Origins and Recovery from Superinfections and Soft Tissue Necrosis

The aim of the study was to gather further information regarding the reasons for superinfections and soft tissue necrosis, and to compare them with common gingivitis and periodontitis. A further aim is to see if there are differences in the recovery from these diseases which all are associated with microorganisms. The information was gathered retrospectively from 250 patients and altogether 4022 visits to a specialist. The material was chosen randomly according to the first letter of the patient’s surname, among the 250 patients that were selected. The treatments of 155 patients took place between 1987-2016. The treatment of some patients had started earlier, but the controls had been continued for a long time after 1987. The examinations have been clinical, microbiological, and based on anamnesis, roentgenograms and histopathological examinations. The follow-up time was between 1 to 40 years. The patients who had periodontitis or superinfection were treated in the same way. Antibiotic therapy was prescribed for recurring infections, or if the patient had a difficult disease. In periodontal-endodontic infections, root canals were treated. Periapical lesions were surgically treated. Both periodontitis and superinfections occurred predominantly in the age group between 41 and 60 years. Narcotic- or snuff-addicts were not included in the material, nor were alcoholics, although 6 patients did report moderate use of alcohol. Diseases and other infections had been treated both in patients with periodontitis and in the superinfection group. Oral symptoms were the same, except that the superinfections were violent. The difference in diagnosis was based on the anamnestic information of the antibiotics which induced the acute reaction, on the clinical and microbiological studies. The patients had received 12 different antibiotics, from which 10 induced superinfection. Extraction of teeth did not prevent normal infection, nor superinfection. The infections appeared as ulcers, white coverings or the flush of mucosa, and if the teeth remained, gingival pockets were purulent. The found micro-organisms were yeasts, mould, bacteria, also periodontopathogens. In the superinfection group, some multiply resistant organisms were found. The prognosis of the treatment was good both for patients with periodontitis and superinfection. Flap necrosis is a local, rare surgical complication, in which one factor is superinfection. Incorrect treatment of soft tissue did not lead to flap necrosis in this study. Superinfection is a different disease to periodontitis or gingivitis, because it is induced by antibiotics, and it is linked with multiply resistant microorganisms that are not sensitive to the antibiotics used. Normal periodontal, surgical and endodontic treatments are suitable for patients with periodontal-endodontic problems or superinfection. Superinfection can be very severe, locally or in the whole periodontium, if the infection is bacterial. When the infection was due to yeasts or moulds, local infection was not found. The recovery prognosis is good both in periodontitis and in superinfection. The connection to other diseases is not clear. Cardiovascular diseases, rheumatoid arthritis, diabetes mellitus, accidents and other infections were in anamnesis both in patients with periodontitis and in patients with superinfection. Patients with urinary tract infections who were prescribed antibiotic treatments were more prone to superinfection. Anyone can contract a superinfection. In a healthy gingival, it appears as ulcers, coverings, flushing or gingival bleeding, whereas in patients with periodontitis, the superinfection is mainly purulent. Endodontic superinfection is also possible.

Hepatic flares in chronic hepatitis C: Spontaneous exacerbation vs hepatotropic viruses superinfection

The hepatitis C virus(HCV)causes an acute infection that is frequently asymptomatic,but a spontaneous eradication of HCV infection occurs only in one-third of patients.The remaining two-thirds develop a chronic infection that,in most cases,shows an indolent course and a slow progression to the more advanced stagesof the illness.Nearly a quarter of cases with chronic hepatitis C(CHC)develop liver cirrhosis with or without hepatocellular carcinoma.The indolent course of the illness may be troubled by the occurrence of a hepatic flare,i.e.,a spontaneous acute exacerbation of CHC due to changes in the immune response,immunosuppression and subsequent restoration,and is characterized by an increase in serum aminotransferase values,a frequent deterioration in liver fibrosis and necroinflammation but also a high frequency of sustained viral response to pegylated interferon plus ribavirin treatment.A substantial increase in serum aminotransferase values during the clinical course of CHC may also be a consequence of a superinfection by other hepatotropic viruses,namely hepatitis B virus(HBV),HBV plus hepatitis D virus,hepatitis E virus,cytomegalovirus,particularly in geographical areas with high endemicity levels.The etiology of a hepatic flare in patients with CHC should always be defined to optimize follow-up procedures and clinical and therapeutic decisions.

Superinfection of hepatitis E Virus as a cause of decompensation in liver cirrhosis due to hepatitis B virus

Objevtive:Super infection with hepatitis A virus(HAV ) and hepatitis E virus(HEV ) in the presence of underlying hepatocellular injury can cause severe illness.In endemic areas such as India,however most patients already have been exposed to HAV but could still be susceptible to HEV infection.In our study we determined the seroprevalence of anti-HAV IgM and anti-HEV IgM to assess the incidence of superinfection with these viruses in cirrhotic patients with the goal of defining the need for protection against these viruses and further correlate the presence of these viruses with the clinical course.Methods:We studied 53 patients of cirrhosis as a result of Hepatitis B virus.Apparent causes of decompensation were ruled out before their inclusion in the study group.Serum sample from these patients was tested for HBsAg,anti HBc IgG,anti HEV IgM and anti HAV IgG and IgM by commercially available ELISA kit.Liver function test was done on all the patients and correlated with various serological markers.Results:anti HBc IgG was present in all the cases of cirrhosis. Hepatitis B surface antigen was present in 20 out of 53 cases of cirrhosis.None of the patients demonstrated anti-HAV IgM,however one patient had anti-HEV IgM.Conclusion:Superinfection with HAV in adult patient is uncommon in India.Prevalence of acute HEV infection in decompensated cirrhosis is low in the present study but presence of HEV superinfection in one patient corroborates the apprehension of liver function deterioration following superinfection with HEV virus.

Multi Drug Resistant <i>Escherichia coli</i>Superinfection in Patient with COVID-19

Background: Coronavirus Disease 2019 (COVID-19) has infected millions people worldwide and is continuing to spread rapidly. Patients with COVID-19 may be superinfected with other microorganisms. The prevalence of bacterial superinfection among coronavirus patients is not well understood. Aim: The aim of presenting this case is to highlight the problem of Multi-Drug Resistant (MDR) bacterial infection in COVID-19 patients. Case Presentation: Here we reported a 46 years old patient with the previous history of Escherichia coli urinary tract infection. A few weeks later, the patient was recovered from COVID-19 infection and was treated with antiviral therapy until PCR results become negative. Meanwhile, the patients developed urinary tract infection with MDR Escherichia coli even resistant to imipenem and required a critical treatment. Conclusion: Our finding suggests that greater attention should be paid to coronavirus infection complications and prophylaxis use of antibiotics. In addition, more studies are required to better understand the risk factors which are responsible for the superinfection and emergence of drug-resistant strains during COVID-19 infection.

Immunological and virological characteristics of human immunodeficiency virus type i superinfection： implications in vaccine design

Superinfection is frequently detected among individuals infected by human immunodeficiency virus type I （HIV-1）. Superinfection occurs at similar frequencies at acute and chronic infection stages but less frequently than primary infection. This observation indicates that the immune responses elicited by natural HIV-1 infection may play a role in curb of superinfection; however, these responses are not sufficiently strong to completely prevent superinfection. Thus, a successful HIV-1 vaccine likely needs to induce more potent and broader immune responses than those elicited by primary infection. On the other hand, potent and broad neutralization responses are more often detected after superinfection than during monoinfection. This suggests that broadly neutralizing antibodies are more likely induced by sequential immunization of multiple different immunogens than with only one form of envelope glycoprotein immunogens. Understanding why the protection from superinfection by immunity induced by primary infection is insufficient and if superinfection can lead to cross-reactive immune responses will be highly informative for HIV-1 vaccine design.

Influence of chronic HBV infection on superimposed acute hepatitis E

AIM:To investigate the influence of chronic hepatitis B virus(HBV)infection[based on the status of hepatitis B e antigen(HBeAg),HBV DNA,and cirrhosis]on superimposed acute hepatitis E.METHODS:A total of 294 patients were recruited from the Department of Infectious Diseases of the Third Affiliated Hospital,Sun Yat-sen University,from January 2003 to January 2012.The patients were classified into two groups:an HBV+hepatitis E virus(HEV)group(a group with chronic HBV infection that was superinfected with acute hepatitis E,n=118)and an HEV group(a group with acute hepatitis E,n=176).We retrospectively analyzed and compared the clinical features of the two groups.Statistical analyses were performed using theχ2test or Fisher’s exact test for categorical variables and the Student’s t test forcontinuous variables.A P value<0.05 was considered statistically significant.RESULTS:The peak values of prothrombin time,serum total bilirubin,and Model for End-Stage Liver Disease scores were significantly higher in the HBV+HEV group.More patients in the HBV+HEV group had complications(39.8%vs 16.5%,P=0.000)and developed liver failure(35.6%vs 8.5%,P=0.000).Additionally,the mortality of the HBV+HEV group was significantly higher(20.3%vs 7.4%,P=0.002).Further analysis of the HBV+HEV group showed that there were no significant differences in complication occurrence,liver failure incidence,or mortality between patients with different HBeAg and HBV DNA statuses.However,in patients with underlying cirrhosis,complication occurrence and liver failure incidence significantly increased.In total,12.7%of the patients in the HBV+HEV group received anti-HBV treatment,but this therapy failed to reduce mortality in patients who developed liver failure.CONCLUSION:The presence of underlying cirrhosis in chronic HBV infection results in more severe clinical outcomes with superimposed acute hepatitis E.AntiHBV treatment cannot improve the prognosis of liver failure caused by HBV-HEV superinfection.

Superinfective Hepatitis E Virus Infection Aggravates Hepatocytes Injury in Chronic Hepatitis B

Hepatitis E virus(HEV)infection is a major cause of morbidity in endemic areas.Its consequences among chronic hepatitis B(CHB)patients have been under-reported.The aim of this study was to assess the impact of superinfective HEV infection(acute and past)on virological and clinical features of patients with CHB infection.Clinical,biochemical,virological and immunological data of 153 CHB patients including 98 with hepatitis B virus(HBV)monoinfection and 55 with HBV-HEV superinfection with both HEV and HBV infection was retrospectively investigated and analyzed in this study conducted in Wuhan,China.An overall anti-HEV IgG seroprevalence was found to be 35.9% in CHB patients.HBV-HEV superinfection patients showed significantly higher rate of complications(ascites,hepato-renal syndrome&encephalopathy)(all with P=0.04),cirrhosis(P<0.001)and acute-on-chronic liver failure(P<0.001)than HBV monoinfection patients.They also displayed elevated ALTs(P<0.001)and total serum bilirubin(P<0.001)with diminished albumin(P<0.001)and HBV viral load(P<0.001).Cytokines assay revealed increased expression of IL-6(P=0.02),IL-10(P=0.009)and TNF-α(P=0.003)in HBVHEV superinfection patients compared to HBV monoinfection patients.Our study demonstrated that HEV superinfection in CHB patients was associated with progressive clinical manifestation,which is likely due to the enhanced expression of cytokines related with hepatocytes necrosis.HEV was also associated with repressed HBV replication,but the underlying mechanism requires further investigation.

Bacteriophage secondary infection

Phages are credited with having been first described in what we now, officially, are commemorating as the 100 th anniversary of their discovery. Those one-hundred years of phage history have not been lacking in excitement, controversy, and occasional convolution. One such complication is the concept of secondary infection, which can take on multiple forms with myriad consequences. The terms secondary infection and secondary adsorption, for example, can be used almost synonymously to describe virion interaction with already phage-infected bacteria, and which can result in what are described as superinfection exclusion or superinfection immunity. The phrase secondary infection also may be used equivalently to superinfection or coinfection, with each of these terms borrowed from medical microbiology, and can result in genetic exchange between phages, phage-on-phage parasitism, and various partial reductions in phage productivity that have been termed mutual exclusion, partial exclusion, or the depressor effect. Alternatively, and drawing from epidemiology, secondary infection has been used to describe phage population growth as that can occur during active phage therapy as well as upon phage contamination of industrial ferments. Here primary infections represent initial bacterial population exposure to phages while consequent phage replication can lead to additional, that is, secondary infections of what otherwise are not yet phage-infected bacteria. Here I explore the varying meanings and resultant ambiguity that has been associated with the term secondary infection. I suggest in particular that secondary infection, as distinctly different phenomena, can in multiple ways influence the success of phage-mediated biocontrol of bacteria, also known as, phage therapy.

Interventional strategies in infected necrotizing pancreatitis:Indications,timing,and outcomes

Acute pancreatitis(AP)is one of the most common gastrointestinal diseases and remains a life-threatening condition.Although AP resolves to restitutio ad integrum in approximately 80%of patients,it can progress to necrotizing pancreatitis(NP).NP is associated with superinfection in a third of patients,leading to an increase in mortality rate of up to 40%.Accurate and early diagnosis of NP and associated complications,as well as state-of-the-art therapy are essential to improve patient prognoses.The emerging role of endoscopy and recent trials on multidisciplinary management of NP established the“step-up approach”.This approach starts with endoscopic interventions and can be escalated to other interventional and ultimately surgical procedures if required.Studies showed that this approach decreases the incidence of new multiple-organ failure as well as the risk of interventional complications.However,the optimal interventional sequence and timing of interventional procedures remain controversial.This review aims to summarize the indications,timing,and treatment outcomes for infected NP and to provide guidance on multidisciplinary decision-making.

Acute hepatitis C in a chronically HIV-infected patient:Evolution of different viral genomic regions

AIM: To analyze the molecular evolution of different viral genomic regions of HCV in an acute HCV infected patient chronically infected with HIV through a 42-month follow-up.METHODS: Serum samples of a chronically HIV infected patient that seroconverted to anti HCV antibodies were sequenced, from the event of superinfection through a period of 17 months and in a late sample (42nd month). Hypervariable genomic regions of HIV (V3 loop of the gp120) and HCV (HVR-1 on the E2 glycoprotein gene) were studied. In order to analyze genomic regions involved in different biological functions and with the cellular immune response, HCV core and NS5A were also chosen to be sequenced. Amplification of the different regions was done by RT-PCR and directly sequenced. Confirmation of sequences was done on reamplified material. Nucleotide sequences of the different time points were aligned with CLUSTAL W 1.5, and the corresponding amino acid ones were deduced.RESULTS: Hypervariable genomic regions of both viruses (HVR1 and gp120 V3 loop) presented several nonsynonymous changes but, while in the gp120 V3 loop mutations were detected in the sample obtained right after HCV superinfection and maintained throughout, they occurred following a sequential and cumulative pattern in the HVR1. In the NS5A region of HCV, two amino acid changes were detected during the follow-up period, whereas the core region presented several amino acid replacements, once the HCV chronic infection had been established.CONCLUSION: During the HIV-HCV superinfection, each genomic region analyzed shows a different evolutionary pattem.Most of the nucleotide substitutions observed are nonsynonymous and clustered in previously described epitopes,thus suggesting an immune-driven evolutionary process.

Mosquito densovirus signifcantly reduces the vector susceptibility to dengue virus serotype 2 in Aedes albopictus mosquitoes(Diptera:Culicidae)

Background Dengue virus(DENV)is a major public health threat,with Aedes albopictus being the confrmed vector responsible for dengue epidemics in Guangzhou,China.Mosquito densoviruses(MDVs)are pathogenic mosquitospecifc viruses,and a novel MDV was previously isolated from Ae.albopictus in Guangzhou.This study aims to determine the prevalence of MDVs in wild Ae.albopictus populations and investigate their potential interactions with DENV and impact on vector susceptibility for DENV.Methods The prevalence of MDV in wild mosquitoes in China was investigated using open access sequencing data and PCR detection in Ae.albopictus in Guangzhou.The viral infection rate and titers in MDV-persistent C6/36 cells were evaluated at 12,24,48,72,96,and 120 h post infection(hpi)by indirect immunofuorescence assay(IFA)and real time quantitative PCR(RT-qPCR).The midgut infection rate(MIR),dissemination rate(DR),and salivary gland infection rate(SGIR)in various tissues of MDV-infected mosquitoes were detected and quantifed at 0,5,10,and 15 days post infection(dpi)by RT-PCR and RT-qPCR.The chi-square test evaluated dengue virus serotype 2(DENV-2)and Aedes aegypti densovirus(AaeDV)infection rates and related indices in mosquitoes,while Tukey’s LSD and t-tests compared viral titers in C6/36 cells and tissues over time.Results The results revealed a relatively wide distribution of MDVs in Aedes,Culex,and Anopheles mosquitoes in China and an over 68%positive rate.In vitro,signifcant reductions in DENV-2 titers in supernatant at 120 hpi,and an appar‑ent decrease in DENV-2-positive cells at 96 and 120 hpi were observed.In vivo,DENV-2 in the ovaries and salivary glands was frst detected at 10 dpi in both monoinfected and superinfected Ae.albopictus females,while MDV super‑infection with DENV-2 suppressed the salivary gland infection rate at 15 dpi.DENV-2 titer in the ovary and salivary glands of Ae.albopictus was reduced in superinfected mosquitoes at 15 dpi.Conclusions MDVs is widespread in natural mosquito populations,and replication of DENV-2 is suppressed in MDVinfected Ae.albopictus,thus reducing vector susceptibility to DENV-2.Our study supports the hypothesis that MDVs may contribute to reducing transmission of DENV and provides an alternative strategy for mosquito-transmitted disease control.

HEV and HBV Dual Infection:A Review

Hepatitis E virus(HEV)is a global health problem,affecting about 20 million people worldwide.There is significant overlap of hepatitis B virus(HBV)and HEV endemicity in many Asian countries where dual infections with HEV and HBV can occur.Though the clinical course of HEV is largely self-limited,HEV superinfection in patients with chronic hepatitis B(CHB)can result in acute exacerbation of underlying CHB.HEV superinfection in patients with CHB-related cirrhosis has been identified as a risk factor for decompensated cirrhosis and an independent predictor of mortality.Whereas acute HEV infection in pregnancy can cause fulminant liver failure,the few studies on pregnant patients with dual HBV and HEV infection have shown a subclinical course.Immunosuppression is a risk factor for the development of chronic HEV infection,which can be managed by decreasing the dose of immune-suppressants and administering ribavirin.Vaccination for HEV has been developed and is in use in China but its efficacy in patients with CHB has yet to be established in the USA.In this review,we appraise studies on dual infection with HEV and HBV,including the effect of HEV superinfection and coinfection in CHB,management strategies used and the role of active vaccination in the prevention of HEV.

Genetic variation and potential coinfection of Wolbachia among widespread Asian citrus psyllid (Diaphorina citri Kuwayama) populations

Wolbachia can profoundly influence the survival, reproduction, and defenses of insect hosts. These interactions could potentially be harnessed for managing pests or insecttransmitted diseases. Diaphorina citri Kuwayama is a phloem-feeding pest capable of transmitting the putative causal agent of citrus greening, Candidatus Liberibacter asiaticus (CLas). Like many insects, D. citri is also infected with Wolbachia (wDi). Recent studies indicate that the relative abundance of wDi could be associated with the abundance of CLas, and that wDi may contribute to regulating expression of phage lytic cycle genes in CLas, suggesting the need for better understanding of wDi biology in general. This study investigated the genetic diversity of wDi among D. citri in populations spanning eleven countries and two U.S. territories. Six Wolbachia genes, wsp, coxA.fbpA.ftsZ, gatB, and hep A, were sequenced and compared across samples. Two prevalent wDi strains were identified across the samples, and screening of clone libraries revealed possible coinfection of wDi strains in specific populations. D. citri mitochondrial cytochrome oxidase subunit I gene (mtCOI) were more divergent between D. citri populations that were infected with different wDi strains or had different infection statuses (single infection vs. coinfection). While we could not eliminate the possibility that maternal transmission may contribute to such patterns, it is also possible that wDi may induce cytoplasmic incompatibility in their host. These fin dings should contribute to the understanding of wDi population ecology, which may facilitate manipulation of this endosymbiont for management of citrus greening disease worldwide.

Corticosteroids for COVID-19

Coronavirus disease 19(COVID-19)is placing a major burden on healthcare,economy and social systems world-wide owing to its fast spread and unacceptably high death toll.The unprecedented research effort has established the role of a deregulated immune response to the severe acute respiratory syndrome coronavirus 2,resulting in systemic inflammation.After that,the immunomodulatory approach has been placed in the top list of the re-search agenda for COVID-19.Corticosteroids have been used for more than 70 years to modulate the immune response in a broad variety of diseases.These drugs have been shown to prevent and attenuate inflammation both in tissues and in circulation via non-genomic and genomic effects.At the bedside,numerous observational cohorts have been published in the past months and have been inconclusive.Randomized controlled trials with subsequent high quality meta-analyses have provided moderate to strong certainty for an increased chance of survival and relief from life supportive therapy with corticosteroids given at a dose of 6 mg per day dexametha-sone or equivalent doses of hydrocortisone or methylprednisolone.The corticotherapy was not associated with an increased risk of bacterial infection or of delayed viral clearance.In daily practice,physicians may be encouraged to use corticosteroids when managing patients with COVID-19 requiring oxygen supplementation.

Some models with repulsion effect on superinfecting viruses by infected cells

In this paper,we study some models with repulsion effect on superinfecting viruses by infected cells{■T/■t=DT△T(x,t)-■(TФ(T,I)■I)+h(x)-dTT(x,t)-β(x)T(x,t)V(x,t),■I/■T=DT△I+β(x)T(x,t)V(x,t)-dII(xt,),■I/■T=■(Dv(I)■V)+γ(x)I(x,t)-dvV(x,t),where T(x,t),I(x,t)and V(x,t)are the density of uninfected cells,infected cells and viruses at time t at location x,respectively.The functions h(x),β(x)andγ(x)are assumed to be positive,continuous and bounded.h(x)denotes the production rate of uninfected cells.The infection rate isβ(x)and the functionγ(x)is the production rate of free viruses.Andβ(x)T(x,t)V(x,t)is the rate of transfer from uninfected cells to infected cells.The positive constants dT,dI and dV denote the death rate of uninfected cells,infected cells and viruses,respectively.The stability of the infection-free equilibrium solution and infection equilibrium solution is discussed.It is shown that if the basic reproduction number R0≤1 then the chemotaxis has no effect,that is,the infection-free constant solution is stable.For the system with chemotactic sensitivityФ(T,I)=1-T,if R0>1,then the infection constant solution will be unstable under some conditions.