Antibiotic Prescribing in Dental Medicine-Best Practices for Successful Implementation.

With rising rates of antimicrobial resistance throughout the world, it is time to revisit antibiotic prescribing policies and practices, and dentistry is an important area for focused intervention, as it accounts for up to 15% of all antimicrobial prescriptions. In this narrative review, we have analyzed the current state of the knowledge, attitudes, and practice regarding antimicrobial use among dental professionals, and we have identified a set of seven recurring themes that drive inappropriate antibiotic prescribing in dental medicine. These include: 1. Prescribing antibiotics to delay or avoid dental treatment. 2. Overlooking the 5Ds-dental treatment (source control), dental condition (indication), drug (antibiotic choice), dose, and duration. 3. Relying on education from the distant past and on previous experience. 4. The heterogeneity of (too many) guideline recommendations leads to confusion and over-prescribing. 5. Decreased access to guideline information in private practice. 6. Psychological factors such as pressure to prescribe, comfort prescribing and the weekend effect, and 7. Feeling removed from antimicrobial resistance and externalizing responsibility. Based on the existing knowledge, we propose a framework based on four key pillars for focused intervention: 1. Education. 2. Internalizing responsibility. 3. Recognizing recurring counter-productive practices, and 4. Addressing recurring counter-productive practices. This framework can be applied in different dental settings to ensure best practices for the successful implementation of rational antimicrobial prescribing.

Exposure to Biological Fluids in Dental Practice-Narrative Review on Appropriate Risk Assessment to Guide Post-Exposure Management.

Accidental exposure to blood or other biological fluids is a common occurrence in dentistry, and its post-exposure management is a key component of infection prevention and control programs designed to prevent the transmission of blood-borne pathogens such as hepatitis B and C viruses (HBV, HCV) and human immunodeficiency virus (HIV). This narrative review aims to comprehensively review the risk assessment process for each of these pathogens at all steps of the epidemiological process, i.e., source-exposure route-receptive person, in order to provide a better understanding of the delicate differences that influence the transmission risk and that drive the individualized post-exposure management.

Acute severe hepatitis outbreak in children: A perfect storm. What do we know, and what questions remain?

During the first half of 2022, the World Health Organization reported an outbreak of acute severe hepatitis of unknown aetiology (AS-Hep-UA) in children, following initial alerts from the United Kingdom (UK) where a cluster of cases was first observed in previously well children aged <6 years. Sporadic cases were then reported across Europe and worldwide, although in most countries incidence did not increase above the expected baseline. There were no consistent epidemiological links between cases, and microbiological investigations ruled out known infectious causes of hepatitis. In this review, we explore the evidence for the role of viral infection, superimposed on a specific host genetic background, as a trigger for liver pathology. This hypothesis is based on a high prevalence of Human Adenovirus (HAdV) 41F in affected children, together with metagenomic evidence of adeno-associated virus (Adeno-associated viruses)-2, which is a putative trigger for an immune-mediated liver injury. Roles for superantigen-mediated pathology have also been explored, with a focus on the potential contribution of SARS-CoV-2 infection. Affected children also had a high frequency of the MHC allele HLA-DRB1*04:01, supporting an immunological predisposition, and may have been vulnerable to viral coinfections due to disruption in normal patterns of exposure and immunity as a result of population lockdowns during the COVID-19 pandemic. We discuss areas of ongoing uncertainty, and highlight the need for ongoing scrutiny to inform clinical and public health interventions for this outbreak and for others that may evolve in future.

Hepatitis of Unknown Origin and Etiology (Acute Non HepA-E Hepatitis) among Children in 2021/2022: Review of the Current Findings.

Several clusters and individual cases of acute hepatitis have been reported in the US, Europe and recently in Asia and Central America since October 2021. A laboratory investigation of the common viral hepatitis agents (HAV, HBV, HCV, HDV and HEV) yielded negative results prompting the use of the term "acute non HepA-E hepatitis" to describe this condition. The cases were characterized by the manifestations of acute hepatitis (abdominal pain, vomiting, diarrhea, jaundice and very high levels of liver enzymes) affecting children with a median age of 3-4 years. The exact underlying etiology has not been revealed yet; however, a leading hypothesis is that an infectious agent is the culprit, underlying cause or a risk factor for acute non HepA-E hepatitis occurrence. So far, laboratory testing has shown the presence of the group F human adenovirus serotype 41 (HAdV-F41) in about three-fourths of the investigated cases. As of 13 May 2022, more than 450 cases were reported worldwide, the majority of which were in the UK (n = 176), the US (n = 109), 13 European countries (at least 103 cases) and in Argentina, Brazil, Canada, Costa Rica, Indonesia, Israel, Japan, Palestine, Panama, Singapore and South Korea. Vigilant surveillance and epidemiologic investigations to identify further cases are warranted to delineate the features of this emergent public health issue. The possible role of environmental and toxic agents including foodborne toxins should also be considered. Specific guidelines for identification of further cases are necessary, particularly in low-income settings where testing for adenoviruses is not considered routinely. A genetic analysis of HAdV-F41 isolates is recommended to assess the potential changes in the virus genome with subsequent possible altered virus behavior. Immunopathogenesis is another possibility that should be evaluated considering the lack of viral structures in liver biopsies of the affected children in the US.

HIV-2 Neutralization Sensitivity in Relation to Co-Receptor Entry Pathways and Env Motifs.

HIV-2, compared to HIV-1, elicits potent and broadly neutralizing antibodies, and uses a broad range of co-receptors. However, both sensitivity to neutralization and breadth of co-receptor use varies between HIV-2 isolates, and the molecular background is still not fully understood. Thus, in the current study, we have deciphered relationships between HIV-2 neutralization sensitivity, co-receptor use and viral envelope glycoprotein (Env) molecular motifs. A panel of primary HIV-2 isolates, with predefined use of co-receptors, was assessed for neutralization sensitivity using a set of HIV-2 Env-directed monoclonal antibodies and co-receptor indicator cell lines. Neutralization sensitivity of the isolates was analysed in relation target cell co-receptor expression, in addition to amino acid motifs and predicted structures of Env regions. Results showed that HIV-2 isolates were more resistant to neutralizing antibodies when entering target cells via the alternative co-receptor GPR15, as compared to CCR5. A similar pattern was noted for isolates using the alternative co-receptor CXCR6. Sensitivity to neutralizing antibodies appeared also to be linked to specific Env motifs in V1/V2 and C3 regions. Our findings suggest that HIV-2 sensitivity to neutralization depends both on which co-receptor is used for cell entry and on specific Env motifs. This study highlights the multifactorial mechanisms behind HIV-2 neutralization sensitivity.

Lack of knowledge regarding HPV and its relation to oropharyngeal cancer among medical students.

BACKGROUND: Oropharyngeal cancer (OPC) is an important cause of cancer-related mortality. Early detection of OPC results in a favorable prognosis and higher survival rates. Infection by high-risk types of human papillomavirus (HPV) is a risk factor for OPC with an upward trend globally. Medical students' knowledge and awareness of HPV-related OPC can be crucial in the preventive efforts. AIM: To assess HPV knowledge among medical students at the University of Jordan, with particular focus on its relation to different cancers. METHODS: This paper-based survey study was conducted in November 2019. The survey items were based on previously validated surveys used to evaluate HPV-related OPC knowledge among dental students and professionals. To assess HPV knowledge and students' confidence in personal history taking and physical examination, we developed a knowledge and confidence scores that showed acceptable reliability. RESULTS: The total number of participants was 1198 students, with a median age of 21 and female predominance (n = 697, 58.2%). Among the participants, 93.3% heard of HPV prior to this survey (n = 1118). Higher levels of knowledge regarding cervical cancer, OPC and HPV vaccination was seen among clinical students compared to their preclinical counterparts, but their overall HPV knowledge was low. Only 18.4% and 21.0% of the clinical students correctly identified the association of HPV with penile and oropharyngeal cancers, respectively. Additionally, 34.5% of the clinical students were not aware of the availability of HPV vaccines. The majority of students (92.0%) reported that the university courses were their major source of knowledge about HPV. CONCLUSION: A profound lack of knowledge regarding HPV role in OPC was found among medical students. This insufficiency included several aspects of the virus and its associated diseases. Such gaps in knowledge could have negative consequences in early detection and prevention of OPC and should be addressed by evaluation of the current curriculum.

Oral Colonization by Entamoeba gingivalis and Trichomonas tenax: A PCR-Based Study in Health, Gingivitis, and Periodontitis.

Background: The etiology of periodontitis remains unclear, as is the place of gingivitis in its pathophysiology. A few studies linked the colonization by oral parasites (Entamoeba gingivalis and Trichomonas tenax) to periodontal disease and its severity. The aim of the current study was to estimate the prevalence of these oral parasites among healthy individuals, and in patients with gingivitis and periodontitis in Jordan. Methods: The study was conducted during July 2019-December 2019. Samples were composed of saliva and periodontal material including dental plaque sampled with probes. The detection of oral parasites was done using conventional polymerase chain reaction (PCR). Results: The total number of study participants was 237: healthy (n=94), gingivitis (n=53) and periodontitis (n=90). The prevalence of E. gingivalis was 88.9% among the periodontitis patients, 84.9% among the gingivitis patients and 47.9% in the healthy group. For T. tenax, the prevalence was 25.6% among the periodontitis patients, 5.7% among the gingivitis patients and 3.2% in the heathy group. Positivity for E. gingivalis was significantly correlated with the presence of periodontal disease compared to the healthy group with odds ratio (OR) of 6.6. Periodontal disease was also correlated with lower monthly income (OR=8.2), lack of dental care (OR=4.8), and history of diabetes mellitus (OR=4.5). Colonization by E. gingivalis was correlated with gingivitis (OR=6.1) compared to the healthy group. Colonization by E. gingivalis and T. tenax were significantly correlated with periodontitis (OR=6.4 for E. gingivalis, and OR=4.7, for T. tenax) compared to the healthy group. T. tenax was only detected among individuals with generalized periodontal disease compared to its total absence among those with localized disease (19.6% vs. 0.0%; p=0.039). The co-infection rate by the two oral parasites was 11.0%. Conclusions: The higher prevalence of human oral parasites in periodontal disease compared to healthy individuals appears to be more than a mere marker for the disease and might also be associated with disease severity and potential for progression. Thus, the dogmatic view of E. gingivalis and T. tenax as commensals needs to be re-evaluated and their contribution to pathophysiology of periodontal diseases cannot be neglected.

Dental students' awareness and attitudes toward HPV-related oral cancer: a cross sectional study at the University of Jordan.

BACKGROUND: The incidence of human papilloma virus (HPV)-related oral cancer has recently increased worldwide. The role of dentists is of prime importance in the early detection of oral cancer which would result in a favourable outcome for the patients. The aim of the current study was to assess the knowledge, awareness and attitudes of dental students, interns and postgraduate maxillofacial residents at the University of Jordan (UJ) to different aspects of oral cancer, particularly those related to HPV. METHODS: A paper-based survey was conducted at UJ among all pre-clinical dental students (pre-clinical group), clinical dental students, interns and postgraduate maxillofacial residents (clinical group). The survey included five sections comprising 29 items. The sections included questions investigating oral cancer knowledge, oral cancer screening, HPV knowledge and the ability to discuss personal topics with patients. RESULTS: A total of 376 respondents out of 1052 potential participants completed at least one item of the survey (study coverage of 35.7%). Among the study participants, the pre-clinical group represented 41.2% (n = 155) and the clinical group represented 58.8% (n = 221). The majority of participants in the clinical group showed better knowledge on oral cancer potential anatomic sites, clinical presentation and possible risk factors compared to the pre-clinical group. Most participants in the clinical group (n = 195, 88.2%) correctly identified HPV as a risk factor for oral cancer development. The majority of participants in the clinical group displayed suitable attitude towards oral cancer screening despite their desire for a reliable screening device and additional training in oral cancer screening. A number of limitations in basic knowledge about HPV was noticed among participants in the clinical group particularly related to unawareness of the vaccine availability. The majority of participants in the clinical group displayed hesitancy in discussing personal topics with the patients, including the history of previous sexually transmitted infections and sexual abuse. CONCLUSIONS: Gaps in knowledge regarding HPV-related oral cancer has been detected which necessitate intervention measures including curricular changes, training workshops and awareness campaigns.

Cross-Reactive Antibodies With the Capacity to Mediate HIV-1 Envelope Glycoprotein-Targeted Antibody-Dependent Cellular Cytotoxicity Identified in HIV-2-Infected Individuals.

Disease progression of human immunodeficiency virus type 1 (HIV-1) is delayed by HIV type 2 (HIV-2) in individuals with dual HIV-1/HIV-2 infection. The protective mechanisms, however, are still to be revealed. In the current study we examined type-specific and cross-reactive antibody-dependent cellular cytotoxicity (ADCC) in HIV-1 and HIV-2 monoinfection or dual infection. Of note, intertype cross-reactive antibodies that mediated HIV-1 envelope glycoprotein (Env)-targeted ADCC were frequently identified in HIV-2-infected individuals. Furthermore, the magnitude of HIV-1 cross-reactive ADCC activity during HIV-2 infections depended on the HIV-1 Env origin and was associated with the duration of infection. These results suggest that preexisting antibodies against HIV-2, which mediate intertype ADCC, might contribute to control of HIV-1 during dual infection.

An update on hepatitis C virus genotype distribution in Jordan: a 12-year retrospective study from a tertiary care teaching hospital in Amman.

BACKGROUND: Nucleic acid hybridization (NAH) of hepatitis C virus (HCV) is a practical and reliable tool for virus genotyping. Genotype assignment is an important factor in the prediction of treatment success in chronic hepatitis C patients. The aim of this study was to determine the genotype distribution among HCV clinical isolates in Jordan between 2007 and 2018. METHODS: Electronic and paper-based clinical data registry records from 2007 to 2018 at the Jordan University Hospital (JUH) were retrospectively examined for individuals with HCV genotype, HCV viral load, and alanine aminotransferase (ALT) testing results. Genotype determination was based on NAH technique using the HCV 5' untranslated region (5' UTR) with 386 requests available from 342 unique individuals. RESULTS: A total of 263 out of 342 unique individuals (76.9%) had genotyping results available for final analysis with 259 individuals each having a single genotyping result. The most common HCV genotypes in the study were: genotype 4 (n = 142, 54.0%), genotype 1 (n = 87, 33.1%), genotype 3 (n = 16, 6.1%), genotype 2 (n = 9, 3.4%), other undetermined genotypes (n = 5, 1.9%) and mixed infections (n = 4, 1.5%). Sub-genotyping results were available for 46 individuals as follows: sub-genotype 4c/d (n = 13, 28.3%), sub-genotype 1a (n = 11, 23.9%), sub-genotype 1b (n = 10, 21.7%), sub-genotype 4a (n = 8, 17.4%), sub-genotype 3a (n = 2, 4.3%), sub-genotypes 2a/c and 4 h (n = 1, 2.2% for both). Individuals infected with genotype 1 showed higher viral load when compared to those infected with genotype 4 (p = 0.048, t-test). Younger HCV-infected individuals (< 52 years) had higher ALT levels compared to older individuals (p = 0.036, t-test). Self-reported risk factors for HCV acquisition included: history of previous surgery, invasive dental procedures, and blood transfusion, delivery at home, circumcision at home and wet cupping therapy (hijama). CONCLUSIONS: High genetic diversity of HCV was found in Jordan, with genotypes 4 and 1 as the most prevalent genotypes co-circulating in the country. Potential impact of virus genotype on disease markers (viral load, ALT) was detected and needs further assessment. The study can be helpful to plan for future prevention and management of HCV infection in Jordan.

Genetic characterization of human immunodeficiency virus type 1 transmission in the Middle East and North Africa.

BACKGROUND: The HIV-1 spread in the Middle East and North Africa (MENA) has not been previously characterised using the phylogenetic approach. The aim of the current study was to investigate the genetic diversity and domestic transmission of HIV-1 in the MENA. METHODS: A total of 2036 HIV-1 sequences available in Genbank and collected in the MENA during 1988-2016 were used together with 715 HIV-1 reference sequences that were retrieved from Genbank based on genetic similarity with the MENA sequences. The REGA and COMET tools were used to determine HIV-1 subtypes and circulating recombinant forms. Maximum Likelihood and Bayesian phylogenetic analyses were used to identify and date HIV-1 transmission clusters. RESULTS: At least 21 HIV-1 subtypes and recombinant forms were prevalent in the MENA. Subtype B was the most common variant (39%), followed by CRF35_AD (19%) and CRF02_AG (14%). The most common genetic region was pol, and 675 partial pol sequences (average of 1005 bp) were eligible for detailed phylogenetic analysis. Fifty-four percent of the MENA sequences formed HIV-1 transmission clusters. Whereas numerous clusters were country-specific, some clusters indicated transmission links between countries for subtypes B, C and CRF02_AG. This was more common in North Africa compared with the Middle East (p < 0.001). Recombinant forms had a larger proportion of clustering compared to pure subtypes (p < 0.001). The largest MENA clusters dated back to 1991 (an Algerian CRF06_cpx cluster of 43 sequences) and 2002 (a Tunisian CRF02_AG cluster of 48 sequences). CONCLUSIONS: We found an extensive HIV-1 diversity in the MENA and a high proportion of sequences in transmission clusters. This study highlights the need for preventive measures in the MENA to limit HIV-1 spread in this region.

Decreasing prevalence of transmitted drug resistance among ART-naive HIV-1-infected patients in Iceland, 1996-2012.

Introduction: Resistance to antiretroviral drugs can complicate the management of HIV-1 infection and impair control of its spread. The aim of the current study was to investigate the prevalence and transmission of HIV-1 drug resistance among 106 antiretroviral therapy (ART)-naïve patients diagnosed in Iceland (1996-2012). Methods: HIV-1 polymerase sequences were analysed using the Calibrated Population Resistance tool. Domestic spread of transmitted drug resistance (TDR) was investigated through maximum likelihood and Bayesian approaches. Results: Among ART-naïve patients, the prevalence of TDR to any of the following classes (NRTIs, NNRTIs and PIs) was 8.5% (95% CI: 4.5%- 15.4%): 6.6% to NRTIs, 0.9% to NNRTIs, and 1.9% to PIs. The most frequent NRTI mutation detected was T215C/D (n=7, 5.7%). The only NNRTI mutation detected was K103N (n=1, 0.9%). PI mutations detected were M46I (n=1, 0.9%) and L90M (n=1, 0.9%). Six patients harbouring T215C/D, were linked in a supported phylogenetic cluster. No significant association was found between TDR and demographic or risk groups. Trend analysis showed a decrease in the prevalence of TDR (1996-2012, p=0.003). Conclusions: TDR prevalence in Iceland was at a moderate level and decreased during 1996-2012. Screening for TDR is recommended to limit its local spread and to optimize HIV-1 therapy. Abbreviations: ART: Anti-retroviral therapy; ARV: antiretroviral; ATV/r: atazanavir/ritonavir; AZT: azidothymidine; BEAST: Bayesian evolutionary analysis by sampling trees; CI: confidence interval; CPR: calibrated population resistance; CRF: circulating recombinant form; d4T: stavudine; EFV: efavirenz; FET: Fishers' exact test; FPV/r: fosamprenavir/ritonavir; HET: heterosexual; IDU: injection drug use; IDV/r: indinavir/ritonavir; LPV/r: lopinavir/ritonavir; MSM: men who have sex with men; M-W: Mann-Whitney U test; NFV: nelfinavir; NNRTIs: non-nucleoside reverse transcriptase inhibitors; NRTIs: nucleoside reverse transcriptase inhibitors; NVP: nevirapine; PIs: protease inhibitors; pol: polymerase gene; SDRM: surveillance drug resistance mutation; SQV/r: saquinavir/ritonavir; TDR: transmitted drug resistance.

A novel fungal pathogen under the spotlight--Acremonium spp. associated fungaemia in an immunocompetent host.

Acremonium spp. are filamentous, cosmopolitan fungi frequently isolated from plant debris and soil, they are known to result in invasive infections in the setting of severe immunosuppression. In this letter, we present a case of catheter-related fungaemia associated with Acremonium spp. in a patient with chronic renal failure. After removal of the subclavian catheter, the patient was treated successfully with voriconazole, with a loading dose of 400 mg followed by a maintenance dose of 200 mg bid. To the best of our knowledge, this is the first paper reporting Acremonium spp. associated fungaemia in a relatively immunocompetent host. We also discuss the diagnosis and treatment of Acremonium spp. associated infections in the context of current literature.

The spectrum of diseases causing fever of unknown origin in Turkey: a multicenter study.

OBJECTIVE: The purpose of this trial was to determine the spectrum of diseases with fever of unknown origin (FUO) in Turkey. METHODS: A prospective multicenter study of 154 patients with FUO in twelve Turkish tertiary-care hospitals was conducted. RESULTS: The mean age of the patients was 42+/-17 years (range 17-75). Fifty-three (34.4%) had infectious diseases (ID), 47 (30.5%) had non-infectious inflammatory diseases (NIID), 22 (14.3%) had malignant diseases (MD), and eight (5.2%) had miscellaneous diseases (Mi). In 24 (15.6%) of the cases, the reason for high fever could not be determined despite intensive efforts. The most common ID etiologies were tuberculosis (13.6%) and cytomegalovirus (CMV) infection (3.2%). Adult Still's disease was the most common NIID (13.6%) and hematological malignancy was the most common MD (7.8%). In patients with NIID, the mean duration of reaching a definite diagnosis (37+/-23 days) was significantly longer compared to the patients with ID (25+/-12 days) (p=0.007). In patients with MD, the mean duration of fever (51+/-35 days) was longer compared to patients with ID (37+/-38 days) (p=0.052). CONCLUSIONS: Although infection remains the most common cause of FUO, with the highest percentage for tuberculosis, non-infectious etiologies seem to have increased when compared with previous studies.

Validation of urinary antigen test for Streptococcus pneumoniae in patients with pneumococcal pneumonia.

The study was undertaken to prospectively evaluate a Streptococcus pneumoniae urinary antigen test for diagnosis of pneumococcal pneumonia among patient and control groups between 2004 and 2006. Microbiological analysis for these patients included Gram staining for sputum, sputum and blood culture. Nonconcentrated urine samples were tested using an immunochromatographic assay, the NOW S.pneumoniae antigen test. The urinary antigen test was positive in 9 (15.3%) of 59 patients enrolled in the study and in 8 (73%) of 11 patients with pneumococcal pneumonia confirmed by conventional methods. The test revealed a sensitivity of 72.7% and a specificity of 97.6% with conventional microbiological criteria used as the reference standard. The positive predictive value was 88.9% and the negative predictive value was 93%. We concluded that the urinary antigen test can supplement conventional microbiological tests in the diagnosis of pneumococcal pneumonia.

Treatment of invasive infections due to rare or emerging yeasts and moulds.

Emerging fungal infections represent a serious problem in an immunocompromised host. Rapid developments in in vitro antifungal susceptibility testing and the availability of several new antifungal agents have provided excellent opportunities to treat infections that are caused by various Candida spp. and to some extend by Aspergillus spp. However, recently the epidemiology of fungal infections has significantly changed and several new pathogens have emerged. This article attempts to summarise the available data on the management of emerging infections with fungal infections that have recently gained importance. Updated recommendations on antifungal treatment are also discussed.