Repeated Infections Research Articles

High Rates of Repeat Chlamydial Infections Among Young Women-Louisiana, 2000-2015.

Chlamydial infections are common among young women and can lead to serious reproductive health complications. We assessed the risk of reported repeat chlamydial infection among young women in Louisiana and time interval between infections by age and race/ethnicity. We analyzed surveillance data on chlamydial infections reported among women in Louisiana from January 1, 2000, to December 31, 2015. Multiple reports for the same person were matched using unique codes. Chlamydial infections reported more than 30 days after a previous positive test were considered new infections. Women aged 15 to 34 years at first infection during 2000 to 2012 were censored after 3 years or after they had a repeat infection. Cumulative incidence and incidence rate of repeat chlamydial infection among women were determined by year of first infection. Race- and age-specific results were obtained using stratified analyses. One in 4 women diagnosed with a chlamydial infection at 15-34 years of age in Louisiana had a reported repeat infection in 3 years or less. Risk of repeat infection increased for younger women, racial/ethnic minorities, and women in more recent cohorts. Young black women aged 15 to 19 years in 2012 had the highest risk (44%). Black women also had shorter intervals between infections than white women. Repeat chlamydial infections were common, especially among young black women. The true number is likely higher because surveillance data only count infections that were detected and reported. Comprehensive prevention strategies are needed to address high rates of repeat chlamydial infections among women.

Laboratory Detection of First and Repeat Chlamydia Cases Influenced by Testing Patterns: A Population-Based Study.

Objectives:The purpose of this study was to describe and explore potential driving factors of trends in reported chlamydia infections over time in Manitoba, Canada.Methods:Surveillance and laboratory testing data from Manitoba Health, Seniors and Active Living were analysed using SAS v9.4. Kaplan-Meier plots of time from the first to second chlamydia infection were constructed, and Cox proportional hazards regression was used to estimate the risk of second repeat chlamydia infections in males and females.Results:Overall, the number of reported infections found mirrored the number of tests conducted. From 2008 to 2014, the number of first infections found among females decreased as the number of first tests conducted among females also decreased. Between 2008 and 2012, the number of repeat tests among females increased and was accompanied by an increase in the number of repeat positive results from 2009 to 2013. From 2008 to 2016, the number of repeat tests and repeat positive results increased steadily among males.Conclusions:Chlamydia infection rates consistently included a subset composed of repeat infections. The number of cases identified appears to mirror testing volumes, drawing into question incidence calculations that do not include testing volumes.Summary Box:1) What is the current understanding of this subject? Chlamydia incidence is high in Manitoba, particularly among young women and in northern Manitoba.2) What does this report add to the literature? This report suggests that incidence calculated using case-based surveillance data alone does not provide an accurate estimate of chlamydia incidence in Manitoba and is heavily influenced by testing patterns.3) What are the implications for public health practice? In general, improving testing rates in clinical practices as well as through the provision of rapid services in non-clinical venues could result in higher screening and treatment rates. In turn, this could lead to a better understanding of true disease occurrence.

What could re-infection tell us about R0? A modeling case-study of syphilis transmission.

Many infectious diseases can lead to re-infection. We examined the relationship between the prevalence of repeat infection and the basic reproductive number (R0). First we solved a generic, deterministic compartmental model of re-infection to derive an analytic solution for the relationship. We then numerically solved a disease-specific model of syphilis transmission that explicitly tracked re-infection. We derived a generic expression that reflects a non-linear and monotonically increasing relationship between proportion re-infection and R0 and which is attenuated by entry/exit rates and recovery (i.e. treatment). Numerical simulations from the syphilis model aligned with the analytic relationship. Re-infection proportions could be used to understand how far regions are from epidemic control, and should be included as a routine indicator in infectious disease surveillance.

Herpes Simplex Virus Type-1 Infection: Associations with Inflammation and Cognitive Aging in Relation to Schizophrenia.

Most persons experience cognitive decline as they grow older. The term "cognitive aging," coined to describe milder varieties of cognitive decline, is likely to be due to multiple causes. Persistent or repeated infections of the central nervous system (whether subclinical or diagnosable) can cause damage to neurons directly or indirectly through inflammation resulting in incremental neuronal damage, thus eroding cognitive reserve. This possibility has not been considered widely. We evaluated the data linking persistent infection with herpes simplex virus type 1 (HSV-1) and cognitive aging by applying the Bradford Hill criteria. Despite inherent problems in establishing causal relations for chronic disorders, our analyses suggest plausible links. These studies are pertinent for patients with schizophrenia, who are particularly vulnerable due to disorder-related cognitive impairment. Further investigations are warranted to test a causal hypothesis, particularly prospective studies and intervention studies.

An Intensive, Active Surveillance Reveals Continuous Invasion and High Diversity of Rhinovirus in Households.

We report on infection patterns in 5 households (78 participants) delineating the natural history of human rhinovirus (HRV). Nasopharyngeal collections were obtained every 3–4 days irrespective of symptoms, over a 6-month period, with molecular screening for HRV and typing by sequencing VP4/VP2 junction. Overall, 311/3468 (8.9%) collections were HRV positive: 256 were classified into 3 species: 104 (40.6%) HRV-A; 14 (5.5%) HRV-B, and 138 (53.9%) HRV-C. Twenty-six known HRV types (13 HRV-A, 3 HRV-B, and 10 HRV-C) were identified (A75, C1, and C35 being most frequent). We observed continuous invasion and temporal clustering of HRV types in households (range 5–13 over 6 months). Intrahousehold transmission was independent of clinical status but influenced by age. Most (89.0%) of HRV infection episodes were limited to <14 days. Individual repeat infections were frequent (range 1–7 over 6 months), decreasing with age, and almost invariably heterotypic, indicative of lasting type-specific immunity and low cross-type protection.

Economic Assessment of Reverse Algorithm Syphilis Screening in a High Prevalence Population.

More laboratories are screening for syphilis with automated treponemal immunoassays. We compared direct costs and downstream consequences when a local public health laboratory switches from a traditional algorithm (nontreponemal screening) to a reverse algorithm (treponemal screening). We created a decision analysis model based on laboratory and surveillance data to estimate the cost-effectiveness of a reverse syphilis-screening algorithm from the perspectives of the Los Angeles County Public Health Laboratory and the Los Angeles County Department of Public Health (laboratory + STD Program costs) in 2015 US dollars. The estimated total costs for the Department (Public Health Laboratories) were $2,153,225 ($367,119) for the traditional algorithm and $2,197,478 ($239,855) for the reverse algorithm. Reverse algorithm screening was estimated to detect an additional 626 cases of syphilis, 9.7% more than the traditional algorithm. The incremental cost-effectiveness ratio for the reverse algorithm from the Public Health Department's perspective was $39 per additional syphilis case detected. Cost of follow-up, screening test costs, positivity rates, and frequency of repeat infections most affected the cost-effectiveness of reverse algorithm. Costs were significantly higher for the reverse algorithm when the enzyme Immunoassay/chemiluminescence immunoassay screening test cost was the same as the published Centers for Medicaid Services treponemal test cost. Using the reverse algorithm would have been slightly more expensive for the Los Angeles County Department of Public Health, but would have identified more syphilis cases and would have resulted in lower laboratory costs.

Purulent Inflatable Penile Prostheses Can Be Safely Immediately Salvaged in Insulin-Dependent Diabetics

IntroductionHistorically, contra-indications for immediate salvage of an infected penile prosthesis have included purulence on the device, purulent infections in diabetic patients, and severe diabetes. These clinical principles are from the 1990s to early 2000s and based on limited retrospective series or expert opinion. Since the publication of these contra-indications there have been improvements in device design, surgical technique, corporal washout protocols, and perioperative antibiotic prophylaxis that allow us to re-evaluate whether we can broaden the criteria for immediate salvage of an infected penile prosthesis. AimTo report whether patients with severe diabetes can safely have a purulent inflatable penile prosthesis (IPP) immediately salvaged. MethodsWe considered a “severe diabetic” as a patient whose disease has progressed past diet control and oral medications and, therefore, has insulin-dependent type 2 diabetes mellitus (IDDM II). We retrospectively reviewed 6 consecutive patients with IDDM II and a purulent IPP who had been immediately salvaged from July 2011 to November 2017. In addition to immediate exchange, each received catheter-directed anti-microbial intracorporal irrigation and device culture. All patients were discharged home the next day with oral antibiotics. Main Outcome MeasureOutcomes included repeat penile prosthesis infection or any other complication following immediate salvage. ResultsAll 6 patients have healed well and remained infection free at their 6- to 8-week post-operative follow-up appointment. 15–39 months after salvage, no patients have had a repeat infection or any other complication. 5 patients received a malleable replacement device and 1 patient was electively converted to an IPP 7 months after his salvage procedure. 1 patient received an IPP during salvage per patient preference. All patients are currently pleased with either their malleable penile prosthesis or IPP. Clinical ImplicationsImmediate salvage attenuates the morbidity associated with an infected penile prosthesis such as irreversible penile shortening and corporal fibrosis. Our findings suggest that more patients than originally thought may be a candidate for immediate salvage. Strength & LimitationsTo our knowledge, this is the first study evaluating outcomes after immediate salvage of a purulent IPP in patients with advanced diabetes. Limitations of the study include the small sample size and retrospective nature. ConclusionOur results suggest that those with IDDM II who have a purulent penile prosthesis may be candidates for safe and effective immediate salvage.Peters CE, Carlos EC, Lentz AC. Purulent Inflatable Penile Prostheses Can Be Safely Immediately Salvaged in Insulin-Dependent Diabetics. J Sex Med 2018;15:1673–1677.

Primary and Repeated Respiratory Viral Infections Among Infants in Rural Nepal.

BackgroundRespiratory viruses cause significant morbidity and death in infants; 99% of such deaths occur in resource-limited settings. Risk factors for initial and repeated respiratory viral infections in young infants in resource-limited settings have not been well described.MethodsFrom 2011 to 2014, a birth cohort of infants in rural Nepal was enrolled and followed with weekly household-based active surveillance for respiratory symptoms until 6 months of age. Respiratory illness was defined as having any of the following: fever, cough, wheeze, difficulty breathing, and/or a draining ear. We tested nasal swabs of infants with respiratory illness for multiple respiratory viruses by using a reverse transcription polymerase chain reaction assay. The risk of primary and repeated infections with the same virus was evaluated using Poisson regression.ResultsOf 3528 infants, 1726 (49%) had a primary infection, and 419 (12%) had a repeated infection. The incidences of respiratory viral infection in infants were 1816 per 1000 person-years for primary infections and 1204 per 1000 person-years for repeated infection with the same virus. Exposure to other children and male sex were each associated with an increased risk for primary infection (risk ratios, 1.13 [95% confidence interval (CI), 1.06–1.20] and 1.14 [95% CI, 1.02–1.27], respectively), whereas higher maternal education was associated with a decreased risk for both primary and repeated infections (risk ratio, 0.96 [95% CI, 0.95–0.98]). The incidence of subsequent infection did not change when previous infection with the same or another respiratory virus occurred. Illness duration and severity were not significantly different in the infants between the first and second episodes for any respiratory virus tested.ConclusionsIn infants in rural Nepal, repeated respiratory virus infections were frequent, and we found no decrease in illness severity with repeated infections and no evidence of replacement with another virus. Vaccine strategies and public health interventions that provide durable protection in the first 6 months of life could decrease the burden of repeated infections by multiple respiratory viruses, particularly in low-resource countries.

Molecular point-of-care testing for chlamydia and gonorrhoea in Indigenous Australians attending remote primary health services (TTANGO): a cluster-randomised, controlled, crossover trial

Timely diagnosis and treatment of sexually transmissible infections will prevent morbidity and onward transmission. We aimed to assess the efficacy of a point-of-care molecular test for Chlamydia trachomatis and Neisseria gonorrhoeae infections at the cluster level to improve infection management among Indigenous Australian communities with high prevalence of sexually transmissible infections. In this cluster-randomised crossover study, we recruited primary health services in Western Australia, Far North Queensland, and South Australia that provide care to Indigenous people in regional or remote locations. The services were eligible if they did 150 or more tests for C trachomatis or N gonorrhoeae infection per year among individuals aged 16-29 years, and if C trachomatis or N gonorrhoeae positivity was 10% or higher. Services were randomly assigned (1:1) by use of a random-number generator, stratified by geographical region, to either standard care conditions with routine laboratory-based sexually transmissible infection testing for 12 months followed by 12 months of intervention with molecular point-of-care testing, or the reverse sequence. The primary outcome was the proportion of people (aged 16-29 years) found to have C trachomatis or N gonorrhoeae who had a positive result at retesting 3 weeks to 3 months after treatment, and a secondary outcome was treatment within 7 days, both in those aged 16-29 years and at the cluster level. We did these analyses using data from all participants who had a positive result at testing, by point-of-care of laboratory testing (ie, the intention-to-treat population). The trial is registered with Australian and New Zealand Clinical Trials Registry (ACTRN12613000808741). Between June 1, 2013, and Feb 29, 2016, 12 health services were enrolled and randomly assigned to standard care followed by intervention (six) and the reverse sequence (six). After randomisation, one health service that was initially assigned to standard care was excluded because it no longer met the inclusion criteria. 455 individuals tested positive for C trachomatis or N gonorrhoeae infection in the intervention group, and 405 tested positive in the standard care group. In the intervention group, 12 (19%) of 63 individuals retested had a positive test result, compared with nine (13%) of 67 with positive retests in the standard care group (relative ratio [RR] 1·42, 95% CI 0·64-3·13; p=0·405), and 347 (76%) were treated within 7 days in the intervention group, compared with 191 (47%) in the standard care group (RR 1·66, 1·41-1·93; p<0·0001). Retesting rates were too low to draw conclusions on the effect of the intervention on repeat infections. Further research will be needed to determine whether point-of-care tests have an effect on reinfection rates, and the sustainability of using this technology. However, our findings show that time to treatment of C trachomatis or N gonorrhoeae infections in primary care clinics in remote areas in Australia with a high prevalence of sexually transmissible infections could be substantially reduced by the use of molecular point-of-care tests. The National Health and Medical Research Council, Australia.

Syphilis reinfection is associated with an attenuated immune profile in the same individual: a prospective observational cohort study

BackgroundAscertaining if the clinical and immunological response to repeat syphilis differs from that in initial syphilis may assist in designing optimal syphilis screening strategies and vaccine design.MethodsWe prospectively recruited 120 patients with a new diagnosis of (baseline) syphilis. During a 24-month follow-up period, 11 of these patients had a further diagnosis of (repeat) syphilis. We conducted a paired comparison of their plasma cyto-chemokines at baseline and repeat syphilis.ResultsComparing to their baseline infection, paired analyses of the 11 individuals with repeat infections during follow-up revealed that these reinfections had lower concentrations of Interferon (IFN)α (0.8 [Interquartile range (IQR) 0.8–0.8 vs. 12.2 [IQR 1.6–24.2], P = 0.004) and Chemokine (C-C motif) ligand (CCL) 4 (0.9 [IQR 0.9–12.2 vs. 17.5 [IQR 4.9–32.8], P = 0.022].ConclusionIn this small study of 11 individuals, repeat syphilis was found to present with an attenuated immune response. The relevance of these findings to the design of optimal syphilis screening programs is discussed.

The Morphology and Assembly of Respiratory Syncytial Virus Revealed by Cryo-Electron Tomography

Human respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract disease in young children. With repeat infections throughout life, it can also cause substantial disease in the elderly and in adults with compromised cardiac, pulmonary and immune systems. RSV is a pleomorphic enveloped RNA virus in the Pneumoviridae family. Recently, the three-dimensional (3D) structure of purified RSV particles has been elucidated, revealing three distinct morphological categories: spherical, asymmetric, and filamentous. However, the native 3D structure of RSV particles associated with or released from infected cells has yet to be investigated. In this study, we have established an optimized system for studying RSV structure by imaging RSV-infected cells on transmission electron microscopy (TEM) grids by cryo-electron tomography (cryo-ET). Our results demonstrate that RSV is filamentous across several virus strains and cell lines by cryo-ET, cryo-immuno EM, and thin section TEM techniques. The viral filament length varies from 0.5 to 12 μm and the average filament diameter is approximately 130 nm. Taking advantage of the whole cell tomography technique, we have resolved various stages of RSV assembly. Collectively, our results can facilitate the understanding of viral morphogenesis in RSV and other pleomorphic enveloped viruses.

The human antibody response in Dengue and Zika virus infection

Dengue is a mosquito borne virus infection occurring in tropical and subtropical countries. There are estimated to be around 400 million infections annually of which approximately one quarter are clinically apparent. The majority of these result in a self-limited, but non the less unpleasant febrile illness, dengue fever. 1-5% of infections lead to a more severe disease, dengue haemorrhagic fever, which is characterized by a severe vascular leak, hypovolaemia and in extreme cases shock and haemorrhage. Dengue exists as four highly divergent serotypes differing in sequence by some 30-35%; infection with one serotype does not provide protection against the other three. In endemic areas serotypes frequently co-circulate and repeat infections are common. Interestingly, severe disease is much more common in secondary as opposed to primary infections, implying a role of the acquired immune system in disease pathogenesis. Understanding this immune enhancement of disease is crucial for the design of safe and effective vaccines. Through clinical collaborations in Thailand and Vietnam we have been studying the immune response to dengue in cohorts of infected children. We will describe the antibody response to the two virion surface glycoproteins prM and E and discuss the E dimer epitope (EDE), a novel site bridging the 90 basic head to tail envelope dimers making up the virion surface and also crossreacts against Zika virus.

Cotton rat lung transcriptome reveals host immune response to Respiratory Syncytial Virus infection

Acute respiratory infection (ARI) with respiratory syncytial virus (RSV) is the most common cause of both hospitalizations and mortality in young infants worldwide. Repeat infections with RSV are common throughout life in both pediatric and elderly populations. Thus far, cotton rats (Sigmodon hispidus) are found to be the best animal model to study RSV infection. However, the lack of a cotton rat reference genome limits genome-wide host gene expression studies. We constructed the first lung tissue de novo transcriptome for the cotton rat. Cotton rat lung tissue transcripts were assigned to 12,211 unique UniProt genes, which were then utilized to profile the host immune response after RSV infection. Differential expression analysis showed up-regulation of host genes involved in cellular functions including defense responses to viral infection and immune system processes. A number of transcripts were downregulated during the later stage of infection. A set of transcripts unique to RSV-infected cotton rats was identified. To validate RNA-Seq data of three such transcripts (TR453762, TR529629, and TR5333), their expression was confirmed by quantitative real-time polymerase chain reaction.

Repeated infections of dengue (serotype DENV-2) in lung cells of BALB/c mice lead to severe histopathological consequences

ABSTRACTTo determine the effect of DENV (serotype 2) repeated infections on lung cells is the main goal of this study. From the result, lung histology of control BALB/c mice showed normal alveolar morphology, while vehicle control BALB/c mice highlighted a slight thickening of the alveolar septum. Lung histopathology of BALB/c mice infected twice by DENV-2 showed the presence of hemorrhage, plasma leakage and presence of hemosiderin-laden macrophages (HLMs). Notably, in the lung of BALB/c mice infected four times by DENV-2, we observed thickening and disruption of the alveolar septum, inflammatory cell infiltration, plasma leakage and increased cellularity. Megakaryocyte releasing platelets were also found into the lung alveolus. Overall, our findings showed severe histopathological damage in lungs repeatedly infected by DENV-2, allowing us to argue that they can be linked to pulmonary complication. Result also showed that the number of infections with similar total DENV-2 titer led to different histopathological changes.

Genomes of all known members of a Plasmodium subgenus reveal paths to virulent human malaria.

Plasmodium falciparum, the most virulent agent of human malaria, shares a recent common ancestor with the gorilla parasite P. praefalciparum. Little is known about the other gorilla and chimpanzee-infecting species in the same (Laverania) subgenus as P. falciparum but none of them are capable of establishing repeated infection and transmission in humans. To elucidate underlying mechanisms and the evolutionary history of this subgenus, we have generated multiple genomes from all known Laverania species. The completeness of our dataset allows us to conclude that interspecific gene transfers as well as convergent evolution were important in the evolution of these species. Striking copy number and structural variations were observed within gene families and one, stevor shows a host specific sequence pattern. The complete genome sequence of the closest ancestor of P. falciparum enables us to estimate the timing of the beginning of speciation to be 40,000-60,000 years ago followed by a population bottleneck around 4,000-6,000 years ago. Our data allow us also to search in detail for the features of P. falciparum that made it the only member of the Laverania able to infect and spread in humans.

Molecular Characterization of Respiratory Syncytial Virus in Children With Repeated Infections With Subgroup B in the Philippines.

BackgroundHuman respiratory syncytial virus (RSV) is the leading cause of severe acute respiratory infection in infants and young children, which is characterized by repeated infections. However, the role of amino acid substitutions in repeated infections remains unclear. Hence, this study aimed to elucidate the genetic characteristics of RSV in children with repeated infections using molecular analyses of F and G genes.MethodsWe conducted a cohort study of children younger than 5 years in the Philippines. We collected nasopharyngeal swabs from children with acute respiratory symptoms and compared F and G sequences between initial and subsequent RSV infections.ResultsWe examined 1802 children from May 2014 to January 2016 and collected 3471 samples. Repeated infections were observed in 25 children, including 4 with homologous RSV-B reinfections. Viruses from the 4 pairs of homologous reinfections had amino acid substitutions in the G protein mostly at O-glycosylation sites, whereas changes in the F protein were identified at antigenic sites V (L173S) and θ (Q209K), considered essential epitopes for the prefusion conformation of the F protein.ConclusionsAmino acid substitutions in G and F proteins of RSV-B might have led to antigenic changes, potentially contributing to homologous reinfections observed in this study.

Optimizing the Impact of Expedited Partner Therapy.

Optimizing the Impact of Expedited Partner Therapy.

Epidemiology and Risk Factors for Cryptosporidiosis in Children From 8 Low-income Sites: Results From the MAL-ED Study.

Cryptosporidium species are enteric protozoa that cause significant morbidity and mortality in children worldwide. We characterized the epidemiology of Cryptosporidium in children from 8 resource-limited sites in Africa, Asia, and South America. Children were enrolled within 17 days of birth and followed twice weekly for 24 months. Diarrheal and monthly surveillance stool samples were tested for Cryptosporidium by enzyme-linked immunosorbent assay. Socioeconomic data were collected by survey, and anthropometry was measured monthly. Sixty-five percent (962/1486) of children had a Cryptosporidium infection and 54% (802/1486) had at least 1 Cryptosporidium-associated diarrheal episode. Cryptosporidium diarrhea was more likely to be associated with dehydration (16.5% vs 8.3%, P < .01). Rates of Cryptosporidium diarrhea were highest in the Peru (10.9%) and Pakistan (9.2%) sites. In multivariable regression analysis, overcrowding at home was a significant risk factor for infection in the Bangladesh site (odds ratio, 2.3 [95% confidence interval {CI}, 1.2-4.6]). Multiple linear regression demonstrated a decreased length-for-age z score at 24 months in Cryptosporidium-positive children in the India (β = -.26 [95% CI, -.51 to -.01]) and Bangladesh (β = -.20 [95% CI, -.44 to .05]) sites. This multicountry cohort study confirmed the association of Cryptosporidium infection with stunting in 2 South Asian sites, highlighting the significance of cryptosporidiosis as a risk factor for poor growth. We observed that the rate, age of onset, and number of repeat infections varied per site; future interventions should be targeted per region to maximize success.

Biological feasibility and importance of a gonorrhea vaccine for global public health

There is a growing public health interest in controlling sexually transmitted infections (STIs) through vaccination due to increasing recognition of the global disease burden of STIs and the role of STIs in women’s reproductive health, adverse pregnancy outcomes, and the health and well-being of neonates. Neisseria gonorrhoeae has historically challenged vaccine development through the expression of phase and antigenically variable surface molecules and its capacity to cause repeated infections without inducing protective immunity. An estimated 78 million new N. gonorrhoeae infections occur annually and the greatest disease burden is carried by low- and middle-income countries (LMIC). Current control measures are clearly inadequate and threatened by the rapid emergence of antibiotic resistance. The gonococcus now holds the status of “super-bug” as there is currently no single reliable monotherapy for empirical treatment of gonorrhea. The problem of antibiotic resistance has elevated treatment costs and necessitated the establishment of large surveillance programs to track the spread of resistant strains. Here we review the need for a gonorrhea vaccine with respect to global disease burden and related socioeconomic and treatment costs, with an emphasis on the impact of gonorrhea on women and newborns. We also highlight the challenge of estimating the impact of a gonorrhea vaccine due to the need for more data on the burden of gonococcal pelvic inflammatory disease and related sequelae and of gonorrhea-associated adverse pregnancy outcomes and the problem of empirical diagnosis and treatment of STIs in LMIC. There is also a lack of clinical and basic science research in the area of gonococcal/chlamydia coinfection, which occurs in a high percentage of individuals with gonorrhea and should be considered when testing the efficacy of gonorrhea vaccines. Finally, we review recent research that suggests a gonorrhea vaccine is feasible and discuss challenges and research gaps in gonorrhea vaccine development.

MicroRNA-4516 Contributes to Different Functions of Epithelial Permeability Barrier by Targeting Poliovirus Receptor Related Protein 1 in Enterovirus 71 and Coxsackievirus A16 Infections.

Enterovirus 71 (EV-A71) and coxsackievirus A16 (CV-A16) remain the predominant etiological agents of hand, foot, and mouth disease (HFMD). The clinical manifestations caused by the two viruses are obviously different. CV-A16 usually triggers a repeated infection, and airway epithelial integrity is often the potential causative factor of respiratory repeated infections. Our previous studies have demonstrated that there were some differentially expressed miRNAs involved in the regulation of adhesion function of epithelial barrier in EV-A71 and CV-A16 infections. In this study, we compared the differences between EV-A71 and CV-A16 infections on the airway epithelial barrier function in human bronchial epithelial (16HBE) cells and further screened the key miRNA which leaded to the formation of these differences. Our results showed that more rapid proliferation, more serious destruction of 16HBE cells permeability, more apoptosis and disruption of intercellular adhesion-associated molecules were found in CV-A16 infection as compared to EV-A71 infection. Furthermore, we also identified that microRNA-4516 (miR-4516), which presented down-regulation in EV-A71 infection and up-regulation in CV-A16 infection was an important regulator of intercellular junctions by targeting Poliovirus receptor related protein 1(PVRL1). The expressions of PVRL1, claudin4, ZO-1 and E-cadherin in CV-A16-infected cells were significantly less than those in EV-A71-infected cells, while the expressions of these proteins were subverted when pre-treated with miR-4516-overexpression plasmid in EV-A71 infected and miR-4516-knockdown plasmid in CV-A16 infected 16HBE cells. Thus, these data suggested that the opposite expression of miR-4516 in EV-A71 and CV-A16 infections might be the initial steps leading to different epithelial impairments of 16HBE cells by destroying intercellular adhesion, which finally resulted in different outcomes of EV-A71 and CV-A16 infections.