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Quantitative evaluation of maxillary bone deformation by computed tomography in patients with leprosy

PLoS Neglected Tropical Diseases News - 9 March 2018 - 10:00pm

by Norio Kasai, Osamu Kondo, Koichi Suzuki, Yoshinori Aoki, Norihisa Ishii, Masamichi Goto

Background

Facial deformation as a sequela of leprosy is caused not only by a saddle nose but also by regression of the maxilla, as well documented in paleopathological observations of excavated skeletal remains of patients with leprosy. However, maxillary changes in living patients have been evaluated only by the subjective visual grading. Here, we attempted to evaluate maxillary bone deformation in patients with leprosy using three-dimensional computed tomography (3D-CT).

Methods

Three-dimensional images centered on the maxilla were reconstructed using multiplanar reconstruction methods in former patients with leprosy (n = 10) and control subjects (n = 5); the anterior-posterior length of the maxilla (MA-P) was then measured. The difference between the MA-P of the patients and those of controls was evaluated after compensating for individual skull size. These findings were also compared with those from previous paleopathological studies.

Findings

Three former patients with lepromatous leprosy showed marked atrophy of the maxilla at the prosthion (-8.6, -11.1 and -17.9 mm) which corresponded with the visual appearance of the maxillary deformity, and these results were consistent with paleopathological findings of excavated skeletal remains. Additionally, the precise bone defects of the maxilla could be individually calculated for accurate reconstructive surgery.

Interpretation

We have successfully illustrated maxillary bone deformities in living patients with leprosy. This study also confirmed the maxillary regression described in paleopathological studies.

Development of a reverse genetics system for Sosuga virus allows rapid screening of antiviral compounds

PLoS Neglected Tropical Diseases News - 9 March 2018 - 10:00pm

by Stephen R. Welch, Ayan K. Chakrabarti, Lisa Wiggleton Guerrero, Harley M. Jenks, Michael K. Lo, Stuart T. Nichol, Christina F. Spiropoulou, César G. Albariño

Sosuga virus (SOSV) is a recently discovered zoonotic paramyxovirus isolated from a single human case in 2012; it has been ecologically and epidemiologically associated with transmission by the Egyptian rousette bat (Rousettus aegyptiacus). Bats have long been recognized as sources of novel zoonotic pathogens, including highly lethal paramyxoviruses like Nipah virus (NiV) and Hendra virus (HeV). The ability of SOSV to cause severe human disease supports the need for studies on SOSV pathogenesis to better understand the potential impact of this virus and to identify effective treatments. Here we describe a reverse genetics system for SOSV comprising a minigenome-based assay and a replication-competent infectious recombinant reporter SOSV that expresses the fluorescent protein ZsGreen1 in infected cells. First, we used the minigenome assay to rapidly screen for compounds inhibiting SOSV replication at biosafety level 2 (BSL-2). The antiviral activity of candidate compounds was then tested against authentic viral replication using the reporter SOSV at BSL-3. We identified several compounds with anti-SOSV activity, several of which also inhibit NiV and HeV. Alongside its utility in screening for potential SOSV therapeutics, the reverse genetics system described here is a powerful tool for analyzing mechanisms of SOSV pathogenesis, which will facilitate our understanding of how to combat the potential public health threats posed by emerging bat-borne paramyxoviruses.

Characterization of the rhesus macaque (<i>Macaca mulatta</i>) scrub typhus model: Susceptibility to intradermal challenge with the human pathogen <i>Orientia tsutsugamushi</i> Karp

PLoS Neglected Tropical Diseases News - 9 March 2018 - 10:00pm

by Piyanate Sunyakumthorn, Suwit J. Somponpun, Rawiwan Im-erbsin, Tippawan Anantatat, Kemajittra Jenjaroen, Susanna J. Dunachie, Eric D. Lombardini, Robin L. Burke, Stuart D. Blacksell, James W. Jones, Carl J. Mason, Allen L. Richards, Nicholas P. J. Day, Daniel H. Paris

Background

Scrub typhus is an important endemic disease in tropical Asia caused by Orientia tsutsugamushi for which no effective broadly protective vaccine is available. The successful evaluation of vaccine candidates requires well-characterized animal models and a better understanding of the immune response against O. tsutsugamushi. While many animal species have been used to study host immunity and vaccine responses in scrub typhus, only limited data exists in non-human primate (NHP) models.

Methodology/Principle findings

In this study we evaluated a NHP scrub typhus disease model based on intradermal inoculation of O. tsutsugamushi Karp strain in rhesus macaques (n = 7). After an intradermal inoculation with 106 murine LD50 of O. tsutsugamushi at the anterior thigh (n = 4) or mock inoculum (n = 3), a series of time course investigations involving hematological, biochemical, molecular and immunological assays were performed, until day 28, when tissues were collected for pathology and immunohistochemistry. In all NHPs with O. tsutsugamushi inoculation, but not with mock inoculation, the development of a classic eschar with central necrosis, regional lymphadenopathy, and elevation of body temperature was observed on days 7–21 post inoculation (pi); bacteremia was detected by qPCR on days 6–18 pi; and alteration of liver enzyme function and increase of white blood cells on day 14 pi. Immune assays demonstrated raised serum levels of soluble cell adhesion molecules, anti-O. tsutsugamushi-specific antibody responses (IgM and IgG) and pathogen-specific cell-mediated immune responses in inoculated macaques. The qPCR assays detected O. tsutsugamushi in eschar, spleen, draining and non-draining lymph nodes, and immuno-double staining demonstrated intracellular O. tsutsugamushi in antigen presenting cells of eschars and lymph nodes.

Conclusions/Significance

These data show the potential of using rhesus macaques as a scrub typhus model, for evaluation of correlates of protection in both natural and vaccine induced immunity, and support the evaluation of future vaccine candidates against scrub typhus.

A rabies lesson improves rabies knowledge amongst primary school children in Zomba, Malawi

PLoS Neglected Tropical Diseases News - 9 March 2018 - 10:00pm

by Jordana L. Burdon Bailey, Luke Gamble, Andrew D. Gibson, Barend M. deC. Bronsvoort, Ian G. Handel, Richard J. Mellanby, Stella Mazeri

Rabies is an important neglected disease, which kills around 59,000 people a year. Over a third of these deaths are in children less than 15 years of age. Almost all human rabies deaths in Africa and Asia are due to bites from infected dogs. Despite the high efficacy of current rabies vaccines, awareness about rabies preventive healthcare is often low in endemic areas. It is therefore common for educational initiatives to be conducted in conjunction with other rabies control activities such as mass dog vaccination, however there are few examples where the efficacy of education activities has been assessed. Here, primary school children in Zomba, Malawi, were given a lesson on rabies biology and preventive healthcare. Subsequently, a mass dog vaccination programme was delivered in the same region. Knowledge and attitudes towards rabies were assessed by a questionnaire before the lesson, immediately after the lesson and 9 weeks later to assess the impact the lesson had on school children’s knowledge and attitudes. This assessment was also undertaken in children who were exposed to the mass dog vaccination programme but did not receive the lesson. Knowledge of rabies and how to be safe around dogs increased following the lesson (both p<0.001), and knowledge remained higher than baseline 9 weeks after the lesson (both p<0.001). Knowledge of rabies and how to be safe around dogs was greater amongst school children who had received the lesson compared to school children who had not received the lesson, but had been exposed to a rabies vaccination campaign in their community (both p<0.001) indicating that the lesson itself was critical in improving knowledge. In summary, we have shown that a short, focused classroom-based lesson on rabies can improve short and medium-term rabies knowledge and attitudes of Malawian schoolchildren.

Cell walls of the dimorphic fungal pathogens <i>Sporothrix schenckii</i> and <i>Sporothrix brasiliensis</i> exhibit bilaminate structures and sloughing of extensive and intact layers

PLoS Neglected Tropical Diseases News - 9 March 2018 - 10:00pm

by Leila M. Lopes-Bezerra, Louise A. Walker, Gustavo Niño-Vega, Héctor M. Mora-Montes, Gabriela W. P. Neves, Hector Villalobos-Duno, Laura Barreto, Karina Garcia, Bernardo Franco, José A. Martínez-Álvarez, Carol A. Munro, Neil A. R. Gow

Sporotrichosis is a subcutaneous mycosis caused by pathogenic species of the Sporothrix genus. A new emerging species, Sporothrix brasiliensis, is related to cat-transmitted sporotrichosis and has severe clinical manifestations. The cell wall of pathogenic fungi is a unique structure and impacts directly on the host immune response. We reveal and compare the cell wall structures of Sporothrix schenckii and S. brasiliensis using high-pressure freezing electron microscopy to study the cell wall organization of both species. To analyze the components of the cell wall, we also used infrared and 13C and 1H NMR spectroscopy and the sugar composition was determined by quantitative high-performance anion-exchange chromatography. Our ultrastructural data revealed a bi-layered cell wall structure for both species, including an external microfibrillar layer and an inner electron-dense layer. The inner and outer layers of the S. brasiliensis cell wall were thicker than those of S. schenckii s. str., correlating with an increase in the chitin and rhamnose contents. Moreover, the outer microfibrillar layer of the S. brasiliensis cell wall had longer microfibrils interconnecting yeast cells. Distinct from those of other dimorphic fungi, the cell wall of Sporothrix spp. lacked α-glucan component. Interestingly, glycogen α-particles were identified in the cytoplasm close to the cell wall and the plasma membrane. The cell wall structure as well as the presence of glycogen α-particles varied over time during cell culture. The structural differences observed in the cell wall of these Sporothrix species seemed to impact its uptake by monocyte-derived human macrophages. The data presented here show a unique cell wall structure of S. brasiliensis and S. schenckii during the yeast parasitic phase. A new cell wall model for Sporothrix spp. is therefore proposed that suggests that these fungi molt sheets of intact cell wall layers. This observation may have significant effects on localized and disseminated immunopathology.

Childhood leptospirosis in an industrialized country: Population-based study in Okinawa, Japan

PLoS Neglected Tropical Diseases News - 8 March 2018 - 10:00pm

by Kouki Tomari, Takao Toyokawa, Takuto Takahashi, Tetsuya Kakita, Sho Okano, Hisako Kyan, Naoya Tonegawa, Teppei Okawa, Takashi Matsuoka, Tsutomu Matsumora

Leptospirosis is considered underdiagnosed because of its nonspecific presentation and lack of proper understanding of its epidemiology. Early diagnosis and treatment are crucial. However, few data are available on confirmed leptospirosis cases in children in industrialized countries. We therefore aimed to describe epidemiologic and clinical characteristics of laboratory-confirmed childhood leptospirosis in Okinawa, Japan. We reviewed the national surveillance data of pediatric leptospirosis in Okinawa, Japan from January 2003 through December 2015. The database included all of laboratory-confirmed leptospirosis diagnosed at the only central laboratory for leptospirosis in the region. There were 44 children (0–20 years of age) with laboratory-confirmed leptospirosis. Of these, 90% were male, 91% were 10–20 years of age, and 96% of cases occurred in August and September. The number of laboratory-confirmed patients ranged from 0 to 11 per year (mean: 3.3 per year), and the estimated annual rate was 1.0 per 100,000 pediatric populations. In all cases, the presumed infection route was recreational exposure to river water. Commonly observed manifestations include fever (95%), myalgia (52%), and conjunctival suffusion (52%). Childhood leptospirosis in Okinawa, Japan occurred predominantly in teenage boys after freshwater exposure in summer, and most patients had characteristic conjunctival suffusion. Cohort studies would be helpful to better understand more detailed clinical manifestations in association with prognosis.

Study of diagnostic accuracy of Helmintex, Kato-Katz, and POC-CCA methods for diagnosing intestinal schistosomiasis in Candeal, a low intensity transmission area in northeastern Brazil

PLoS Neglected Tropical Diseases News - 8 March 2018 - 10:00pm

by Catieli Gobetti Lindholz, Vivian Favero, Carolina de Marco Verissimo, Renata Russo Frasca Candido, Renata Perotto de Souza, Renata Rosa dos Santos, Alessandra Loureiro Morassutti, Helio Radke Bittencourt, Malcolm K. Jones, Timothy G. St. Pierre, Carlos Graeff-Teixeira

Control initiatives have successfully reduced the prevalence and intensity of schistosomiasis transmission in several localities around the world. However, individuals that release low numbers of eggs in their feces may not be detected by classical methods that are limited by low sensitivity. Given that accurate estimates of prevalence are key to implementing planning control actions for the elimination of schistosomiasis, new diagnostic tools are needed to effectively monitor infections and confirm transmission interruption. The World Health Organization recommends the Kato-Katz (KK) thick smear as a parasitological test for epidemiological surveys, even though this method has been demonstrated to underestimate prevalence when egg burdens are low. The point-of-care immunodiagnostic for detecting schistosome cathodic circulating antigen (POC-CCA) method has been proposed as a more sensitive substitute for KK in prevalence estimations. An alternative diagnostic, the Helmintex (HTX) method, isolates eggs from fecal samples with the use of paramagnetic particles in a magnetic field. Here, a population-based study involving 461 individuals from Candeal, Sergipe State, Brazil, was conducted to evaluate these three methods comparatively by latent class analysis (LCA). The prevalence of schistosomiasis mansoni was determined to be 71% with POC-CCA, 40.% with HTX and 11% with KK. Most of the egg burdens of the individuals tested (70%) were < 1 epg, thereby revealing a dissociation between prevalence and intensity in this locality. Therefore, the present results confirm that the HTX method is a highly sensitive egg detection procedure and support its use as a reference method for diagnosing intestinal schistosomiasis and for comparative evaluation of other tests.

Paradoxical worsening of <i>Emergomyces africanus</i> infection in an HIV-infected male on itraconazole and antiretroviral therapy

PLoS Neglected Tropical Diseases News - 8 March 2018 - 10:00pm

by Kenneth Crombie, Zandile Spengane, Michael Locketz, Sipho Dlamini, Rannakoe Lehloenya, Sean Wasserman, Tsidiso G. Maphanga, Nelesh P. Govender, Chris Kenyon, Ilan S. Schwartz

Participatory approaches and open data on venomous snakes: A neglected opportunity in the global snakebite crisis?

PLoS Neglected Tropical Diseases News - 8 March 2018 - 10:00pm

by Lester Darryl Geneviève, Nicolas Ray, François Chappuis, Gabriel Alcoba, Maria Rosa Mondardini, Isabelle Bolon, Rafael Ruiz de Castañeda

Zika virus epidemiology in Bolivia: A seroprevalence study in volunteer blood donors

PLoS Neglected Tropical Diseases News - 7 March 2018 - 10:00pm

by Paola Mariela Saba Villarroel, Elif Nurtop, Boris Pastorino, Yelin Roca, Jan Felix Drexler, Pierre Gallian, Thomas Jaenisch, Isabelle Leparc-Goffart, Stéphane Priet, Laetitia Ninove, Xavier de Lamballerie

Background

Zika virus (ZIKV), was widely reported in Latin America and has been associated with neuropathologies, as microcephaly, but only few seroprevalence studies have been published to date. Our objective was to determine the seroprevalence amongst Bolivian blood donors and estimate the future potential circulation of the virus.

Methodology

A ZIKV seroprevalence study was conducted between December 2016 and April 2017 in 814 asymptomatic Bolivian volunteer blood donors residing in various eco-environments corresponding to contrasting entomological activities. It was based on detection of IgG to ZIKV using NS1 ELISA screening, followed by a seroneutralisation test in case of positive or equivocal ELISA result.

Conclusions/Significance

Analysis revealed that ZIKV circulation occurred in tropical areas (Beni: 39%; Santa Cruz de la Sierra: 21.5%) but not in highlands (~0% in Cochabamba, La Paz, Tarija). It was modulated by Aedes aegypti activity and the virus spread was not limited by previous immunity to dengue. Cases were geo-localised in a wide range of urban areas in Santa Cruz and Trinidad. No differences in seroprevalence related to gender or age-groups could be identified. It is concluded that ZIKV has been intensely circulating in the Beni region and has still a significant potential for propagating in the area of Santa Cruz.

Changing demographics of visceral leishmaniasis in northeast Brazil: Lessons for the future

PLoS Neglected Tropical Diseases News - 6 March 2018 - 10:00pm

by Iraci Duarte Lima, Adila L. M. Lima, Carolina de Oliveira Mendes-Aguiar, José F. V. Coutinho, Mary E. Wilson, Richard D. Pearson, José Wilton Queiroz, Selma M. B. Jeronimo

Background

Visceral leishmaniasis (VL) caused by Leishmania infantum became a disease of urban areas in Brazil in the last 30 years and there has been an increase in asymptomatic L. infantum infection with these areas.

Methodology/Principal findings

A retrospective study of human VL was performed in the state of Rio Grande do Norte, Brazil, for the period of 1990–2014. The data were divided into five-time periods. For all VL cases, data on sex, age, nutritional status and childhood vaccination were collected. Geographic information system tools and statistical models were used to analyze the dispersion of human VL. The mean annual incidence of VL was 4.6 cases/100,000 inhabitants, with total 3,252 cases reported. The lethality rate was 6.4%. Over time the annual incidence of VL decreased in the 0–4 years (p<0.0001) and 5–9 (p <0.0001) age groups, but increased in ages 20–39 (p<0.001) and >40 years (p<0.0001). VL occurred more often in males (β2 = 2.5; p<0.0001). The decreased incidence of VL in children was associated with improved nutritional status and childhood immunizations including measles, poliomyelitis, BCG, and hepatitis B. Human VL correlated temporally and geographically with canine L. infantum infection (p = 0.002, R2 = 0.438), with rainfall and with Lutzomyia longipalpis density (r = 0.762). Overall, the incidence of VL decreased, while VL-AIDS increased, especially between 2010–2014. VL was more frequently found in areas that lacked urban infrastructure, detected by lack of garbage collection and sewers, whereas HIV infection was associated with higher levels of schooling and evidence of higher socioeconomic status.

Conclusion/Significance

The demographics of VL in northeastern Brazil have changed. Disease incidence has decreased in children and increased in adults. They were associated with improvements in nutrition, socioeconomic status and immunization rates. Concurrent VL-AIDS poses a serious challenge for the future.

Altered vector competence in an experimental mosquito-mouse transmission model of Zika infection

PLoS Neglected Tropical Diseases News - 5 March 2018 - 10:00pm

by Ryuta Uraki, Andrew K. Hastings, Andrea Gloria-Soria, Jeffrey R. Powell, Erol Fikrig

Few animal models of Zika virus (ZIKV) infection have incorporated arthropod-borne transmission. Here, we establish an Aedes aegypti mosquito model of ZIKV infection of mice, and demonstrate altered vector competency among three strains, (Orlando, ORL, Ho Chi Minh, HCM, and Patilas, PAT). All strains acquired ZIKV in their midguts after a blood meal from infected mice, but ZIKV transmission only occurred in mice fed upon by HCM, and to a lesser extent PAT, but not ORL, mosquitoes. This defect in transmission from ORL or PAT mosquitoes was overcome by intrathoracic injection of ZIKV into mosquito. Genetic analysis revealed significant diversity among these strains, suggesting a genetic basis for differences in ability for mosquito strains to transmit ZIKV. The intrathoracic injection mosquito-mouse transmission model is critical to understanding the influence of mosquitoes on ZIKV transmission, infectivity and pathogenesis in the vertebrate host, and represents a natural transmission route for testing vaccines and therapeutics. (152 words)

<i>Onchocerca volvulus</i> infection in Tihama region - West of Yemen: Continuing transmission in ivermectin-targeted endemic foci and unveiled endemicity in districts with previously unknown status

PLoS Neglected Tropical Diseases News - 5 March 2018 - 10:00pm

by Mohammed A. K. Mahdy, Rashad Abdul-Ghani, Thaker A. A. Abdulrahman, Samira M. A. Al-Eryani, Abdulsalam M. Al-Mekhlafi, Sami A. A. Alhaidari, Ahmed A. Azazy

Background

Onchocerciasis in Yemen is one of the most neglected diseases, where baseline estimates of onchocerciasis and monitoring of the impact of ivermectin regularly administered to the affected individuals on its transmission are lacking. Therefore, this study aimed to determine the anti-Ov16 IgG4 seroprevalence among local communities of Hodeidah and Al-Mahwit governorates of Tihama Region. The factors possibly associated with previous exposure to infection were also studied.

Methodology/Principal findings

This cross-sectional study was conducted in two ivermectin-targeted districts endemic for onchocerciasis in Hodeidah and Al-Mahwit and two untargeted districts with unknown previous endemicity in Hodeidah between February and July 2017. For 508 residents sampled by a multi-stage random approach, data were collected and blood specimens were screened for anti-Ov16 IgG4 using the SD BIOLINE Onchocerciasis IgG4 rapid tests. The study revealed an overall anti-Ov16 IgG4 rate of 18.5% (94/508) in all surveyed districts, with 10.2% (12/118) of children aged ≤10 years being seropositive. Moreover, rates of 8.0% (4/50) and 6.1% (4/66) were found in districts not officially listed as endemic for the disease. Multivariable analysis confirmed the age of more than ten years and residing within a large family as the independent predictors of exposure to infection.

Conclusions/Significance

Onchocerciasis transmission is still ongoing as supported by the higher anti-Ov16 IgG4 seroprevalence rate among children aged ≤10 years compared to that (<0.1%) previously set by the World Health Organization as a serologic criterion for transmission interruption. Further large-scale studies combining serologic and entomologic criteria are recommended for the mapping of O. volvulus in human and blackfly populations in endemic foci and their neighboring areas of uncertain endemicity. In addition, ivermectin distribution, coverage and impact on disease transmission need to be continually assessed.

CD39 and immune regulation in a chronic helminth infection: The puzzling case of <i>Mansonella ozzardi</i>

PLoS Neglected Tropical Diseases News - 5 March 2018 - 10:00pm

by Nathália F. Lima, Raquel M. Gonçalves-Lopes, Yvonne C. M. Kruize, Maria Yazdanbakhsh, Marcelo U. Ferreira

Background

Chronic helminth infections typically induce an immunoregulatory environment, with markedly reduced immune responses to both parasite-specific and unrelated bystander antigens. Here we tested whether these changes are also observed in human infections with Mansonella ozzardi, a neglected filarial nematode widely distributed across Latin America.

Methods

CD4+ T cell populations from microfilaremic (Fil+) and uninfected (Fil-) inhabitants in M. ozzardi-endemic riverine communities in Brazil were characterized by flow cytometry analysis. Plasma concentrations of a wide range of cytokines and chemokines were measured. We examined whether M. ozzardi infection is associated with suppressed in vitro lymphoproliferative and inflammatory cytokine responses upon stimulation with filarial antigen, unrelated antigens or mitogens.

Principal findings/Conclusions

Fil+ subjects had lower plasma levels of selected inflammatory cytokines, such as TNF-α, IL-8, and IL-6, than their Fil- counterparts. However, we found no evidence for attenuated T-cell responses to filarial antigens or co-endemic pathogens, such as malaria parasites and Toxoplasma gondii. CD4+ T cells expressing CD39, an ectonucleosidase involved in the generation of the anti-inflammatory molecule adenosine, were increased in frequency in Fil+ subjects, compared to uninfected controls. Significantly, such an expansion was directly proportional to microfilarial loads. Surprisingly, CD39 blocking with a neutralizing antibody suppressed antigen-driven lymphoproliferation in vitro, while decreasing inflammatory cytokine responses, in Fil+ and Fil- individuals. These findings suggest that circulating CD4+ CD39+ T cells comprise subsets with both regulatory and stimulatory roles that contribute to the immune homeostasis in chronic M. ozzardi infection.

Pathogenesis of bat rabies in a natural reservoir: Comparative susceptibility of the straw-colored fruit bat (<i>Eidolon helvum</i>) to three strains of Lagos bat virus

PLoS Neglected Tropical Diseases News - 5 March 2018 - 10:00pm

by Richard Suu-Ire, Lineke Begeman, Ashley C. Banyard, Andrew C. Breed, Christian Drosten, Elisa Eggerbauer, Conrad M. Freuling, Louise Gibson, Hooman Goharriz, Daniel L. Horton, Daisy Jennings, Ivan V. Kuzmin, Denise Marston, Yaa Ntiamoa-Baidu, Silke Riesle Sbarbaro, David Selden, Emma L. Wise, Thijs Kuiken, Anthony R. Fooks, Thomas Müller, James L. N. Wood, Andrew A. Cunningham

Rabies is a fatal neurologic disease caused by lyssavirus infection. People are infected through contact with infected animals. The relative increase of human rabies acquired from bats calls for a better understanding of lyssavirus infections in their natural hosts. So far, there is no experimental model that mimics natural lyssavirus infection in the reservoir bat species. Lagos bat virus is a lyssavirus that is endemic in straw-colored fruit bats (Eidolon helvum) in Africa. Here we compared the susceptibility of these bats to three strains of Lagos bat virus (from Senegal, Nigeria, and Ghana) by intracranial inoculation. To allow comparison between strains, we ensured the same titer of virus was inoculated in the same location of the brain of each bat. All bats (n = 3 per strain) were infected, and developed neurological signs, and fatal meningoencephalitis with lyssavirus antigen expression in neurons. There were three main differences among the groups. First, time to death was substantially shorter in the Senegal and Ghana groups (4 to 6 days) than in the Nigeria group (8 days). Second, each virus strain produced a distinct clinical syndrome. Third, the spread of virus to peripheral tissues, tested by hemi-nested reverse transcriptase PCR, was frequent (3 of 3 bats) and widespread (8 to 10 tissues positive of 11 tissues examined) in the Ghana group, was frequent and less widespread in the Senegal group (3/3 bats, 3 to 6 tissues positive), and was rare and restricted in the Nigeria group (1/3 bats, 2 tissues positive). Centrifugal spread of virus from brain to tissue of excretion in the oral cavity is required to enable lyssavirus transmission. Therefore, the Senegal and Ghana strains seem most suitable for further pathogenesis, and for transmission, studies in the straw-colored fruit bat.

The non-canonical Notch signaling is essential for the control of fertility in <i>Aedes aegypti</i>

PLoS Neglected Tropical Diseases News - 5 March 2018 - 10:00pm

by Chia-Hao Chang, Yu-Ting Liu, Shih-Che Weng, I-Yi Chen, Po-Nien Tsao, Shin-Hong Shiao

The Notch signaling pathway is a highly evolutionarily-conserved cell-cell signaling pathway that regulates many events during development. It plays a pivotal role in the regulation of fundamental cellular processes, such as cell proliferation, stem cell maintenance, and differentiation during embryonic and adult development. However, functions of Notch signaling in Aedes aegypti, the major mosquito vector for dengue, are largely unknown. In this study, we identified a unique feature of A. aegypti Notch (AaNotch) in the control of the sterile-like phenotype in female mosquitoes. Silencing AaNotch with a reverse genetic approach significantly reduced the fecundity and fertility of the mosquito. Silencing AaNotch also resulted in the prevention of micropyle formation, which led to impaired fertilization. In addition, JNK phosphorylation (a signaling molecule in the non-canonical Notch signaling pathway) was inhibited in the absence of AaNotch. Furthermore, treatment with a JNK inhibitor in the mosquito resulted in impaired fecundity and fertility. Taken together, our results demonstrate that non-canonical Notch signaling is essential for controlling fertility in the A. aegypti mosquito.

<i>Clonorchis sinensis</i> adult-derived proteins elicit Th2 immune responses by regulating dendritic cells via mannose receptor

PLoS Neglected Tropical Diseases News - 5 March 2018 - 10:00pm

by Lu Zhao, Mengchen Shi, Lina Zhou, Hengchang Sun, Xiaona Zhang, Lei He, Zeli Tang, Caiqin Wang, Yinjuan Wu, Tingjin Chen, Mei Shang, Xinyi Zhou, Zhipeng Lin, Xuerong Li, Xinbing Yu, Yan Huang

Background

Clonorchis sinensis (C. sinensis) is the most widespread human liver fluke in East Asia including China and Korea. Clonorchiasis as a neglected tropical zoonosis, leads to serious economic and public health burden in China. There are considerable evidences for an etiological relation between chronic clonorchiasis and liver fibrosis in human beings. Liver fibrosis is a highly conserved and over-protected response to hepatic tissue injury. Immune cells including CD4+ T cell as well as dendritic cell (DC), and pro-fibrogenic cytokines like interleukin 4 (IL-4), IL-13 have been identified as vital manipulators in liver fibrogenesis. Our previous studies had a mere glimpse of T helper type 2 (Th2) dominant immune responses as key players in liver fibrosis induced by C. sinensis infection, but little is known about the involved mechanisms in this pathological process.

Methodology/Principal findings

By flow cytometry (FACS), adult-derived total proteins of C. sinensis (CsTPs) down-regulated the expression of surface markers CD80, CD86 and major histocompatibility complex class II (MHC-II) on lipopolysaccharide (LPS) induced DC. ELISA results demonstrated that CsTPs inhibited IL-12p70 release from LPS-treated bone marrow-derived dendritic cells (BMDC). IL-10 level increased in a time-dependent manner in LPS-treated BMDCs after incubation with CsTPs. CD4+ T cells incubated with LPS-treated BMDCs plus CsTPs could significantly elevate IL-4 level by ELISA. Meanwhile, elevated expression of pro-fibrogenic mediators including IL-13 and IL-4 were detected in a co-culture system of LPS-activated BMDCs and naive T cells containing CsTPs. In vivo, CsTPs-immunized mice enhanced expression of type 2 cytokines IL-13, IL-10 and IL-4 in both splenocytes and hepatic tissue. Exposure of BMDCs to CsTPs activated expression of mannose receptor (MR) but not toll like receptor 2 (TLR2), TLR4, C-type lectin receptor DC-SIGN and Dectin-2 on the cell surface by RT-PCR and FACS. Blockade of MR almost completely reversed the capacity of CsTPs to suppress LPS-induced BMDCs surface markers CD80, CD86 and MHC-II expression, and further made these BMDCs fail to induce a Th2-skewed response as well as Th2 cell-associated cytokines IL-13 and IL-4 release in vitro.

Conclusions/Significance

Collectively, we validated that CsTPs could suppress the maturation of BMDCs in the presence of LPS via binding MR, and showed that the CsTPs-pulsed BMDCs actively polarized naive T helper cells to Th2 cells though the production of IL-10 instead of IL-12. CsTPs endowed host with the capacity to facilitate Th2 cytokines production including IL-13 and IL-4 in vitro and vivo. The study might provide useful information for developing potential therapeutic targets against the disease.

Rift Valley Fever: A survey of knowledge, attitudes, and practice of slaughterhouse workers and community members in Kabale District, Uganda

PLoS Neglected Tropical Diseases News - 5 March 2018 - 10:00pm

by Annabelle de St. Maurice, Luke Nyakarahuka, Lawrence Purpura, Elizabeth Ervin, Alex Tumusiime, Stephen Balinandi, Jackson Kyondo, Sophia Mulei, Patrick Tusiime, Craig Manning, Pierre E. Rollin, Barbara Knust, Trevor Shoemaker

Background

Rift Valley Fever virus (RVF) is a zoonotic virus in the Phenuiviridae family. RVF outbreaks can cause significant morbidity and mortality in humans and animals. Following the diagnosis of two RVF cases in March 2016 in southern Kabale district, Uganda, we conducted a knowledge, attitudes and practice (KAP) survey to identify knowledge gaps and at-risk behaviors related to RVF.

Methodology/Principal findings

A multidisciplinary team interviewed 657 community members, including abattoir workers, in and around Kabale District, Uganda. Most participants (90%) had knowledge of RVF and most (77%) cited radio as their primary information source. Greater proportions of farmers (68%), herdsmen (79%) and butchers (88%) thought they were at risk of contracting RVF compared to persons in other occupations (60%, p<0.01). Participants most frequently identified bleeding as a symptom of RVF. Less than half of all participants reported fever, vomiting, and diarrhea as common RVF symptoms in either humans or animals. The level of knowledge about human RVF symptoms did not vary by occupation; however more farmers and butchers (36% and 51%, respectively) had knowledge of RVF symptoms in animals compared to those in other occupations (30%, p<0.01). The use of personal protective equipment (PPE) when handling animals varied by occupation, with 77% of butchers using some PPE and 12% of farmers using PPE. Although most butchers said that they used PPE, most used gumboots (73%) and aprons (60%) and less than 20% of butchers used gloves or eye protection when slaughtering.

Conclusions

Overall, knowledge, attitudes and practice regarding RVF in Kabale District Uganda could be improved through educational efforts targeting specific populations.

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