Self-limiting Infection Research Articles

Delayed prescribing of antibiotics for self-limiting respiratory tract infections in an urgent care out-of-hours setting

Long-term overuse of antibiotics and inappropriate prescribing has led to widespread development of antimicrobial resistance. The Department of Health and Social Care recently published a five-year national action plan to reduce antimicrobial resistance, with the aim of reducing inappropriate antibiotic prescribing. This is mirrored in the NHS Long Term Plan, which aims to reduce unintentional exposure through a combination of antibiotic stewardship and leadership at all levels. An acute respiratory tract infection is one of the most common presentations in primary care, with 16.7% of all prescriptions issued attributed to it. Therefore, out-of-hours prescribers contribute significantly to general antibiotic consumption. This article analyses the practice of delayed prescribing of antibiotics for the treatment of self-limiting respiratory tract infections in an out-of-hours service. The advantages and disadvantages associated with delayed prescribing, to safely treat patients whilst facilitating the reduction of antimicrobial resistance, are discussed. In addition, recommendations for future practice are offered. This article also focuses on the development of an advanced nurse practitioner, reflecting on the four pillars of advanced practice, which underpin advanced clinical practice and associated competencies.

Pneumonia recovery reprograms the alveolar macrophage pool.

Community-acquired pneumonia is a widespread disease with significant morbidity and mortality. Alveolar macrophages are tissue-resident lung cells that play a crucial role in innate immunity against bacteria that cause pneumonia. We hypothesized that alveolar macrophages display adaptive characteristics after resolution of bacterial pneumonia. We studied mice 1 to 6 months after self-limiting lung infections with Streptococcus pneumoniae, the most common cause of bacterial pneumonia. Alveolar macrophages, but not other myeloid cells, recovered from the lung showed long-term modifications of their surface marker phenotype. The remodeling of alveolar macrophages was (a) long-lasting (still observed 6 months after infection), (b) regionally localized (observed only in the affected lobe after lobar pneumonia), and (c) associated with macrophage-dependent enhanced protection against another pneumococcal serotype. Metabolomic and transcriptomic profiling revealed that alveolar macrophages of mice that recovered from pneumonia had new baseline activities and altered responses to infection that better resembled those of adult humans. The enhanced lung protection after mild and self-limiting bacterial respiratory infections includes a profound remodeling of the alveolar macrophage pool that is long-lasting; compartmentalized; and manifest across surface receptors, metabolites, and both resting and stimulated transcriptomes.

Genetic variants in class II transactivator are associated with chronic hepatitis B virus infection in the Han Chinese population.

Class II transactivator (CIITA) is a master regulator of MHC gene expression and plays a role in inducing the expression of other immune system genes, including IL-4, IL-10 and Fas ligand, as well as more than 60 other immunologically significant genes. We used CIITA as a candidate gene to analyse whether any single-nucleotide polymorphisms (SNPs) are associated with chronic hepatitis B virus (HBV) infection. In total, 773 patients with chronic HBV infection were enrolled in this hospital-based case-control study. The patients were divided into groups according to their clinical characteristics: 596 patients had chronic hepatitis B (CHB), and 177 patients had hepatocellular carcinoma (HCC). A total of 313 patients with self-limited HBV infection were selected as the control group. CIITA gene variants were screened using Haploview 4.2 software; improved multiplex ligation detection reaction technology was then used for genotype detection, and HaploReg v4.1 was employed to predict the functions of 15 variants. The results showed that SNPs in introns in the CIITA gene, namely, rs13333382 (TT+TA vs. AA: p=.003, odds ratio (OR)=0.65, 95% confidence interval (CI)=0.49-0.87) and rs4780335 (CC+CG vs. GG: p=9.40×10-5 , OR=0.55, 95% CI=0.41-0.74), were positively associated with self-limited HBV infection in the dominant genetic model. Additionally, SNP rs1139564 (TT+TC vs. CC: p=.002, OR=1.61, 95% CI=1.19-2.16) in the 3' untranslated region may increase the risk of CHB. According to in silico analysis, all three statistically significant variants act as transcription factor binding motifs. However, we did not find that these 15 mutations are associated with HCC risk. Therefore, we believe that CIITA is a susceptibility gene for CHB rather than for HCC.

Molluscum Contagiosum: Review and Update on Clinical Presentation, Diagnosis, Risk, Prevention, and Treatment

Molluscum contagiosum (MC) is a self-limited cutaneous viral infection that most commonly affects children and immunocompromised populations. This review provides an update on the clinical manifestations, risk, diagnosis, treatment, and prevention of this frequently encountered infection. A recent Cochrane review concluded that there is insufficient evidence to establish the superiority of any specific treatment modality or to confirm that active intervention is superior to benign neglect (van der Wouden JC et al., Cochrane Database Syst Rev 5:CD004767, 2017). Interim pilot study data suggests that cantharidin outperforms placebo (Guzman AK et al., Int J Dermatol 57:1001–1006, 2018). Imiquimod is no longer recommended for treatment of MC (van der Wouden JC et al., Cochrane Database Syst Rev 5:CD004767, 2017; Papadopoulos EJ, https://www.fda.gov/files/drugs/published/N20-723S020-Imiquimod-Clinical-BPCA.pdf, 2006; Katz KA et al., Pediatr Dermatol 35:282–283, 2018). Optimal management strategies for MC remain unclear due to the multitude of proposed therapies, lack of high-quality evidence, and uncertain benefit of intervention for uncomplicated disease. Aside from watchful waiting, destructive therapies such as cantharidin and curettage are among the best studied methods and remain the treatment of choice for most patients.

Digital interventions for parents of acutely ill children and their treatment-seeking behaviour: a systematic review.

Consultations for self-limiting infections in children are increasing. It has been proposed that digital technology could be used to enable parents' decision making in terms of self-care and treatment seeking. To evaluate the evidence that digital interventions facilitate parents deciding whether to self-care or seek treatment for acute illnesses in children. Systematic review of studies undertaken worldwide. Searches of MEDLINE and EMBASE were made to identify studies (of any design) published between database inception and January 2019 that assessed digital interventions for parents of children (from any healthcare setting) with acute illnesses. The primary outcome of interest was whether the use of digital interventions reduced the use of urgent care services. Three studies were included in the review. They assessed two apps and one website: Children's On-Call - a US advice-only app; Should I See a Doctor? - a Dutch self-triage app for any acute illness; and Strategy for Off-Site Rapid Triage (SORT) for Kids - a US self-triage website for influenza-like illness. None of the studies involved parents during intervention development and it was shown that many parents did not find the two apps easy to use. The sensitivity of self-triage interventions was 84% for Should I See a Doctor? compared with nurse triage, and 93.3% for SORT for Kids compared with the need for emergency-department intervention; however, both had lower specificity (74% and 13%, respectively). None of the interventions demonstrated reduced use of urgent-care services. There is little evidence to support the use of digital interventions to help parent and/or carers looking after children with acute illness. Future research should involve parents during intervention development, and adequately powered trials are needed to assess the impact of such interventions on health services and the identification of children who are seriously ill.

Human genetics of life-threatening influenza pneumonitis.

Influenza viruses infect millions of people around the globe annually, usually causing self-limited upper respiratory tract infections. However, a small but non-negligible proportion of patients suffer from life-threatening pulmonary disease. Those affected include otherwise healthy individuals, and children with primary infections in particular. Much effort has been devoted to virological studies of influenza and vaccine development. By contrast, the enormous interindividual variability in susceptibility to influenza has received very little attention. One interesting hypothesis is that interindividual variability is driven largely by the genetic makeup of the infected patients. Unbiased genomic approaches have been used to search for genetic lesions in children with life-threatening pulmonary influenza. Four monogenic causes of severe influenza pneumonitis—deficiencies of GATA2, IRF7, IRF9, and TLR3—have provided evidence that severe influenza pneumonitis can be genetic and often in patients with no other severe infections. These deficiencies highlight the importance of human type I and III IFN-mediated immunity for host defense against influenza. Clinical penetrance is incomplete, and the underlying mechanisms are not yet understood. However, human genetic studies have clearly revealed that seemingly sporadic and isolated life-threatening influenza pneumonitis in otherwise healthy individuals can be genetic.

Enough is enough – is it time for the Scottish Antimicrobial Prescribing Group (SAPG) to develop the third age of antimicrobial stewardship in primary care in Scotland?

Background From 2008 the SAPG focused on ‘what to prescribe’ to tackle Clostridium difficile infection and from 2013 on ‘whether to prescribe’ to tackle unnecessary prescribing for self-limiting infections. Following these successes SAPG is now moving to the age of ‘how much to prescribe’ to ensure correct duration of therapy. We aimed to compare current prescribing practice with guidance from Public Health England (PHE)/NICE which recommends five days’ treatment for most common community respiratory infections (RTI). Methods The durations of antibiotic courses for treatment of respiratory tract infections was derived from data on dispensed prescriptions in 2018 from the Prescribing Information System, a national database of all NHS prescriptions dispensed in Scotland. Observed course durations were compared to course lengths recommended by PHE/NICE and modelling was undertaken on the impact on antibiotic use if durations were in line with guidance. Results For antibiotics recommended for RTI, the most common length of treatment used was seven days. For amoxicillin the proportion of five day prescriptions varied across health boards from 1.8% to 68.7%. Modelling estimated if 75% of seven day prescriptions for antibiotics recommended for RTI were changed to five days this would deliver a 4.1% reduction in antibiotic use. Conclusion SAPG has agreed to lead work to encourage the use of five day courses of antibiotics where indicated. Switching to five day courses would support reduction in total antibiotic use to achieve the ambitions of the UK AMR National Action Plan.

Outbreak of acute undifferentiated febrile illness in Kathmandu, Nepal: clinical and epidemiological investigation

BackgroundOutbreaks of acute undifferentiated febrile illness (AUFI) are common in Nepal, but the exact etiology or risk factors for them often go unrecognized. Diseases like influenza, enteric fever and rickettsial fevers account for majority of such outbreaks. Optimal diagnostic tests to inform treatment decisions are not available at the point-of-care. A proper epidemiological and clinical characterization of such outbreaks is important for appropriate treatment and control efforts.MethodsAn investigation was initiated as a response to increased presentation of patients at Patan Hospital from Chalnakhel locality in Dakchinkali municipality, Kathmandu with AUFI from June 10 to July 1, 2016. Focused group discussion with local inhabitants and the epidemiological curve of febrile patients at local primary health care centre confirmed the outbreak. The household-survey was conducted in the area with questionnaire administered on patients to characterize their illnesses and their medical records were reviewed. A different set of questionnaire was administered on the patients and controls to investigate the association with common risk factors. Water samples were collected and analyzed microbiologically.ResultsEighty one patients from 137 households suffered from febrile illness within 6 weeks window before the investigation. All the 67 sampled patients with acute fever had a generalized illness without a discernible focus of infection. Only 38% of the patients had received a clinical diagnosis while the rest were treated empirically without a diagnosis. Three patients had blood culture confirmed enteric fever. Forty-two (63%) patients had been administered antibiotics, most commonly, ofloxacin, cefixime or azithromycin with a mean fever clearance time of 4 days. There was no definite association between several risk factors and fever. Fecal contamination was noted in tap water samples.ConclusionBased on the pattern of illness, this outbreak was most likely a mixture of self-limiting viral infections and enteric fever. This study shows that even in the absence of a confirmed diagnosis, a detailed characterization of the illness at presentation and the recovery course can suggest the diagnosis and help in formulating appropriate recommendation for treatment and control.

Blastomycosis

Blastomycosis is a serious fungal disease of humans and other mammals caused by environmentally acquired infection with geographically restricted, thermally dimorphic fungi belonging to the genus Blastomyces. The genetic and geographic diversity of these pathogens is greater than previously appreciated. In addition to Blastomyces dermatitidis and the cryptic species Blastomyces gilchristii, which cause blastomycosis in mid-western and various eastern areas of North America, atypical blastomycosis is occasionally caused by Blastomyces helicus in western parts of North America and Blastomyces percursus in Africa. Blastomycosis is acquired by inhalation of the conidia that are produced in the mold phase; in the lungs, temperature-dependent transformation occurs to the yeast phase. In this form, the organism is phagocytized by macrophages and can spread hematogenously to various organs causing disseminated infection. Pulmonary disease is most common and varies from mild, self-limited infection to severe, potentially fatal adult respiratory distress syndrome. Disseminated infection is manifested primarily by skin lesions, but many other organs can be involved. Diagnosis is established by growth of the organism in culture; however, a tentative diagnosis can be made quickly by histopathological identification of the classic yeast form in tissues or by finding Blastomyces antigen in urine or serum. Blastomycosis is treated initially with amphotericin B when the disease is severe, involves the central nervous system, or the host is immunosuppressed. Itraconazole is recommended for primary therapy in mild-to-moderate infection and for step-down therapy after initial amphotericin B treatment. Voriconazole and posaconazole can be used for patients in whom itraconazole is not tolerated.

An RNA thermometer dictates production of a secreted bacterial toxin.

Frequent transitions of bacterial pathogens between their warm-blooded host and external reservoirs are accompanied by abrupt temperature shifts. A temperature of 37°C serves as reliable signal for ingestion by a mammalian host, which induces a major reprogramming of bacterial gene expression and metabolism. Enteric Yersiniae are Gram-negative pathogens accountable for self-limiting gastrointestinal infections. Among the temperature-regulated virulence genes of Yersinia pseudotuberculosis is cnfY coding for the cytotoxic necrotizing factor (CNFY), a multifunctional secreted toxin that modulates the host’s innate immune system and contributes to the decision between acute infection and persistence. We report that the major determinant of temperature-regulated cnfY expression is a thermo-labile RNA structure in the 5’-untranslated region (5’-UTR). Various translational gene fusions demonstrated that this region faithfully regulates translation initiation regardless of the transcription start site, promoter or reporter strain. RNA structure probing revealed a labile stem-loop structure, in which the ribosome binding site is partially occluded at 25°C but liberated at 37°C. Consistent with translational control in bacteria, toeprinting (primer extension inhibition) experiments in vitro showed increased ribosome binding at elevated temperature. Point mutations locking the 5’-UTR in its 25°C structure impaired opening of the stem loop, ribosome access and translation initiation at 37°C. To assess the in vivo relevance of temperature control, we used a mouse infection model. Y. pseudotuberculosis strains carrying stabilized RNA thermometer variants upstream of cnfY were avirulent and attenuated in their ability to disseminate into mesenteric lymph nodes and spleen. We conclude with a model, in which the RNA thermometer acts as translational roadblock in a two-layered regulatory cascade that tightly controls provision of the CNFY toxin during acute infection. Similar RNA structures upstream of various cnfY homologs suggest that RNA thermosensors dictate the production of secreted toxins in a wide range of pathogens.

Clinical Profile of Patients of Leptospirosis and Its Outcome

Background: Leptospirosis is an emerging spirochetal zoonosis worldwide. It is underreported and under diagnosed in India. The clinical manifestations of Leptospirosis range from an asymptomatic illness, self-limiting systemic infection to severe and potentially fatal disease. Approximately 1 million severe cases occur per year . Aims and Objectives: To study the clinical profile of acute onset fever (less than 7 days) that are IgM positive for leptospira and to study their in hospital outcome. Methods: This observational study was conducted in Dr. Hedgewar Hospital, Aurangabad, Maharashtra. The IgM positive leptospirosis patients admitted during January 2014 to December 2018 were included in the study. The information on demographic and clinical profile of these patients was recorded and analyzed based on modified Faine’s criteria. Their in hospital outcome was assessed. Result: The study included 62 leptospirosis IgM positive patients. The mean age was 38.14±15.84 years. All patients presented with fever. Acute Respiratory Distress Syndrome (ARDS) was the most common complication seen in 48.38%. Case Fatality Rate (CFR) was found to be 16.12% (10 out of 62 ) patients . Conclusion• High proportion of cases indirectly reflects the endemic nature of the disease.• The clinical presentation of leptospirosis is highly protean and may vary from sub-clinical to mild illness to life-threatening complications and death. How to cite this article:Ratnaparkhe V, Ratnaparkhe R, Vaishnav S. Clinical Profile of Patients of Leptospirosis and Its Outcome. J Adv Res Med 2019; 6(3): 19-22. DOI: https://doi.org/10.24321/2349.7181.201916

Treatment timing shifts the benefits of short and long antibiotic treatment over infection.

Antibiotics are the major tool for treating bacterial infections. Rising antibiotic resistance, however, calls for a better use of antibiotics. While classical recommendations favor long and aggressive treatments, more recent clinical trials advocate for moderate regimens. In this debate, two axes of ‘aggression’ have typically been conflated: treatment intensity (dose) and treatment duration. The third dimension of treatment timing along each individual’s infection course has rarely been addressed. By using a generic mathematical model of bacterial infection controlled by immune response, we examine how the relative effectiveness of antibiotic treatment varies with its timing, duration and antibiotic kill rate. We show that short or long treatments may both be beneficial depending on treatment onset, the target criterion for success and on antibiotic efficacy. This results from the dynamic trade-off between immune response build-up and resistance risk in acute, self-limiting infections, and uncertainty relating symptoms to infection variables. We show that in our model early optimal treatments tend to be ‘short and strong’, while late optimal treatments tend to be ‘mild and long’. This suggests a shift in the aggression axis depending on the timing of treatment. We find that any specific optimal treatment schedule may perform more poorly if evaluated by other criteria, or under different host-specific conditions. Our results suggest that major advances in antibiotic stewardship must come from a deeper empirical understanding of bacterial infection processes in individual hosts. To guide rational therapy, mathematical models need to be constrained by data, including a better quantification of personal disease trajectory in humans. Lay summary: Bacterial infections are becoming more difficult to treat worldwide because bacteria are becoming resistant to the antibiotics used. Addressing this problem requires a better understanding of how treatment along with other host factors impact antibiotic resistance. Until recently, most theoretical research has focused on the importance of antibiotic dosing on antibiotic resistance, however, duration and timing of treatment remain less explored. Here, we use a mathematical model of a generic bacterial infection to study three aspects of treatment: treatment dose/efficacy (defined by the antibiotic kill rate), duration, and timing, and their impact on several infection endpoints. We show that short and long treatment success strongly depends on when treatment begins (defined by the symptom threshold), the target criterion to optimize, and on antibiotic efficacy. We find that if administered early in an infection, “strong and short” therapy performs better, while if treatment begins at higher bacterial densities, a “mild and long” course of antibiotics is favored. In the model host immune defenses are key in preventing relapses, controlling antibiotic resistant bacteria and increasing the effectiveness of moderate intervention. In order to improve rational treatments of human infections, we call for a better quantification of individual disease trajectories in bacteria-immunity space.

Ongoing strategies to improve the management of upper respiratory tract infections and reduce inappropriate antibiotic use particularly among lower and middle-income countries: findings and implications for the future

Introduction: Antibiotics are indispensable to maintaining human health; however, their overuse has resulted in resistant organisms, increasing morbidity, mortality and costs. Increasing antimicrobial resistance (AMR) is a major public health threat, resulting in multiple campaigns across countries to improve appropriate antimicrobial use. This includes addressing the overuse of antimicrobials for self-limiting infections, such as upper respiratory tract infections (URTIs), particularly in lower- and middle-income countries (LMICs) where there is the greatest inappropriate use and where antibiotic utilization has increased the most in recent years. Consequently, there is a need to document current practices and successful initiatives in LMICs to improve future antimicrobial use.Methodology: Documentation of current epidemiology and management of URTIs, particularly in LMICs, as well as campaigns to improve future antimicrobial use and their influence where known.Results: Much concern remains regarding the prescribing and dispensing of antibiotics for URTIs among LMICs. This includes considerable self-purchasing, up to 100% of pharmacies in some LMICs. However, multiple activities are now ongoing to improve future use. These incorporate educational initiatives among all key stakeholder groups, as well as legislation and other activities to reduce self-purchasing as part of National Action Plans (NAPs). Further activities are still needed however. These include increased physician and pharmacist education, starting in medical and pharmacy schools; greater monitoring of prescribing and dispensing practices, including the development of pertinent quality indicators; and targeted patient information and health education campaigns. It is recognized that such activities are more challenging in LMICs given more limited resources and a lack of healthcare professionals.Conclusion: Initiatives will grow across LMICs to reduce inappropriate prescribing and dispensing of antimicrobials for URTIs as part of NAPs and other activities, and these will be monitored.

Serological and molecular study of Hepatitis E virus in pediatric patients in Mexico

Introduction and objectivesCases of viral hepatitis reported in Mexico are typically identified as hepatitis A, B and C. However, unspecified cases are reported annually. Hepatitis E virus (HEV) is an emergent agent that causes a self-limiting infection that can evolve to chronic in immunosuppressed individuals. In Mexico, HEV genotype 2 is considered endemic, though it's the prevalence is not well known. Therefore, the present study was designed to determine the prevalence of HEV among patients at the “Hospital Infantil de Mexico Federico Gomez”. Materials and methodsThe study included 99 patients, anti-HEV antibody (IgG and IgM) were detected by indirect ELISA and viral genome was identified using RT-PCR technique. Two PCR products of positive cases were sequenced. ResultsELISA results were positive in 3% and 6%, for IgG and IgM respectively, 54.5% prevalence was found by PCR. Low lymphocyte count (p<0.05) and malnutrition (p<0.005) were significant factors for high PCR prevalence and could increase the possibility of infection. Two samples were sequenced and confirmed the presence of HEV genotype 3. ConclusionsThis report reveals the incidence of HEV in pediatric patients in Mexico. Moreover, the identification of HEV genotype 3 in human samples suggests a potential zoonotic risk that requires further research.

Delayed prescribing of antibiotics for acute respiratory infections by GP registrars: a qualitative study.

Antibiotic prescribing for acute self-limiting respiratory tract infections (ARTIs) in Australia is higher than international benchmarks. Antibiotics have little or no efficacy in these conditions, and unnecessary use contributes to antibiotic resistance. Delayed prescribing has been shown to reduce antibiotic use. GP registrars are at a career-stage when long-term prescribing patterns are being established. To explore experiences, perceptions and attitudes of GP registrars and supervisors to delayed antibiotic prescribing for ARTIs. A qualitative study of Australian GP registrars and supervisors using a thematic analysis approach. GP registrars and supervisors were recruited across three Australian states/territories, using maximum variation sampling. Telephone interviews explored participants' experience and perceptions of delayed prescribing of antibiotics in ARTIs. Data collection and analysis were concurrent and iterative. A total of 12 registrars and 10 supervisors were interviewed. Key themes included the use of delayed prescribing as a safety-net in cases of diagnostic uncertainty or when clinical review was logistically difficult. Delayed prescribing was viewed as a method of educating and empowering patients, and building trust and the doctor-patient relationship. Conversely, it was also seen as a loss of control over management decisions. Supervisors, more so than registrars, appreciated the psychosocial complexity of ARTI consultations and the importance of delayed antibiotic prescribing in this context. Better awareness and understanding by GP registrars of the evidence for delayed antibiotic prescription may be a means of reducing antibiotic prescribing. Understanding both registrar and supervisor usage, uncertainties and attitudes should inform educational approaches on this topic.

Current management of children with acute otitis media: a feasibility survey for a pragmatic study

Background Acute otitis media (AOM) is a common self-limiting infection where antibiotics confer limited benefit. Other treatments, such as anti-inflammatory agents have been proposed as an alternative to antibiotics, but no high-quality clinical trials have tested this.&#x0D; Objective To identify current AOM management practices among Indonesian clinicians. We also required this information for our proposed corticosteroids clinical trial for AOM.&#x0D; Methods This cross-sectional study surveyed a convenience sample of general practitioners (GPs), pediatricians, and Ear-Nose-Throat (ENT) specialists in Jakarta, Depok, and Bekasi. We addressed their current AOM management practices and willingness to participate in a future trial on corticosteroids.&#x0D; Results We distributed 2,694 questionnaires through conferences, primary care/hospital visits, and by mail-list group. Of 492 questionnaires received (response rate 18%), 352 were from eligible clinicians. Most clinicians diagnosed AOM by using an otoscope (64-91%). Tympanometry was used by a quarter of ENT specialists. Amoxicillin-clavulanate was the most common antibiotic for AOM, prescribed by pediatricians and ENT specialists, whilst most GPs prescribed amoxicillin. Clinical scenarios indicated most ENT specialists (88%) would prescribe antibiotics and most pediatricians (54%) would choose expectant observation by withholding antibiotics for mild AOM. Almost half of clinicians would consider using corticosteroids in a trial.&#x0D; Conclusion Most clinicians would prescribe antibiotics for mild AOM. However, slightly over half of pediatricians would solely choose expectant observation. Adequate numbers of potential participating clinicians, who would consider using corticosteroids, make our proposed corticosteroids trial for AOM feasible. We found gaps between clinical practice and evidence requiring further investigation to improve AOM management in Indonesia.

Immunopathogenesis of HBV Infection.

More than 95% of adult infected with HBV show acute self-limited infection and eventually eliminate the virus. In contrast, about 90% of people exposed to HBV in early childhood develop chronic infection. The specificity of the virus and the host's antiviral immune responses together determine the outcome of HBV infection. It is generally believed that viral genome variation, viral titers, and inhibition of viral components against the host immune system are associated with persistent infection and liver damage. The dysfunction of innate immune cells (NK cells, monocyte/macrophages, NKT cells, etc.) and adaptive immune cells (antigen-presenting cells, T cells, B cells) is a key factor leading to virus clearance failure and liver inflammation. In this chapter, we summarize these viral factors and host factors in acute and chronic hepatitis B and update recent understanding of the immune-tolerant phase and pathological mechanisms associated with age and vertical transmission. This will help us to understand more fully the mechanisms of chronic HBV infection and liver injury and to develop combined treatment strategies of direct antiviral drugs for HBV life cycle and immunomodulators.

The Trends of Complicated Acute Colonic Diverticulitis-A Systematic Review of the National Administrative Databases.

Background and Objectives: The diverticular disease includes a broad spectrum of different “clinical situations” from diverticulosis to acute diverticulitis (AD), with a full spectrum of severity ranging from self-limiting infection to abscess or fistula formation to free perforation. The present work aimed to assess the burden of complicated diverticulitis through a comparative analysis of the hospitalizations based on the national administrative databases. Materials and Methods: A review of the international and national administrative databases concerning admissions for complicated AD was performed. Results: Ten studies met the inclusion criteria and were included in the analysis. No definition of acute complicated diverticulitis was reported in any study. Complicated AD accounted for approximately 42% and 79% of the hospitalizations. The reported rates of abscess varied between 1% and 10% from all admissions for AD and 5–29% of the cases with complicated AD. An increasing temporal trend was found in one study–from 6% to 10%. The rates of diffuse peritonitis ranged from 1.6% to 10.2% of all hospitalizations and 11% and 47% of the complicated cases and were stable in the time. Conclusions: The available data precluded definitive conclusions because of the significant discrepancy between the included studies. The leading cause was the presence of heterogeneity due to coding inaccuracies in all databases, absence of ICD codes to distinguish the different type of complications, and the lack of coding data about some general conditions such as sepsis, shock, malnutrition, steroid therapy, diabetes, pulmonary, and heart failure.

Knowledge and Expectations on Antibiotic Use among Older Adults in Malaysia: A Cross-Sectional Survey.

Antibiotics are commonly prescribed among older adults, and inappropriate use of antibiotics has been noted. However, there is limited information about their knowledge and expectations for antibiotics. This study aimed to assess older adults’ knowledge of antibiotic use and resistance, their expectations for antibiotics and the relationship between knowledge, expectation and inappropriate practices related to antibiotic use. A cross-sectional survey involving respondents aged 60 years and above was conducted, using a validated questionnaire. A lack of knowledge about the role of antibiotics was observed, whereby more than half of the respondents incorrectly believed that antibiotics can treat viral infections (53.5%) and colds and coughs (53.7%). Also, 67.9% of respondents incorrectly believed that antibiotic resistance occurs when the body becomes resistant to antibiotics. Almost half of the respondents would expect antibiotics for symptoms of self-limiting viral infections. Respondents who answered correctly for the role of antibiotics in viral infections were more likely not to expect antibiotics for cold, flu and cough (p < 0.001). Respondents who answered correctly regarding the need to adhere to antibiotics were more likely to have completed their antibiotic course (p < 0.001). Future educational initiatives should provide key information on the role of antibiotics and the importance of complying with antibiotics in this population.

2591. The Role of Neutralizing Antibodies (nAb) Against Cytomegalovirus (CMV) Epithelial Cell-entry in Patients with Self-limited (SL) CMV infection after Hematopoietic Cell Transplantation (HCT)

BackgroundCMV transmission after HCT occurs in 20–30% of CMV-seronegative recipients with CMV-seropositive donors (i.e., CMV D+/R−) and a distinct subset develop transient CMV DNAemia without progression to culture positivity in the absence of antivirals (BMT 1992; 9:221; J Med Virol 2019; 91:1128). The mechanism of SL CMV infection is unknown but may involve nAb, which have been implicated in primary viral clearance, including nAb that inhibit viral epithelial and endothelial cell-entry via CMV pentameric complex (PC). We aimed to describe viral kinetics and the influence of nAb on CMV infection progression in SL CMV-infected patients and controls within a unique cohort from the pre-antiviral era.MethodsWeekly serum samples from 456 CMV D+/R− allogeneic HCT patients collected between 1978–95 were screened using quantitative CMV DNA PCR. Patients with CMV DNAemia in the first 100 days after HCT followed by a sustained return to undetectable levels without positive surveillance CMV cultures were defined as having SL CMV infection. SL CMV-infected patients were matched 1:1:1 to CMV-infected controls (patients with CMV infection by culture in the same period after HCT ± 14 days) and non-infected controls (patients without CMV DNA or culture positivity) to compare viral kinetics and nAb. A modified nAb assay was used to evaluate serum nAb activity against CMV PC-mediated cell entry (Vaccine 2008; 26:5760; JID 2019; in press).ResultsWe identified 9 patients with SL CMV infection and baseline demographics are shown (Table 1). SL CMV-infected patients had a median of 21 days (range 7–54 days) until first positive CMV DNAemia. The median peak CMV DNAemia was 94.2 IU/mL (range 40.2–225.9 IU/mL) and 46,118 IU/mL (range 1,132–284,362 IU/mL) in SL CMV-infected and CMV-infected controls respectively. There was no difference in nAb titers between groups at infection day 0 or in the preceding 4 weeks (Figure 1, Figure 2).ConclusionnAb against CMV PC-mediated cell entry did not appear to play a critical role in viral clearance in SL CMV infection after CMV D+/R- allogeneic HCT. Our study illustrates the potential for clearance of relatively low CMV DNAemia after HCT without the addition of antivirals. CMV-specific T-cell immunity or innate immune mechanisms may be more important in early viral control. Disclosures All authors: No reported disclosures.