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Background: The immunoglobulin E (IgE) response to Angiostrongylus cantonensis infection increases in the host. This study analyzed the IgG and IgE responses detected in different body fluids of A. cantonensis-infected mice. Methods: BALB/c (high susceptibility), CBA (medium), and C57BL/6 and C57BL/10 (resistance) strain mice were used in this study. The levels of IgM, IgG, and IgE in the serum and cerebrospinal fluid (CSF) from infected mice were compared. A. cantonensis-reactive antigens from BALB/c and C57BL/6 mice CSF were also analyzed. Results: Antibodies against fifth-stage larvae (L5) antigens increased in mice CSF, particularly IgE, relate to worm rejection and the susceptibility of different mouse strains. The increased IgE level in BALB/c mice CSF is lower than that from others, suggesting IgE response in brain is more important than that in serum. Anti-L5 and anti-excretory/secretory (ES) antigen IgE and IgG responses in CSF were analyzed. In addition, the antibody-dependent eosinophil-mediated cytotoxicity induced by anti-excretory/secretory (ES) antigen antibodies may be the reason of severe brain inflammation in infected BALB/c mice. IgE and IgG antibodies against a 105 kDa protein of L5 antigen was detected at week 3 post-infection in C57BL/6 mice and week 5 post-infection in BALB/c mice. We suggest that 105 kDa protein is related with the antibody response of A. cantonensis-infected mice. Conclusion: We found that IgE antibodies in mice CSF against L5 antigens related to worm rejection in mice brains. This study may help to identify specific angiostrongyliasis markers that can be applied for clinical diagnosis and treatment in future.

Singlet oxygen (1O2) is a potent biocide potentially deployable for integrated control of tropical diseases and their insect vectors. This very short-lived free radical is highly destructive of cellular molecules when generated intracellularly. Most organisms, including parasites and vectors, are defenseless against 1O2 except for plants, which produce it abundantly during photosynthesis, hence, the acquisition of specific mechanisms for its detoxification. In the presence of O2 under physiological conditions, certain dyes or photosensitizers (PS), e.g., porphyrins and phthalocyanines (PC), are excitable by light to produce biocidal 1O2. Its half-life is in the order of microseconds, necessitating its intracellular generation in order to harness its biocidal activity most effectively. This is achievable by loading cells with PS for excitation with light to produce 1O2in situ. One example to achieve this is the genetic engineering of Leishmania to complement its inherent defects in porphyrin biosynthesis, resulting in cytosolic accumulation of abundant PS in the form of uroporphyrin 1 (URO). Another example is the chemical engineering of PC for hydrophilicity, thereby facilitating the endocytosis of such PS by cells. Leishmania loaded with cytosolic URO and endosomal PC are inactivated by the 1O2 produced via light-activation of these PS in the two different cell compartments. The inactivated Leishmania are nonviable, but have their natural vaccines and adjuvants well-preserved for prophylactic vaccination against experimental leishmaniasis. 1O2-inactivated Leishmania is potentially useful to serve as a platform for the safe and effective delivery of transgenically add-on vaccines against malignant and viral diseases in experimental models. Hydrophilic and cationic PC were also shown experimentally to act as a new type of dim light-activable insecticides, i.e., their mosquito larvicidal activities with

Diphyllobothriosis is an infectious disease caused by the consumption of raw freshwater or marine fish containing larvae of broad tapeworms (Diphyllobothriidae). In the present study, we critically reviewed all cases of human diphyllobothriosis reported from Taiwan, including unpublished reports from hospitals in Taipei. Genotyping based on mitochondrial DNA marker (cox1) confirmed that two of the recent cases were caused by Dibothriocephalus nihonkaiensis, which is not native to Taiwan and was probably imported with Pacific salmon infected with larvae of D. nihonkaiensis. The causative species previously reported in Taiwan could not be definitively confirmed. However, considering the distribution of Dibothriocephalus latus, which is not endemic in Taiwan, past cases diagnosed as D. latus are questionable.

Emerging and re-emerging parasitic diseases can cause significant economic burdens at national and global levels. However, governments often underestimate or ignore these diseases, especially in developed countries. This retrospective, case-oriented study analyzed parasitic diseases reported in Taiwan between 2001 and 2018. One hundred and thirty-two eligible clinical profiles of Taiwanese patients obtained from the NCBI, Scopus, Google Scholar, and Web of Science databases and local journals according to age, sex, source of infection, symptoms, risk factors, and geographical regions were analyzed. The analysis results showed that the number/frequency of cases caused by nematodes (46.97%) or protozoa (37.88%) was significantly higher than that of trematodes (9.85%) or cestodes (5.30%) (p < 0.0001). Northern Taiwan (46.97%) had a significantly higher rate than Southern Taiwan (33.33%), Central Taiwan (8.33%), and Eastern Taiwan (5.30%) (p < 0.05). The 15–65 age group (68.94%) had a significantly higher rate than the 65–90 age group (22.73%) and the 0–15 age group (8.33%) (p < 0.0001). Males (70.46%) had a significantly higher number/frequency of cases than females (29.54%) (p < 0.0001). People who acquired the infection through the food/soil route (32.58%) or who had a low immune status (32.58%) had a higher rate than travel-related infections (15.15%) (p < 0.001). The present study showed that emerging/reemerging parasitic infections continue to be of great concern to the lives and health of Taiwanese citizens and, if ignored, will threaten the health of the Taiwanese people; therefore, the delineation of preventive measures by health authorities is urgently warranted.

Abstract Background Actinomyces odontolyticus is not commonly recognized as a causative microbe of liver abscess. The detection and identification of A. odontolyticus in laboratories and its recognition as a pathogen in clinical settings can be challenging. However, in the past decades, knowledge on the clinical relevance of A. odontolyticus is gradually increasing. A. odontolyticus is the dominant oropharyngeal flora observed during infancy [Li et al. in Biomed Res Int 2018:3820215, 2018]. Herein we report a case of severe infection caused by A. odontolyticus in an immunocompromised patient with disruption of the gastrointestinal (GI) mucosa. Case presentation We present a unique case of a patient with human immunodeficiency virus infection who was admitted due to liver abscess and was subsequently diagnosed as having coinfection of A. odontolyticus, Streptococcus constellatus, and Candida albicans during the hospital course. The empirical antibiotics metronidazole and ceftriaxone were replaced with the intravenous administration of fluconazole and ampicillin. However, the patient’s condition deteriorated, and he died 3 weeks later. Conclusion This report is one of the first to highlight GI tract perforation and its clinical relevance with A. odontolyticus infection. A. odontolyticus infection should be diagnosed early in high-risk patients, and increased attention should be paid to commensal flora infection in immunocompromised individuals.

Toxocariasis is a zoonosis disease with high sero-prevalence in Southeast Asian. Neurotoxocariasis has never been reported in Taiwan. Herein, we presented 2 cases of neurotoxocariasis. The first case is a 48-year-old man with febrile headache, rapid progressive cognitive problems and later thoracic myelitis. Meningeal enhancements on the corresponding sites were found on magnetic resonance imaging (MRI). Eosinophilic pleocytosis was present in peripheral blood and cerebrospinal fluid (CSF). A positive Toxocara canis larval excretory-secretory antigen (TcES)-based immunoblotting test for CSF confirmed the diagnosis. The second case is a 42-year-old woman of progressive headache with features of increased intracranial pressure. CSF analysis showed lymphocytic pleocytosis initially and eosinophilic pleocytosis later. Her brain MRI was normal. The diagnosis was confirmed by the presence of anti-TcES IgG in CSF. The two cases were soonly cured by mebendazole. Neurotoxocariasis presented a broad spectrum of neurological symptoms and the CSF profile can be non-eosinophilic pleocytosis. The prevalence of neurotoxocariasis may be seriously underestimated due to low awareness of physicians and lack of standard conventional diagnostic test in Taiwan. The two cases of neurotoxocariasis firstly reported in Taiwan will raise physician's awareness in recognizing this curable disease particularly in managing patients with aseptic meningitis or meningoencephalitis of undetermined pathogen.

Background: The regulation of the balance between inflammatory and anti-inflammatory events during the treatment of pulmonary infection is very important. Soluble Schistosoma egg antigens (SEA) can effectively inhibit the expression of cytokines during hepatic acute inflammation. However, the mechanisms by which these proteins suppress the inflammatory responses in lung cells remain unclear. The purpose of this study was to investigate the ability of SEA to inhibit pulmonary inflammation. Methods: The effects of SEA were investigated in LPS-treated lung IMR-90 cells. The involvement of the JAK/STAT-1 signaling pathway in these effects was evaluated by employing CBA assays, quantitative polymerase chain reaction, and western blotting experiments. Results: Pretreatment of IMR-90 cells with appropriate concentrations of SEA protected cells against the cytotoxic effects of LPS-induced inflammation in a time-dependent manner. SEA pretreatment significantly attenuated the LPS-induced activation of the JAK/STAT1 signaling pathway, including the upregulation of JAK1/2 and STAT1, as well as the production of inflammatory cytokines. The level of phosphorylated STAT1 gradually declined in response to increasing concentrations of SEA. Based on these findings, we hypothesize that SEA-induced anti-inflammatory effects initiate with the downregulation of the IFN-γ-JAK-STAT1 signaling pathway, resulting in the attenuation of LPS-induced inflammation in IMR-90 cells. Conclusion: Our study is the first to demonstrate the anti-inflammatory activity of SEA in an in vitro model of pulmonary inflammation, involving the modulation of JAK/STAT1 signaling. We propose SEA as potential therapeutic or preventive agents for the selective suppression of STAT1 and the control of inflammatory response in lung IMR-90 cells.

Background: Patients with diabetes mellitus (DM) have higher incidence and more severe urinary tract infections (UTIs) for longer duration than those of the patients without DM. It causes more complicated etiologies during uropathogenic Escherichia coli (UPEC) infection. However, studies regarding the molecular mechanism are scarce. Methods: The present study (1) aimed to verify if sugar influences the process of UPEC-induced cystitis and invasion into the uroepithelial cells and (2) illustrated the mechanism of effects for sugar enhanced the UPEC infection into uroepithelial cells is related to TLR-4-mediated and JAK/STAT1-dependent pathway. Results: The results of the present study indicated that sugar can enhance UPEC infection in uroepithelial cells by up-regulating the transduced circuit between TLR-4-mediated UPEC interaction and JAK/STAT-1 signal pathways. The results of the inhibitor-co-incubating experiments demonstrated that the mechanism involved in the synergistic amplification of TLR-4-mediated UPEC interaction and JAK/STAT1 signaling pathways is responsible for the increased UPEC infection in uroepithelial cells. Conclusion: The results also proved that STAT-1 plays a critical role in the regulation of UPEC invasion and infection in the uroepithelial cells, especially those pretreated with glucose. The present study suggests a possible therapeutic approach to preferentially suppress UPEC infection during UTIs in the patients with diabetes.

Abstract Gyrocotylideans are evolutionary ancient parasitic flatworms, and like their hosts—a relict group of holocephalan fishes (Chimaeriformes)—they are considered to be “living fossils” of a vanished past. However, the species diversity, host associations and biogeography of these most basal tapeworms are poorly known. Herein, we provide evidence of a conspicuous contrast between the genetic and morphological data based on an examination of newly collected and properly processed Gyrocotyle specimens (hologenophores) isolated from holocephalans off Taiwan and Argentina. Our molecular data, inferred from three genes (COI, 28S rRNA, 18S rRNA), showed unexpected genetic interrelationships among isolates of the genus Gyrocotyle, because each of the four genotypes from Taiwan clustered with isolates of distinct gyrocotylideans from the North Atlantic. Three genotypes of Gyrocotyle from Taiwan were morphologically almost indistinguishable from each other but represented distinct genetic lineages; a single specimen of Gyrocotyle sp. genotype 4 exhibited a clear genetic and morphological distinctness, though its formal description as a new species would be premature. Additionally, specimens of Gyrocotyle rugosa Diesing, 1850, from the type host Callorhinchus callorynchus from Argentina, provided the first genetic data on the type species of the genus and enabled us to characterise it, which is necessary for future taxonomic studies. The finding of some specimens of Gyrocotyle sp. genotype 3 in Chimaera phantasma, and another one in C. cf. argiloba, together with the putative conspecificity of an unidentified gyrocotylidean from Callorhinchus milii off Australia and G. rugosa from C. callorynchus off Argentina, represent evidence that one gyrocotylidean species may parasitise more than one holocephalan host species. Existing taxonomic problems and conflicts between morphological and molecular data on species of Gyrocotyle can only be resolved if hologenophores from type hosts and localities of nominal taxa are properly characterised genetically and morphologically.

Background: Anisakid larvae are the food-borne pathogen highly prevalent among numerous marine fishes. Accidental consumption of infected raw or poorly cooked fish fillets may cause anisakiasis. Methods: This study used the multidisciplinary approach to investigate the occurrence of Anisakis nematodes in commonly consumed fish species, Scomber australasicus and Trichiurus lepturus purchased in Taipei Xinyi traditional fish market. Results: All the Anisakis larvae collected herein were identified morphologically as Anisakis type I or Anisakis type II. The prevalence and the mean intensity of Anisakis larvae collected from S. australasicus was 80.77%, 26.8 (10–32) and 100%, 49.0 (27–70) for T. lepturus. Using molecular analysis, 83.33% (180/216) were identified as Anisakis pegreffii, 6.05% (13/216) as Ascaris typica, 1.85% (4/216) as Ascaris physeteris and 8.80% (19/216) as hybrid genotype (A. pegreffii + Anisakis simplex) in S. australasicus. In T. lepturus, 86.31% (290/336) were identified as A. pegreffii, 2.38% (8/336) as A. typica, and 11.31% (38/336) as hybrid genotype (A. pegreffii + A. simplex [s.s]). The molecular phylogenetic analysis shows two cluster clades, one group includes A. pegreffii complex and the other include Ascaris paggiae, Ascaris brevispiculata, and A. physeteris. Conclusion: Thus, A. pegreffii is the most abundant species and may be the potential causes of human infection.

Abstract Obstructive uropathy is one of the leading causes of urosepsis. In patients with severe hydronephrosis, underlying sepsis and renal dysfunction should be treated with caution. The immediate drainage of hydronephrosis is crucial for infectious source removal and is hence related to the patient's prognosis.

Background/purpose: Toxocariasis is a worldwide parasitic zoonosis and mainly caused by Toxocara canis. Humans can be infected by accidental ingestion of T. canis embryonated ova through contacting with contaminated food, water, or encapsulated larvae in paratenic hosts' viscera or meat. Since humans are the paratenic host of T. canis, the wandering and neuroinvasive larvae can cause mechanical tissue damage and the excretory-secretory antigens (TcES Ag) might induce neuroinflammatory responses in the brain. Human cerebral toxocariasis (CT) has been reported to cause several neurological symptoms and may develop into neurodegenerative diseases. However, the roles of astrocytes involved in the pathogenesis of CT remained largely unclear. Methods: This study intended to investigate the cytotoxic effects of TcES Ag on astrocytes as assessed by apoptosis and autophagy expression. Results: Our results showed TcES Ag treatment reduced cell viability and caused morphological changes. Expressions of autophagy associated proteins including Beclin 1, phosphor-mTOR and LC3-Ⅱ were not significantly changed; however, p62 as well as the cell survival protein, mTOR, was concomitantly decreased in TcES Ag treatment. Significantly accelerated cleaved caspase-3 and cytochrome c expression as well as enhanced caspase-9 and caspase-8 activation were found in astrocytes with TcES Ag treatment. Caspase-3 activity and apoptotic cells numbers were also increased as detected by fluorescence microscopy. Conclusion: We concluded that TcES Ag may trigger astrocytes apoptosis predominantly through intrinsic and extrinsic pathways rather autophagy, revealing a novel role of astrocytes in the pathogenesis of CT. Keywords: Astrocyte, T. canis excretory-secretory antigens, Apoptosis, Autophagy, Cerebral toxocariasis

Although the deworming program has been executed since 2000, the intestinal parasitic infection (IPI) rates among primary schoolchildren (PSC) in the two provinces of the Kingdom of Eswatini investigated in 2010 remained high, reaching 32.2%. In this study, we monitored the IPI status along with the associated risk factors for PSC in two provinces—Manzini and Lubombo. After consent from their parents/guardians, a total of 316 samples collected from PSC with grades 1 to 3 from four primary schools in Manzini and Lubombo were examined by the Merthiolate-Iodine-Formaldehyde (MIF) method. In addition, demographic characteristics and risk factors acquired by questionnaire surveys were included to be statistically analyzed. The overall prevalence was 40.5% (128/316), of which the infection rate in Manzini and Lubombo was 28.8% (19/66) and 58.3% (74/140), respectively. Pathogenic protozoa had the highest infection rate of 20.6% (65/316), including Entamoeba histolytica/dispar (8.5%, 27/316), Giardia duodenalis (14.6%, 46/316), and Blastocystis hominis (9.8%, 31/316). In terms of helminth infection, the infection rate was quite low, 1.6% only, and these five infected cases included four cases of Hymenolepis nana and one case of Enterobius vermicularis infection. Present study showed that 27.8% (88/316) of PSC were infected by more than one pathogenic parasite. Personal hygiene like washing hands before a meal has a significant protection effect (OR = 0.32, 95% CI = 0.14–0.75, p=0.009). Rain or well water and the type of water supply from which they drank also showed a considerable risk factor (OR = 2.44, 95% CI = 1.25–4.79, p=0.04). The IPI rate in PSC seems unlikely changed compared to that of the previous survey conducted in 2010, especially when the pathogenic protozoan infection rate remains high. Treatment of infected PSC with appropriate medication to reduce intestinal pathogenic protozoan infection should be seriously considered by Eswatini Health Authority.

JAK/STAT plays a key role in regulating uropathogenic Escherichia coli (UPEC) infection in urothelial cells, probably via antimicrobial peptide (AMP) production, in diabetic patients with urinary tract infections. Whether multiple pathways regulate AMPs, especially lipid-carrying protein-2 (LCN2), to achieve a vital effect is unknown. We investigated the effects of an LCN2 pretreatment on the regulation of the JAK/STAT pathway in a high-glucose environment using a bladder cell model with GFP-UPEC and phycoerythrin-labeled TLR-4, STAT1, and STAT3. Pretreatment with 5 or 25 μg/mL LCN2 for 24 h dose-dependently suppressed UPEC infections in bladder cells. TLR-4, STAT1, and STAT3 expression were dose-dependently downregulated after LCN2 pretreatment. The LCN2-mediated alleviation of UPEC infection in a high-glucose environment downregulated TLR-4 and the JAK/STAT transduction pathway and decreased the UPEC-induced secretion of exogenous inflammatory interleukin (IL)-6 and IL-8. Our study provides evidence that LCN2 can alleviate UPEC infection in bladder epithelial cells by decreasing JAK/STAT pathway activation in a high-glucose environment. LCN2 dose-dependently inhibits UPEC infection via TLR-4 expression and JAK/STAT pathway modulation. These findings may provide a rationale for targeting LCN2/TLR-4/JAK/STAT regulation in bacterial cystitis treatment. Further studies should explore specific mechanisms by which the LCN2, TLR-4, and JAK/STAT pathways participate in UPEC-induced inflammation to facilitate the development of effective therapies for cystitis.

Background: To determine whether intestinal Angiostrongylus cantonensis antigens can induce protective immunity in rats, gut antigens prepared from female adults (FAGP) and somatic antigens prepared from both male (MA) and female (FA) adult worms were used to immunize rats. Methods: Rats were immunized twice with MA, FA, or FAGP antigens and then challenged with 50 third-stage A. cantonensis larvae, and different readouts were used to monitor protective immunity. Additionally, protein profiles of MA, FA, and FAGP extracts were analyzed and characterized by immunodetection methods. Results: A 15% reduction in fifth-stage larvae from brains and a 14% reduction in adult worms from pulmonary arteries were observed in rats immunized with FAGP compared to controls. However, there was a >50% reduction in rats immunized with MA or FA. The lengths of larvae and adults recovered from FAGP-immunized rats were shorter than those recovered from other groups. The number of first-stage larvae recovered from fecal material in FAGP-immunized rats was significantly reduced. Additionally, FAGP induced the highest splenocyte proliferation. Serum IgG titers were not directly correlated with protective immunity. An 84 kDa gut membrane protein was strongly recognized by anti-FAGP antibodies. Conclusion: We demonstrated that immune responses induced by FAGP reduced the growth, development, and reproduction of A. cantonensis in subsequent infections. While the possibility of using FAGP combining with MA or FA antigens as a multi-function vaccine in immune protection against A. cantonensis needs to be further elucidated, we hope that it provides a novel strategy for this parasite vaccine development. Keywords: Angiostrongylus cantonensis, Intestinal proteins, Protective immunity, Anti-fertility

Background/Purpose: Pediculus capitis is the most common human ectoparasite. When it feeds on the blood through the scalp of its host, the anticoagulant in its saliva causes scalp inflammation and itching, and consequent scratching by the host causes further inflammation from bacterial infection. P. capitis infestation is currently a common parasitic dermatosis and a critical public health concern in underdeveloped countries. Methods: Through naked eye inspection of P. capitis on or in the hair from 323 school children in Cambodia. Results: A total of 143 children (44.3%) were found to have P. capitis infestation. Univariate analysis revealed that girls had a significantly higher infection rate than boys. Overall, young aged schoolchildren (10 yrs old ≤) showed significantly higher infection rate than old aged schoolchildren (>10 yrs old). Groups stratified by time revealed that schoolchildren studied at the afternoon classes than morning classes in Tuol Prum Muoy Primary School had a significantly higher risk in acquisition of P. capitis infestation. Multivariate analysis results indicated that relative to the boys, the girls were at a significantly higher risk of contracting P. capitis infection. When stratified by inspection time with the Tuol Prum Muoy Primary School morning classes as the reference, the Tuol Prum Muoy Primary School afternoon classes exhibited a significantly higher risk of P. capitis infection. Conclusion: Primary school children in Cambodia have a high P. capitis infection rate and thus require effective treatment and prevention measures to treat symptoms and lower the infection rate. Keywords: Pediculus capitis, Schoolchildren, Cambodia

Abstract Background Enterobius vermicularis (pinworm) is one of the most common human parasitic helminths, and children are the most susceptible group. Some behavioral and environmental factors may facilitate pinworm infection. In the Republic of the Marshall Islands (RMI), the status of pinworm infections among children remains unknown. Methods In Majuro City, there are 14 kindergartens with a total of 635 preschool children (PSC) whose age range of 5~6 years. The present investigation attempted to determine the pinworm prevalence and associated risk factors as well as investigate whether eggs contaminated the clothes of PSC or the ground and tables in classrooms of 14 kindergartens. Informed consent form and a self-administered questionnaire were given to parents prior to pinworm screening. Perianal specimens were collected by an adhesive scotch tape method, and clothing of belly and hip sites and the ground and tables of the classrooms were inspected using a cellophane tape method to detect any eggs contamination. Results In total, 392 PSC (5.28 ± 0.56 yrs. old) participated in this project. The overall prevalence of pinworm infection was 22.4% (88/392). Boys (24.5%) had higher prevalence than girls (20.31%) (p = 0.32). PSC aged > 5 years (32.77%) showed a significantly higher prevalence than those aged ≤5 years (17.95%) (p = 0.01). A univariate analysis indicated that PSC who lived in urban areas (22.95%) had a higher prevalence than those who lived in rural areas (20.69%) (p = 0.69). The employment status of the parents showed no association with the pinworm infection rate (p > 0.05). A logistic regression analysis indicated that “having an older sister” produced a higher risk of acquiring pinworm infection for PSC compared to those who did not have an older sister (OR = 2.02; 95%CI = 1.05~3.88; p = 0.04). No significant association between various other risk factors and pinworm infection was found (p > 0.05). Also, no eggs contamination was found on the clothes of the belly and hip sites or on the ground and tables in the 14 kindergartens. Conclusions Mass screening and treatment of infected PSC are important measures in pinworm control in the RMI.

Abstract Background Cysticercosis is an emerging and neglected tropical disease (NTD) that poses a serious public health concern worldwide. Disseminated cysticercosis (DCC) is an uncommon manifestation of cysticercosis, also found in China. Case presentation We report three cases of DCC in patients living in China, with different clinical and radiological presentations. All three patients had DCC with active ocular cysticercosis, including one patient with widespread DCC caused by direct ingestion of Taenia solium eggs. The intravitreal cysticercus cyst in this patient was completely extracted entirely by 23-gauge pars plana vitrectomy, and the cyst was oval in shape on the flat mount preparation. Conclusion The clinical presentation of DCC is highly sophisticated. The diagnosis depended on the typical radiological presentations, biopsy and flat mount preparations of the cyst.

Background/purpose: Intestinal parasitic infections (IPIs) among school aged children (SAC) in Nigeria remains endemic, hence the need for regular surveillance to attract the attention of policy makers. This cross-sectional study investigated the current prevalence and factors associated with intestinal parasitic infections among school aged children in an urban slum of Lagos City, Nigeria. Methods: Single stool samples from 384 school aged children (188 boys and 196 girls) were examined by employing Merthiolate-iodine-formaldehyde concentration (MIFC) and Kato-Katz methods. Demographic characteristics and risk factors were obtained by questionnaires investigation. Results: The overall prevalence was 86.2% in school children, out of them 39.1% had polyparasitism. IPIs showed the highest to the lowest prevalence of 62% (238/384), 25% (97/384), 12.3% (47/384), 11.8% (45/384), 9.9% (38/384), 8.4% (32/384), 3.4% (13/384), and 0.5% (2/384) found in Ascaris lumbricoides, Entamoeba histolytica/dispar, Giardia duodenalis, Endolimax nana, Entamoeba coli, Trichuris trichiura, Blastocystis hominis, and hookworm infections, respectively. MIFC technique showed superiority to Kato-Katz technique in the detection of IPIs (p

The prevalence and risk factors of Enterobius vermicularis (pinworm) infection among primary schoolchildren (PSC) in the Marshall Islands remain unknown; thus, investigation on the status of pinworm infection rate is necessary to establish baseline data. After parents’/guardians’ consent, a total of 346 children (179 boys and 167 girls) participated in this study. Individual’s perianal area and thumbs were inspected by using the Scotch tape technique and cellophane tape method, respectively. For each child, demographic and risk factor data were collected by a structured questionnaire and statistically analyzed. The overall prevalence of pinworm infection was 12.14% (42/346). Univariate analysis indicated significant differences in PSC who live in an urban area compared to those who live in the rural area p=0.01. Multivariate analysis still found that PSC who live in the rural area had higher chances to acquire pinworm infection. However, no risk factors were identified to be associated with personal hygiene, sibling number, and parent’s educational level or occupation. Nevertheless, a pinworm-like egg was detected on the thumb of one male participant. Children living in the rural area and thumb-sucking behavior are two of the important risk factors of transmitting pinworm infection in the PSC in the Marshall Islands. We suggested an urgent and continuous provision of adequate hygienic sensitization in the school and the community.

Antimicrobial peptides (AMPs), which are natural antibiotics, protect against pathogens invading the urinary tract. RNase 7 with antimicrobial properties has rapid and powerful suppressive effects against Gram-positive and Gram-negative bacterial infections. However, its detailed antibacterial mechanisms have not been fully determined. Here, we investigate whether RNase 7 had an impact on bladder cells under uropathogenic Escherichia coli (UPEC) infection in a high-glucose environment using in vitro GFP-UPEC-infected bladder cell and PE-labeled TLR4, STAT1, and STAT3 models. We provide evidence of the suppressive effects of RNase 7 on UPEC infection and UPEC-induced inflammatory responses by regulating the JAK/STAT signaling pathway using JAK inhibitor and STAT inhibitor blocking experiments. Pretreatment with different concentrations of RNase 7 for 24 h concentration-dependently suppressed UPEC invasion in bladder cells (5 μg/mL reducing 45%; 25 μg/mL reducing 60%). The expressions of TLR4, STAT1, and STAT3 were also downregulated in a concentration-dependent manner after RNase 7 pretreatment (5 μg/mL reducing 35%, 54% and 35%; 25 μg/mL reducing 60%, 75% and 64%, respectively). RNase 7-induced decrease in UPEC infection in a high-glucose environment not only downregulated the expression of TLR4 protein and the JAK/STAT signaling pathway but also decreased UPEC-induced secretion of exogenous inflammatory IL-6 and IL-8 cytokines, although IL-8 levels increased in the 25 μg/mL RNase 7-treated group. Thus, inhibition of STAT affected pSTAT1, pSTAT3, and TLR4 expression, as well as proinflammatory IL-6 and IFN-γ expression. Notably, blocking JAK resulted in the rebound expression of related proteins, especially pSTAT1, TLR4, and IL-6. The present study showed the suppressive effects of RNase 7 on UPEC infection and induced inflammation in bladder epithelial cells in a high-glucose environment. RNase 7 may be an anti-inflammatory and anti-infective mediator in bladder cells by downregulating the JAK/STAT signaling pathway and may be beneficial in treating cystitis in DM patients. These results will help clarify the correlation between AMP production and UTI, identify the relationship between urinary tract infection and diabetes in UTI patients, and develop novel diagnostics or possible treatments targeting RNase 7.

Background: UPEC can internalize clonally in prostate to form biofilm-like intracellular bacterial communities (IBCs) for recurrent or chronic infection. We previously indicated that the exposure of prostate cells to testosterone could suppress UPEC invasion and their persistent survival within cells by effectively inhibiting the JAK/STAT1 signaling pathway. However, the regulatory mechanism by which testosterone affects UPEC-induced prostatitis via STAT3, another latent transcription factor signaling pathway is still unclear. The present study aimed to clarify the role of STAT3 in the process of UPEC-induced inflammation and colonization in prostate epithelial cells. Methods: The effects of testosterone-mediated inhibition were compared between the prostatitis by different UPEC strains (CFT073 and J96) through the specific GFP-UPEC-infected prostate cell model. Fluorescence microscopy was used for UPEC IBCs detection and quantifying, and Flow cytometry, RT-PCR and western blotting were used for analyzing related gene and protein expressions. Pretreatment of JAK and STAT3 inhibitors were also applied to verify the regulation of transduction pathway in testosterone-mediated anti-UPEC infection. Results: This study revealed that testosterone effectively suppresses UPEC infection and IBC formation in prostate cells through the JAK/STAT3 pathway. The results show that CFT073 and J96 UPEC infection rates and colony numbers were dose-dependently reduced in RWPE-1 cells pretreated with 5 and 20 μg/mL testosterone at 0 and 24 h post-infection. Further, testosterone reduced the amounts of UPEC infecting and surviving within the prostate cells, as well as suppressed the size of IBCs formed. We demonstrated that pretreating testosterone effectively inhibited UPEC infection along with dose-dependent suppression of STAT3 and the phosphorylated-STAT3 expression in prostate cells, especially in 24 h J96 UPEC infected groups. The STAT inhibitor, SOCS3 also up-regulated at the same time. In addition, we pretreated the JAK1 or STAT3 inhibitor with testosterone to block the signaling transduction before CFT073 and J96 UPEC infection, and found the significant restoring in both the sizes of IBCs and bacterial numbers in RWPE-1 cells. Therefore, our results suggest that the suppression of STAT3 by testosterone treatment attenuate UPEC growing within IBCs and interfere with their infection to prostate cells. Conclusions: Overall, our study demonstrates that testosterone suppresses the initial infection of prostate epithelial cells by UPEC and reduces the survival of UPEC within IBCs after infection. These results indicate a critical role for STAT3 in facilitating UPEC infection and persistence, and its participation in driving testosterone-suppressive responses in prostate epithelial cells. In conclusion, this study suggests that testosterone may be beneficial in treating clinically recurrent UPEC infections and, thus, the persistent recurrence of prostatic inflammation.

Background: Schistosomiasis, a worldwide concern, has received attention in Swaziland through control programs such as deworming programs, education programs, and school health programs; however, these programs neglect the importance of monitoring and evaluation strategies such as assessing children's knowledge, attitudes and practices (KAPs) and the prevalence of the disease. Children are a high-risk group because of their water contact practices, and need to be informed about schistosomiasis to influence their attitudes and practices. Social and cultural factors are involved in schistosomiasis control because they instill myths and misconceptions about the disease. As a result, children in the community may be comfortable with bad practices. This study aimed to assess the KAPs of schoolchildren on schistosomiasis, and to identify practices that support or hinder the progress of schistosomiasis control. Methods: In 2014, a descriptive quantitative cross-sectional survey was conducted through questionnaires among Siphofaneni primary schools, an area hit by schistosomiasis in the Lowveld of Swaziland. A logistic regression model was applied to analyze the data. Results: Moderate knowledge, good attitudes, and fairly good practices were observed in the children. However, practices of certain children were risky and they still had some misconceptions. Knowledge was correlated with practice and with predictors of good and bad practices such as male sex, always urinating in water, and always using river water for domestic practices. Conclusion: This study suggests that empowering children with knowledge and attempting to modify their water contact, and improved human waste disposal practices are necessary for schistosomiasis control.

Abstract Background Toxocariasis is a worldwide zoonotic parasitic disease mainly caused by Toxocara canis. Humans can be infected by accidental ingestion of T. canis embryonated ovum-contaminated food, water, or encapsulated larvae in paratenic hosts’ viscera or meat. Since humans and mice are paratenic hosts of T. canis, the wandering larvae might cause mechanical tissue damage and excretory-secretory antigens may trigger inflammatory injuries to local organs. Long-term residence of T. canis larvae in a paratenic host’s brain may cause cerebral toxocariasis (CT) that contributes to cerebral damage, neuroinflammation and neuropsychiatric disorders in mice and clinical patients. Since the hippocampus has been long recognized as being responsible for learning and memory functions, parasitic invasion of this site may cause neuroinflammatory and neurodegenerative disorders. The present study intended to assess pathological changes, expressions of neurodegeneration-associated factors (NDAFs), including transforming growth factor (TGF)-β1, S100B, glial fibrillary acidic protein (GFAP), transglutaminase type 2 (TG2), claudin-5, substance P (SP) and interleukin (IL)-1β, and the ubiquitin-proteasome system (UPS) function in the hippocampus and associated cognitive behavior in ICR mice orally inoculated with a high, medium or low-dose of T. canis embryonated ova during a 20-week investigation. Results Results indicated although there were insignificant differences in learning and memory function between the experimental mice and uninfected control mice, possibly because the site where T. canis larvae invaded was the surrounding area but not the hippocampus per se. Nevertheless, enhanced expressions of NDAF, persistent UPS impairment and excess amyloid β (Aβ) accumulation concomitantly emerged in the experimental mice hippocampus at 8, 16 and 20 weeks post-infection. Conclusions We thus postulate that progressive CT may still progress to neurodegeneration due to enhanced NDAF expressions, persistent UPS impairment and excess Aβ accumulation in the hippocampus.

Diabetic individuals have a higher incidence of urinary tract infection (UTI) than non-diabetic individuals, and also require longer treatment. We evaluated the effects of insulin pretreatment on the regulation of JAK/STAT transduction pathways in UPEC-infected bladder cells in a high-glucose environment. A bladder cell model with GFP-UPEC and fluorescent-labeled TLR4, STAT1, STAT3, and insulin receptor antibodies, was used to evaluate the relationship between insulin receptor signaling, TLR-4-mediated, and JAK/STAT-dependent pathways. Pretreatment with 20 and 40 µg/mL insulin for 24 h significantly and dose-dependently reduced UPEC infection in SV-HUC-1 cells. Additionally, the expression levels of STAT1 and STAT3 were downregulated in a dose-dependent manner. However, insulin receptor (IR) expression was not affected by insulin pretreatment. Our results showed that insulin-mediated reduction of UPEC infection in a high-glucose environment was not only due to the downregulation of JAK1/2 and phosphorylated STAT-1/3, but also because of the decreased expression of TLR-4 proteins and pro-inflammatory IL-6. Here, we demonstrated that insulin reduced not only UPEC infection in bladder epithelial cells, but also inhibited the JAK/STAT transduction pathway during infection in a high-glucose environment. This study provides evidence to support the use of insulin in the treatment of UPEC infection in patients with type 2 diabetes (T2D).

Although malaria control programs have made rapid progress recently, they neglect important social and behavioral factors associated with the disease. Social, political, and cultural factors are involved in malaria control, and individuals in a community may be comfortable in behaving in ways that, to an outsider, may seem contrary to commonly held perceptions. Malaria control efforts can no longer afford to overlook the multidimensional human contexts that create and support varying notions of malaria and its prevention, treatment, and control. This study aimed to assess the knowledge and perceptions of malaria issues in the community, and to identify practices that support or hinder the progress of malaria control programs. Methods: A triangulation study involving individual interviews, focus group discussions, and observatory analysis between 2003 and 2010 at Lomahasha, a malarious community on the eastern border of Swaziland and Mozambique, was conducted. Results: Results indicated that a high knowledge level and good perception of the disease were observed in the age group of < 40 years, contrary to those in higher age groups, among the Lomahasha community members. However, behavior of certain community groups includes practices that are not supportive of the national control program's aspirations, such as delay in seeking medical attention, staying outdoors until late, maintaining stagnant water in roadside excavations, and seeking medical assistance from wrong sources. Malpractices are more commonly observed among men, boys, and those who drink alcohol. Conclusion: This study suggests a thorough community diagnosis before all intervention programs for malaria control are instituted.

INTRODUCTION: Toxoplasma gondii infection has been described as the most widespread zoonotic infection of humans and other animals. Information concerning T. gondii infection among schoolchildren is unavailable in Lagos City, Nigeria. METHODS: This cross-sectional study investigated the seroprevalence and risk factors associated with T. gondii infection among primary schoolchildren (PSC) from a community located in the center of Lagos, southern Nigeria, from November 2013 to March 2014. A total of 382 PSC were screened for the presence of sera anti-T. gondii antibodies using a latex agglutination test (TOXO Test-MT, Tokyo, Japan). A cutoff titer of ≥ 1:32 was considered positive, while titers ≥ 1:1,024 indicated high responders. Questionnaires were also used to obtain data on possible risk factors from parents/guardians. RESULTS: The overall seroprevalence was 24% (91/382), and 83.5% (76/91) of seropositive PSC were classified as high responders. Among the risk factors tested, including contact with cats and soil, consumption of raw meat and vegetables, and drinking unboiled water, none showed statistical significance after multivariate adjustment. No associations were observed among age, gender, body mass index (BMI), and parents' occupation/educational level. CONCLUSIONS: The findings in this study show evidence of active infection, and hence, there is need for urgent preventive measures in this city. Further investigation is required to clarify the transmission routes. Policy makers also need to initiate prevention and control programs to protect pregnant women and immunocompromised patients in particular because they are more severely affected by T. gondii infection.

Angiostrongylus cantonensis is of increasing public health importance as the main zoonotic pathogen causing eosinophilic meningitis or meningoencephalitis, which has been documented all over the world. However, there are very limited studies about its phylogeography and spread pattern. In the present study, the phylogeography of A. cantonensis in southern China (including Taiwan) and partial areas of Southeast Asia were studied based on the sequences of complete mitochondrial cytochrome b (Cytb) gene. A total of 520 individuals of A. cantonensis obtained from 13 localities were sequenced for the analyses and grouped into 42 defined haplotypes. The phylogenetic tree (NJ tree and BI tree) revealed a characteristic distribution pattern of the four main lineages, with detectable geographic structure. Genetic differentiation among populations was significant, but demographic expansion could not be detected by either neutrality tests or mismatch distribution analysis, which implied a low gene flow among the local populations in different regions where the samples were collected. Two unique lineages of the A. cantonensis population in Taiwan were detected, which suggests its multiple origin in the island. Populations in Hekou (China) and Laos showed the highest genetic diversities, which were supported by both genetic diversity indices and AMOVA. These results together infer that the area around Thailand or Hekou in Yunnan province, China are the most likely origins of Angiostrongylus cantonensis.

[This corrects the article DOI: 10.1371/journal.pone.0180244.].

Prostatitis is a common condition in adult men of all ages. Uropathogenic Escherichia coli (UPEC) are most frequent pathogen involved in bacterial prostatitis by refluxing the infected urine into prostatic ducts and resulting in an ascending urethral infection. However, the study about the mechanisms of UPEC to invade, replicate and persist in normal prostate epithelial cell is only few. Given the fact that UPEC is pathogen most frequently involved in prostatitis and that testosterone has been demonstrated to attenuate prostate inflammation caused by other etiologies. In this study we investigated whether the testosterone reduces the prostatitis and related mechanism by regulating IFN-γ/STAT1 signaling pathway. In the current study aimed to clarify whether testosterone influences the process of UPEC-induced prostate inflammation and invasion into the prostate epithelial cells. In addition, we set up a normal prostate cell model for UPEC infection to evaluate the ability to invade the urothelial cells as well as the colonization of intercellular bacterial communities in vitro. By using the model, we examine the effects of testosterone to suppress effectively the invasion and survival of UPEC in the prostate cells, and inhibit LPS-induced inflammatory responses through the JAK/STAT1 pathway have also been indicated. Our results demonstrated testosterone not only suppressed the invasion and colonization of UPEC, but also inhibited the expression of pro-inflammatory IL-1β, IL-6 and IL-8 cytokines expression induced by UPEC in a dose-dependent manner. We found the effective dose of testosterone to suppress UPEC infect prostate cells may be appropriate under 40μg/ml. Our data also revealed 20μg/ml testosterone treated PZ-HPV-7 cells significantly suppressed the LPS-induced JAK/STAT1 pathway and inflammatory responses, and reached to maximal effects at 40μg/ml treatment. These results indicate that testosterone plays an anti-inflammatory role in LPS-induced prostate cell inflammation by down-regulating JAK/STAT1 signaling pathway. Interestingly, the JAK inhibitor and testosterone for 24hr pretreatment rather markedly induced the colonization of UPEC in the PZ-HPV-7 cells. Based on the above data, the suppression of UPEC colonization in the prostate cells by testosterone seems to be unrelated with JAK/STAT signaling pathway, whereas the JAK may involve into the UPEC infection. Summing up these data, our findings have demonstrated the suppressive effects of testosterone on the invasion and survival of UPEC and induced inflammation in prostate epithelial cells. These findings indicate the action mechanism of testosterone as an anti-inflammatory mediator in the prostate cells is regulated through JAK/STAT1 signaling pathway, may be beneficial in treating prostate inflammation. Altogether, this study has provided the possibility that using testosterone in the prevention and clinical treatment of prostatitis is a new direction.

[This corrects the article DOI: 10.1371/journal.pone.0063613.].

Background: Infection by Toxocara spp. is known to be significantly associated with partial epilepsy. It has become popular for people to raise dogs/cats as pets and consume roasted meat/viscera, and the status of Toxocara spp. infection, epi­lepsy awareness, and associated risk factors among the general population are cur­rently unknown in Taiwan. Methods: A seroepidemiological investigation among 203 college students (CSs), consisting of 110 males and 93 females with an average age of 21.5 ± 1.2 years, was conducted in 2009 in Taipei City. A Western blot analysis based on excretory-secre­tory antigens derived from Toxocara canis larvae (TcESs) was applied to determine the positivity of serum immunoglobulin G antibodies. A self-administered question­naire was also given to obtain information about demographic characteris­tics, epilepsy awareness, and risk factors. A logistic regression model was applied for the statistical analysis using SPSS software. Results: The overall seropositive rate of Toxocara spp. infection was 8.4% (17/203). As to epilepsy awareness, a non-significantly higher seroprevalence was found in CSs who claimed to "know" about epilepsy compared to those who did not know (P > 0.05). Conclusions: It appears that appropriate educational programs are urgently needed to provide correct knowledge related to the prevention and control measures against Toxocara spp. infections to avoid potential threats by this parasite to the general population in Taiwan.

Ocular injury to ICR mice from embryonated eggs of Toxocara canis, which had been maintained in 2% formalin for 14 months at 4°C, was evaluated by microscopic and pathologic assessments at 1, 2, 3, 5, 7, 28, 56, 84, 112, 140, 168, 196, 294 and 469 days post infection (DPI). On each date, three infected mice and two age-matched uninfected control mice were sacrificed; left eyeballs from infected mice were examined for larvae under a dissecting microscope while all right eyeballs were embedded in paraffin for histologic study. No larvae were observed in the left eyeball of any of the 42 infected mice, while pathologic changes were observed in right eyeballs. Pathologically, the predominant changes were retinal detachment, iridocyclitis, and pars planitis, followed by optic nerve papillitis and superficial infarcts, as observed in one of three infected mice per group at 56, 140, and 168 DPI, respectively. No infiltrating cells surrounding the larvae in the retina were observed in the infected mice. This is the first report that larvae hatched from T. canis embryonated eggs maintained for a long time can cause murine ocular toxocariasis. These results further extend our knowledge of the pathogenicity of T. canis embryonated eggs.

An epidemiologic survey of Pediculus capitis infestation among Akka aboriginal and Han children of Chinese refugees living in mountainous areas at elevations of 1,100 to 1,400 m in Chiang-Rai Province of northern Thailand was conducted during January 2003. Of the 303 children examined, 43 (14.2%) had P. capitis infestation. The overall infestation rate for P. capitis in Akka children (29.3%, 12/41) was significantly higher than that in Han children (11.8%, 31/262; c2 = 8.161, p = 0.002). The prevalence in Akka (52.2%, 12/23) and Han girls (19.7%, 31/157) was higher than that in Akka (0%) and Han boys (0%), respectively (p < 0.001), and the prevalence was higher in Akka girls than in Han girls (c2 = 10.978, p = 0.001). The high prevalence of P. capitis infestation among these girls was possibly due to poor environmental hygiene and unavailability of sufficient water.

INTRODUCTION: Whether Enterobius vermicularis (pinworm) infections among preschool children in Taipei City had truly declined was investigated. METHODS: A total of 6,661 preschool children from 28 nurseries were randomly selected from 4 major geographic districts in Taipei City to examine the status of pinworm infection by using adhesive thin cellophane tape swab method. RESULTS: The overall prevalence of pinworm infection was 0.5% (30/6,661). Boys (0.6%; 21/3,524) had higher prevalence than girls (0.3%; 9/3,137) (p=0.06). Southern district (0.6%; 10/1,789) showed insignificantly higher prevalence than Western district (0.2%; 1/606) (p=0.22). CONCLUSIONS: Pinworm screening program remains necessary for some parts of Taipei City.

The Notch pathway plays a role in the processes of cell proliferation, differentiation, and apoptosis, which affect the development and function of various organs. Dendritic cells (DCs), as professional antigen-presenting cells (APCs), induce T cell activation and promote T cell differentiation by antigen stimulation. Research has shown that Notch ligand delta-like 4 (Dll4) in APCs is associated with stimulation of a Th1-type response. However, the regulatory roles of Dll4 in the activation and function of DCs have yet to be clearly elucidated. In this study, we demonstrated that activation of Dll4-pretreated bone marrow-derived DCs by performing ovalbumin (OVA) stimulation expressed a high level of interleukin (IL)-10 without diminishing IL-12 production. By contrast, the proinflammatory cytokines, IL-1β, IL-6, and tumor necrosis factor (TNF)-α, decreased in Dll4-pretreated DCs by performing either lipopolysaccharide (LPS) or OVA stimulation. Compared to fully mature DCs, lower levels of MHC class II CD40 and higher levels of CD80 and CD86 molecules were expressed in these semi-mature like DCs. Dll4 Notch signaling also enhanced Notch ligand mRNA expression of Dll1, Dll4, and Jagged1 in DCs. Dll4-modified DCs exhibited a reduced capacity to stimulate the proliferation of OVA-specific CD4(+) T cells, but actively promoted large amounts of IL-10 production in these activated T cells. Furthermore, immunomodulatory effects of Dll4-modified DCs were examined in an established asthmatic animal model. After adoptive transfer of OVA-pulsed plus Dll4-pretreated DCs in OVA-immunized mice, OVA challenge induced lower OVA-specific immunoglobulin E (IgE) and higher IgG2a antibody production, lower eotaxin, keratinocyte-derived chemokine (KC), IL-5, and IL-13 release in bronchial alveolar lavage fluid, attenuated airway hyper-responsiveness, and promoted higher IL-10 and interferon (IFN)-γ production in the spleen. In summary, our findings elucidate the new role of Dll4 in the phenotype and function of DCs and provide a novel approach for manipulating T cell-driven deleterious immune diseases.