RSS news feeds

Anthelminthic activity of glibenclamide on secondary cystic echinococcosis in mice

PLoS Neglected Tropical Diseases News - 30 November 2017 - 10:00pm

by Julia A. Loos, María Sandra Churio, Andrea C. Cumino

Cystic echinococcosis (CE) is a worldwide parasitic zoonosis caused by the larval stage of Echinococcus granulosus. Current chemotherapy against this disease is based on the administration of benzimidazoles (BZMs). However, BZM treatment has a low cure rate and causes several side effects. Therefore, new treatment options are needed. The antidiabetic drug glibenclamide (Glb) is a second-generation sulfonylurea receptor inhibitor that has been shown to be active against protozoan parasites. Hence, we assessed the in vitro and in vivo pharmacological effects of Glb against the larval stage of E. granulosus. The in vitro activity was concentration dependent on both protoscoleces and metacestodes. Moreover, Glb combined with the minimum effective concentration of albendazole sulfoxide (ABZSO) was demonstrated to have a greater effect on metacestodes in comparison with each drug alone. Likewise, there was a reduction in the cyst weight after oral administration of Glb to infected mice (5 mg/kg of body weight administered daily for a period of 8 weeks). However, in contrast to in vitro assays, no differences in effectiveness were found between Glb + albendazole (ABZ) combined treatment and Glb monotherapy. Our results also revealed mitochondrial membrane depolarization and an increase in intracellular Ca2+ levels in Glb-treated protoscoleces. In addition, the intracystic drug accumulation and our bioinformatic analysis using the available E. granulosus genome suggest the presence of genes encoding sulfonylurea transporters in the parasite. Our data clearly demonstrated an anti-echinococcal effect of Glb on E. granulosus larval stage. Further studies are needed in order to thoroughly investigate the mechanism involved in the therapeutic response of the parasite to this sulfonylurea.

Chagas disease vector control and Taylor's law

PLoS Neglected Tropical Diseases News - 30 November 2017 - 10:00pm

by Joel E. Cohen, Lucía I. Rodríguez-Planes, María S. Gaspe, María C. Cecere, Marta V. Cardinal, Ricardo E. Gürtler

Background

Large spatial and temporal fluctuations in the population density of living organisms have profound consequences for biodiversity conservation, food production, pest control and disease control, especially vector-borne disease control. Chagas disease vector control based on insecticide spraying could benefit from improved concepts and methods to deal with spatial variations in vector population density.

Methodology/Principal findings

We show that Taylor's law (TL) of fluctuation scaling describes accurately the mean and variance over space of relative abundance, by habitat, of four insect vectors of Chagas disease (Triatoma infestans, Triatoma guasayana, Triatoma garciabesi and Triatoma sordida) in 33,908 searches of people's dwellings and associated habitats in 79 field surveys in four districts in the Argentine Chaco region, before and after insecticide spraying. As TL predicts, the logarithm of the sample variance of bug relative abundance closely approximates a linear function of the logarithm of the sample mean of abundance in different habitats. Slopes of TL indicate spatial aggregation or variation in habitat suitability. Predictions of new mathematical models of the effect of vector control measures on TL agree overall with field data before and after community-wide spraying of insecticide.

Conclusions/Significance

A spatial Taylor's law identifies key habitats with high average infestation and spatially highly variable infestation, providing a new instrument for the control and elimination of the vectors of a major human disease.

TNF-α blockade suppresses pericystic inflammation following anthelmintic treatment in porcine neurocysticercosis

PLoS Neglected Tropical Diseases News - 30 November 2017 - 10:00pm

by Siddhartha Mahanty, Miguel A. Orrego, Carla Cangalaya, M. Paz Adrianzen, Gianfranco Arroyo, Juan Calcina, Armando E. Gonzalez, Héctor H. García, Cristina Guerra-Giraldez, Theodore E. Nash, for the Cysticercosis Working Group in Peru

Background

Neurocysticercosis (NCC) is an infection of the brain with the larval cyst of the tapeworm, Taenia solium. Cysticidal treatment induces parasite killing resulting in a post inflammatory response and seizures, which generally requires corticosteroid treatment to control inflammation. The nature of this response and how to best control it is unclear. We investigated the anti-inflammatory effects of pretreatment with etanercept (ETN), an anti-tumor necrosis factor agent, or dexamethasone (DEX), a high potency corticosteroid, on the post treatment inflammatory response in naturally infected pigs with neurocysticercosis after a single dose of the cysticidal drug praziquantel (PZQ).

Methodology/Principal findings

We followed the methods from a previously developed treatment model of NCC in naturally infected swine. The four study groups of infected pigs included 3 groups treated with PZQ on day 0: PZQ-treated alone (100 mg/kg PO; n = 9), pretreated with dexamethasone (DEX, 0.2 mg/kg IM administered on days -1, +1 and +3; n = 6), and pretreated with etanercept (ETN, 25 mg IM per animal on days -7 and 0; n = 6). The fourth group remained untreated (n = 3). As measured by quantitative RT-PCR, ETN pretreatment depressed transcription of a wide range of proinflammatory, regulatory and matrix protease encoding genes at 120 hr post PZQ treatment in capsules of cysts that demonstrated extravasated Evans Blue (EB) (a measure of blood brain barrier dysfunction) compared to animals not receiving ETN. Transcription was significantly depressed for the proinflammatory genes tumor necrosis factor (TNF)-α, and interferon (IFN)-γ; the inflammation regulating genes cytotoxic T-lymphocyte-associated protein (CTLA)4, interleukin (IL)-13 and transforming growth factor (TGF)-β; the tissue remodeling genes matrix metalloprotease (MMP)1 and 9, tissue inhibitors of metalloproteases (TIMP)1 and 2, and the genes regulating endothelial function vascular endothelial growth factor (VEGF)1, angiopoietin (Ang)1, Ang 2, and platelet endothelial cell adhesion molecule (PECAM)-1. In contrast, transcription was only modestly decreased in the DEX pretreated pigs compared to PZQ alone, and only for TNF-α, IL-6, IFN-γ, TGF-β and Ang1. IL-10 was not affected by either ETN or DEX pretreatments. The degree of inflammation, assessed by semi-quantitative inflammatory scores, was modestly decreased in both ETN and DEX pretreated animals compared to PZQ treated pigs whereas cyst damage scores were moderately decreased only in cysts from DEX pretreated pigs. However, the proportion of cysts with EB extravasation was not significantly changed in ETN and DEX pretreated groups.

Conclusions/Significance

Overall, TNF-α blockade using ETN treatment modulated expression of a large variety of genes that play a role in induction and control of inflammation and structural changes. In contrast the number of inflammatory cells was only moderately decreased suggesting weaker effects on cell migration into the inflammatory capsules surrounding cysts than on release of modulatory molecules. Taken together, these data suggest that TNF-α blockade may provide a viable strategy to manage post-treatment pericystic inflammation that follows antiparasitic therapy for neurocysticercosis.

The "F" in SAFE: Reliability of assessing clean faces for trachoma control in the field

PLoS Neglected Tropical Diseases News - 30 November 2017 - 10:00pm

by Sheila K. West, Derick Ansah, Beatriz Munoz, Nicodemus Funga, Harran Mkocha

Background

Although facial cleanliness is part of the SAFE strategy for trachoma there is controversy over the reliability of measuring a clean face. A child’s face with no ocular and nasal discharge is clean and the endpoint of interest, regardless of the number of times it must be washed to achieve that endpoint. The issue of reliability rests on the reproducibility of graders to assess a clean face. We report the reproducibility of assessing a clean face in a field trial in Kongwa, Tanzania.

Methods/Findings

Seven graders were trained to assess the presence and absence of nasal and ocular discharge on children’s faces. Sixty children ages 1–7 years were recruited from a community and evaluated independently by seven graders, once and again about 50 minutes later. Intra-and inter-observer variation was calculated using unweighted kappa statistics. The average intra-observer agreement was kappa = 0.72, and the average inter-observer agreement was kappa = 0.78.

Conclusions

Intra-observer and inter-observer agreement was substantial for the assessment of clean faces using trained Tanzania staff who represent a variety of educational backgrounds. As long as training is provided, the estimate of clean faces in children should be reliable, and reflect the effort of families to keep ocular and nasal discharge off the faces. These data suggest assessment of clean faces could be added to trachoma surveys, which already measure environmental improvements, in districts.

Scabies in the age of increasing drug resistance

PLoS Neglected Tropical Diseases News - 30 November 2017 - 10:00pm

by Samar Khalil, Ossama Abbas, Abdul Ghani Kibbi, Mazen Kurban

Scabies is an infestation of the skin by the mite Sarcoptes scabiei. It manifests with pruritic erythematous papules and excoriations, in addition to the pathognomonic burrows. Multiple drugs can be used for treatment, but resistance to conventional therapy is increasing throughout the years. This paper will review the mechanisms of resistance proposed in the literature and some of the potential solutions to this problem.

Internet-based biosurveillance methods for vector-borne diseases: Are they novel public health tools or just novelties?

PLoS Neglected Tropical Diseases News - 30 November 2017 - 10:00pm

by Simon Pollett, Benjamin M. Althouse, Brett Forshey, George W. Rutherford, Richard G. Jarman

Internet-based surveillance methods for vector-borne diseases (VBDs) using “big data” sources such as Google, Twitter, and internet newswire scraping have recently been developed, yet reviews on such “digital disease detection” methods have focused on respiratory pathogens, particularly in high-income regions. Here, we present a narrative review of the literature that has examined the performance of internet-based biosurveillance for diseases caused by vector-borne viruses, parasites, and other pathogens, including Zika, dengue, other arthropod-borne viruses, malaria, leishmaniasis, and Lyme disease across a range of settings, including low- and middle-income countries. The fundamental features, advantages, and drawbacks of each internet big data source are presented for those with varying familiarity of “digital epidemiology.” We conclude with some of the challenges and future directions in using internet-based biosurveillance for the surveillance and control of VBD.

Seroprevalence of rickettsial infections and Q fever in Bhutan

PLoS Neglected Tropical Diseases News - 27 November 2017 - 10:00pm

by Tshokey Tshokey, John Stenos, David N. Durrheim, Keith Eastwood, Chelsea Nguyen, Stephen R. Graves

Background

With few studies conducted to date, very little is known about the epidemiology of rickettsioses in Bhutan. Due to two previous outbreaks and increasing clinical cases, scrub typhus is better recognized than other rickettsial infections and Q fever.

Methodology

A descriptive cross-sectional serosurvey was conducted from January to March 2015 in eight districts of Bhutan. Participants were 864 healthy individuals from an urban (30%) and a rural (70%) sampling unit in each of the eight districts. Serum samples were tested by microimmunofluorescence assay for rickettsial antibodies at the Australian Rickettsial Reference Laboratory.

Results

Of the 864 participants, 345 (39.9%) were males and the mean age of participants was 41.1 (range 13–98) years. An overall seroprevalence of 49% against rickettsioses was detected. Seroprevalence was highest against scrub typhus group (STG) (22.6%) followed by spotted fever group (SFG) rickettsia (15.7%), Q fever (QF) (6.9%) and typhus group (TG) rickettsia (3.5%). Evidence of exposure to multiple agents was also noted; the commonest being dual exposure to STG and SFG at 5%. A person’s likelihood of exposure to STG and SFG rickettsia significantly increased with age and farmers were twice as likely to have evidence of STG exposure as other occupations. Trongsa district appeared to be a hotspot for STG exposure while Punakha district had the lowest STG exposure risk. Zhemgang had the lowest exposure risk to SFG rickettsia compared to other districts. People living at altitudes above 2000 meters were relatively protected from STG infections but this was not observed for SFG, TG or QF exposure.

Conclusion

This seroprevalence study highlights the endemicity of STG and SFG rickettsia in Bhutan. The high seroprevalence warrants appropriate public health interventions, such as diagnostic improvements and clinical treatment guidelines. Future studies should focus on vector profiles, geospatial, bio-social and environmental risk assessment and preventive and control strategies.

The importance of thinking beyond the water-supply in cholera epidemics: A historical urban case-study

PLoS Neglected Tropical Diseases News - 27 November 2017 - 10:00pm

by Matthew D. Phelps, Andrew S. Azman, Joseph A. Lewnard, Marina Antillón, Lone Simonsen, Viggo Andreasen, Peter K. M. Jensen, Virginia E. Pitzer

Background

Planning interventions to respond to cholera epidemics requires an understanding of the major transmission routes. Interrupting short-cycle (household, foodborne) transmission may require different approaches as compared long-cycle (environmentally-mediated/waterborne) transmission. However, differentiating the relative contribution of short- and long-cycle routes has remained difficult, and most cholera outbreak control efforts focus on interrupting long-cycle transmission. Here we use high-resolution epidemiological and municipal infrastructure data from a cholera outbreak in 1853 Copenhagen to explore the relative contribution of short- and long-cycle transmission routes during a major urban epidemic.

Methodology/Principal findings

We fit a spatially explicit time-series meta-population model to 6,552 physician-reported cholera cases from Copenhagen in 1853. We estimated the contribution of long-cycle waterborne transmission between neighborhoods using historical municipal water infrastructure data, fitting the force of infection from hydraulic flow, then comparing model performance. We found the epidemic was characterized by considerable transmission heterogeneity. Some neighborhoods acted as localized transmission hotspots, while other neighborhoods were less affected or important in driving the epidemic. We found little evidence to support long-cycle transmission between hydrologically-connected neighborhoods. Collectively, these findings suggest short-cycle transmission was significant.

Conclusions/Significance

Spatially targeted cholera interventions, such as reactive vaccination or sanitation/hygiene campaigns in hotspot neighborhoods, would likely have been more effective in this epidemic than control measures aimed at interrupting long-cycle transmission, such as improving municipal water quality. We recommend public health planners consider programs aimed at interrupting short-cycle transmission as essential tools in the cholera control arsenal.

Cross-sectional interview study of fertility, pregnancy, and urogenital schistosomiasis in coastal Kenya: Documented treatment in childhood is associated with reduced odds of subfertility among adult women

PLoS Neglected Tropical Diseases News - 27 November 2017 - 10:00pm

by Sarah C. Miller-Fellows, Laura Howard, Rebekah Kramer, Vanessa Hildebrand, Jennifer Furin, Francis M. Mutuku, Dunstan Mukoko, Julianne A. Ivy, Charles H. King

Background

Previous research has documented an increased risk of subfertility in areas of sub-Saharan Africa, as well as an ecological association between urogenital schistosomiasis prevalence and decreased fertility. This pilot project examined reproductive patterns and the potential effects of childhood urogenital Schistosoma haematobium infection and individual treatment experience on adult subfertility among women who were long-term residents in an S. haematobium-endemic region of coastal Kenya.

Methodology/Principal findings

We analyzed findings from 162 in-depth interviews with women of childbearing age in a rural, coastal community, linking them, if possible, to their individual treatment records from previous multi-year longitudinal studies of parasitic infections. Reproductive histories indicated a much local higher local rate of subfertility (44%) than worldwide averages (8–12%). Although, due to the very high regional prevalence of schistosomiasis, a clear relationship could not be demonstrated between a history of S. haematobium infection and adult subfertility, among a convenience sub-sample of 61 women who had received documented treatment during previous interventional trials, a significant association was found between age at first anti-schistosomal treatment and later fertility in adulthood, with those women treated before age 21 significantly less likely to have subfertility (P = 0.001).

Conclusions/Significance

The high subfertility rate documented in this pilot study suggests the importance of programs to prevent and treat pelvic infections in their early stages to preclude reproductive tract damage. The available documented treatment data also suggest that early anti-schistosomal treatment may prevent the fertility-damaging effects of urogenital schistosomiasis, and lend support for programs that provide universal treatment of children in S. haematobium-endemic regions.

Quantitative proteomic analysis of amastigotes from <i>Leishmania (L</i>.<i>) amazonensis</i> LV79 and PH8 strains reveals molecular traits associated with the virulence phenotype

PLoS Neglected Tropical Diseases News - 27 November 2017 - 10:00pm

by Eloiza de Rezende, Rebeca Kawahara, Mauricio S. Peña, Giuseppe Palmisano, Beatriz S. Stolf

Background

Leishmaniasis is an antropozoonosis caused by Leishmania parasites that affects around 12 million people in 98 different countries. The disease has different clinical forms, which depend mainly on the parasite genetics and on the immunologic status of the host. The promastigote form of the parasite is transmitted by an infected female phlebotomine sand fly, is internalized by phagocytic cells, mainly macrophages, and converts into amastigotes which replicate inside these cells. Macrophages are important cells of the immune system, capable of efficiently killing intracellular pathogens. However, Leishmania can evade these mechanisms due to expression of virulence factors. Different strains of the same Leishmania species may have different infectivity and metastatic phenotypes in vivo, and we have previously shown that analysis of amastigote proteome can give important information on parasite infectivity. Differential abundance of virulence factors probably accounts for the higher virulence of PH8 strain parasites shown in this work. In order to test this hypothesis, we have quantitatively compared the proteomes of PH8 and LV79 lesion-derived amastigotes using a label-free proteomic approach.

Methodology/Principal findings

In the present work, we have compared lesion development by L. (L.) amazonensis PH8 and LV79 strains in mice, showing that they have different virulence in vivo. Viability and numbers of lesion-derived amastigotes were accordingly significantly different. Proteome profiles can discriminate parasites from the two strains and several proteins were differentially expressed.

Conclusions/Significance

This work shows that PH8 strain is more virulent in mice, and that lesion-derived parasites from this strain are more viable and more infective in vitro. Amastigote proteome comparison identified GP63 as highly expressed in PH8 strain, and Superoxide Dismutase, Tryparedoxin Peroxidase and Heat Shock Protein 70 as more abundant in LV79 strain. The expression profile of all proteins and of the differential ones precisely classified PH8 and LV79 samples, indicating that the two strains have proteins with different abundances and that proteome profiles correlate with their phenotypes.

Turning poop into profit: Cost-effectiveness and soil transmitted helminth infection risk associated with human excreta reuse in Vietnam

PLoS Neglected Tropical Diseases News - 27 November 2017 - 10:00pm

by Ngan Tran-Thi, Rachel J. Lowe, Janna M. Schurer, Tu Vu-Van, Lauren E. MacDonald, Phuc Pham-Duc

Human excreta is a low cost source of nutrients vital to plant growth, but also a source of pathogens transmissible to people and animals. We investigated the cost-savings and infection risk of soil transmitted helminths (STHs) in four scenarios where farmers used either inorganic fertilizer or fresh/composted human excreta supplemented by inorganic fertilizer to meet the nutrient requirements of rice paddies in the Red River Delta, Vietnam. Our study included two main components: 1) a risk estimate of STH infection for farmers who handle fresh excreta, determined by systematic review and meta-analysis; and 2) a cost estimate of fertilizing rice paddies, determined by nutrient assessment of excreta, a retailer survey of inorganic fertilizer costs, and a literature review to identify region-specific inputs. Our findings suggest that farmers who reuse fresh excreta are 1.24 (95% CI: 1.13–1.37, p-value<0.001) times more likely to be infected with any STH than those who do not handle excreta or who compost appropriately, and that risk varies by STH type (Ascaris lumbricoides RR = 1.17, 95% CI = 0.87–1.58, p-value = 0.29; Hookworm RR = 1.02, 95% CI = 0.50–2.06, p-value = 0.96; Trichuris trichiura RR = 1.38, 95% CI = 0.79–2.42, p-value = 0.26). Average cost-savings were highest for farmers using fresh excreta (847,000 VND) followed by those who composted for 6 months as recommended by the WHO (312,000 VND) and those who composted for a shorter time (5 months) with lime supplementation (37,000 VND/yr); however, this study did not assess healthcare costs of treating acute or chronic STH infections in the target group. Our study provides evidence that farmers in the Red River Delta are able to use a renewable and locally available resource to their economic advantage, while minimizing the risk of STH infection.

Revisiting primary neural leprosy: Clinical, serological, molecular, and neurophysiological aspects

PLoS Neglected Tropical Diseases News - 27 November 2017 - 10:00pm

by Diogo Fernandes dos Santos, Matheus Rocha Mendonça, Douglas Eulálio Antunes, Elaine Fávaro Pípi Sabino, Raquel Campos Pereira, Luiz Ricardo Goulart, Isabela Maria Bernardes Goulart

Background

Leprosy neuropathy is considered the most common peripheral neuropathy of infectious etiology worldwide, representing a public health problem. Clinical diagnosis of primary neural leprosy (PNL) is challenging, since no skin lesions are found and the slit skin smear bacilloscopy is negative. However, there are still controversial concepts regarding the primary-neural versus pure-neural leprosy definition, which will be explored by using multiple clinical-laboratory analyses in this study.

Methodology/Principal findings

Seventy patients diagnosed with primary neural leprosy from 2014 to 2016 underwent clinical, laboratorial and neurophysiological evaluation. All patients presented an asymmetric neural impairment, with nerve thickening in 58.6%. Electroneuromyography showed a pattern of mononeuropathy in 51.4%. Positivity for ELISA anti-PGL1 was 52.9%, while the qPCR of slit skin smear was 78.6%. The qPCR of nerve biopsies was positive in 60.8%. Patients with multiple mononeuropathy patterns showed lower levels of anti-PGL-1 (p = 0.0006), and higher frequency of neural thickening (p = 0.0008) and sensory symptoms (p = 0.01) than those with mononeuropathy.

Conclusions/Significance

PNL is not a synonym of pure neural leprosy, as this condition may include a generalized immune response and also a skin involvement, documented by molecular findings. Immunological, molecular, and neurophysiological tools must be implemented for diagnosing primary neural leprosy to achieve effective treatment and reduction of its resultant disabilities that still represent a public health problem in several developing nations. Finally, we propose a algorithm and recommendations for the diagnosis of primary neural leprosy based on the combination of the three clinical-laboratorial tools.

Safety and efficacy of a freeze-dried trivalent antivenom for snakebites in the Brazilian Amazon: An open randomized controlled phase IIb clinical trial

PLoS Neglected Tropical Diseases News - 27 November 2017 - 10:00pm

by Iran Mendonça-da-Silva, Antônio Magela Tavares, Jacqueline Sachett, José Felipe Sardinha, Lilian Zaparolli, Maria Fátima Gomes Santos, Marcus Lacerda, Wuelton Marcelo Monteiro

Background

In tropical areas, a major concern regarding snakebites treatment effectiveness relates to the failure in liquid antivenom (AV) distribution due to the lack of an adequate cold chain in remote areas. To minimize this problem, freeze-drying has been suggested to improve AV stability.

Methods and findings

This study compares the safety and efficacy of a freeze-dried trivalent antivenom (FDTAV) and the standard liquid AV provided by the Brazilian Ministry of Health (SLAV) to treat Bothrops, Lachesis and Crotalus snakebites. This was a prospective, randomized, open, phase IIb trial, carried out from June 2005 to May 2008 in the Brazilian Amazon. Primary efficacy endpoints were the suppression of clinical manifestations and return of hemostasis and renal function markers to normal ranges within the first 24 hours of follow-up. Primary safety endpoint was the presence of early adverse reactions (EAR) in the first 24 hours after treatment. FDTAV thermal stability was determined by estimating AV potency over one year at 56°C. Of the patients recruited, 65 and 51 were assigned to FDTAV and SLAV groups, respectively. Only mild EARs were reported, and they were not different between groups. There were no differences in fibrinogen (p = 0.911) and clotting time (p = 0.982) recovery between FDTAV and SLAV treated groups for Bothrops snakebites. For Lachesis and Crotalus snakebites, coagulation parameters and creatine phosphokinase presented normal values 24 hours after AV therapy for both antivenoms.

Conclusions/Significance

Since promising results were observed for efficacy, safety and thermal stability, our results indicate that FDTAV is suitable for a larger phase III trial.

Trial registration

ISRCTNregistry: ISRCTN12845255; DOI: 10.1186/ISRCTN12845255 (http://www.isrctn.com/ISRCTN12845255).

A 23-year retrospective investigation of <i>Salmonella</i> Typhi and <i>Salmonella</i> Paratyphi isolated in a tertiary Kathmandu hospital

PLoS Neglected Tropical Diseases News - 27 November 2017 - 10:00pm

by Raphaël M. Zellweger, Buddha Basnyat, Poojan Shrestha, Krishna G. Prajapati, Sabina Dongol, Paban K. Sharma, Samir Koirala, Thomas C. Darton, Christiane Dolecek, Corinne N. Thompson, Guy E. Thwaites, Stephen G. Baker, Abhilasha Karkey

Background

Salmonella serovars Typhi (S. Typhi) and Paratyphi A (S. Paratyphi A), the causative agents of enteric fever, have been routinely isolated organisms from the blood of febrile patients in the Kathmandu Valley since the early 1990s. Susceptibility against commonly used antimicrobials for treating enteric fever has gradually changed throughout South Asia since this time, posing serious treatment challenges. Here, we aimed to longitudinally describe trends in the isolation of Salmonella enterica and assess changes in their antimicrobial susceptibility in Kathmandu over a 23-year period.

Methods

We conducted a retrospective analysis of standardised microbiological data from April 1992 to December 2014 at a single healthcare facility in Kathmandu, examining time trends of Salmonella-associated bacteraemia and the corresponding antimicrobial susceptibility profiles of the isolated organisms.

Results

Over 23 years there were 30,353 positive blood cultures. Salmonella enterica accounted for 65.4% (19,857/30,353) of all the bacteria positive blood cultures. S. Typhi and S. Paratyphi A were the dominant serovars, constituting 68.5% (13,592/19,857) and 30.5% (6,057/19,857) of all isolated Salmonellae. We observed (i) a peak in the number of Salmonella-positive cultures in 2002, a year of heavy rainfall and flooding in the Kathmandu Valley, followed by a decline toward pre-flood baseline by 2014, (ii) an increase in the proportion of S. Paratyphi in all Salmonella-positive cultures between 1992 and 2014, (iii) a decrease in the prevalence of MDR for both S. Typhi and S. Paratyphi, and (iv) a recent increase in fluoroquinolone non-susceptibility in both S. Typhi and S. Paratyphi isolates.

Conclusions

Our work describes significant changes in the epidemiology of Salmonella enterica in the Kathmandu Valley during the last quarter of a century. We highlight the need to examine current treatment protocols for enteric fever and suggest a change from fluoroquinolone monotherapy to combination therapies of macrolides or cephalosporins along with older first-line antimicrobials that have regained their efficacy.

Pre-clinical antigenicity studies of an innovative multivalent vaccine for human visceral leishmaniasis

PLoS Neglected Tropical Diseases News - 27 November 2017 - 10:00pm

by Pedro Cecílio, Begoña Pérez-Cabezas, Laura Fernández, Javier Moreno, Eugenia Carrillo, José M. Requena, Epifanio Fichera, Steven G. Reed, Rhea N. Coler, Shaden Kamhawi, Fabiano Oliveira, Jesus G. Valenzuela, Luigi Gradoni, Reinhard Glueck, Gaurav Gupta, Anabela Cordeiro-da-Silva

The notion that previous infection by Leishmania spp. in endemic areas leads to robust anti-Leishmania immunity, supports vaccination as a potentially effective approach to prevent disease development. Nevertheless, to date there is no vaccine available for human leishmaniasis. We optimized and assessed in vivo the safety and immunogenicity of an innovative vaccine candidate against human visceral leishmaniasis (VL), consisting of Virus-Like Particles (VLP) loaded with three different recombinant proteins (LJL143 from Lutzomyia longipalpis saliva as the vector-derived (VD) component, and KMP11 and LeishF3+, as parasite-derived (PD) antigens) and adjuvanted with GLA-SE, a TLR4 agonist. No apparent adverse reactions were observed during the experimental time-frame, which together with the normal hematological parameters detected seems to point to the safety of the formulation. Furthermore, measurements of antigen-specific cellular and humoral responses, generally higher in immunized versus control groups, confirmed the immunogenicity of the vaccine formulation. Interestingly, the immune responses against the VD protein were reproducibly more robust than those elicited against leishmanial antigens, and were apparently not caused by immunodominance of the VD antigen. Remarkably, priming with the VD protein alone and boosting with the complete vaccine candidate contributed towards an increase of the immune responses to the PD antigens, assessed in the form of increased ex vivo CD4+ and CD8+ T cell proliferation against both the PD antigens and total Leishmania antigen (TLA). Overall, our immunogenicity data indicate that this innovative vaccine formulation represents a promising anti-Leishmania vaccine whose efficacy deserves to be tested in the context of the “natural infection”.

Neurogenic mediators contribute to local edema induced by <i>Micrurus lemniscatus</i> venom

PLoS Neglected Tropical Diseases News - 21 November 2017 - 10:00pm

by Luciana Lyra Casais-e-Silva, Catarina Teixeira

Background/Aims

Micrurus is one of the four snake genera of medical importance in Brazil. Coral snakes have a broad geographic distribution from the southern United States to Argentina. Micrurine envenomation is characterized by neurotoxic symptoms leading to dyspnea and death. Moreover, various local manifestations, including edema formation, have been described in patients bitten by different species of Micrurus. Thus, we investigated the ability of Micrurus lemniscatus venom (MLV) to induce local edema. We also explored mechanisms underlying this effect, focussing on participation of neuropeptides and mast cells.

Methodology/Principal findings

Intraplantar injection of MLV (1–10μg/paw) in rats caused dose- and time-dependent edema with a peak between 15 min and 1 h after injection. MLV also induced degranulation of peritoneal mast cells (MCs). MC depletion by compound 48/80 markedly reduced MLV-induced edema. Pre-treatment (30 min) of rats with either prometazine, a histamine H1 receptor antagonist or methysergide, a nonselective 5-HT receptor antagonist, reduced MLV-induced edema. However, neither thioperamide, a histamine H3/H4 receptor antagonist, nor co-injection of MLV with HOE-140, a BK2 receptor antagonist, altered the response. Depletion of neuropeptides by capsaicin or treatment of animals with NK1- and NK2-receptor antagonists (SR 140333 and SR 48968, respectively) markedly reduced MLV-induced edema.

Conclusions/Significance

In conclusion, MLV induces paw edema in rats by mechanisms involving activation of mast cells and substance P-releasing sensory C-fibers. Tachykinins NKA and NKB, histamine, and serotonin are major mediators of the MLV-induced edematogenic response. Targeting mast cell- and sensory C-fiber-derived mediators should be considered as potential therapeutic approaches to interrupt development of local edema induced by Micrurus venoms.

Poverty and health among CDC plantation labourers in Cameroon: Perceptions, challenges and coping strategies

PLoS Neglected Tropical Diseases News - 20 November 2017 - 10:00pm

by Valerie Makoge, Lenneke Vaandrager, Harro Maat, Maria Koelen

Creating better access to good quality healthcare for the poor is a major challenge to development. In this study, we examined inter-linkages between poverty and disease, referred to as poverty-related diseases (PRDs), by investigating how Cameroon Development Corporation (CDC) camp dwellers respond to diseases that adversely affect their health and wellbeing. Living in plantation camps is associated with poverty, overcrowding, poor sanitation and the rapid spread of diseases. In a survey of 237 CDC camp dwellers in Cameroon, we used the health belief model to understand the drivers (perceived threats, benefits and cues for treatment seeking) of reported responses. Using logistic regression analysis, we looked for trends in people’s response to malaria. We calculated the odds ratio of factors shown to have an influence on people’s health, such as food, water, sanitation challenges and seeking formal healthcare for malaria. Malaria (40.3%), cholera (20.8%) and diarrhoea (17.7%) were the major PRDs perceived by camp dwellers. We found a strong link between what respondents perceived as PRDS and hygiene conditions. Poverty for our respondents was more about living in poor hygiene conditions than lack of money. Respondents perceived health challenges as stemming from their immediate living environment. Moreover, people employed self-medication and other informal health practices to seek healthcare. Interestingly, even though respondents reported using formal healthcare services as a general response to illness (84%), almost 90% stated that, in the case of malaria, they would use informal healthcare services. Our study recommends that efforts to curb the devastating effects of PRDs should have a strong focus on perceptions (i.e. include diseases that people living in conditions of poverty perceive as PRDs) and on hygiene practices, emphasising how they can be improved. By providing insights into the inter-linkages between poverty and disease, our study offers relevant guidance for potentially successful health promotion interventions.

Environmental and socio-demographic individual, family and neighborhood factors associated with children intestinal parasitoses at Iguazú, in the subtropical northern border of Argentina

PLoS Neglected Tropical Diseases News - 20 November 2017 - 10:00pm

by Maria Romina Rivero, Carlos De Angelo, Pablo Nuñez, Martín Salas, Carlos E. Motta, Alicia Chiaretta, Oscar D. Salomón, Song Liang

Background

Intestinal parasitoses are a major concern for public health, especially in children from middle and low-income populations of tropical and subtropical areas. We examined the presence and co-infection of parasites in humans as well as parasitic environmental contamination in Puerto Iguazú, Argentina. We explored the environmental and socio-demographic characteristics of the persistence of parasites in children and their environment.

Methodology/Principal findings

This cross-section survey was conducted among children population comprised into the area of the public health care centers of Iguazú during June 2013 to May 2016. Copro-parasitological status of 483 asymptomatic children was assessed. Simultaneously, a design-based sampling of 744 soil samples and 530 dog feces was used for characterize the environmental contamination. The 71.5% of these sites were contaminated. Sixteen genera were detected in the environment being hookworms (62.0%) the main pathogens group detected followed by Toxocara spp (16.3%), Trichuris spp (15.2%) and Giardia (6.5%). Total children prevalence raised 58.8%, detecting twelve genera of parasite with Giardia intestinalis as the most prevalent pathogen (29.0%) followed by Enterobius vermicularis (23.0%), Hymenolepis nana (12.4%) and hookworms (4.4%). Through questionnaires and census data, we characterized the socio-demographics conditions at an individual, family and neighborhood levels. A multi-level analysis including environmental contamination data showed that the ´presence of parasites´ was mostly determined by individual (e.g. age, playing habits, previous treatment) and household level (e.g. UBN, WASH, mother's literacy) determinants. Remarkably, to define the level of ‘parasite co-infection’, besides individual and household characteristics, environmental factors at a neighborhood level were important.

Conclusion/Significance

Our work represents the major survey of intestinal parasites in human and environmental samples developed in the region. High prevalence was detected in the children population as well as in their environment. This work shows the importance of considering and promoting multi-level actions over the identified determinants to face this public health problem from integrative approaches.

Prevalence and risk factors associated with <i>Leishmania</i> infection in Trang Province, southern Thailand

PLoS Neglected Tropical Diseases News - 20 November 2017 - 10:00pm

by Jipada Manomat, Saovanee Leelayoova, Lertwut Bualert, Peerapan Tan-ariya, Suradej Siripattanapipong, Mathirut Mungthin, Tawee Naaglor, Phunlerd Piyaraj

Background

Autochthonous cutaneous and visceral leishmaniasis (VL) caused by Leishmania martiniquensis and Leishmania siamensis have been considered emerging infectious diseases in Thailand. The disease burden is significantly underestimated, especially the prevalence of Leishmania infection among HIV-positive patients.

Methods

A cross-sectional study was conducted to determine the prevalence and risk factors associated with Leishmania infection among patients with HIV/AIDS living in Trang province, southern Thailand, between 2015 and 2016. Antibodies against Leishmania infection were assayed using the direct agglutination test (DAT). DNA of Leishmania was detected by ITS1-PCR using the buffy coat. Species of Leishmania were also identified.

Results

Of 724 participants, the prevalence of Leishmania infection was 25.1% (182/724) using either DAT and/or PCR assays. Seroprevalence of Leishmania infection was 18.5% (134/724), while Leishmania DNA detected by the PCR method was 8.4% (61/724). Of these, 24.9% (180/724) were asymptomatic, whereas 0.3% (2/724) were symptomatic VL and VL/CL (cutaneous leishmaniosis). At least five species were identified: L siamensis, L. martiniquensis, L. donovani complex, L. lainsoni, and L. major. Multivariate analysis showed that CD4+ levels <500 cells/μL and living in stilt houses were independently associated with Leishmania infection. Those who were PCR positive for Leishmania DNA were significantly associated with a detectable viral load, whereas non-injection drug use (NIDU) and CD4+ levels <500 cells/μL were potential risk factors of Leishmania seropositivity.

Conclusions

A magnitude of the prevalence of underreporting Leishmania infection among Thai patients with HIV was revealed in this study. Effective public health policy to prevent and control disease transmission is urgently needed.

Liposomal amphotericin B in travelers with cutaneous and muco-cutaneous leishmaniasis: Not a panacea

PLoS Neglected Tropical Diseases News - 20 November 2017 - 10:00pm

by Romain Guery, Benoit Henry, Guillaume Martin-Blondel, Claire Rouzaud, Florence Cordoliani, Gundel Harms, Jean-Pierre Gangneux, Françoise Foulet, Emmanuelle Bourrat, Michel Baccard, Gloria Morizot, Paul-Henri Consigny, Antoine Berry, Johannes Blum, Olivier Lortholary, Pierre Buffet, the French Cutaneous Leishmaniasis Study group & the LeishMan network

Background

Complex cutaneous and muco-cutaneous leishmaniasis (CL and MCL) often requires systemic therapy. Liposomal amphotericin B (L-AmB) has a strong potential for a solid clinical benefit in this indication.

Methods

We conducted a retrospective analysis of data from a French centralized referral treatment program and from the “LeishMan” European consortium database. All patients with parasitologically proven CL or MCL who received at least one dose of L-AmB were included. Positive outcome was based on ulcer closure as per recent WHO workshop guidelines.

Results

From 2008 through 2016, 43 travelers returning from 18 countries (Old World n = 28; New World n = 15) were analyzed with a median follow-up duration of 79 days [range 28–803]. Main clinical forms were: localized CL with one or multiple lesions (n = 32; 74%) and MCL (n = 8; 19%). As per published criteria 19 of 41 patients (46%) were cured 90 days after one course of L-AmB. When the following items -improvement before day 90 but no subsequent follow-up, delayed healing (>3 months) and healing after a second course of L-AmB- were included in the definition of cure, 27 of 43 patients (63%) had a positive outcome. Five patients (MCL = 1; CL = 4) experienced a relapse after a median duration of 6 months [range 3–27] post treatment and 53% of patients (23/43) experienced at least one adverse event including severe hypokalaemia and acute cardiac failure (one patient each). In multivariate analysis, tegumentary infection with L. infantum was associated with complete healing after L-AmB therapy (OR 5.8 IC 95% [1.03–32]) while infection with other species had no impact on outcome.

Conclusion

In conditions close to current medical practice, the therapeutic window of L-AmB was narrow in travellers with CL or MCL, with the possible exception of those infected with L. infantum. Strict follow-up is warranted when using L-AmB in patients with mild disease.

Pages