These obstacles call for a revised strategy in the attempt to uncover the potential role of infectious agents in OC. It is fair to assume that signs of micro- biological presence will be easier to detect when the interval between primary infection and investigation is short. Therefore, it seems more relevant to investigate precursor lesions for the presence of potential micro- biological agents . Until recently, this has been impossible due to the lack of a clearly defined prema- lignant lesion to OC. However, this has changed be- cause increasing evidence indicates that STIC lesions in the distal fallopian tubes are precursor lesions to serous epithelial OC, which constitutes the majority of OC cases . Yet, no explanation has been formu- lated as to why STIC lesions arise. Since the fallopian tubes are often affected and damaged by chronic PID, it is biological plausible that pathogens with trans- forming capacities, or the chronic inflammation they induce, could lead to subsequent neoplastic trans- formation. We therefore recommend that future stud- ies focus on the detection of bacterial or viral agents in fallopian tube tissue samples with STIC lesions verified through the “ Sectioning and Extensively Examining of the Fimbriated end” protocol.
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There are many other types of benign and malignant tu- mors which occur rarely in children. A case study of a child diagnosed with both sialoblastoma and hepatoblas- toma demonstrated elevated levels of procalcitonin, pro- inflammatory stimulus to bacteria, and increased levels of C reactive protein, suggesting a response against bac- terial infections . Sialoblastoma affects parotid glands during infancy, and is rare, with only 24 cases reported in MedLine (1990–2008). Hepatoblastoma originates in the liver, and comprises less than 1% of reported tumors among children from infancy to 3 years of age . An- other liver tumor, a hepatocellular carcinoma (HCC), is also rare in children . Hepatitis B virus (HBV) was found to be responsible for HCC in children in Taiwan, where HBV was endemic . This relationship of HBV and childhood cancer was established as a result of dis- covering 100% HBsAg seropositivity among children with HCC and HBV DNA in their neoplasms [69,70]. The role of HBV infection in the cause of hepatocellular carcinoma is further confirmed when Taiwanese HBV immunization programme significantly reduced the cancer incidence in vaccinated children compared to non- vaccinated children . In addition to this, the twenty- year study has shown lower incidence of HCC in those Thai children who received HBV vaccine at birth .
Since the late 1990s, infectious agents have been thought to play a role in the pathogenesis of approximately 15% of cancers. It is now widely accepted that infection of stomach tissue with the bacteria Helicobacter pylori is an important cause of stomach adenocarcinoma. In addition, oncogenic viruses, such as papilloma viruses, herpes viruses, and hepadnaviruses are strongly associated with increased risk of cervical cancer, lymphomas, liver cancer, amongst others. However, in the scientific community the percentage of cancers caused by pathogens is believed to be far higher than 15%. A significant volume of data collected to date show an association between infectious agents and urogenital cancers. These agents include Chlamydia trachomatis, Neisseria gonorrhoea, Mycoplasma genitalium and certain viruses that have been implicated in ovarian cancer. Other pathogens include the hepatitis C and Epstein-Barr viruses, which are potentially involved in kidney cancer. In addition, infections with Schistosoma haematobium, the human papillomavirus, and human polyomaviruses are strongly associated with an increased risk of urinary bladder cancer. This article reviews publications available to date on the role of infectious agents in urogenital cancers. A greater understanding of the role of such agents could aid the identification of novel methods of urogenital cancer treatment.
contrast the clinical picture of influenza virus infection has a large overlap with that of other respiratory viruses, and mixed outbreaks have been documented . Thus, a prevalent misconception in the field has been to study ‘respiratory viruses’ as a group. However, given that these viruses belong to different genera and families, have different chemical and physical properties and dif- fering viral characteristics, it is unwise and inaccurate to assume that any conclusions about one virus can be ap- plied to another, e.g. in a Cochrane review of 59 pub- lished studies on interventions to reduce the spread of respiratory viruses, there were actually only two studies specifically about influenza viruses . As the authors themselves pointed out, no conclusion specific to influ- enza viruses was possible.
Moreover, changes in ecological systems in which pigs are raised may promote the emergence of new infectious agents through a host jump or mutation and, therefore, modify the pattern of infectious agent discovery [9,10]. While production systems within HIC and LMIC groups are heterogeneous, the assumption of higher biosecurity standards and more industrial and specialized production units in HIC than in LMIC seems reasonable. In inte- grated pig production systems, reduced contacts with humans and other animal species may reduce the likeli- hood of inter-species transmission; however, the high pig density and rate of turn-over may increase the likelihood of intra-species transmission, as evidenced by the spread of PRRS and PMWS [32,33]. The genetic homogeneity of pig populations to some extent may restrict the range of infectious agents with the potential to jump host species . However, when combined with a high population density of pigs, it may in fact provide ideal conditions for a major epidemic in pigs resulting from a successful host species jump (i.e. an increased likelihood that if an agent successfully jumps to pigs, it will spread widely among the pig population) . This may lead to the very rapid spread of infectious agents through regional and even glo- bal pig populations as demonstrated by PRRS, PMWS and, more recently, a new variant of porcine epidemic diarrhea virus [36-38]. Even if the pathogen first has lim- ited transmissibility, the aforementioned pig population characteristics may promote infectious agent fitness gain [39-41], leading to the emergence of swine-specific, and more virulent infectious agents . The interface be- tween high density pig populations and potential sources of pathogens (human, other livestock, companion and wild animal populations) becomes particularly permeable for infectious agents when large numbers of pigs are kept at a low level of biosecurity. Such examples include out- door herds or large numbers of small-scale and backyard farms in rural villages or semi-urban situations. In this scenario the risk of cross-species jumps will be increased, promoting the infection of pigs by agents infecting mul- tiple host species (e.g. Nipah virus , Trichinella papuae ), possibly including humans.
When Burroughs and Baum  formed the hypothesis that molecular mimicry between human and E. coli PDC- E2 is responsible for the induction of AMA and autore- active lymphocytes reacting with PDC-E2, they did not know what was going to follow. Several studies have been conducted based on the assumption that E. coli infection may trigger PBC (Table 2). Several reports have shown that sera from PBC patients cross-react with bacterial and human PDC-E2 [20, 89–91, 121, 122]. Subsequent immunological findings have been obtained to demonstrate the presence of cross-reactive antibodies targeting human PDC-E2 and E. coli mimics from proteins unrelated to PDC-E2 or other members of the 2-OADC [66, 84]. While protein–protein BLAST search has identified several E-coli sequences sharing homology with human PDC-E2, very few of those were cross-recognised by PBC sera [66, 82, 99, 110].
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An association of HIV with head and neck cancers was revealed back in the early 1980s along with the first clin- ical observation of its association with symptoms such as lymph node hyperplasias, candidiasis, herpes virus infections, and neoplasias such as Kaposi’s sarcoma (KS) or HIV-associated Non-Hodgkin’s lymphomas (HIV-NHL) that were previously recognised as common ear, nose, and throat (ENT) disorders . The most common HIV- associated malignancy is Kaposi’ s sarcoma, accounting for up to 80% of HIV-related cancers . KS is normally a rare type of cancer, but after HIV-1 infection its incidence is greatly elevated, reaching a 70,000-fold increased inci- dence in HIV-infected homosexual men . The oral cavity is the most common site of otolaryngological mani- festations, and nearly 95% of lesions are found on the pal- ate. Other sites include gingival surfaces of the oropharynx, external ear, larynx, and nose . Endemic KS and AIDS- associated KS (AIDS-KS) tend to be more aggressive than classical KS and AIDS-KS lesions often rapidly progress to plaques and nodules affecting the upper trunk, face, and oral mucosa.
Fig. 1 Flow chart of patient selection. Definitions: Acute fever is an increase of body temperature to 38 °C or more for a period of 21 days or less. Initial investigations refer to comprehensive clinical assessment and basic laboratory and radiology tests; this included tests that are normally reported within 6 h from admission. Comprehensive clinical assessment includes complete history taking and thorough physical examination. Basic laboratory tests usually include complete blood count and urinalysis. Basic radiology tests could include chest X-ray, abdomen and pelvic X-ray, and ultrasonography. Fever with obvious likely diagnosis is any case of fever with definitive diagnosis immediately after initial investigations. This includes fever cases with an obvious focus of infection or local inflammation, such as community-acquired pneumonia, urinary tract infection, skin and soft tissue infection, bone and dental infection, pelvic inflammatory disease and intra-abdominal infection. Acute undifferentiated fever is any case of acute fever with unclear aetiology and the results of initial investigations are not conclusive in achieving a diagnosis. Thus, the condition is characterised by a requirement for further investigation to explain the cause of fever and to consider differential diagnoses. Rational diagnostic investigations are further tests as judged by an attending doctor to deter- mine the cause of fever, such as further serology, cerebrospinal fluid analysis and/or advanced radiology tests [computed tomography (CT) scan, magnetic resonance imaging (MRI)]. Samples were collected from both groups of participants (diagnosed subjects and undiagnosed sub- jects) for fever investigation using the deep sequencing approach
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autoreactive T cells. Mechanisms by which an infection can lead to an autoimmune process have been examined in experimental animal models, and these concepts as well as their relevance to human diseases will be discussed here. Basic mechanisms for the induction of autoimmunity by pathogens In general terms, mechanisms based on microbial products — such as peptides or superantigens — need to be distinguished from mechanisms based on the inflammatory setting that results from an infection. Infection can also result in lymphocyte activation when intracellular signaling pathways are manipulated by lymphotropic viruses (Table 1). Peptides from microbial proteins that have sufficient structural similarity with self- peptides can activate autoreactive T cells, a mechanism that is referred to as molecular mimicry (2–12). Microbial superantigens activate large numbers of T cells that express particular Vb gene segments, and a subpopulation of these activated cells can be specific for a self-antigen (13–17). The inflammatory setting that results from a viral or […]
This prospective observational study was done in a tertiary hospital located in Tamil Nadu, the southernmost state of India. The study was conducted for one year duration from June 2015 to May 2016.All patients admitted in the emergency department were screened for the eligibility criteria and a total of 265 patients were included in the study. Presenting symptoms, signs, comorbidities, laboratory findings viz haematological, biochemical tests and CSF findings were obtained. They were further classified into infectious and non-infectious category based on the pre specified diagnostic criteria. The infectious causes accounted for majority of the aetiology (70.5%) while non-infectious aetiology contributed to (29.5 %). The infectious group was classified further based on whether it was a primary central nervous system (CNS) related infection or sepsis associated. The CNS infections have been classified based on the type of organism as bacterial, viral, fungal or protozoal infections.
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This study showed the co-endemicity of P. falciparum and M. perstans in the Akonolinga Health District with a high frequency of P. falciparum but low frequencies of M. perstans and co-infection of both parasites. In general, many parasite species are endemic in tropical regions of the world and in sub-Saharan Africa in particular, where multiparasitism appears as the rule rather than the exception. Therefore, new approaches to easily detect and recognize multiple infections should be developed in this part of the world. Actually, the most exciting challenge for researchers, specific for disease ecologists is moving from “one parasite species - one host” system towards an ecosystem view “multiple parasites species - multiple hosts", embracing the real complexity of natural systems . Understanding parasitic interactions within-host and landscape level is necessary for good knowledge of the transmission and pathogenesis of diseases caused, and for developing more effective strategies to fight against parasitic diseases .
The surprisingly high rate of C. difficile cytotoxin in the stools of patients who had not been receiving antimicrobial agents when samples were collected (12.1% in the present study) has also been reported by others (27). It has been observed that C. difficile-associated diarrhea and colitis may occur up to 10 weeks after the offending antimicrobial agent has been discontinued (16). We noticed a low rate of cytotoxi- genic C. difficile in patients receiving flucloxacillin, ceftriaxone, glycopeptides, amoxicillin, macrolides, quinolones, or tri- methoprim-sulfamethoxazole. On the other hand, higher inci- dences were noted in patients who received amoxicillin-clavu- lanic acid, imipenem, or clindamycin, confirming other reports (8, 14, 27). The relatively high rate of positive samples with detectable C. difficile cytotoxin (10 of 55; 18.2%) among pa- tients receiving metronidazole was associated with follow-up specimens ordered within 14 days of a previously positive sam- ple for seven patients. So, the samples were collected and analyzed as follow-up for a previously positive result; metro- nidazole was not the offending agent but was the agent admin- istered to treat C. difficile colitis, as recommended in our in- stitution (27). Symptoms of C. difficile enterocolitis may persist for up to 16 days during metronidazole treatment (27). In only two patients, a treatment failure or relapse with metronidazole may have occurred, and the treatment was changed to vanco- mycin, as recommended by others (19, 24). Considering the importance of unrecognized C. difficile enterocolitis in hospi- tals and the high incidence of transmission, we recommend that at least two stool samples be analyzed, since in our study analysis of a second specimen increased the sensitivity from 85.3 to 97.1%.
An alternative approach to vaccine development is the generation of genetically engineered live virus vaccines where a gene or genes are inserted or d eleted decreasing the virulence of the virus but still allowing replication to occur. The thymidine kinase (TK) gene is involved in the neuropathogenicity of alphaherpesviruses and has a role in latency and reactivation (Field and Wildy, 1 978; B ecker et al., 1 984). Comick et al. ( 1 990) showed that a TK deficient mutant ofEHV - 1 was less pathogenic than wild-type virus in horses but this work was carried out in naturally reared horses which may have been previously exposed to either EHV - 1 , EHV -4 or both viruses. Reduced virulence was also shown in SPF foals vaccinated intranasally with a TK-deficient mutant (Slater et al., 1 993; Tewari et al., 1 993). There was evidence of local replication as mutant virus could be recovered from nasal mucus in high titres but no evidence of viraemia (Slater et al., 1993). In both studies however, the vaccine only gave partial protection to subsequent challenge with wild-type virus and viraemia was detected. Whether TK-deficient virus is capable of causing abortion or establishing a latent infection is unknown. A TK-deficient virus vaccine is commercially available for Aujesky's disease and latency has been shown to occur with this mutant virus (van Oirschot et al.,
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nor in faeces at parturition the potential misclassifica- tion does not interfere with the research question. This non-differential misclassification of “dam status” would bias the HR towards null. Intra-uterine transmission of MAP has been described to occur in clinical but also in lower levels in subclinical infected cows and was not controlled for in this study [33,34]. Another limitation of the study is the long study period. Even when expos- ure at parturition was determined it is difficult to differ- entiate between infection due to exposure to MAP at parturition and infection due to exposure during calf rearing. But due to disease characteristics and diagnos- tic methods available long follow-up periods are neces- sary to be able to identify the outcome. It is often stated that calves are most susceptible in the first days of life and transmission occurs most effectively from dam to calf at parturition. However, recent data showed that a clear age dependent susceptibility does not exist be- cause calves up to one year of age were successfully infected with MAP under experimental conditions . But if transmission in the first day of life is most effective the difference between exposed and unex- posed daughters is not expected to diminish during calf rearing.
poxvirus-associated illnesses in their practices. The major- ity (96.7%) had seen at least one case of molluscum conta- giosum with 74.5% having seen five or more cases. 6% reported having seen at least 1 case of monkeypox, with six of these physicians practicing in the Midwest region (Figure 3). 4.7% reported having seen a case of vaccinia in a lab worker while 8.9% had seen a vaccinia infection in a social contact of a vaccinee. Respondents from each of the EIN regions reported having seen orf, with the largest number of those being in the Pacific, East North Central and South Atlantic region. Four respondents reported see- ing a case of sealpox (one respondent in Providence, Hali- fax, and Sacramento and one in an unknown location). No one reported seeing a case of tanapox or a case of oral rabies vaccine (ORV) related human infection.
S. maltophilia was detected from sputum (eight cases), blood (five cases), ascites (four cases), surgical site (three cases), and pleural effusion (one case). The primary infec- tious foci were surgical site infection (six cases), respiratory infection (four cases), blood stream infection (three cases), and burn site infection (one case). The doses of LMOX administered ranged from 1 g/d to 3 g/d for adult patients and from 40 mg/kg/d to 80 mg/kg/d for pediatric patients. Eleven patients (91.7%) were administered LMOX com- bined with other antimicrobials. Significant adverse effects of LMOX were unapparent. The 30-day mortality rate was 25% (3/12 cases), and hospital mortality rate was 50% (6/12 cases).
the inclusion and exclusion criteria is provided in the supplementary material (Figures S1A- S1C). Cohort 1 was assembled from 441 OTRs followed until death or cessation of follow- up in 2016. βPV infection was assessed in eyebrow hair by using polymerase chain reaction–based methods. βPV IgG serore- sponses were determined with multiplex serology. A competing risk model with de- layed entry was used to estimate cumulative incidence of histologically proven cSCC and the effect of βPV by using a multivariable Cox regression model. Results are re- ported as adjusted hazard ratios (HRs). OTRs with 5 or more different βPV types in eyebrow hair had 1.7 times the risk of cSCC vs OTRs with 0 to 4 different types (HR 1.7, 95% confidence interval 1.1- 2.6). A similar risk was seen with high βPV loads (HR 1.8, 95% confidence interval 1.2- 2.8). No significant associations were seen between serum antibodies and cSCC or between βPV and basal cell carcinoma. The diversity and load of βPV types in eyebrow hair are associated with cSCC risk in OTRs, providing evi- dence that βPV is associated with cSCC carcinogenesis and may present a target for future preventive strategies.
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recognized GP epitopes in the sGP or non-essential mucin-like domain of GP1, while neutralizing antibodies were specific to RBD in GP1 or conformation-dependent epitopes at the base of the GP1,2 spike where GP1 meets GP2. Two neutralizing antibodies (KZ52 and JP3K11) against EBOV—that recognize conformation-dependent epitopes comprising residues in GP1 and GP2—were iden- tified to have quite distinct mechanisms of neutralization. KZ52 is a human recombinant IgG1 neutralizing antibody derived from a human survivor of a natural EBOV infec- tion during the 1995 outbreak in Kikwit, Democratic Republic of Congo. KZ52 has impaired recognition for the sGP and binding was dependent on the presence of GP2 residues which are not present in the sGP. KZ52 is able to inhibit cathepsin cleavage of GP1,2. JP3K11, a monkey derived neutralizing monoclonal antibody against EBOV, recognized the cleaved, fusion-active form of GP . 16 F6 is a mice derived monoclonal IgG1 antibody that neutralizes Sudan EBOV by preventing the conformational changes in GP1,2 required for membrane fusion. Both 16 F6 and KZ52 recognize GP1–GP2-bridging epitopes at the base of the GP1,2 trimer, indicating that this overlap- ping epitope may be one of the key sites for neutralization of the EBOV, and is thus a target for immunotherapy and a key goal of vaccine design . Antibody subclass may be another important factor in protection against the EBOV. IgG2 isotype may offer more effective protection against EBOV [110,111]. Although fully protecting guinea pigs from infection, KZ52 fails to slow viral replication and protect NHPs from the EBOV infection . In contrast, rVSV-EBOGP [113-116] and rChAd-EBOGP [117-120]- based vaccination have demonstrated both prophylactic and post-exposure protection in NHPs . This was pre- viously attributed to the protective action of EBOV-specific CD4+ and CD8+ T-cell response induced by these vaccines in limiting infection and the inability of KZ52 to com- pletely block all entries of the EBOV into cells and its subsequent explosive replication . rChAd-EBOGP- based vaccination is able to generate potent humoral and cell-mediated responses. Significant antibody titers are de- tectable at 48 weeks post vaccination [122,123]. CD8+ cell- mediated immunity has been shown to play a critical role in protection against the EBOV infection in NHPs in rChAd-EBOGP-based vaccination . On the other hand, humoral rather than the cell-mediated response con- tributes to protection against the EBOV infection in NHPs in rVSV-EBOGP-based vaccination [125,126].
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Three different coronaviruses, SARS-CoV, MHV-2, and 229E, have been shown to enter cells directly from the cell surface, when the virion S proteins adsorbed to the cell surface receptor are cleaved with proteases such as trypsin that acti- vate the fusion activity of those S proteins. In agreement with those findings, the cleaved S protein of SARS-CoV was re- cently shown to mediate the infection from the cell surface (43). In SARS-CoV infection, cell surface entry seemed to be more efficient than entry via the endosomes (26), which could account for the extraordinarily high replication in the lungs, where elastase, a protease to enable SARS-CoV entry from the cell surface (26), is secreted during the development of mild pneumonia. This efficient infection in the lungs could be a trigger for SARS, which was reproduced recently in mice in- fected with SARS-CoV and respiratory bacteria (1). Although 229E fails to induce a serious respiratory disease in humans, selective infection in the upper respiratory tract could be at- tributed to the specific proteases that could enable 229E in- fection from the cell surface. Since the 229E receptor APN is expressed in a wide variety of cells in the body (17), and 229E infection is limited in the upper respiratory tract, a host factor other than the receptor that determines the tissue specificity of 229E must exist. Protease, which enhances the infection, as observed for SARS-CoV infection (1, 26), may also participate in the pathogenesis of 229E infection. To delineate the patho- genesis of 229E, an analysis of such proteases would be an important direction.
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the transmission of such a disease is called zoonotic (Fiennes, 1967). Likewise, a disease of humans that can be transmitted to other animals is sometimes termed an anthroponosis. Using these definitions, however, we lack a word for the combined collection of these diseases as well as those from mixed or uncertain sources but that are known to be transmitted back and forth between humans and other animals. Here I choose the broader, WHO/FAO Expert Committee on Zoonoses definition of zoonoses to mean those diseases and infections naturally transmitted between vertebrate animals and humans (World Health Organization, 1959). Using this broad definition some have argued that one should rely on the specific terms anthropozoonosis and zooanthroponosis to define the direction of transmission (Nelson, 1960). Yet, even these terms are not uniformly used as anthropozoonoses has been used both for diseases transmissible between man and other animals (Ott- Joslin, 1993), and for diseases of animals transmissible to humans (see Nelson, 1960, and subsequent editorial discussions). This project was focused on health risks that humans may pose to wild apes. Therefore most attention is on those infectious agents that can pass from humans to other primates, which I refer to simply as zoonoses while others might call them anthroponoses. It must be stressed that there are certainly a number of very serious zoonoses that humans can contract from nonhuman primates in the wild (Kalter and Heberling, 1990a; Ott-Joslin, 1993).
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