Route Of Infection Research Articles

Knowledge, attitude, and practices towards hepatitis infection and its associated factors among adults in Gondar town, northwest Ethiopia; a community-based study, 2021

BackgroundHepatitis virus infection remains a serious public health concern worldwide. Percutaneous, mucosal, or non-intact skin exposure to infectious blood, semen, and other body fluids are the major routes of infection in endemic areas, including Ethiopia, where little is known about the community’s knowledge, attitudes, and practice toward hepatitis infection. Thus, this study aimed to determine the knowledge, attitude, and practices towards hepatitis infection among adults in Gondar town.MethodsA community-based cross-sectional study was conducted from July to August 2021 on a total of 390 participants. Proportional sample allocation was used in 3 randomly selected sub-cities. Then, study participants from randomly selected households were recruited by using a systematic random sampling technique. Socio-demographic data and questions regarding KAP were collected via a self-administered and interviewer-administered questionnaire. Statistical analysis was performed using SPSS version 20. Logistic regression analyses were used to identify the associated factors and a p-value < 0.05 was considered statistically significant.ResultsThe mean age of the study participants was 30 ± 8.43 years and more than half ½ (53.3%) ranged from 26 to 40 years old. In this study, 335 (85.9%) of study participants had poor knowledge about hepatitis infection. About 344 (88.2%) had a negative attitude toward hepatitis infections, and 344 (88.2%) of the participants had a poor practice to prevent hepatitis infections. Multivariate analysis affirmed that having vaccination for hepatitis infection was significantly associated with a positive attitude (AOR, with 95% CI: 2.135 (1.006–4.532) and good practice levels (AOR, with 95% CI: 22.623 (0.032–0.156).Conclusions and recommendationsIn this study majority of the participants have poor knowledge, attitudes, and practices toward hepatitis infection. Therefore, targeted community-based interventions are necessary. However, this study revealed that having vaccination for hepatitis infection was significantly associated with a positive attitude and good practice levels among the study participants.

Current Trends in HIV Infection in the Republic of Crimea

The aim of this study was to analyse the trends in HIV infection, including diagnostic ones, in the Republic of Crimea in the period of 2014–2023. The source of data for this study was various statistical forms and reports. The findings revealed a significant downward trend in HIV incidence and a significant upward trend in HIV prevalence. The mortality rate was stable. The coverage of HIV testing and antiretroviral therapy increased over time. The number of patients with a suppressed viral load in the Republic fluctuated in different years of observation and reached 81% in 2023. In the second part of this study, we analysed the demographic and clinical laboratory characteristics of newly diagnosed patients with HIV. A predominance of men was noted. The proportion of injection drug users (IDUs) decreased, and the proportion of new HIV infection cases through heterosexual contacts increased. An increase in the median age of patients was also noted. Analysis of CD4 cell counts revealed significant differences between subgroups by gender, age, and route of infection. The longest time to disease detection was typical for IDUs. A comprehensive assessment of HIV infection trends in Crimea allows us to evaluate the effectiveness of measures and decisions taken on the issue of HIV infection.

Olfactory and trigeminal routes of HSV-1 CNS infection with regional microglial heterogeneity.

Herpes simplex virus type 1 (HSV-1) primarily targets the oral and nasal epithelia before establishing latency in the trigeminal ganglion (TG) and other peripheral ganglia. HSV-1 can also infect and become latent in the central nervous system (CNS) independent of latency in the TGs. Recent studies suggest entry to the CNS via two distinct routes: the TG-brainstem connection and olfactory nerve; however, to date, there is no characterization of brain regions targeted during HSV-1 primary infection. Furthermore, the immune response by microglia may also contribute to the heterogeneity between different brain regions. However, the response to HSV-1 by microglia has not been characterized in a region-specific manner. This study investigated the time course of HSV-1 spread within the olfactory epithelium (OE) and CNS following intranasal inoculation and the corresponding macrophage/microglial response in a C57BL/6 mouse model. We found an apical to basal spread of HSV-1 within the OE and underlying tissue accompanied by an inflammatory response of macrophages. OE infection was followed by infection of a small subset of brain regions targeted by the TG in the brainstem and other cranial nerve nuclei, including the vagus and hypoglossal nerve. Furthermore, other brain regions were positive for HSV-1 antigens, such as the locus coeruleus (LC), raphe nucleus (RaN), and hypothalamus while sparing the hippocampus and cortex. Within each brain region, microglia activation also varied widely. These findings provide critical insights into the region-specific dissemination of HSV-1 within the CNS, elucidating potential mechanisms linking viral infection to neurological and neurodegenerative diseases.IMPORTANCEThis study shows how herpes simplex virus type 1 (HSV-1) spreads within the brain after infecting the nasal passages. Our data reveal the distinct pattern of HSV-1 through the brain during a non-encephalitic infection. Furthermore, microglial activation was also temporally and spatially specific, with some regions of the brain having sustained microglial activation even in the absence of viral antigens. Previous reports have identified specific brain regions found to be positive for HSV-1 infection; however, to date, there has not been a concise investigation of the anatomical spread of HSV-1 and the brain regions consistently vulnerable to viral entry and spread. Understanding these region-specific differences in infection and immune response is crucial because it links HSV-1 infection to potential triggers for neurological and neurodegenerative diseases.

Bipolar disorder in people with HIV: A nationwide, population-based matched case-control and matched cohort study.

To assess whether bipolar disorders are associated with the risk of HIV infection and whether the risk of bipolar disorders is increased among people with HIV (PWH) and their siblings. Nationwide, population-based, combined matched nested case-control and cohort study of PWH of Danish origin (1995-2021), a comparison cohort from the background population, matched on date of birth and sex, and sibling cohorts. Conditional logistic regression and Cox regression was used to calculate adjusted odds ratios (aORs) for HIV infection and hazard ratios (HRs) among PWH for bipolar disorder and receipt of lithium. We included 5322 PWH and 53,220 comparison cohort members. In the case-control study, bipolar disorder was associated with an increased risk of HIV infection (aOR: 1.9, 95% confidence interval (CI): 1.2-3.0), especially when injection drug use was the route of infection (aOR: 7.6, 95% CI: 2.0-28.9). In the cohort study, we observed an increased risk of bipolar disorders among PWH, especially in the first 2 years of observation (HR: 4.2, 95% CI: 2.4-7.4), whereas the risk of receipt of lithium was lower and the CI crossed 1. The 20-year risk of bipolar disorders for PWH was approximately 1%. Siblings of PWH also had an increased risk of bipolar disorder, but not to the same degree as PWH and not of receipt of lithium. Bipolar disorders are associated with the risk of HIV infection, and PWH have increased risk of bipolar disorder and receipt of lithium beyond what familial factors could explain.

Genetic Spatio-Temporal Analysis of Hepatitis D Virus Infection in Western Brazilian Amazon

The Brazilian Amazon region is a highly endemic area for hepatitis Delta and has areas that are difficult to access. Understanding the dynamics of HDV transmission in these remote locations is important for elucidating the routes of infection. To investigate this, a molecular analysis of HDV was conducted to assess the spatio-temporal dynamics of HDV cases. Between 2010 and 2023, 35 patients were recruited from the Viral Hepatitis Outpatient Clinic in Rondônia, Brazil. Conventional PCR was used to amplify the complete HDV genome followed by nucleotide sequencing via the Sanger method. The HDV genotype was determined using maximum likelihood phylogenetic reconstruction. A Skygrid coalescent approach with a Relaxed Random Walk phylogeographic model was used for the spatio-temporal analysis. Most individuals were males (21/35), with a median age of 39 years. HDV-3 was identified in all samples (35/35; 100%). The tMRCA was estimated to be 1824, with a substitution rate of 8.2 × 10−4 substitutions/site/year. The results suggest that HDV likely entered Brazil around 1820, in the state of Amazonas, subsequently spreading to Acre and Rondônia. Notable migration events were observed starting from 2010. This study suggests that HDV-3 has a complex evolutionary history spanning over two centuries, with intricate transmission routes in different locations in Brazil.

Knowledge, Attitude and Practice of Nurses and Midwives towards Hepatitis B Infection and Control Measures in Alban Gaded Hospital, Khartoum, Sudan

Purpose: Infection with the hepatitis B virus (HBV) causes severe morbidity and death, burdening world health. Nurses and midwives, among other healthcare professionals, are more likely to contract the illness. Few studies have looked at the knowledge, attitude, and practices (KAP) of healthcare professionals in Sudan with regard to HBV infection, despite the fact that diverse components of KAP have an impact on health-related behaviors. This study's objective was to assess the knowledge, attitude, and practice (KAP) level of nurses and midwives concerning HBV viral infection in, Khartoum, Sudan.  Methods: In the Sudanese state of Khartoum, a public hospital (Alban Gaded Hospital) underwent a cross-sectional descriptive hospital-based study. To assess KAP's understanding of nurses and midwives about HBV infection. Self-administered questionnaires were used and approved by the supervisor for distribution to the population chosen for the study. The data was handed over to the Medical Director whom personally ensured the questionnaires were signed and filled by the Healthcare workers (HCWs) of the chosen criteria at the field. A member of group (23:B) took care of the supervision aside with the medical director, and made sure the data was collected as needed. The data at hand were subjected to statistical analysis using SPSS version 24.0 (Statistical Package for Social Sciences).  Results: 95 samples out of 99 were collected. According to participants’ knowledge: 67.95% have good knowledge about HBV, while 32.05% lack basic knowledge about it. The participants’ attitude towards HBV is above average showing 60.3% safe attitude. Lastly, the study shows excellent practice of the participants’ behavior towards HBV safety measures with a score of 92.3% safe practice. From the hospital, a total of 95 out of 99 nurses and midwives took part in the study. Two thirds of the respondents practiced safety, and the majority of respondents had a positive attitude about HBV preventative measures. More than half of the respondents (58.2%) had an average level of understanding. A minor but serious score of (12.6%) was noticed of the individuals, dealing with patients without wearing gloves. More over half of the nurses and midwives were not vaccinated against HBV; more than 50% of participants had incorrect ideas regarding the symptoms and route of HBV infection and all 95 participants voted (NO) for ever being infected by HBV.  Conclusion: In Alban Gaded hospital, the majority of the nurses and midwives were aware of HBV infection. But a sizeable majority of the participants lacked the necessary understanding of early immunization after birth. The study found a probability of high risk infection due to exposure under the poor level of HBV vaccine coverage rate. Moreover a clear point of limitation was noticed in Table 4 third question, where it asks whether you are or ever was infected by HBV. All the participants denied, showing a sense of partiality. Further occupational exposure prevention measures, training programs on HBV infection, including post-exposure prophylaxis, and increasing the vaccination rate of all HCWS are also strongly encouraged.

Corynebacterium parakroppenstedtii secretes a novel glycolipid to promote the development of granulomatous lobular mastitis

Granulomatous lobular mastitis (GLM) is a chronic idiopathic granulomatous mastitis of the mammary gland characterized by significant pain and a high propensity for recurrence, the incidence rate has gradually increased, and has become a serious breast disease that should not be ignored. GLM is highly suspected relative to microbial infections, especially those of Corynebacterium species; however, the mechanisms involved are unclear, and prevention and treatment are difficult. In this study, we demonstrated the pathogenicity of Corynebacterium parakroppenstedtii in GLM using Koch’s postulates. Based on the drug sensitization results of C. parakroppenstedtii, and utilizing a retrospective study in conjunction with a comprehensive literature review, we suggested an efficacious, targeted antibiotic treatment strategy for GLM. Subsequently, we identified the pathogenic factor as a new type of glycolipid (named corynekropbactins) secreted by C. parakroppenstedtii. Corynekropbactins may chelate iron, cause the death of mammary cells and other mammary -gland-colonizing bacteria, and increase the levels of inflammatory cytokines. We further analyzed the prevalence of C. parakroppenstedtii infection in patients with GLM. Finally, we suggested that the lipophilicity of C. parakroppenstedtii may be associated with its infection route and proposed a possible model for the development of GLM. This research holds significant implications for the clinical diagnosis and therapeutic management of GLM, offering new insights into targeted treatment approaches.

PERFIL EPIDEMIOLÓGICO DOS CASOS DE HEPATITE C NA CIDADE MANAUS DE 2019 A 2023

Hepatitis is a multifactorial disease caused by viruses, drugs, alcohol, medications, or genetic, autoimmune, and metabolic conditions that cause inflammation in the liver. Among viral hepatitis, hepatitis C stands out, belonging to the Flaviviridae family, identified in patients with non-A and non-B hepatitis. Hepatitis C represents a major public health challenge, and can lead to serious complications, such as cirrhosis and liver carcinoma, in addition to causing systemic conditions, such as cryoglobulinemic vasculitis and chronic inflammation. The general objective of the research was to characterize the epidemiological profile of hepatitis C cases in the city of Manaus from 2019 to 2023. This is a cross-sectional descriptive epidemiological study, based on data from SINAN and the FVS-RCP Viral Hepatitis Monitoring Panel, involving 804 cases of hepatitis C reported in Manaus-AM between 2019 and 2023. Between 2019 and 2023, 804 cases of hepatitis C were recorded in Manaus, with variations over the years, with the highest percentage in 2019 (27%) and the lowest in 2020 (15%). There was a predominance of cases among men (54%) compared to women (46%). The most affected age group was 40 to 59 years old (42%), followed by people aged 60 and over (40%). The main route of infection identified was sexual transmission, responsible for 35% of cases, and deaths, which totaled 103, occurred mostly among men (74%). The strengthening of primary care and awareness campaigns are essential to contain the spread of hepatitis C. The data collected can guide the planning of specific public health actions in Manaus.

Development of bioluminescent Group B streptococcal strains for longitudinal infection studies.

Group B Streptococcus (GBS) remains the leading bacterial cause of invasive neonatal disease, resulting in substantial morbidity and mortality. New therapeutic approaches beyond antibacterial treatment to prevent neonatal disease outcomes are urgent. One significant limitation in studying GBS disease and progression is the lack of non-invasive technologies for longitudinal studies. Here, we develop and compare three bioluminescent GBS strains for in vivo pathogenic analysis. Bioluminescence is based on the luxABCDE operon on a replicative vector (luxGBS-CC17), and the red-shifted firefly luciferase on a replicative vector (fflucGBS-CC17) or integrated in the genome (glucGBS-CC17). We show that luxGBS-CC17 is suitable for in vitro analysis but does not produce a significant bioluminescent signal in infected pups. In contrast, the fflucGBS-CC17 results in a strong bioluminescent signal proportional to the organ colonisation level. However, the stability of the replicative vector depends on the route of infection, especially when pups acquire the bacteria from infected vaginal mucosa. Stable chromosomal integration of luciferase in glucGBS-CC17 leads to significant bioluminescence in both haematological and vertical infection models associated with high systemic colonisation. These strains will allow the preclinical evaluation of treatment efficacy against GBS invasive disease using whole-mouse bioluminescence imaging.

Brucellosis Coinfecting with Liver Hydatid Cyst: Case Report and Literature Review of Zoonoses Coinfection of Human Brucellosis.

Background: Brucellosis is a major global public health problem. Brucellosis usually coinfects with zoonoses because of their similar reservoir and infection routes. Materials and Methods: Here, we present a patient who was diagnosed with coinfecting with liver cyst and brucellosis. Results: A 57-year-old female farmer was hospitalized with right hip joint pain approximately 4 weeks earlier. The patient reported a history of hydatid cysts and a family history of brucellosis. Abdominal computerized tomography and ultrasonography revealed a liver hydatid cyst. The standard agglutination test titer of Wright's test was 1:100. Computerized tomography and magnetic resonance imaging revealed brucellosis hip arthritis. The patient was treated with a combination of doxycycline, rifampicin, and cefotaxime. The symptoms immediately improved. The patient was well and asymptomatic during the 6-month follow-up. We reviewed the literature on other zoonoses superinfection with brucellosis. Conclusion: Brucellosis coinfects with multiple zoonosis organisms and poses a serious health threat to humans. Awareness of possible brucellosis coinfection with other zoonoses, especially professionally exposed persons in endemic regions, is warranted.

A genome-wide association study of adults with community-acquired pneumonia

BackgroundCommunity-acquired pneumonia (CAP) is associated with high morbidity and hospitalization rate. In infectious diseases, host genetics plays a critical role in susceptibility and immune response, and the immune pathways involved are highly dependent on the microorganism and its route of infection. Here we aimed to identify genetic risk loci for CAP using a case-control genome-wide association study (GWAS).MethodsWe performed a GWAS on 3,765 Spanish individuals, including 257 adult patients hospitalized with CAP and 3,508 population controls. Pneumococcal CAP was documented in 30% of patients; the remaining 70% were selected among patients with unidentified microbiological etiology. We tested 7,6 million imputed genotypes using logistic regressions. UK Biobank GWAS of bacterial pneumonia were used for results validation. Subsequently, we prioritized genes and likely causal variants based on Bayesian fine mapping and functional evidence. Imputation and association of classical HLA alleles and amino acids were also conducted.ResultsSix independent sentinel variants reached the genome-wide significance (p < 5 × 10-8), three on chromosome 6p21.32, and one for each of the chromosomes 4q28.2, 11p12, and 20q11.22. Only one variant at 6p21.32 was validated in independent GWAS of bacterial and pneumococcal pneumonia. Our analyses prioritized C4orf33 on 4q28.2, TAPBP on 6p21.32, and ZNF341 on 20q11.22. Interestingly, genetic defects of TAPBP and ZNF341 are previously known inborn errors of immunity predisposing to bacterial pneumonia, including pneumococcus and Haemophilus influenzae. Associations were all non-significant for the classical HLA alleles.ConclusionsWe completed a GWAS of CAP and identified four novel risk loci involved in CAP susceptibility.

Dairy cows inoculated with highly pathogenic avian influenza virus H5N1.

Highly pathogenic avian influenza (HPAI) H5N1 hemagglutinin clade 2.3.4.4b was detected in the United States in 2021. These HPAI viruses caused mortality events in poultry, wild birds, and wild mammals. On March 25, 2024, HPAI H5N1 clade 2.3.4.4b was confirmed in a dairy cow in Texas in response to a multi-state investigation into milk production losses.1 Over 200 positive herds were identified in 14 U.S. states. The case description included reduced feed intake and rumen motility in lactating cows, decreased milk production, and thick yellow milk.2,3 The diagnostic investigation revealed viral RNA in milk and mammary tissue with alveolar epithelial degeneration and necrosis and positive immunoreactivity of glandular epithelium. A single transmission event, likely from birds, was followed by limited local transmission and onward horizontal transmission of H5N1 clade 2.3.4.4b genotype B3.13.4 We sought to experimentally reproduce infection with genotype B3.13 in Holstein yearling heifers and lactating cows. Heifers were inoculated by aerosol respiratory route and cows by intramammary route. Clinical disease was mild in heifers, but infection was confirmed by virus detection, lesions, and seroconversion. Clinical disease in lactating cows included decreased rumen motility, changes to milk appearance, and production losses. Infection was confirmed by high levels of viral RNA detected in milk, virus isolation, lesions in mammary tissue, and seroconversion. This study provides the foundation to investigate additional routes of infection, pathogenesis, transmission, and intervention strategies.

Coxiella burnetii Nine Mile phase I primary infection derived protective immunity against C. burnetii reinfection in mice depends on both B and T cells, but T cells play a critical role.

Coxiella burnetii is an obligate intracellular Gram-negative bacterium that causes acute and chronic Q fever in humans. Acute Q fever is usually a flu-like, self-limiting or treatable illness, but some infections can turn into a severe and sometimes fatal chronic disease. There is currently no FDA-approved vaccine available for the prevention of human Q fever in the US, development of a safe and effective vaccine for the prevention of human Q fever remains an important goal for public health. However, there is a fundamental gap in knowledge regarding the mechanism of protective immunity against C. burnetii infection. To understand the mechanism of C. burnetii infection induced protective immunity, we examined if C. burnetii Nine Mile phase I (NMI) infection induces protection against C. burnetii reinfection in mice. Our results indicate that NMI-infected mice conferred significant protection against C. burnetii reinfection. We also found that NMI infection derived protection did not depend on the routes of infection and antibodies are required for NMI infection derived protection. In addition, NMI infection elicited a comparable level of protection in Wild type, CD4+ T cell deficient, and CD8+ T cell deficient mice, partial protection in B cell deficient mice but no protection in T cell deficient mice. These results suggest that both B cells and T cells are required for NMI-infection derived protection, but T cells may play a critical role. Therefore, the new generation vaccine for the prevention of human Q fever should be focused on boosting both humoral and T cell immune responses.

Tenacibaculum maritimum can boost inflammation in Dicentrarchus labrax upon peritoneal injection but cannot trigger tenacibaculosis disease.

Despite being a bacterial pathogen with devastating consequences, Tenacibaculum maritimum's pathogenesis is not fully understood. The aim of the present study was to elucidate if different inoculation routes (intraperitoneal - i.p - injection and bath challenge - known to induce mortality) can induce tenacibaculosis (i.e., using the same T. maritimum inoculum), as well as evaluate the short-term immune response of European sea bass (D. labrax). Additionally, the host response against i.p. injection of extracellular products (ECPs) was also studied. Fish were i.p. challenged with 5.5 × 105 CFU mL-1 of T. maritimum cells with or without ECPs (BECPs and BWO, respectively), ECPs alone or marine broth (mock). Another group of fish was bath-challenged with 5.5 × 105 CFU mL-1 to confirm the virulence of the bacterial inoculum. Undisturbed specimens were used as controls. The severity of both challenges was determined by following percentage survival. Blood, liver and head-kidney samples were collected at 0, 3, 6, 24 and 48h post-challenge for assessing immune parameters, oxidative stress and gene expression. Total and differential peritoneal cell counts were performed. The presence of viable bacteria in the blood and peritoneal cavity was studied. Symptoms of tenacibaculosis, such as skin/fin abrasions, were only observed in the bath-challenged fish, where 0% survival was recorded, whereas 100% survival was observed after i.p. injection of the same bacterial inoculum. An increase in total leukocyte numbers in the peritoneal cavity was observed 3h post-injection of BECPs when compared to the other treatments. Blood total leukocytes, lymphocytes, and thrombocyte numbers dropped after the challenge, mainly in fish challenged with BECPs. At 48h post-challenge, bactericidal activity in the plasma increased in fish injected with bacteria (with and without ECPs). The same tendency was seen for some of the oxidative stress parameters. The increased expression of il1β, il6, il8, and hamp1 in fish challenged with ECPs and BECPs suggests a more exacerbated pro-inflammatory response in the head-kidney against these inocula. The infection trial and the observed immune responses showed that the infection route is a determinant factor regarding T. maritimum-induced pathogenesis in European sea bass.

Functional genomics screens reveal a role for TBC1D24 and SV2B in antibody-dependent enhancement of dengue virus infection.

Under some conditions, dengue virus (DENV) can hijack IgG antibodies to facilitate its uptake into target cells expressing Fc gamma receptors (FcgR)-a process known as antibody-dependent enhancement (ADE) of infection. Beyond a requirement for FcgR, host dependency factors for this unusual IgG-mediated infection route remain unknown. To identify cellular factors exclusively required for ADE, here, we performed CRISPR knockout (KO) screens in an in vitro system poorly permissive to infection in the absence of IgG antibodies. Validating our approach, a top hit was FcgRIIa, which facilitates the binding and internalization of IgG-bound DENV but is not required for canonical infection. Additionally, we identified host factors with no previously described role in DENV infection, including TBC1D24 and SV2B, which have known functions in regulated secretion. Using genetic knockout and trans-complemented cells, we validated a functional requirement for these host factors in ADE assays performed with monoclonal antibodies and polyclonal sera in multiple cell lines and using all four DENV serotypes. We show that knockout of TBC1D24 or SV2B impaired the binding of IgG-DENV complexes to cells without affecting FcgRIIa expression levels. Thus, we identify cellular factors beyond FcgR that promote efficient ADE of DENV infection. Our findings represent a first step toward advancing fundamental knowledge behind the biology of a non-canonical infection route implicated in disease.IMPORTANCEAntibodies can paradoxically enhance rather than inhibit dengue virus (DENV) infection in some cases. To advance knowledge of the functional requirements of antibody-dependent enhancement (ADE) of infection beyond existing descriptive studies, we performed a genome-scale CRISPR knockout (KO) screen in an optimized in vitro system permissive to efficient DENV infection only in the presence of IgG. In addition to FcgRIIa, a known receptor that facilitates IgG-mediated uptake of IgG-bound, but not naked DENV particles, our screens identified TBC1D24 and SV2B, cellular factors with no known role in DENV infection. We validated a functional role for TBC1D24 and SV2B in mediating ADE of all four DENV serotypes in different cell lines and using various antibodies. Thus, we identify cellular factors beyond Fc gamma receptors that promote ADE mechanisms. This study represents a first step toward advancing fundamental knowledge beyond a poorly understood non-canonical viral entry mechanism.

Shengji ointment combined with bromelain promotes granulation of exposed tendons in diabetic foot ulcers: a multicenter, randomized, positive-controlled clinical trial

BackgroundExposed, infected and necrotic tendons often occur in the middle and late stages of diabetic foot ulcers (DFUs). The exposed tendon is both a potential source and route of infection, which prolongs the treatment period and affects recovery, leading to amputation and even death. Therefore, management of the exposed tendon in patients with DFU is the key to treatment. This study aimed to evaluate the clinical efficacy of Shengji ointment combined with bromelain in the treatment of DFU with tendon exposure and to provide clinical treatment options and evidence-based medicine. MethodsThis study was a multicenter, nonblinded, randomized, positive controlled clinical trial involving 180 patients with DFU with tendon exposure at five tertiary-grade A-class hospitals. The included patients were randomly assigned 1:1 to an observation group (n=90) that received Shengji ointment combined with bromelain and a control group (n=90) that received hydrocolloid dressing, with dressing changes once daily for 4 weeks. Patients in both groups continued with conventional treatments, such as blood glucose and blood pressure medication, lipid regulation, and antiplatelets. The primary outcome measure was wound coverage with granulation tissue. The secondary outcome measures included the wound healing rate, time to granulation, Maryland foot score, time to debridement of necrotic tendon tissue, and granulation tissue score. We performed measurements before enrollment and after the end of treatment for comparison. ResultsThere was no significant difference in the baseline data between the two groups before treatment (P > 0.05). After treatment, the primary outcome indicators of the two groups were compared, and the wound granulation tissue coverage rate of the treatment group was greater than that of the control group (P = 0.003). For the secondary outcome outcomes, the wound healing rate, time to granulation, Maryland foot function score, time to debridement of necrotic tendon tissue, and granulation tissue score in the treatment group were significantly better than those in the control group (P < 0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P = 0.444). ConclusionsShengji ointment combined with bromelain effectively promotes the removal of exposed necrotic tendons in patients with DFU, promotes the regeneration of healthy granulation tissue, accelerates wound healing, and protects the limb and its function. It also appears to be safe as an intervention for the treatment of patients with DFU. Trial registrationThe study protocol was registered in the Chinese Clinical Trial Registry (ChiCTR) under the code ChiCTR2000039327 on 23/10/2020. The public title is “Study on evidence-based evaluation and therapeutic mechanism of integrated Chinese and Western medicine for treatment of diabetic foot - An evidence-based evaluation of The combination of Rubber Shengji Paste and compound bromelain to promote the healing of the exposed wound of diabetic foot tendon”.

Inter and Intraserotype Variations of Streptococcus Pneumoniae Pathogenicity in Mice and Rabbits

The small mammalian labratory animals, the mice and the rabbits were tempted to be pathogenicity models for S. pneumoniae serotypes 1 and 6, the infecting doses were 0.3ml for mice and 0.5 ml for rabbits. These infectious doses were rated to a count of 1X 10 to 7 CFU/ml. The infection routes were intrapreritoneal for mice and intranasal for rabbits. The gold standard criteria for pathogenicity were the death end point DEP.DEP was up to 24hr for mice and ranged from four to 14 days in rabbits. Mice was more susciptable than rabbits for S. pneumoniae serotypes infections. Autopsy cultures of blood, lungs, liver and kideys were producing same infecting serotype both from mice and rabbits. This isolation profile was indicating bacterimic state induced by infection. Different serotypes have shown different death end points duration time. There were inter and intraserotype variations in DEP. Moderate to severe respiratory disease conditions RDC was noted in mice while mild RDC in rabbits. Both of the tested models were similar lung histology to man. The histological features of this experimental infections have shown that the infected mice and rabbits were of bronchopneumonia type. It appears that both mice and rabbits were standing as valid laboratory animal models for these local clinical isolates of S. pneumoniae serotypes.

Olfactory and Trigeminal Routes of HSV-1 CNS Infection with Regional Microglial Heterogeneity.

This study sheds light on how herpes simplex virus type 1 (HSV-1) spreads within the brain after infecting the nasal passages. Our data reveals the distinct pattern of HSV-1 through the brain during a non-encephalitic infection. Furthermore, microglial activation was also temporally and spatially specific, with some regions of the brain having sustained microglial activation even in the absence of viral antigen. Previous reports have identified specific regions of the brain found to be positive for HSV-1 infection; however, to date, there has not been a concise investigation of the anatomical spread of HSV-1 and the regions of the brain consistently vulnerable to viral entry and spread. Understanding these region-specific differences in infection and immune response is crucial because it links HSV-1 infection to potential triggers for neurological and neurodegenerative diseases.

Infection route influence the consequences of Nocardia farcinica infection in BALB/c mice

BackgroundNocardia, a rare but potentially fatal pathogen, can induce systemic infections with diverse manifestations. This study aimed to investigate the tissue and organ damage caused by Nocardia farcinica (N. farcinica) in mice via different infection routes, evaluate the resulting host immune responses, and assess its invasiveness in brain tissue.MethodsBALB/c mice were infected with N. farcinica through intranasal, intraperitoneal, and intravenous routes (doses: 1 × 10^8, 1 × 10^7, 1 × 10^7 CFU in 50 µl PBS). Over a 7-day period, body temperature, weight, and mortality were monitored, and samples were collected for histopathological analysis and bacterial load assessment. Serum was isolated for cytokine detection via ELISA. For RNA-seq analysis, mice were infected with 1 × 107 CFU through three infection routes, after which brain tissue was harvested.ResultsIntraperitoneal and intravenous N. farcinica infections caused significant clinical symptoms, mortality, and neural disruption in mice, resulting in severe systemic infection. Conversely, intranasal infection primarily affected the lungs without causing significant damage to other organs. Intraperitoneal and intravenous infections significantly increased serum cytokines, particularly TNF-α and IFN-γ. RNA-seq analysis of brains from intravenously infected mice revealed significant differential gene expression, whereas the intranasal and intraperitoneal routes showed limited differences (only three genes). The enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in the intravenous group were primarily related to immune processes.ConclusionThe study demonstrated that intravenous N. farcinica infection induces significant clinical symptoms, triggers an inflammatory response, damages multiple organs, and leads to systemic infections.

Incidence of mother-to-child transmission of HIV and predictors of positivity among HIV exposed infants in South Gondar public hospitals, Northwest Ethiopia: competing risk regression model

BackgroundThe principal route of HIV infection in children is vertical transmission. Thus, this study aimed to assess the incidence of mother-to-child transmission of HIV and predictors of positivity among HIV-exposed infants.MethodInstitutions-based retrospective follow-up study was conducted in South Gondar Public hospitals, Northwest Ethiopia from December 2019 to November 2021. The data were taken from PMTCT logbooks and patient medical records, with death being the competing event. Data were entered in to Epi info version 7 and exported to STATA version 14 for final analysis. Both bivariable and multiple variable proportional subdistribution hazard analysis were conducted to identify predictors. P-value < 0.05 was level of significance.ResultA total of 469 exposed infant mother pairs records were included. The cumulative incidence rate at the end of the study period was 5.2 per 1000 person months (5.2; 95% CI: 3.4-8.0).Infants’ absence of ARV prophylaxis at birth (aSHR = 3.7; 95% CI: 1.33–10.48), Mothers with no PMTCT intervention (aSHR = 5.1; 95% CI: 1.83–14.03), home delivery (aSHR = 4.1; 95%CI: 1.46–11.63) and maternal disclosure of HIV status to partner/families (aSHR = 2.9; 95% CI: 1.06–7.78) were predictors of HIV positivity.ConclusionThe study found that Infants’ absence of ARV prophylaxis at birth, mothers without PMTCT intervention, home delivery and mothers who were not disclosing their HIV status to families were predictors of HIV positivity.