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Nontuberculous mycobacterial (NTM) genitourinary (GU) infections are relatively rare, and there is frequently a delay in diagnosis. Mycobacterium avium-intracellulare complex (MAC) cases seem to be less frequent than other NTM as a cause of these infections. In addition, there are no set treatment guidelines for these organisms in the GU tract. Given the limitations of data this review summarizes a case presentation of this infection and the literature available on the topic. Many different antimicrobial regimens and durations have been used in the published literature. While the infrequency of these infections suggests that there will not be randomized controlled trials to determine optimal therapy, our case suggests that a brief course of amikacin may play a useful role in those who cannot tolerate other antibiotics.

ObjectivesThe aim of this study was to assess the association between maternal occupational exposure to solvents and gastroschisis in offspring.MethodsWe used data from the National Birth Defects Prevention Study, a large population-based case-control study of major birth defects conducted in 10 US states from 1997 to 2011. Infants with gastroschisis were ascertained by active birth defects surveillance systems. Control infants without major birth defects were selected from vital records or birth hospital records. Self-reported maternal occupational histories were collected by telephone interview. Industrial hygienists reviewed this information to estimate exposure to aromatic, chlorinated and petroleum-based solvents from 1 month before conception through the first trimester of pregnancy. Cumulative exposure to solvents was estimated for the same period accounting for estimated exposure intensity and frequency, job duration and hours worked per week. ORs and 95% CIs were estimated to assess the association between exposure to any solvents or solvent classes, and gastroschisis risk.ResultsAmong 879 cases and 7817 controls, the overall prevalence of periconceptional solvent exposure was 7.3% and 7.4%, respectively. Exposure to any solvent versus no exposure to solvents was not associated with gastroschisis after adjusting for maternal age (OR 1.00, 95% CI 0.75 to 1.32), nor was an association noted for solvent classes. There was no exposure-response relationship between estimated cumulative solvent exposure and gastroschisis after adjusting for maternal age.ConclusionOur study found no association between maternal occupational solvent exposure and gastroschisis in offspring. Further research is needed to understand risk factors for gastroschisis.

Introduction Solid organ transplant (SOT) recipients are at increased risk of Human Papillomavirus (HPV) persistent infection and disease. This study aimed to evaluate HPV seroprevalence, cervical HPV prevalence, genotype distribution, and frequency of HPV-related cervical lesions in SOT recipients in comparison to immunocompetent women. Methods Cross-sectional study including SOT and immunocompetent women aged 18 to 45 years who denied previous HPV-related lesions. Cervical samples were screened for HPV-DNA by a polymerase chain reaction (PCR)-based DNA microarray system (PapilloCheck®) and squamous intraepithelial lesions (SIL) by liquid-based cytology. A multiplexed pseudovirion-based serology assay (PsV-Luminex) was used to measure HPV serum antibodies. Results 125 SOT and 132 immunocompetent women were enrolled. Cervical samples were collected from 113 SOT and 127 immunocompetent women who had initiated sexual activity. HPV-DNA prevalence was higher in SOT than in immunocompetent women (29.6% vs. 20.2%, p = 0.112), but this difference was not statistically significant. High-risk (HR)-HPV was significantly more frequent in SOT than in immunocompetent women (19.4% vs. 7.9%, p = 0.014). Simultaneous infection with ≥2 HR-HPV types was found in 3.1% of SOT and 0.9% of immunocompetent women. HPV seropositivity for at least one HPV type was high in both groups: 63.8% of 105 SOT and 69.7% of 119 immunocompetent women (p = 0.524). Low-grade (LSIL) and high-grade SIL (HSIL) were significantly more frequent in SOT (9.7% and 5.3%, respectively) than in immunocompetent women (1.6% and 0.8%, respectively) (p = 0.001). Conclusions These results may reflect the increased risk of HPV persistent infection and disease progression in SOT women due to chronic immunosuppression.

Recovery of Neisseria gonorrhoeae isolates exposed to a range of transport times and temperatures was quantitatively assessed for two transport devices, BioMed Diagnostics’ InTray GC® and Copan Diagnostics’ Liquid Amies Elution Swab (ESwab®) Collection and Transport System. Respective devices were inoculated with N. gonorrhoeae, exposed to simulated transport conditions and spread-plated from serial dilutions in duplicates onto chocolate agar in order to count CFU (colony-forming units) in the range of 25–250. Baseline CFU/mL averages of time-zero transport for each device was compared to either 24 hour (Eswab) or 72 hour (InTray GC) CFU/mL average to assess recovery of six clinical isolates of N. gonorrhoeae, and differences showing no greater than a 3 log10 (± 10%) decline between comparative time points qualified as acceptable. Our findings suggest that the InTray GC system has the potential to transport clinical isolates for ≤72 hours with acceptable N. gonorrhoeae recovery.

Despite the importance ofHelicobacter pyloriinfection and portal hypertension (PH)-associated gastrointestinal (GI) diseases, such as esophageal varices and portal hypertensive gastropathy (PHG), the impact ofH.pyloriinfection on PH-related GI complications has not yet been elucidated. This meta-analysis investigated the association betweenH.pyloriinfection and the risk of PH-related GI complications. An electronic search for original articles published before May 2020 was performed using PubMed, EMBASE, and the Cochrane Library. Independent reviewers conducted the article screening and data extraction. We used the generic inverse variance method for the meta-analysis, and Begg’s rank correlation test and Egger’s regression test to assess publication bias. A total of 1,148 cases ofH.pyloriinfection and 1,231 uninfected controls were included from 13 studies.H.pyloriinfection had no significant association with esophageal varices [relative risk (RR) = 0.96, 95% confidence interval (CI) = 0.87–1.06 for all selected studies; RR = 0.95, 95% CI = 0.84–1.07 for cohort studies; odds ratio (OR) = 0.96, 95% CI = 0.60–1.54 for case-control studies]. AlthoughH.pyloriinfection was significantly associated with PHG in case-control studies [OR = 1.86, 95% CI = 1.17–2.96], no significant differences were found in the cohort studies [RR = 0.98, 95% CI = 0.91–1.05] or all studies combined [RR = 1.18, 95% CI = 0.93–1.52]. In conclusion,H.pyloriinfection was not associated with the risk of PH-related GI complications. Clinicians should carefully treat cirrhotic patients with PH-related GI complications, regardless ofH.pyloriinfection.

BackgroundPneumonia and sepsis are among the most common causes of hospitalization in the United States and often result in discharges to a skilled nursing facility (SNF) for rehabilitation. We described the timing and most common causes of 30-day unplanned hospital readmission following an index hospitalization for pneumonia or sepsis.Methods and findingsThis national retrospective cohort study included adults ≥65 years who were hospitalized for pneumonia or sepsis and were discharged to a SNF between July 1, 2012 and July 4, 2015. We quantified the ten most common 30-day unplanned readmission diagnoses and estimated the daily risk of first unplanned rehospitalization for four causes of readmission (circulatory, infectious, respiratory, and genitourinary). The index hospitalization was pneumonia for 92,153 SNF stays and sepsis for 452,254 SNF stays. Of these SNF stays, 20.9% and 25.9%, respectively, resulted in a 30-day unplanned readmission. Overall, septicemia was the single most common readmission diagnosis for residents with an index hospitalization for pneumonia (16.7% of 30-day readmissions) and sepsis (22.4% of 30-day readmissions). The mean time to unplanned readmission was approximately 14 days overall. Respiratory causes displayed the highest daily risk of rehospitalization following index hospitalizations for pneumonia, while circulatory and infectious causes had the highest daily risk of rehospitalization following index hospitalizations for sepsis. The day of highest risk for readmission occurred within two weeks of the index hospitalization discharge, but the readmission risk persisted across the 30-day follow-up.ConclusionAmong older adults discharged to SNFs following a hospitalization for pneumonia or sepsis, hospital readmissions for infectious, circulatory, respiratory, and genitourinary causes occurred frequently throughout the 30-day post-discharge period. Our data suggests further study is needed, perhaps on the value of closer monitoring in SNFs post-hospital discharge and improved communication between hospitals and SNFs, to reduce the risk of potentially preventable hospital readmissions.

Whether having a tattoo increases the risk of transfusion-transmitted diseases (TTDs) is controversial. Although a few studies have suggested a strong association between having tattoos and TTDs, other studies have not shown the significance of the association. In addition, previous studies mainly focused only on hepatitis C viral infections. The objective of our study was to identify the prevalence and risk of TTDs in people with tattoos as compared with the non-tattooed population. A systematic review of the studies published before January 22, 2021, was performed using the Pubmed, Embase, and Web of Science databases. Observational studies on hepatitis C virus (HCV), hepatitis B virus (HBV), human immunodeficiency virus (HIV), and syphilis infections in people with and without tattoos were included. Studies that reported disease status without serological confirmation were excluded. A total of 121 studies were quantitatively analyzed. HCV (odds ratio [OR], 2.37; 95% confidence interval [CI], 2.04–2.76), HBV (OR, 1.55; 95% CI, 1.31–1.83), and HIV infections (OR, 3.55; 95% CI, 2.34–5.39) were more prevalent in the tattooed population. In subgroup analyses, the prevalence of HCV infection was significantly elevated in the general population, hospital patient, blood donor, intravenous (IV) drug user, and prisoner groups. IV drug users and prisoners showed high prevalence rates of HBV infection. The prevalence of HIV infection was significantly increased in the general population and prisoner groups. Having a tattoo is associated with an increased prevalence of TTDs. Our approach clarifies in-depth and supports a guideline for TTD screening in the tattooed population.

Background Hemodialysis patients who undergo surgery have a high risk of postoperative complications. The aim of this study was to determine whether colon cancer surgery can be safely performed in hemodialysis patients. Methods This multicenter retrospective study included 1372 patients who underwent elective curative resection surgery for colon cancer between April 2016 and March 2020. Results Of the total patients, 19 (1.4%) underwent hemodialysis, of whom 19 (100%) had poor performance status and 18 had comorbidities (94.7%). Minimally invasive surgery was performed in 78.9% of hemodialysis patients. The postoperative complication rate was significantly higher in hemodialysis than non-hemodialysis patients (36.8% vs. 15.5%, p = 0.009). All postoperative complications in the hemodialysis patients were infectious type. Multivariate analysis revealed a significant association of hemodialysis with complications (odds ratio, 2.9362; 95%CI, 1.1384–7.5730; p = 0.026). Conclusion Despite recent advances in perioperative management and minimally invasive surgery, it is necessary to be aware that short-term complications can still occur, especially infectious complications in hemodialysis patients.

Background Antimicrobial resistance in community-associated infections is an increasing worldwide concern. In low-to-middle income countries, over-the-counter (OTC) sales of antimicrobials without medical prescription have been blamed for increasing consumption and resistance. We studied the impact of restriction of OTC sales of antimicrobials in Brazil (instituted in October 2010) on resistance trends of Escherichia coli from community-onset urinary tract infections. Methods We analyzed monthly resistance trend of Escherichia coli from community-onset urinary tract infections from 2005 through 2018. The data were submitted to interrupted time series analysis in both linear and Poisson regression models. Results We found impact on cefazolin (p Conclusion At the present study, we found that OTC sales restriction did not generally impact on antimicrobial resistance.

The uropathogens is the main cause of urinary tract infection (UTI). The aim of the study was to isolate bacteria from urine samples of UTI patients and find out the susceptibility of isolated bacteria. Bacteria were identified using both conventional and molecular methods. Sanger sequence procedure used for 16S ribosomal RNA and phylogenetic analysis was performed using Molecular Evolutionary Genetics Analysis (MEGA-7) software. In this study,Escherichia coli,Klebsiella pneumonia,Staphylococcuswere reported as 58, 28 and 14.0% respectively. Phylogenetic tree revealed that 99% of sample No. Ai (05) is closely related toE.colito (NR 114042.1E.colistrain NBRC 102203). Aii (23) is 99% similar toK.pneumoniaeto (NR 117686.1K.pneumoniastrain DSM 30104) and 90% Bi (48) is closely linked toS.aureusto (NR 113956.1S.aureusstrain NBRC 100910). The antibiotic susceptibility ofE.colirecorded highest resistance towards ampicillin (90%) and least resistant to ofloxacin (14%). Some of the other antibiotics such amoxicillin, ciprofloxacin, gentamicin, ceftazidime, cefuroxime and nitrofurantoin resistance were observed 86, 62, 24, 55, 48 and 35% respectively. The cefuroxime showed the highest antibiotic resistance againstK.pneumoniaewith 85% followed by amoxicillin, ciprofloxacin, gentamicin, ceftazidime, ampicillin and nitrofurantoin resulted in 60, 45, 67, 70, 75 and 30% respectively. The resistance ofS.aureusagainst erythromycin, cefuroxime and ampicillin were found with 72%. The resistance against amoxicillin, gentamicin, ceftazidime and ceftriaxone found 57, 43, 43 and 15% respectively. Phylogenetic analysis shows that sequences are closely related with the reference sequences andE.coliis the dominant bacteria among UTI patients and is resistant to the commercially available antibiotics.

Human Papillomaviruses (HPV) are one of the most prevalent sexually transmitted infections (STI) and the most oncogenic viruses known to humans. The vast majority of HPV infections clear in less than 3 years, but the underlying mechanisms, especially the involvement of the immune response, are still poorly known. Building on earlier work stressing the importance of randomness in the type of cell divisions in the clearance of HPV infection, we develop a stochastic mathematical model of HPV dynamics that combines the previous aspect with an explicit description of the intracellular level. We show that the random partitioning of virus episomes upon stem cell division and the occurrence of symmetric divisions dramatically affect viral persistence. These results call for more detailed within-host studies to better understand the relative importance of stochasticity and immunity in HPV infection clearance., Author summary Every year, infections by Human Papillomaviruses (HPV) are responsible for a large share of infectious cancers. The prevalence of HPVs is very high, which makes it a major public health issue. Fortunately, most HPV infections (80 to 90%) are cleared naturally within three years. Among the few that persist into chronic infections, the majority also naturally regress. Hence for a given HPV infection, the risk of progression towards cancerous status is low. The immune response is often invoked to explain HPV clearance in non-persisting infections, but many uncertainties remain. Besides immunity, randomness was also suggested to play an important role. Here, we examine how random events occurring during the life cycle of the virus could alter the persistence of the virus inside the host. We develop a mechanistic model that explicitly follows the dynamic of viral copies inside host cells, as well as the dynamics of the epithelium. In our model, infection extinction occurs when all viral copies end up in differentiated cells and migrate towards the surface. This can happen upon cell division during the random allocation of the episomes (i.e. independent circular DNA copies of the viral genome) or when a stem cell divides symmetrically to generate two differentiated cells. We find that the combination of these random events drastically affects infection persistence. More generally, the importance of random fluctuations could match that of immunity and calls for further studies at the within-host and the epidemiological level.

Background Public trust in the human papilloma virus (HPV) vaccination programme has been challenged by reports of potential severe adverse effects. The reported adverse symptoms were heterogeneous and overlapping with those characterised as chronic fatigue syndrome (CFS) and have been described as CFS-like symptoms. Evidence suggests that CFS is often precipitated by an infection. The aim of the study was to examine if an infection in temporal proximity to HPV vaccination is a risk factor for suspected adverse effects following HPV vaccination. Methods and findings The study was a nationwide register-based cohort study and case-crossover analysis. The study population consisted of all HPV vaccinated females living in Denmark, born between 1974 and 2006, and vaccinated between January 1, 2006 and December 31, 2017. The exposure was any infection in the period ± 1 month around time of first HPV vaccination and was defined as (1) hospital-treated infection; (2) redemption of anti-infective medication; or (3) having a rapid streptococcal test done at the general practitioner. The outcome was referral to a specialised hospital setting (5 national HPV centres opened June 1, 2015) due to suspected adverse effects following HPV vaccination. Multivariable logistic regression was used to estimate the association between infection and later HPV centre referral. The participants were 600,400 HPV-vaccinated females aged 11 to 44 years. Of these, 48,361 (9.7%) females had a hospital-treated infection, redeemed anti-infective medication, or had a rapid streptococcal test ± 1 month around time of first HPV vaccination. A total of 1,755 (0.3%) females were referred to an HPV centre. Having a hospital-treated infection in temporal proximity to vaccination was associated with significantly elevated risk of later referral to an HPV centre (odds ratio (OR) 2.75, 95% confidence interval (CI) 1.72 to 4.40; P < 0.001). Increased risk was also observed among females who redeemed anti-infective medication (OR 1.56, 95% CI 1.33 to 1.83; P < 0.001) or had a rapid streptococcal test (OR 1.45, 95% CI 1.10 to 1.93; P = 0.010). Results from a case-crossover analysis, which was performed to adjust for potential unmeasured confounding, supported the findings. A key limitation of the study is that the HPV centres did not open until June 1, 2015, which may have led to an underestimation of the risk of suspected adverse effects, but stratified analyses by year of vaccination yielded similar results. Conclusions Treated infection in temporal proximity to HPV vaccination is associated with increased risk for later referral with suspected adverse vaccine effects. Thus, the infection could potentially be a trigger of the CFS-like symptoms in a subset of the referred females. To our knowledge, the study is the first to investigate the role of infection in the development of suspected adverse effects after HPV vaccination and replication of these findings are needed in other studies., Lene Wulff Krogsgaard and co-workers study temporal associations between infections and HPV vaccination., Author summary Why was this study done? In Denmark, there was a human papilloma virus (HPV) vaccination crisis in 2015, where reports of suspected adverse effects after HPV vaccination started increasing and the HPV vaccination uptake decreased dramatically. All available evidence has found the HPV vaccine to be safe and the specific cause of the reported adverse effects remains unknown. The reported symptoms were overlapping with those characterised as chronic fatigue syndrome (CFS) and have been described as CFS-like. Infections are thought to be triggers of CFS, and we hypothesise that infections in temporal proximity to vaccination could also play a role for the development of suspected adverse effects following HPV vaccination. What did the researchers find? Females who had a treated infection in temporal proximity to HPV vaccination were more likely to be referred to a specialised hospital setting (HPV centre) because of suspected adverse effects after HPV vaccination compared to HPV-vaccinated females without an infection. The case-crossover and case time-control analyses made to control for potential unmeasured confounding supported this finding. What do these findings mean? Infections might be a trigger of the suspected adverse effects in a subset of females referred to an HPV centre. More research is needed in order to confirm these findings and to clarify whether infections alone or in combination with HPV vaccine could have caused the reported symptoms.

Herpes simplex virus 1 (HSV1) infects the stratified epithelia of the epidermis, oral or genital mucosa, where the main cell type is the keratinocyte. Here we have used nTERT human keratinocytes to generate a CRISPR-Cas9 knockout (KO) of the primary candidate HSV1 receptor, nectin1, resulting in a cell line that is refractory to HSV1 entry. Nonetheless, a small population of KO cells was able to support infection which was not blocked by a nectin1 antibody and hence was not a consequence of residual nectin1 expression. Strikingly at later times, the population of cells originally resistant to HSV1 infection had also become infected. Appearance of this later population was blocked by inhibition of virus genome replication, or infection with a ΔUL34 virus defective in capsid export to the cytoplasm. Moreover, newly formed GFP-tagged capsids were detected in cells surrounding the initial infected cell, suggesting that virus was spreading following replication in the original susceptible cells. Additional siRNA depletion of the second major HSV1 receptor HVEM, or PTP1B, a cellular factor shown elsewhere to be involved in cell-to-cell transmission, had no effect on virus spread in the absence of nectin1. Neutralizing human serum also failed to block virus transmission in nectin1 KO cells, which was dependent on the receptor binding protein glycoprotein D and the cell-to-cell spread glycoproteins gI and gE, indicating that virus was spreading by direct cell-to-cell transmission. In line with these results, both HSV1 and HSV2 formed plaques on nectin1 KO cells, albeit at a reduced titre, confirming that once the original cell population was infected, the virus could spread into all other cells in the monolayer. We conclude that although nectin1 is required for extracellular entry in to the majority of human keratinocytes, it is dispensable for direct cell-to-cell transmission., Author summary Herpes simplex virus 1 (HSV1) infects the epithelia of the epidermis, oral or genital mucosa to cause cold sores, genital herpes, or more serious outcomes such as keratitis and neonatal herpes. Like many viruses, HSV1 can spread through the extracellular environment or by direct cell-to-cell transmission, with the latter mechanism being important for avoiding antibody responses in the host. Here we have studied HSV1 entry and transmission in the human keratinocyte, the main cell type in the target epithelia, by generating a CRISPR-Cas9 knockout of the primary candidate virus receptor, nectin1. While HSV1 was unable to infect the majority of nectin1 knockout keratinocytes, a small population of these nectin1 KO cells remained susceptible to virus entry, and once infected, the virus was able to spread into the rest of the monolayer. This spread continued in the presence of neutralising serum which blocks extracellular virus, and required glycoprotein D, the main virus receptor-binding protein, and glycoproteins gE and gI which are known to be involved in cell-to-cell spread. Hence, while nectin1 is required for virus entry into the majority of human keratinocyte cells, it is dispensable for cell-to-cell transmission of the virus. These data have implications for the mechanism of HSV1 epithelial spread and pathogenesis.

Digestive Chagas disease (DCD) is an enteric neuropathy caused by Trypanosoma cruzi infection. The mechanism of pathogenesis is poorly understood and the lack of a robust, predictive animal model has held back research. We screened a series of mouse models using gastrointestinal tracer assays and in vivo infection imaging systems to discover a subset exhibiting chronic digestive transit dysfunction and significant retention of faeces in both sated and fasted conditions. The colon was a specific site of both tissue parasite persistence, delayed transit and dramatic loss of myenteric neurons as revealed by whole-mount immunofluorescence analysis. DCD mice therefore recapitulated key clinical manifestations of human disease. We also exploited dual reporter transgenic parasites to home in on locations of rare chronic infection foci in the colon by ex vivo bioluminescence imaging and then used fluorescence imaging in tissue microdomains to reveal co-localisation of infection and enteric nervous system lesions. This indicates that long-term T. cruzi-host interactions in the colon drive DCD pathogenesis, suggesting that the efficacy of anti-parasitic chemotherapy against chronic disease progression warrants further pre-clinical investigation., Author summary Chagas disease (American trypanosomiasis) is caused by the protozoan parasite Trypanosoma cruzi. Chagas disease has two types, the cardiac form and the digestive form; some patients have symptoms of both. How the parasite causes digestive disease is poorly understood. It is known that damage to the gut’s nervous system is an important factor, but it has been unclear exactly where and when this damage occurs during the course of an infection and also why only a subset of infected people suffer from this outcome. We studied infections in mice and found certain combinations of strains of parasites and mice that exhibited symptoms similar to human digestive Chagas patients, including a problem with peristalsis that localised specifically to the colon. Using parasites that were genetically engineered to emit both bioluminescent and fluorescent light, we tracked infections over time and were able to analyse rare infected cells deep within the muscle tissue of the wall of the colon. We found evidence of damaged neurons in the same location as these infection foci over 6 months after initial infection. Our results show that digestive Chagas disease probably develops as a result of chronic infection and inflammation, which potentially changes approaches to treatment.

The Gram-positive bacterium Listeria monocytogenes is the causative agent of the foodborne disease listeriosis, one of the deadliest bacterial infections known. In order to cause disease, L. monocytogenes must properly coordinate its metabolic and virulence programs in response to rapidly changing environments within the host. However, the mechanisms by which L. monocytogenes senses and adapts to the many stressors encountered as it transits through the gastrointestinal (GI) tract and disseminates to peripheral organs are not well understood. In this study, we investigated the role of the redox-responsive transcriptional regulator Rex in L. monocytogenes growth and pathogenesis. Rex is a conserved canonical transcriptional repressor that monitors the intracellular redox state of the cell by sensing the ratio of reduced and oxidized nicotinamide adenine dinucleotides (NADH and NAD+, respectively). Here, we demonstrated that L. monocytogenes Rex represses fermentative metabolism and is therefore required for optimal growth in the presence of oxygen. We also show that in vitro, Rex represses the production of virulence factors required for survival and invasion of the GI tract, as a strain lacking rex was more resistant to acidified bile and invaded host cells better than wild type. Consistent with these results, Rex was dispensable for colonizing the GI tract and disseminating to peripheral organs in an oral listeriosis model of infection. However, Rex-dependent regulation was required for colonizing the spleen and liver, and L. monocytogenes lacking the Rex repressor were nearly sterilized from the gallbladder. Taken together, these results demonstrated that Rex functions as a repressor of fermentative metabolism and suggests a role for Rex-dependent regulation in L. monocytogenes pathogenesis. Importantly, the gallbladder is the bacterial reservoir during listeriosis, and our data suggest redox sensing and Rex-dependent regulation are necessary for bacterial survival and replication in this organ., Author summary Listeriosis is a foodborne illness caused by Listeria monocytogenes and is one of the deadliest bacterial infections known, with a mortality rate of up to 30%. Following ingestion of contaminated food, L. monocytogenes disseminates from the gastrointestinal (GI) tract to peripheral organs, including the spleen, liver, and gallbladder. In this work, we investigated the role of the redox-responsive regulator Rex in L. monocytogenes growth and pathogenesis. We demonstrated that alleviation of Rex repression coordinates expression of genes necessary in the GI tract during infection, including fermentative metabolism, bile resistance, and invasion of host cells. Accordingly, Rex was dispensable for colonizing the GI tract of mice during an oral listeriosis infection. Interestingly, Rex-dependent regulation was required for bacterial replication in the spleen, liver, and gallbladder. Taken together, our results demonstrate that Rex-mediated redox sensing and transcriptional regulation are important for L. monocytogenes metabolic adaptation and virulence.

Background WHO recommends use of rapid dual HIV/syphilis tests for screening pregnant women (PW) during antenatal care to prevent mother-to-child transmission. Scale-up of testing implies a need to accurately forecast and procure benzathine penicillin (BPG) to treat the additionally identified PW with syphilis. Methods Country-reported ANC coverage, PW syphilis screening and treatment coverage values in 2019 were scaled linearly to EMTCT targets by 2030 (constant increasing slope from 2019 figures to 95% in 2030) for 11 focus countries. Antenatal syphilis screening coverage was substituted with HIV screening coverage to estimate potential contribution of rapid dual HIV/syphilis tests in identifying additional PW with syphilis. BPG demand was calculated for 2019–2030 accordingly. Results The estimated demand for BPG (in 2.4 million unit vials) using current maternal syphilis prevalence and treatment coverage will increase from a baseline of 414,459 doses in 2019 to 683,067 doses (+65%) in 2021 assuming immediate replacement of single HIV test kits with rapid dual HIV/syphilis tests for these 11 countries. Continued scale up of syphilis screening and treatment coverage to reach elimination coverage of 95% will result in an estimated demand increase of 160%, (663,969 doses) from 2019 baseline for a total demand of 1,078,428 BPG doses by 2030. Conclusions Demand for BPG will increase following adoption of rapid dual HIV/syphilis test kits due to increases in maternal diagnoses of syphilis. To eliminate congenital syphilis, MNCH clinical programs will need to synergize with disease surveillance programs to accurately forecast BPG demand with scale up of antenatal syphilis screening to ensure adequate treatment is available for pregnant women diagnosed with syphilis.

Given rising antibiotic resistance and increasing use of delayed prescription for uncomplicated lower urinary tract infections (UTI), patients at risk for treatment failure should be identified early. We assessed risk factors for clinical and microbiological failure in women with lower UTI. This case-control study nested within a randomized clinical trial included all women in the per-protocol population (PPP), those in the PPP with microbiologically confirmed UTI, and those in the PPP with UTI due to Escherichia coli. Cases were women who experienced clinical and/or microbiologic failure; controls were those who did not. Risk factors for failure were assessed using multivariate logistic regression. In the PPP, there were 152 clinical cases for 307 controls. Among 340 women with microbiologically confirmed UTI, 126 and 102 cases with clinical and microbiological failure were considered with, respectively, 214 and 220 controls. Age ≥52 years was independently associated with clinical (adjusted OR 3.01; 95%CI 1.84–4.98) and microbiologic failure (aOR 2.55; 95%CI 1.54–4.25); treatment with fosfomycin was associated with clinical failure (aOR 2.35; 95%CI 1.47–3.80). The association with age persisted among all women, and women with E. coli-related UTI. Diabetes was not an independent risk factor, nor were other comorbidities. Postmenopausal age emerged as an independent risk factor for both clinical and microbiological treatment failure in women with lower UTI and should be considered to define women at-risk for non-spontaneous remission, and thus for delayed antibiotic therapy; diabetes mellitus was not associated with failure.

MmuPV1 is a useful model for studying papillomavirus-induced tumorigenesis. We used RNA-seq to look for chimeric RNAs that map to both MmuPV1 and host genomes. In tumor tissues, a higher proportion of total viral reads were virus-host chimeric junction reads (CJRs) (1.9‰ - 7‰) than in tumor-free tissues (0.6‰ - 1.3‰): most CJRs mapped to the viral E2/E4 region. Although most of the MmuPV1 integration sites were mapped to intergenic regions and introns throughout the mouse genome, integrations were seen more than once in several genes: Malat1, Krt1, Krt10, Fabp5, Pard3, and Grip1; these data were confirmed by rapid amplification of cDNA ends (RACE)-Single Molecule Real-Time (SMRT)-seq or targeted DNA-seq. Microhomology sequences were frequently seen at host-virus DNA junctions. MmuPV1 infection and integration affected the expression of host genes. We found that factors for DNA double-stranded break repair and microhomology-mediated end-joining (MMEJ), such as H2ax, Fen1, DNA polymerase Polθ, Cdk1, and Plk1, exhibited a step-wise increase and Mdc1 a decrease in expression in MmuPV1-infected tissues and MmuPV1 tumors relative to normal tissues. Increased expression of mitotic kinases CDK1 and PLK1 appears to be correlated with CtIP phosphorylation in MmuPV1 tumors, suggesting a role for MMEJ-mediated DNA joining in the MmuPV1 integration events that are associated with MmuPV1-induced progression of tumors., Author summary Persistent high-risk HPV infection leads viral DNA integration into the host genome and promotes viral carcinogenesis. We have been using the MmuPV1 mouse-infection model to study papillomavirus tumorigenesis and asked whether MmuPV1 DNA also integrates into the genomes of infected mouse cells. Strikingly, we found that MmuPV1 integration into the infected host genome, like high-risk HPV infections, is very common and the mapped integration sites were distributed on all of the mouse chromosomes. Consistently, we identified microhomology sequences in the range of 2–10 nts always at the integration junction regions. We further verified the MMEJ-mediated viral DNA integration in tumor tissues during MmuPV1 infection and a step-wise increase in the expression of the DNA repair MMEJ host factors from normal tissues, to tumor-free MmuPV1 infected tissues, and then to MmuPV1 tumors. Our observations provide the first evidence of MmuPV1 integration in virus-infected cells and a conceptual advance of how papillomavirus DNA integration contributes to the development of papillomavirus-associated precancers to cancers.

Despite more than a century of research, genetic manipulation of Treponema pallidum subsp. pallidum (T. pallidum), the causative agent of syphilis, has not been successful. The lack of genetic engineering tools has severely limited understanding of the mechanisms behind T. pallidum success as a pathogen. A recently described method for in vitro cultivation of T. pallidum, however, has made it possible to experiment with transformation and selection protocols in this pathogen. Here, we describe an approach that successfully replaced the tprA (tp0009) pseudogene in the SS14 T. pallidum strain with a kanamycin resistance (kanR) cassette. A suicide vector was constructed using the pUC57 plasmid backbone. In the vector, the kanR gene was cloned downstream of the tp0574 gene promoter. The tp0574prom-kanR cassette was then placed between two 1-kbp homology arms identical to the sequences upstream and downstream of the tprA pseudogene. To induce homologous recombination and integration of the kanR cassette into the T. pallidum chromosome, in vitro-cultured SS14 strain spirochetes were exposed to the engineered vector in a CaCl2-based transformation buffer and let recover for 24 hours before adding kanamycin-containing selective media. Integration of the kanR cassette was demonstrated by qualitative PCR, droplet digital PCR (ddPCR), and whole-genome sequencing (WGS) of transformed treponemes propagated in vitro and/or in vivo. ddPCR analysis of RNA and mass spectrometry confirmed expression of the kanR message and protein in treponemes propagated in vitro. Moreover, tprA knockout (tprAko-SS14) treponemes grew in kanamycin concentrations that were 64 times higher than the MIC for the wild-type SS14 (wt-SS14) strain and in infected rabbits treated with kanamycin. We demonstrated that genetic manipulation of T. pallidum is attainable. This discovery will allow the application of functional genetics techniques to study syphilis pathogenesis and improve syphilis vaccine development., Author summary Syphilis is still an endemic disease in many low- and middle-income countries, and it has been resurgent in high-income nations for almost two decades. In endemic areas, syphilis causes significant morbidity and mortality, particularly when its causative agent, the spirochete Treponema pallidum subsp. pallidum (T. pallidum) is transmitted to the fetus during pregnancy. A better understanding of T. pallidum biology and syphilis pathogenesis would help devise better control strategies for this infection. One of the limitations associated with working with T. pallidum was our inability to genetically alter this pathogen to evaluate the function of genes encoding virulence factors or create attenuated strains that could be informative for vaccine development when studied using the rabbit model of the disease. Here, we report a transformation protocol that allowed us to replace a specific region of the T. pallidum genome containing a pseudogene (i.e., a non-functional gene) with a stably integrated kanamycin resistance gene. To our knowledge, this is the first-ever report of a method to achieve a genetically modified T. pallidum strain.

Objective A screening centre in Soweto, South Africa (SA), investigated high-risk human papillomavirus (HR-HPV), HIV, cervical cancer risk amongst women. Methods This cross-sectional study (June 2018-March 2019) describes screening results (Roche Linear Array HPV test and Pap smear liquid based cytology) and history of screening (known HIV status, antiretroviral therapy [ART] use, previous Pap smears). Data were stratified by age group (18–29, 30+ years), HIV status, Pap smear results and tested for statistical significance. Results Of 280 women, 20.4% were HIV-positive, 18.2% had abnormal Pap smears, 41.8% had HR-HPV. Of older women, 48.2% (n = 78/162) had never had a Pap smear. Of younger women, 89.0% (n = 105/118) never had a Pap smear, but had significantly more low-grade squamous intraepithelial lesions (LSIL) and other HR-HPV infection than older women (12.7%[n = 15/118] vs 4.9%[n = 8/162], p = 0.0193; and 49.2%[n = 58/118] vs 29.0%[n = 47/162], p = 0.0006; respectively). HIV-positive women had more abnormal cytology results and infection with other HR-HPV types or co-infection with other HR-HPV type(s)/HPV-16 compared to HIV-negative women (35.1%[n = 20/57] vs 13.9%[n = 31/223], p = 0.0002; 56.1%[n = 32/57] vs 32.7%[n = 73/223], p = 0.001; and 12.3%[n = 7/57] vs 4.9%[n = 11/223], p = 0.044; respectively). Of 57 HIV-positive women, 45.6% (n = 26) already knew their HIV status; of which 69.2% were on ART and 34.6% never had a Pap smear. Conclusion South African women have high rates of HIV, Pap smear abnormalities and HR-HPV, with low cervical cancer screening coverage. SA cervical cancer screening policy excludes (undiagnosed) HIV-positive and HIV-negative women

The Caribbean ranks seventh among the world regions most affected by cervical cancer. HPV-prevalence and genotype distributions also differ from regions. Knowledge of HPV genotype profiles is important for patients care and HPV vaccination implementation. The objective of this study was to describe HPV genotype distribution and risk factors in a population-based cohort of women in Martinique. In this study, 1312 women were included and underwent cervical cancer screening with successful sample collection between 2009 and 2014. Sociodemographic and clinical variables were recorded. Cytological examination of cervical vaginal smear was performed and classified(Bethesda). Detection of HPV DNA was performed with the PapilloCheck© Kit from Greiner Bio-one. Genotypes were analyzed for18 high-risk HPV (hrHPV) and 6low-risk HPV(lrHPV) types. A total of 1075 women were included with a mean age of 49.1±10.5 years. HPV prevalence was 27.6% (297/1075) with 19.4% (209/1075) women with only hrHPV, 5.3% (57/1075) with only lrHPV. Multiple infections (hrHPV/lrHPV) were detected in 31/240 cases of hrHPV (12.9%). A total of 353 hrHPV genotypes were analyzed; the most common HPV types were HPV51 (11.0%), HPV68 (10.8%), HPV53 (9.1%) and HPV 52 (7.1%). HPV16 and HPV18 represented respectively 4.8% and 4.0% of hrHPV genotypes. Abnormal cytology was observed in 34 cases (3.2%), with 14 ASCUS (1.3%), 10 LSIL (0.9%), 5 HSIL (0.5%), 3 ASC-H (0.3%) and 2 AGC (0.2%). Fifteen (44.1%) were hrHPV and 4 (14.7%) lrHPV; 7 cases of hrPHV were in the age-group 25–34 years. Among 1041cases of normal cytology, 225 had positive hrHPV detection (21.6%). This is the first population-based study of HPV profiles in our country, and we found a high prevalence of hrHPV. The most common genotypes were HPV51, 68, 53. These results could serve for cancer vaccination strategies and HPV surveillance in Martinique.

BackgroundPaediatric global antibiotic guidelines are inconsistent, most likely due to the limited pharmacokinetic and efficacy data in this population. We investigated factors underlying variation in antibiotic dosing using data from five global point prevalence surveys.Methods & findingsData from 3,367 doses of the 16 most frequent intravenous antibiotics administered to children 1 month–12 years across 23 countries were analysed. For each antibiotic, we identified standard doses given as either weight-based doses (in mg/kg/day) or fixed daily doses (in mg/day), and investigated the pattern of dosing using each strategy. Factors underlying observed variation in weight-based doses were investigated using linear mixed effects models. Weight-based dosing (in mg/kg/day) clustered around a small number of peaks, and all antibiotics had 1–3 standard weight-based doses used in 5%-48% of doses. Dosing strategy was more often weight-based than fixed daily dosing for all antibiotics apart from teicoplanin, which had approximately equal proportions of dosing attributable to each strategy. No strong consistent patterns emerged to explain the historical variation in actual weight-based doses used apart from higher dosing seen in central nervous system infections, and lower in skin and soft tissue infections compared to lower respiratory tract infections. Higher dosing was noted in the Americas compared to the European region.ConclusionsAntibiotic dosing in children clusters around a small number of doses, although variation remains. There is a clear opportunity for the clinical, scientific and public health communities to consolidate behind a consistent set of global antibiotic dosing guidelines to harmonise current practice and prioritise future research.

Background Sexually transmitted and genital infections in pregnancy are associated with adverse pregnancy and birth outcomes. Point-of-care tests for these infections facilitate testing and treatment in a single antenatal clinic visit and may reduce the risk of adverse outcomes. Successful implementation and scale-up depends on understanding comparative effectiveness of such programmes and their comparative costs and cost effectiveness. This systematic review synthesises and appraises evidence from economic evaluations of point-of-care testing and treatment for sexually transmitted and genital infections among pregnant women in low- and middle-income countries. Methods Medline, Embase and Web of Science databases were comprehensively searched using pre-determined criteria. Additional literature was identified by searching Google Scholar and the bibliographies of all included studies. Economic evaluations were eligible if they were set in low- and middle-income countries and assessed antenatal point-of-care testing and treatment for syphilis, chlamydia, gonorrhoea, trichomoniasis, and/or bacterial vaginosis. Studies were analysed using narrative synthesis. Methodological and reporting standards were assessed using two published checklists. Results Sixteen economic evaluations were included in this review; ten based in Africa, three in Latin and South America and three were cross-continent comparisons. Fifteen studies assessed point-of-care testing and treatment for syphilis, while one evaluated chlamydia. Key drivers of cost and cost-effectiveness included disease prevalence; test, treatment, and staff costs; test sensitivity and specificity; and screening and treatment coverage. All studies met 75% or more of the criteria of the Drummond Checklist and 60% of the Consolidated Health Economics Evaluation Reporting Standards. Conclusions Generally, point-of-care testing and treatment was cost-effective compared to no screening, syndromic management, and laboratory-based testing. Future economic evaluations should consider other common infections, and their lifetime impact on mothers and babies. Complementary affordability and equity analyses would strengthen the case for greater investment in antenatal point-of-care testing and treatment for sexually transmitted and genital infections.

Mounting evidence suggests that Lactobacillus species may not necessarily be the sine qua non of healthy cervicovaginal microbiota (CVM), especially among reproductive-age African women. A majority of African women have high-diversity non-Lactobacillus-dominated CVM whose bacterial functions remain poorly characterized. Functional profiling of the CVM is vital for investigating human host-microbiota interactions in health and disease. Here, we investigated the functional potential of L. iners-dominated and high-diversity non-Lactobacillus-dominated CVM of 75 African women with and without bacterial vaginosis (BV) and high-risk human papillomavirus (HR-HPV) infection. Functional contents were predicted using PICRUSt. Microbial taxonomic diversity, BV, and HR-HPV infection statuses were correlated with the inferred functional composition of the CVM. Differentially abundant inferred functional categories were identified using linear discriminant analysis (LDA) effect size (LEfSe) (p-value 2.0). Of the 75 women, 56 (74.7%), 35 (46.7%), and 29 (38.7%) had high-diversity non-Lactobacillus-dominated CVM, BV, and HR-HPV infection, respectively. Alpha diversity of the inferred functional contents (as measured by Shannon diversity index) was significantly higher in women with high-diversity non-Lactobacillus-dominated CVM and BV than their respective counterparts (H statistic ≥11.5, q-value

BackgroundInstitution-specific guidelines (ISGs) within the framework of antimicrobial stewardship programs offer locally tailored decision support taking into account local pathogen and resistance epidemiology as well as national and international guidelines.ObjectivesTo assess the impact of ISGs for antimicrobial therapy on antibiotic consumption and subsequent changes in resistance rates and Clostridioides difficile infections (CDIs).MethodsThe study was conducted at the Leipzig University Hospital, a 1,451-bed tertiary-care medical center, and covered the years 2012 to 2020. Since 2014, ISGs were provided to optimize empirical therapies, appropriate diagnostics, and antimicrobial prophylaxis. We used interrupted time series analysis (ITSA) and simple linear regression to analyze changes in antimicrobial consumption, resistance and CDIs.ResultsOver the study period, 1,672,200 defined daily doses (DDD) of antibiotics were dispensed, and 85,645 bacterial isolates as well as 2,576 positive C. difficile cultures were collected. Total antimicrobial consumption decreased by 14% from 2012 to 2020, without clear impact of the deployment of ISGs. However, implementation of ISGs was associated with significant decreases in the use of substances that were rarely recommended (e.g., fluoroquinolones). Over the whole study period, we observed declining resistance rates to most antibiotic classes of up to 25% in Enterobacterales, staphylococci, and Pseudomonas aeruginosa. Switching from ceftriaxone to cefotaxime was associated with reduced resistance to third-generation cephalosporins. The number of CDI cases fell by 65%, from 501 in 2012 to 174 in 2020.ConclusionsWell-implemented ISGs can have a significant, immediate, and lasting impact on the prescription behavior. ISGs might thereby contribute to reduce resistance rates and CDI incidences in the hospital setting.

Background Treatment of cervical intraepithelial neoplasia (CIN) is associated with an increased risk of preterm delivery (PTD) although the exact pathomechanism is not yet understood. Women with untreated CIN also seem to have an increased risk of PTD. It is unclear whether this is attributable to human papillomavirus (HPV) infection or other factors. We aimed to investigate whether HPV infection shortly before or during pregnancy, as well as previous treatment for CIN, is associated with an increased risk of PTD and other adverse obstetric and neonatal outcomes. Methods and findings This was a retrospective population-based register study of women with singleton deliveries registered in the Swedish Medical Birth Register 1999–2016 (n = 1,044,023). The study population had a mean age of 30.2 years (SD 5.2) and a mean body mass index of 25.4 kg/m2 (SD 3.0), and 44% of the women were nulliparous before delivery. Study groups were defined based on cervical HPV tests, cytology, and histology, as registered in the Swedish National Cervical Screening Registry. Women with a history of exclusively normal cytology (n = 338,109) were compared to women with positive HPV tests (n = 2,550) or abnormal cytology (n = 11,727) within 6 months prior to conception or during the pregnancy, women treated for CIN3 before delivery (n = 23,185), and women with CIN2+ diagnosed after delivery (n = 33,760). Study groups were compared concerning obstetric and neonatal outcomes by logistic regression, and comparisons were adjusted for socioeconomic and health-related confounders. HPV infection was associated with PTD (adjusted odds ratio [aOR] 1.19, 95% CI 1.01–1.42, p = 0.042), preterm prelabor rupture of membranes (pPROM) (aOR 1.52, 95% CI 1.18–1.96, p < 0.001), prelabor rupture of membranes (PROM) (aOR 1.24, 95% CI 1.08–1.42, p = 0.002), and neonatal mortality (aOR 2.69, 95% CI 1.25–5.78, p = 0.011). Treatment for CIN was associated with PTD (aOR 1.85, 95% CI 1.76–1.95, p < 0.001), spontaneous PTD (aOR 2.06, 95% CI 1.95–2.17, p < 0.001), pPROM (aOR 2.36, 95% CI 2.19–2.54, p < 0.001), PROM (aOR 1.11, 95% CI 1.05–1.17, p < 0.001), intrauterine fetal death (aOR 1.35, 95% CI 1.05–1.72, p = 0.019), chorioamnionitis (aOR 2.75, 95% CI 2.33–3.23, p < 0.001), intrapartum fever (aOR 1.24, 95% CI 1.07–1.44, p = 0.003), neonatal sepsis (aOR 1.55, 95% CI 1.37–1.75, p < 0.001), and neonatal mortality (aOR 1.79, 95% CI 1.30–2.45, p < 0.001). Women with CIN2+ diagnosed within 3 years after delivery had increased PTD risk (aOR 1.18, 95% CI 1.10–1.27, p < 0.001). Limitations of the study include the retrospective design and the fact that because HPV test results only became available in 2007, abnormal cytology was used as a proxy for HPV infection. Conclusions In this study, we found that HPV infection shortly before or during pregnancy was associated with PTD, pPROM, PROM, and neonatal mortality. Previous treatment for CIN was associated with even greater risks for PTD and pPROM and was also associated with PROM, neonatal mortality, and maternal and neonatal infectious complications., In a retrospective analysis of population-based registry data, Johanna Wiik and colleagues investigate relationships between HPV infection, treatment for cervical intraepithelial neoplasia, and pregnancy and birth outcomes., Author summary Why was this study done? Treatment of cervical intraepithelial neoplasia (CIN) is associated with an increased risk of preterm delivery (PTD), preterm prelabor rupture of the membranes (pPROM), and neonatal mortality. However, the exact biological mechanism is still unknown. Women with untreated CIN also seem to have an increased risk of PTD. It is unknown whether HPV infection can cause PTD or other adverse obstetric outcomes. Although ascending bacterial infection is an established leading cause of PTD, there is limited knowledge concerning whether PTD after excisional treatment for CIN is associated with infectious complications. What did the researchers do and find? This retrospective population-based register study (1999–2016) found that HPV infection shortly before or during pregnancy is associated with an increased risk of PTD, pPROM, prelabor rupture of the membranes, and neonatal mortality. Treatment for CIN was also associated with these adverse outcomes and with an even higher risk for PTD and pPROM. This study presents new evidence that previous treatment for CIN is associated with an increased risk of maternal and neonatal infectious complications. What do these findings mean? Although we cannot claim causality due to the register-based study design, our results suggest that pregnancies after treatment for CIN should be regarded as high-risk pregnancies and counseled accordingly. These results support the idea that strategies to mitigate HPV infection, such as vaccination programs, may be beneficial for maternal and neonatal pregnancy outcomes.

Urinary tract infections (UTIs) are a common bacterial infectious disease in humans, and strains of uropathogenic Escherichia coli (UPEC) are the most frequent cause of UTIs. During infection, UPEC must cope with a variety of stressful conditions in the urinary tract. Here, we demonstrate that the small RNA (sRNA) RyfA of UPEC strains is required for resistance to oxidative and osmotic stresses. Transcriptomic analysis of the ryfA mutant showed changes in expression of genes associated with general stress responses, metabolism, biofilm formation and genes coding for cell surface proteins. Inactivation of ryfA in UPEC strain CFT073 decreased urinary tract colonization in mice and the ryfA mutant also had reduced production of type 1 and P fimbriae (pili), adhesins which are known to be important for UTI. Furthermore, loss of ryfA also reduced UPEC survival in human macrophages. Thus, ryfA plays a key regulatory role in UPEC adaptation to stress, which contributes to UTI and survival in macrophages., Author summary Small regulatory RNAs play a critical role in bacterial adaptation, physiology, and metabolism. We investigated the role of the small RNA ryfA in uropathogenic E. coli, by using genetic, molecular and cell culture approaches, and mouse infection models. We demon-strate that RyfA is important for resistance to oxidative and osmotic stresses and affects the global transcription of multiple responses to stress. Deletion of ryfA also reduced production of type 1 and P fimbriae (pili) and increased swimming motility. RyfA also plays an important role in urinary tract infection (UTI) in the mouse model and for survival in human primary macrophages and cell lines. Elucidating a role for RyfA in adaptation to stress response and virulence provides insight into new regulatory mechanisms important for virulence in pathogenic E. coli and likely other Enterobacteria that may lead to development of targeted therapeutic or prophylactic approaches against these pathogens.

Funding: The authors would like to acknowledge support from the University of Aberdeen and Abia State University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

IntroductionThe longstanding inadequacies of syndromic management for genital ulceration and inflammation are well-described. The Rwanda National Guidelines for sexually transmitted infection (STI) syndromic management are not yet informed by the local prevalence and correlates of STI etiologies, a component World Health Organization guidelines stress as critical to optimize locally relevant algorithms.MethodsRadio announcements and pharmacists recruited symptomatic patients to seek free STI services in Kigali. Clients who sought services were asked to refer sexual partners and symptomatic friends. Demographic, behavioral risk factor, medical history, and symptom data were collected. Genital exams were performed by trained research nurses and physicians. We conducted phlebotomy for rapid HIV and rapid plasma reagin (RPR) serologies and vaginal pool swab for microscopy of wet preparation to diagnose Trichomonas vaginalis (TV), bacterial vaginosis (BV), and vaginal Candida albicans (VCA). GeneXpert testing for Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) were conducted. Here we assess factors associated with diagnosis of NG and CT in men and women. We also explore factors associated with TV, BV and VCA in women. Finally, we describe genital ulcer and RPR results by HIV status, gender, and circumcision in men.ResultsAmong 974 men (with 1013 visits), 20% were positive for CT and 74% were positive for NG. Among 569 women (with 579 visits), 17% were positive for CT and 27% were positive for NG. In multivariate analyses, factors associated with CT in men included younger age, responding to radio advertisements, vs. never, using hormonalvs. non-hormonal contraception, not having genital ulcer or itching, having symptoms < = 10 days, HIV+ status, having BV, endocervical discharge noted on speculum exam, and negative vaginal wet mount for VCA. In multivariate analyses, only reporting >1 partner was associated with BV; being single and RPR+ was associated with TV; and having < = 1 partner in the last month, being pregnant, genital itching, discharge, and being HIV and RPR negative were associated with VCA. Genital ulcers and positive RPR were associated with being HIV+ and lack of circumcision among men. HIV+ women were more likely to be RPR+. In HIV+ men and women, ulcers were more likely to be herpetic rather than syphilitic compared with their HIV- counterparts.ConclusionsSyndromic management guidelines in Rwanda can be improved with consideration of the prevalence of confirmed infections from this study of symptomatic men and women representative of those who would seek care at government health centers. Inclusion of demographic and risk factor measures shown to be predictive of STI and non-STI dysbioses may also increase diagnostic accuracy.

During pregnancy, the vaginal microbiome plays an important role in both maternal and neonatal health outcomes. Throughout pregnancy, the vaginal microbial composition undergoes significant changes, including a decrease in overall diversity and enrichment with Lactobacillus spp. In turn, the modifications in the microbial profiles are associated with shifts in the composition of vaginal metabolites. In this study, we characterized the vaginal metabolic profiles throughout pregnancy at two different gestational ages, correlating them with a microscopic evaluation of the vaginal bacterial composition. A total of 67 Caucasian pregnant women presenting to the Family Advisory Health Centres of Ravenna (Italy) were enrolled and a vaginal swab was collected at gestational ages 9–13 weeks (first trimester) and 20–24 weeks (second trimester). The composition of the vaginal microbiome was assessed by Nugent score and women were divided in ‘H’ (normal lactobacilli-dominated microbiota), ‘I’ (intermediate microbiota), and ‘BV’ (bacterial vaginosis) groups. Starting from the cell-free supernatants of the vaginal swabs, a metabolomic analysis was performed by means of a 1H-NMR spectroscopy. From the first to the second trimester, a greater number of women showed a normal lactobacilli-dominated microbiota, with a reduction of cases of dysbiosis. These microbial shifts were associated with profound changes in the vaginal metabolic profiles. Over the weeks, a significant reduction in the levels of BV-associated metabolites (e.g. acetate, propionate, tyramine, methylamine, putrescine) was observed. At the same time, the vaginal metabolome was characterized by higher concentrations of lactate and of several amino acids (e.g. tryptophan, threonine, isoleucine, leucine), typically found in healthy vaginal conditions. Over time, the vaginal metabolome became less diverse and more homogeneous: in the second trimester, women with BV showed metabolic profiles more similar to the healthy/intermediate groups, compared to the first trimester. Our data could help unravel the role of vaginal metabolites in the pathophysiology of pregnancy.

Background Gut colonization by ESBL-producing Enterobacteriaceae (ESBL-PE) is widespread and is promoted by antibiotic exposure. Higher fecal abundance of ESBL-PE promotes the dissemination of the bacteria in the environment and is associated with increased risk of infection. Ceftriaxone and temocillin are commonly used antibiotics with a different activity on gut flora. Their impact on fecal abundance of ESBL-producing Enterobacteriaceae has not been studied. The objective of this study was to compare the propensity of ceftriaxone and temocillin to modify the abundance of ESBL-producing Escherichia coli in feces of colonized mice. Methods Mice received broad-spectrum antibiotics in order to disrupt their normal gut flora. A CTX-M-type ESBL-producing E. coli clinical isolate was then administered orally, leading to durable colonization. Thirty days later, mice received either temocillin or ceftriaxone with drinking water at a concentration simulating human intestinal exposure. Third-generation-cephalosporin resistant (3GCR) E. coli were enumerated in feces on selective medium before, 2 days and 10 days after the end of antibiotic exposure. The experiment was performed with two E. coli isolates with different temocillin minimum inhibitory concentrations. Results Exposure to ceftriaxone induced an increase in the fecal abundance of 3GCR E. coli. In contrast, temocillin had no effect or transiently decreased the number of 3GCR E. coli. Results obtained with the two strains were similar. Conclusion Contrary to ceftriaxone, temocillin does not promote expansion of ESBL-producing E. coli in feces of colonized mice. Thus temocillin may be a therapeutic of choice when a temocillin-susceptible strain infection is suspected or proven to prevent the expansion of ESBL-PE in a previously colonized patient.

Background and objectives Only few smaller studies have examined if impaired kidney function increases the risk of acute kidney injury in patients with acute pyelonephritis. Therefore, we estimated 30-day risk of acute kidney injury by preadmission kidney function in patients with acute pyelonephritis. Furthermore, we examined if impaired kidney function was a risk factor for development of acute kidney injury in pyelonephritis patients. Methods This cohort study included patients with a first-time hospitalization with pyelonephritis from 2000 to 2017. Preadmission kidney function (estimated glomerular filtration rate (eGFR) 2) and acute kidney injury within 30 days after admission were assessed using laboratory data on serum creatinine. The absolute 30-days risk of acute kidney injury was assessed treating death as a competing risk. The impact of eGFR on the odds of acute kidney injury was compared by odds ratios (ORs) with 95% confidence intervals estimated using logistic regression adjusted for potential confounding factors. Results Among 8,760 patients with available data on preadmission kidney function, 25.8% had a preadmission eGFR Conclusion Acute kidney injury is a common complication in patients hospitalized with acute pyelonephritis. Preadmission impaired kidney function is a strong risk factor for development of acute kidney injury in pyelonephritis patients and more attention should be raised in prevention of pyelonephritis in patients with a low kidney function.

Background Human papillomavirus (HPV) infection is considered as the major risk factor for the development of cervical cancer, second most frequent cancer in Ethiopia. However, the magnitude of the problem and the associated factors remain unrevealed in the Amhara region. This study aimed to determine the prevalence of HPV infection and factors contributing to the progression of HPV infection to cervical cancer. Methods Facility-based cross-sectional study design was employed among women aged 21 to 49 years of age who came for routine cervical cancer screening to 4 randomly selected hospitals (2 general and 2 referral) of Amhara region from May to October, 2019. The sample size was calculated by using the single population proportion formula, proportionated to hospitals, and women were recruited consecutively. Socio demographic and clinical data were collected using a pretested questionnaire and detection of HPV infection was done using HPV test (OncoE6TM Cervical Test) specific to HPV16/18 in cervical swabs. Visual inspection with acetic acid (VIA) was used to determine cervical lesions (precancerous and cancerous). Descriptive statistics and bivariate and multivariate logistic regression were used to describe HR-HPV and cervical lesions burden and association between HR-HPV, and cervical lesions and potential risk factors. Results Among 337 women 21 to 49 years (median age of 35 years ±SD = 7.1 years) of age enrolled in the study, The overall prevalence of oncogenic HPVs (HPV16/18) and the VIA-positivity rate, possible an indicative of cervical lesions, were 7.1% and 13.1%, respectively. Logistic regression analysis showed a significant association between early age of first sexual intercourse (COR = 2.26; 95% CI: 1.0–5.05) and level of education (COR = 0.31; 95% CI: 0.12–0.78) with cervical lesions. Higher odds of HPV positivity (COR = 1.56; 95% CI: 0.59–4.11, p = 0.36) and VIA positivity (COR = 1.39; 95% CI: 0.64–3.00, p = 0.39) were observed among participants who had a history of sexually transmitted illnesses (STIs). Conclusions There was a relatively low prevalence of oncogenic HPV 16/18 and VIA-positivity in women attending four hospitals in the Amhara Region. Early age sexual contact, high parity, and being uneducated/low level of education were independently associated factors with HR-HPV infection and development of cervical lesions, highlighting the importance of prioritizing the limited HPV testing to those risk groups.

BackgroundEach of the currently available (1→3)-β-D-glucan (BDG) measurement kits follows a different measurement method and cut-off value. Comparisons of diagnostic performance for invasive fungal infections (IFIs) are desirable. Additionally, ecological considerations are becoming increasingly important in the development of new measurement kits.MethodsThe plasma BDG levels in clinical samples were measured using the following currently available kits: the Fungitec G test MKII, the Fungitec G test ES, Fungitell, the β-Glucan test Wako, and the newly developed Wako kit (Wako-Eu). Wako-Eu uses a pre-treatment solution that conforms to European regulations for the registration, evaluation, authorisation, and restriction of chemicals. The values obtained for the samples using each kit were studied and compared.ResultsOf the 165 patients evaluated, 12 had IFIs, including pneumocystis pneumonia, aspergillosis, and candidiasis. BDG values obtained using the kits were moderately correlated with each other. Clinical diagnoses of the evaluated cases indicated that 21 false positives were diagnosed by at least one kit. The sensitivity of the Fungitell kit was relatively low, but those of the other four were over 90%. The specificity was above 90% for all kits. For positive predictive value, the Wako and the Wako-Eu methods were superior to the others owing to fewer false positive results.ConclusionsThe newly developed Wako-Eu method, which considers ecological concerns, shows diagnostic performance equivalent to that of its predecessor. To improve the diagnostic accuracy of IFIs, it is necessary to interpret the results carefully, giving due consideration to the characteristics of each measurement kit.

BackgroundDetailed longitudinal studies of HIV-positive individuals in West Africa are lacking. Here the HIV prevalence, incidence, all-cause mortality, and the proportion of individuals receiving treatment with cART in two cohorts of participants in Ebola-related studies are described.SettingIndividuals of all ages were enrolled and followed at four sites in the area of Monrovia, Liberia.MethodsTwo cohorts identified in response to the Ebola epidemic are described to provide insights into the current state of the HIV epidemic. HIV testing was performed at baseline for participants in both cohorts and during follow-up in one cohort.ResultsPrevalence and incidence of HIV (prevalence of 3.1% for women and 1.4% for men and incidence of 3.3 per 1,000) were higher in these cohorts compared to 2018 national estimates (prevalence of 1.3% and incidence of 0.39 per 1,000). Most participants testing positive did not know their status prior to testing. Of those who knew they were HIV positive, 7.9% reported being on antiretroviral treatment. The death rate among those with HIV was 12.3% compared to 1.9% in HIV-negative individuals (adjusted odds ratio of 6.87). While higher levels of d-dimer were associated with increased mortality, this was not specific to those with HIV, however lower hemoglobin levels were associated with increased mortality among those with HIV.ConclusionThese findings point to a need to perform further research studies aimed at fulfilling these knowledge gaps and address current shortcomings in the provision of care for those living with HIV in Liberia.

Background Infant morbidity is a topic of interest because it is used globally as an indicator of the status of health care in a country. A large body of evidence supports an association between bacterial vaginosis (BV) and infant morbidity. When estimating the relationship between the predictors and the estimated variable of morbidity severity, the latter exhibits imbalanced data, which means that violation of symmetry is expected. Two competing methods of analysis, that is, (1) probit and (2) logit techniques, can be considered in this context and have been applied to model such outcomes. However, these models may yield inconsistent results. While non-normal modeling approaches have been embraced in the recent past, the skewed logit model has been given little attention. In this study, we exemplify its usefulness in analyzing imbalanced longitudinal responses data. Methodology While numerous non-normal methods for modeling binomial responses are well established, there is a need for comparison studies to assess their usefulness in different scenarios, especially under a longitudinal setting. This is addressed in this study. We use a dataset from Kenya about infants born to human immunodeficiency virus (HIV) positive mothers, who are also screened for BV. We aimed to investigate the effect of BV on infant morbidity across time. We derived a score for morbidity incidences depending on illnesses reported during the month of reference. By adjusting for the mother’s BV status, the child’s HIV status, sex, feeding status, and weight for age, we estimated the standard binary logit and skewed logit models, both using Generalized Estimating Equations. Results Results show that accounting for skewness in imbalanced binary data can show associations between variables in line with expectations documented by the literature. In addition, an in-depth analysis accounting for skewness has shown that, over time, maternal BV is associated with multiple health conditions in infants. Interpretation Maternal BV status was positively associated with infant morbidity incidences, which highlights the need for early intervention in cases of HIV-infected pregnant women.

Acquired syphilis is a sexually transmitted infection that affects the general population and has been growing in recent years in many countries. A study was developed aiming to analyze the trends of acquired syphilis associated with sociodemographic aspects and primary health care in Brazil, in the period from 2011 to 2019. This study used secondary data from the national notification systems of the 5570 Brazilian cities and a database of 37,350 primary health care teams, as well as socioeconomic and municipal demographic indicators. The trends of acquired syphilis at the municipal level were calculated from the log-linear regression, crossing them with variables of primary health care and sociodemographic indicators. Finally, a multiple model was built from logistic regression. 724,310 cases of acquired syphilis have been reported. In primary care units, 47.8% had partial coverage and 74.1% had health teams with poor or regular scores. 52.6% had rapid test for syphilis partially available. Male and female condoms are available in 85.9% and 62.9% respectively and 54.4% had penicillin available in the health facility. The increase in trends of acquired syphilis was associated with better availability of the rapid test; lower availability of male condoms; lower availability of female condoms; lower availability of benzathine penicillin; partial coverage of the teams in primary health care; limited application of penicillin in primary health care; higher proportion of teams classified as Poor/Regular in primary health care; higher proportion of women aged 10 to 17 years who had children; higher HDI; higher proportion of people aged 15 to 24 years who do not study, do not work and are vulnerable; and population size with more than 100,000 inhabitants. The following variables remained in the multiple model: not all primary health care teams apply penicillin; higher proportion of primary health care teams with poor/regular scores; population size >100000 inhabitants; partially available female condom. Thus, the weakness of primary health care linked to population size may have favored the growth of the acquired syphilis epidemic in Brazilian cities., Author summary Acquired syphilis is a sexually transmitted infection that continues to impact health services around the world. For decades, studies and public health policies in the fight against syphilis have focused on syphilis in pregnant women and congenital, mainly because of their importance in the health of women and children. However, the behavior of the epidemic in people aged over 13 years shows that the epidemic is comprehensive and challenging. The exponential increase in the syphilis epidemic in the general population is one of the most neglected in many parts of the world. Primary health care plays a fundamental role in the control of syphilis, but few studies have sought to analyze the impact of primary health care on the growth of acquired syphilis. Our work used two large databases of the national notification systems of the 5570 Brazilian cities and a database of 37,350 primary health care teams, as well as municipal sociodemographic indicators. Our results demonstrated several indicators that influence the growth of acquired syphilis, especially the most neglected, which can guide more effective strategies to fight the syphilis epidemic in several countries.

Introduction Maternal and newborn infections are important causes of mortality but morbidity data from low- and middle-income countries is limited. We used telephone surveillance to estimate infection incidence and risk factors in women and newborns following hospital childbirth in Dar es Salaam. Methods We recruited postnatal women from two tertiary hospitals and conducted telephone interviews 7 and 28 days after delivery. Maternal infection (endometritis, caesarean or perineal wound, or urinary tract infection) and newborn infection (umbilical cord or possible severe bacterial infection) were identified using hospital case-notes at the time of birth and self-reported symptoms. Adjusted Cox regression models were used to assess the association between potential risk-factors and infection. Results We recruited 879 women and interviewed 791 (90%). From day 0–7, 6.7% (49/791) women and 6.2% (51/762) newborns developed infection. Using full follow-up data, the infection rate was higher in women with caesarean childbirth versus women with a vaginal delivery (aHR 1.93, 95%CI 1.11–3.36). Only 24% of women received pre-operative antibiotic prophylaxis before caesarean section. Infection was higher in newborns resuscitated at birth versus newborns who were not resuscitated (aHR 4.45, 95%CI 2.10–9.44). At interview, 66% (37/56) of women and 88% (72/82) of newborns with possible infection had sought health-facility care. Conclusions Telephone surveillance identified a substantial risk of postnatal infection, including cases likely to have been missed by hospital-based data-collection alone. Risk of maternal endometritis and newborn possible severe bacterial infection were consistent with other studies. Caesarean section was the most important risk-factor for maternal infection. Improved implementation of pre-operative antibiotic prophylaxis is urgently required to mitigate this risk.

Objectives To analyze the trends of HIV/syphilis/HSV-2 seropositive rate and explore the related factors with HSV-2 infection to provide the basis for adjusting STD intervention strategies and formulating prevention and control measures among MSM in Shenzhen. Methods Time-location sampling was conducted among MSM in Shenzhen in 2012, 2014, 2016, and 2018. Data on demographics, sexual behaviors and the laboratory test results of HIV, syphilis, HSV-2 were collected. The χ2 trend test was used to analyze the trends of HIV/syphilis/HSV-2 seropositive rate. The binary logistic regression model was used to explore the factors associated with HSV-2 infection. Results The seropositive rate of HIV fell significantly from 15.9% in 2012 to 8.7% in 2018 (Ptrend = 0.003), syphilis seropositive rate was significantly decreased from 20.4% in 2012 to 14.8% in 2018 (Ptrend = 0.025), HSV-2 seropositive rate had no significant change (16.7% in 2012 to 14.0% in 2018; Ptrend = 0.617). In principal component logistic regression analysis showed that FAC1_1 (X1 = Ever had sex with female, X2 = Gender of first sexual partner, X3 = Marital status, X4 = Age group), FAC2_1 (X5 = Education, X6 = Monthly income (RMB), X7 = Frequency of condom use in anal sex with men in the past 6 months), and FAC4_1 (X9 = History of STDs) were significantly associated with HSV-2 infection. Conclusions The seropositive rates of HIV and syphilis have dropped significantly but are still high. HSV-2 seropositive rate had no significant change and maintained a high level. It is necessary to continue strengthening HIV and syphilis interventions among MSM in Shenzhen. HSV-2 detection and intervention are urgently required for MSM, which might be another effective biological strategy further to control the HIV epidemic among MSM in Shenzhen.

This study evaluates the pre-vaccination prevalence of HPV infection in women from Vojvodina, Serbia, according to age and cytological status. A total of 1,495 women, ranging from 18 to 65 years of age, with different cytological results were enrolled. The HPV genotyping assay was performed using the EUROArray HPV test in order to detect thirty genitally relevant HPV subtypes. In our study, the most prevalent genotypeswere HPV 16, 31, 51, and 53. Among these, HPV 16 was consistently present in all cytological subgroups. Twelve HPV genotypes classified as carcinogenic to humans (Group 1) were detected in 77.8.0% of HSIL/ASCH and 55.0% of NILM with abnormal colposcopy findings. Six possible carcinogens—HRs (group 2B) were often found in women with normal cytology (14.8%) and mild abnormalities (ASCUS and LSIL), but with lower frequence in HSIL/ASCH lesions (7.1%). HPVs 6 and 11(Group 3) were not found in the cases of HSIL/ASCH. Unclassified HPV types were equally distributed in all cytology groups: 20.7%, 19.1%, 16.3% and 13% of NILM, ASCUS, LSIL and HSIL/ASCH, respectively. Our findings highlight that majority of abnormal Pap test results are caused by Group 1 HPVs among women from our region. Low frequency HPVs of group 2A/2B, especially HSIL/ASCH, supports the conclusion that individual genotypes require consideration of each type as an individual agent. We expect a positive impact of HPV vaccine in reducing HPV-associated cervical lesions among women from Vojvodina province, after establishing vaccination programs in our country.

Unlike many traditional measures of centrality based onpathsthat do not allow any repeated nodes or lines, we propose a new measure of centrality based onwalks,walk-betweenness, that allows any number of repeated nodes or lines. To illustrate the value of walk-betweenness, we examine the transmission of syphilis in Chicago area and the diffusion of microfinance in 43 rural Indian villages. Walk-betweenness allows us to identify hidden bridging communities in Chicago that were essential in the transmission dynamics. We also find that village leaders with high walk-betweenness are more likely to accelerate the rate of microfinance take-up among their followers, outperforming other traditional centrality measures in regression analyses.

HIV care provides an opportunity to integrate comprehensive sexual and reproductive healthcare, including sexually transmitted infection (STI) management. We describe STI prevalence and correlates among men living with HIV (MLWH) accessing safer conception care to conceive a child with an HIV-uninfected partner while minimizing HIV transmission risks. This study reflects an ongoing safer conception program embedded within a regional referral hospital HIV clinic in southwestern Uganda. We enrolled MLWH, planning for pregnancy with an HIV-uninfected partner and accessing safer conception care. Participants completed interviewer-administered questionnaires detailing socio-demographics, gender dynamics, and sexual history. Participants also completed STI laboratory screening for syphilis (immunochromatographic testing confirmed by rapid plasma reagin), and chlamydia, gonorrhea, trichomoniasis, and HIV-RNA via GeneXpert nucleic acid amplification testing. Bivariable associations of STI covariates were assessed using Fisher’s exact test. Among the 50 men who completed STI screening, median age was 33 (IQR 31–37) years, 13/50 (26%) had ≥2 sexual partners in the prior three months, and 46/50 (92%) had HIV-RNA

Background A nonavalent human papillomavirus (HPV) vaccine has been licensed for use in women and men up to age 45 years in the United States. The cost-effectiveness of HPV vaccination for women and men aged 30 to 45 years in the context of cervical cancer screening practice was evaluated to inform national guidelines. Methods and findings We utilized 2 independent HPV microsimulation models to evaluate the cost-effectiveness of extending the upper age limit of HPV vaccination in women (from age 26 years) and men (from age 21 years) up to age 30, 35, 40, or 45 years. The models were empirically calibrated to reflect the burden of HPV and related cancers in the US population and used standardized inputs regarding historical and future vaccination uptake, vaccine efficacy, cervical cancer screening, and costs. Disease outcomes included cervical, anal, oropharyngeal, vulvar, vaginal, and penile cancers, as well as genital warts. Both models projected higher costs and greater health benefits as the upper age limit of HPV vaccination increased. Strategies of vaccinating females and males up to ages 30, 35, and 40 years were found to be less cost-effective than vaccinating up to age 45 years, which had an incremental cost-effectiveness ratio (ICER) greater than a commonly accepted upper threshold of $200,000 per quality-adjusted life year (QALY) gained. When including all HPV-related outcomes, the ICER for vaccinating up to age 45 years ranged from $315,700 to $440,600 per QALY gained. Assumptions regarding cervical screening compliance, vaccine costs, and the natural history of noncervical HPV-related cancers had major impacts on the cost-effectiveness of the vaccination strategies. Key limitations of the study were related to uncertainties in the data used to inform the models, including the timing of vaccine impact on noncervical cancers and vaccine efficacy at older ages. Conclusions Our results from 2 independent models suggest that HPV vaccination for adult women and men aged 30 to 45 years is unlikely to represent good value for money in the US., Jane Kim and co-workers estimate the potential cost-effectiveness of papillomavirus vaccination for adults aged 30-45 years in the United States., Author summary Why was this study done? Policies for increasing the upper age limit for human papillomavirus (HPV) vaccination to women and men up to age 45 years are being considered in several countries, but the public health value of such policies is uncertain. An important background consideration is to understand the impact and costs of HPV vaccination in the context of existing cervical cancer screening. This study was conducted to directly inform the deliberations of the Advisory Committee on Immunization Practices (ACIP) to guide HPV vaccination policy for women and men in the United States. What did the researchers do and find? Two modeling groups that are part of the Cancer Intervention and Surveillance Modeling Network (CISNET) used independent mathematical models calibrated to the US population to evaluate the cost-effectiveness of extending HPV vaccination in females and males up to ages 30, 35, 40, or 45 years. We conducted the analysis in the context of HPV transmission dynamics, historical HPV vaccination uptake, and detailed cervical cancer screening practice patterns in the US population. We evaluated cost and health outcomes of HPV vaccination up to age 45 years for cervical disease, as well as 6 other disease outcomes (5 noncervical HPV-related cancers and genital warts) in both women and men. Findings from both models suggest that at current prices, HPV vaccination beyond age 26 years is not cost-effective, even under a range of sensitivity analyses and favorable assumptions regarding HPV vaccination effectiveness and costs. What do these findings mean? HPV vaccination of women and men aged 30 to 45 years provides limited health benefit at the population level, at a substantial cost (at current HPV vaccine prices). Public health decision-makers considering the option to extend HPV vaccination to adults up to age 45 years should consider this evaluation of the value—and the opportunity costs—of adopting such a policy.

Introduction Streptococcus pneumoniae is a cause of infections that range in severity from acute otitis media (AOM) to pneumonia and invasive pneumococcal disease (IPD). The 10-valent pneumococcal conjugate vaccine (PHiD-CV10) was introduced into the Icelandic paediatric immunisation programme in 2011. The aim was to estimate the population impact and cost-effectiveness of PHiD-CV10 introduction. Methods Data on primary care visits from 2005–2015 and hospitalisations from 2005–2017 were obtained from population-based registries. A Bayesian time series analysis with synthetic controls was employed to estimate the number of cases of AOM, pneumonia and IPD that would have occurred between 2013–2017, had PHiD-CV10 not been introduced. Prevented cases were calculated by subtracting the observed number of cases from this estimate. The cost of the programme was calculated accounting for cost-savings due to prevented cases. Results The introduction of PHiD-CV10 prevented 13,767 (95% credible interval [CI] 2,511–29,410) visits for AOM from 2013–2015, and prevented 1,814 (95%CI -523-4,512) hospitalisations for pneumonia and 53 (95%CI -17-177) admissions for IPD from 2013–2017. Visits for AOM decreased both among young children and among children 4–19 years of age, with rate ratios between 0.72–0.89. Decreases were observed in both pneumonia hospitalisations (rate ratios between 0.67–0.92) and IPD (rate ratios between 0.27–0.94). The total cost of implementing PHiD-CV10 in Iceland was -7,463,176 United States Dollars (USD) (95%CI -16,159,551–582,135) with 2.1 USD (95%CI 0.2–4.7) saved for every 1 USD spent. Conclusions The introduction of PHiD-CV10 was associated with large decreases in visits and hospitalisations for infections commonly caused by pneumococcus and was cost-saving during the first five years of the immunisation programme.

As individual sexual behavior is variable over time, the timing of interventions might be vital to reducing HIV transmission. We aimed to investigate transitions between HIV risk levels among men who have sex with men (MSM), and identify determinants associated with behavior change. Participants in a longitudinal cohort study among HIV-negative MSM (Amsterdam Cohort Studies) completed questionnaires about their sexual behavior during biannual visits (2008–2017). Visits were assigned to different HIV risk levels, based on latent classes of behavior. We modelled transitions between risk levels, and identified determinants associated with these transitions at the visit preceding the transition using multi-state Markov models. Based on 7,865 visits of 767 participants, we classified three risk levels: low (73% of visits), medium (22%), and high risk (5%). For MSM at low risk, the six-month probability of increasing risk was 0.11. For MSM at medium risk, the probability of increasing to high risk was 0.08, while the probability of decreasing to low risk was 0.33. For MSM at high risk, the probability of decreasing risk was 0.43. Chemsex, erection stimulants and poppers, high HIV risk perception, and recent STI diagnosis were associated with increased risk at the next visit. High HIV risk perception and young age were associated with decreasing risk. Although the majority of MSM showed no behavior change, a considerable proportion increased HIV risk. Determinants associated with behavior change may help to identify MSM who are likely to increase risk in the near future and target interventions at these individuals, thereby reducing HIV transmission.

Bacterial sexually transmitted infections (STIs) continue to be a worsening public health concern in the United States (US). Though the national incidence of HIV infection has decreased over recent years, that of chlamydia, gonorrhea, and syphilis have not. Despite national recommendations on prevention, screening, and treatment of these STIs, these practices have not been standardized. Nine Health Resources and Services Administration Ryan White HIV/AIDS Program funded clinics across 3 US jurisdictions (Florida, Louisiana, and Washington, DC), were selected as clinical demonstration sites to be evaluated in this mixed method needs assessment to inform a multi-site, multi-level intervention to evaluate evidence-based interventions to improve STI screening and testing of bacterial STIs among people with or at risk for HIV. These 3 US jurisdictions were selected due to having higher than national average incidence rates of HIV and bacterial STIs. Descriptive statistics and deductive analysis were used to assess quantitative and qualitative needs assessment data. Results indicate the following needs across participating sites: inconsistent and irregular comprehensive sexual behavior history taking within and among sites, limited routine bacterial STI testing (once/year and if symptomatic) not in accordance with CDC recommendations, limited extragenital site gonorrhea/chlamydia testing, limited annual training on STI-related topics including LGBTQ health and adolescent/young adult sexual health, and limited efforts for making high-STI incidence individuals feel welcome in the clinic (primarily LGBTQ individuals and adolescents/young adults). These findings were used to identify interventions to be used to increase routine screenings and testing for bacterial STIs.

Background & aim Screening for genital infection (GI) such as bacterial vaginosis (BV) and yeast infection, for sexually transmitted infection (STI), and for asymptomatic carriage of group B streptococcus (GBS) in pregnant women are common reason for medical appointments. The diagnosis and control of GIs, STIs, and GBS are major issues, for fertility and overall well-being of affected women. Conventional testing is performed using vaginal/cervical classical sampling (VCS); this procedure requires pelvic examination performed by health care professionals which raises concerns among women. Vaginal-self-sampling (VSS), as an alternative to VCS, might capture more women. The aim was first to show non-inferiority of VSS compared with VCS to screen for GIs, STIs, and GBS; second to determine the feasibility of VSS. Methods VSS and VCS from 1027 women were collected by health care professionals and simultaneously carried out on each patient. GIs, STIs, and GBS were systematically screened in both paired VSS and VCS samples. Non-inferiority of VSS compared with VCS was assessed using z statistic for binomial proportions. Results Prevalence of GIs were 39.7% using VSS and 38.1% using VCS (p = 0.0016). Prevalence of STIs was 8.5% (VSS) vs 8.1% (VCS) (p = 0.0087). Prevalence of GBS was 13.4% (VSS) and 11.5% (VCS) (p = 0.0001). Most participants (84%) recommended the use of VSS. Conclusions This study shows that VSS was not inferior to VCS for the detection of GIs, STIs, and GBS. This study provides evidence that VSS can be used as a universal specimen for detection of lower genital tract infections in women. Study identification number ID-RCB 2014-A01250-4.

Introduction The continuum of care is a recommended framework for comprehensive health service delivery for maternal health, and it integrates health system and social determinants of health. There is a current lack of knowledge on a measurement approach to monitor performance on the framework. In this study we aim to develop and test a composite index for assessing the maternal health continuum in a province in South Africa with the possibility of nationwide use. Materials and methods The composite index was computed as a geometric mean of four dimensions of adequacy of the continuum of care. Data was sourced from the district health information system, household surveys and the census. The index formula was tested for robustness when alternative inputs for indicators and standardization methods were used. The index was used to assess performance in service delivery in the North West province of South Africa, as well as its four districts over a five-year period (2013–2017). The index was validated by assessing associations with maternal health and other outcomes. And factor analysis was used to assess the statistical dimensions of the index. Results The provincial level index score increased from 62.3 in 2013 to 74 in 2017, showing general improvement in service delivery over time. The district level scores also improved over time, and our analysis identified areas for performance improvement. These include social determinants of health in some districts, and access and linkages to care in others. The provincial index was correlated with institutional maternal mortality rates (rs = -0.90, 90% CI = (-1.00, -0.25)) and the Human Development Index (r = 0.97, 95% CI = (0.63, 0.99). It was robust to alternative approaches including z-score standardization of indicators. Factor analysis showed three groupings of indicators for the health system and social determinants of health. Conclusions This study demonstrated the development and testing of a composite index to monitor and assess service delivery on the continuum of care for maternal health. The index was shown to be robust and valid, and identified potential areas for service improvement. A contextualised version can be tested in other settings within and outside of South Africa.

Objective Since the recent introduction of preexposure prophylaxis (PrEP), several studies have reported a decrease in the use of condoms and a rise in STIs among users. This rise in risk behavior associated with the advent of PrEP is known as “risk compensation.” The aim of this study is to measure clinical and behavioral changes associated with the introduction of PrEP by analyzing condom use for anal intercourse, number of sexual partners, sexualized drug use and STI incidence. Methods We performed a retrospective descriptive study of PrEP users followed every 3months over a 2-year period spanning 2017–2019 in a referral clinic specializing in STI/HIV in Madrid, Spain. One hundred ten men who have sex with men and transgender women underwent regular screening for STIs and hepatitis C virus (HCV) infection. Sociodemographic, clinical, and behavioral data were gathered for all subjects studied. Results The risk compensation observed in this study consisted primarily of a lower rate of condom use, while the number of sexual partners and recreational drug consumption remained stable. We observed a very high incidence of STIs in this sample, particularly rectal gonorrhea and chlamydia. The factors shown to be independently associated with the presence of an STI on multivariate analysis were age below 30 years and over 10 sexual partners/month. Conclusion The incidence of STI acquisition was higher than expected, indicating a need for strategies to minimize this impact, particularly among younger individuals with a higher number of sexual partners.