inputs) and the response variable (output), and express the relationship mathematically. The goodness-of-fit of the constructed model was determined by Generalized cross-validation (GCV) score and residual test. There were a total of 1019 notified ZCL cases from July 2009 to June 2015. The results showed seasonal distribution of reported ZCL cases from August to January. The model highlighted that rodent density, average temperature, cumulative rainfall and average relative humidity, with different time lags, all play role in sustaining and increasing the ZCL incidence. The GAMM model could be applied to predict the occurrence of ZCL in central Tunisia and could help for the establishment of an early warning system to control and prevent ZCL in central Tunisia.

"We are survivors and not a virus:" Content analysis of media reporting on Ebola survivors in Liberia

24 August 2017 - 9:00pm

by Elisabeth Anne-Sophie Mayrhuber, Thomas Niederkrotenthaler, Ruth Kutalek

Background

The Ebola virus disease epidemic between 2013 and 2016 in West Africa was unprecedented. It resulted in approximately 28.000 cases and 10.000 Ebola survivors. Many survivors face social, economic and health-related predicaments and media reporting is crucially important in infectious disease outbreaks. However, there is little research on reporting of the social situation of Ebola survivors in Liberia.

Methods

The study used a mixed methods approach and analysed media reports from the Liberian Daily Observer (DOL), a daily newspaper available online in English. We were interested to know how the situation of Ebola survivors was portrayed; in what way issues such as stigma and discrimination were addressed; and which stigma reduction interventions were covered and how. We included all articles on the situation of Ebola survivors in the quantitative and in-depth qualitative analysis published between April 2014 and March 2016.

Results

The DOL published 148 articles that portrayed the social situation of Ebola survivors between the 24 months observation period. In these articles, Ebola survivors were often defined beyond biological terms, reflecting on a broader social definition of survivorship. Survivorship was associated with challenges such as suffering from after-effects, social and economic consequences and psychological distress. Almost 50% of the articles explicitly mentioned stigmatisation in their reporting on Ebola survivors. This was contextualised in untrustworthiness towards international responses and the local health care system and inconclusive knowledge on cures and transmission routes. In the majority of DOL articles stigma reduction and engaging survivors in the response was reported as crucially important.

Discussion

Reporting in the DOL was educational-didactical and well-balanced in terms of disseminating available medical knowledge and reflecting the social situation of Ebola survivors. While the articles contextualised factors contributing to stigmatisation throughout the reporting, journalistic scrutiny regarding effectiveness of interventions by government and NGOs was missing.

Pages