Prevalence of persistent SARS-CoV-2 in a large community surveillance study.

Persistent SARS-CoV-2 infections may act as viral reservoirs that could seed future outbreaks1-5, give rise to highly divergent lineages6-8 and contribute to cases with post-acute COVID-19 sequelae (long COVID)9,10. However, the population prevalence of persistent infections, their viral load kinetics and evolutionary dynamics over the course of infections remain largely unknown. Here, using viral sequence data collected as part of a national infection survey, we identified 381 individuals with SARS-CoV-2 RNA at high titre persisting for at least 30 days, of which 54 had viral RNA persisting at least 60 days. We refer to these as 'persistent infections' as available evidence suggests that they represent ongoing viral replication, although the persistence of non-replicating RNA cannot be ruled out in all. Individuals with persistent infection had more than 50% higher odds of self-reporting long COVID than individuals with non-persistent infection. We estimate that 0.1-0.5% of infections may become persistent with typically rebounding high viral loads and last for at least 60 days. In some individuals, we identified many viral amino acid substitutions, indicating periods of strong positive selection, whereas others had no consensus change in the sequences for prolonged periods, consistent with weak selection. Substitutions included mutations that are lineage defining for SARS-CoV-2 variants, at target sites for monoclonal antibodies and/or are commonly found in immunocompromised people11-14. This work has profound implications for understanding and characterizing SARS-CoV-2 infection, epidemiology and evolution.

Chronic wound isolates and their minimum inhibitory concentrations against third generation cephalosporins at a tertiary hospital in Uganda.

Globally, the burden of chronic wound infections is likely to increase due to the rising levels of bacterial resistance to antibiotics. In the United States of America alone, more than 6.5 million chronic wounds with evidence of bacterial infection are diagnosed every year. In addition, the polymicrobial environment in chronic wound infections has been observed from several studies as a risk factor for development of resistance to many antibiotics including the third generation cephalosporins currently used in Mbarara Regional Referral Hospital for treatment of chronic wound infections. Therefore the main objective of this study was to determine the prevalence of chronic wound isolates and their minimum inhibitory concentrations (MIC) against third generation cephalosporins. This study was a cross-sectional descriptive and analytical survey of bacterial isolates from chronic wound infection among 75 study participants admitted in the surgical ward of Mbarara Regional Referral Hospital (MRRH), a tertiary Hospital in Western Uganda. Standard laboratory bacterial culture and identification techniques as well as broth microdilution method were used to isolate, identify pathogens and test for MIC respectively. We found that 69/75 study participants had samples with bacterial growth and the most prevalent pathogens isolated were staphylococcus aureus (40.6%) and Klebsiella spp. (29%). Generally, most isolates were susceptible to cefoperazone + sulbactum 2 g (Sulcef) and ceftriaxone 1 g (Epicephin). The overall prevalence of isolates in chronic wound infection among patients admitted in the surgical ward of MRRH was 92% and the most prevalent isolates were Staphylococcus aureus, Klebsiella species and proteus species respectively. The observed MIC values were higher than the CLSI clinical breakpoint, implying a decreasing trend in susceptibility of chronic wound isolates to third generation cephalosporins.

Persistent Plasmodium falciparum infections enhance transmission-reducing immunity development.

Subclinical infections that serve as reservoir populations to drive transmission remain a hurdle to malaria control. Data on infection dynamics in a geographical area is required to strategically design and implement malaria interventions. In a longitudinal cohort, we monitored Plasmodium falciparum infection prevalence and persistence, and anti-parasite immunity to gametocyte and asexual antigens for 10 weeks. Of the 100 participants, only 11 were never infected, whilst 16 had persistent infections detected by reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR), and one participant had microscopic parasites at all visits. Over 70% of the participants were infected three or more times, and submicroscopic gametocyte prevalence was high, ≥ 48% of the parasite carriers. Naturally induced responses against recombinant Pfs48/45.6C, Pfs230proC, and EBA175RIII-V antigens were not associated with either infection status or gametocyte carriage, but the antigen-specific IgG titers inversely correlated with parasite and gametocyte densities consistent with partial immunity. Longitudinal analysis of gametocyte diversity indicated at least four distinct clones circulated throughout the study period. The high prevalence of children infected with distinct gametocyte clones coupled with marked variation in infection status at the individual level suggests ongoing transmission and should be targeted in malaria control programs.

Development and Validation of a Tool for the Prediction of Vancomycin-Resistant Enterococci Colonization Persistence-the PREVENT Score.

Vancomycin-resistant enterococci (VRE) are nosocomial pathogens with increasing prevalence worldwide. Extensive hygiene measures have been established to prevent infection transmission in hospitals. Here, we developed a predictive score system (the predictive vancomycin-resistant enterococci [PREVENT] score) to identify the clearance or persistence in patients with a history of VRE carrier status at readmission. Over a cumulative 3-year period, patients with a positive VRE carrier status were included. The study population was recruited in two successive time periods and separated into training data for predictive score development and validation data for evaluation of the predictive power. The risk factors for persistent VRE colonization were analyzed in a univariable analysis before development of a logistic regression model based on the potential risk factors. The score points were determined proportionally to the beta coefficients of the logistic regression model. The data from 448 (79%) patients were used as the training data, and those from 119 (21%) as the validation data. Multivariable analysis revealed the following variables as independent risk factors: age of ≥60 years, hemato-oncological disease, cumulative antibiotic treatment for >4 weeks, and a VRE infection. The resulting logistic regression model exhibited an acceptable area under the curve (AUC) of 0.81 (95% confidence interval [CI], 0.72 to 0.91). The predictive score system had a sensitivity of 82% (95% CI, 65 to 93%) and a specificity of 77% (95% CI, 66 to 85%). The developed predictive score system is a useful tool to assess the VRE carrier status of patients with a history of VRE colonization. On the basis of this risk assessment, more focused and cost-effective infection control measures can be implemented. IMPORTANCE Given the increasing relevance of VRE as nosocomial pathogens worldwide, infection prevention and control measures, including patient isolation and contact precautions, are indispensable to avoid their spread in the hospital setting. In this study, we developed and validated the PREVENT score, a tool for rapid risk assessment of VRE persistence in patients with a history of previous VRE colonization. The score is designed to be easily performed, employing clinical information available in a regular admission setting and immediately providing information to inform the decision of whether to adopt patient isolation and contact precautions during the hospital stay. After validation, the score was shown to accurately identify patients with persistent VRE colonization upon admission, representing a suitable option as (i) a complementary method yielding preliminary results significantly more quickly than culture-based VRE detection techniques and (ii) an alternative strategy for VRE detection in settings in which microbiological VRE screening is not routinely performed due to limited resources.

Persistent Helicobacter pylori infection for more than 3 years leads to elevated serum homocysteine concentration: A retrospective cohort study based on a healthy Chinese population.

BACKGROUND AND AIM: The relationship between the Helicobacter pylori (H. pylori) infection and homocysteine is unclear. We evaluated the effect of H. pylori on serum homocysteine in a healthy Chinese population. METHODS: A total of 21 184 individuals aged over 18 years underwent 13 C/14 C urease breath test (13 C/14 C-UBT) and blood tests and 5042 individuals with follow-up intervals greater than 6 months. Homocysteine levels are classified according to the Chinese expert consensus. RESULTS: The rates of H. pylori infection of normal level, mild level, moderate level, and severe level were 40.9%, 43.8%, 45.8%, and 46.6%, respectively (P = 0.000). H. pylori infection increased the risk of higher homocysteine concentration (OR = 1.406, P = 0.000). In the case-control study, the rates of persistent negative, new infection, persistent infection, and eradication infection were 43.6%, 11.2%, 22.9%, and 22.3%, respectively. The percentage of changes in serum homocysteine levels varied significantly among the different H. pylori infection statuses only in mild level (P = 0.024). Mean changed homocysteine values were higher in the subgroup of persistent infection than in the persistent negative subgroup (P = 0.004) and the eradication infection subgroup (P = 0.034). Serum homocysteine values were elevated only in the subgroup with over 3 years interval time and persistent infection (n = 107, mean paired differences = 1.1 ± 4.6 µmol/L, P = 0.014). CONCLUSIONS: There is a relationship between H. pylori and serum homocysteine, and persistent infection leads to elevation of the latter.

Male Circumcision Reduces Penile HPV Incidence and Persistence: A Randomized Controlled Trial in Kenya.

BACKGROUND: Male circumcision reduces the risk of human immunodeficiency virus infection in men. We assessed the effect of male circumcision on the incidence and natural history of human papillomavirus (HPV) in a randomized clinical trial in Kisumu, Kenya. METHODS: Sexually active, 18- to 24-year-old men provided penile exfoliated cells for HPV DNA testing every 6 months for 2 years. HPV DNA was detected via GP5+/6+ PCR in glans/coronal sulcus and in shaft samples. HPV incidence and persistence were assessed by intent-to-treat analyses. RESULTS: A total of 2,193 men participated (1,096 randomized to circumcision; 1,097 controls). HPV prevalence was 50% at baseline for both groups and dropped to 23.7% at 24 months in the circumcision group, and 41.0% in control group. Incident infection of any HPV type over 24 months was lower among men in the circumcision group than in the control group [HR = 0.61; 95% confidence interval (CI), 0.52-0.72]. Clearance rate of any HPV infection over 24 months was higher in the circumcision group than in the control group (HR = 1.87; 95% CI, 1.49-2.34). Lower HPV point-prevalence, lower HPV incidence, and higher HPV clearance in the circumcision group were observed in glans but not in shaft samples. CONCLUSION: Male circumcision reduced the risk of HPV acquisition and reinfection, and increased HPV clearance in the glans. IMPACT: Providing voluntary, safe, and affordable male circumcision should help reduce HPV infections in men, and consequently, HPV-associated disease in their partners.