Topical betamethasone and systemic colchicine for treatment of recurrent aphthous stomatitis: a randomised clinical trial.

BACKGROUND: Recurrent Aphthous Stomatitis (RAS) is painful oral ulceration frequently treated with topical steroids. There is limited published evidence for the efficacy of any treatment for RAS and there remains a need for longitudinal randomised clinical trials to evaluate and compare the effectiveness of different therapies in the management of RAS. The aim of the current project was to assess the efficacy of betamethasone mouthwash and colchicine tablets, individually and combined, for the treatment of RAS, and to establish the optimum treatment period necessary for a significant reduction in the disease severity. METHODOLOGY: A randomised, prospective, parallel-group clinical trial was conducted over one year, to compare the efficacy of three therapies in RAS. One hundred and six patients were randomized into three groups; 35 received betamethasone mouthwash, 35 had colchicine tablets and 36 received both therapies. The response was evaluated quantitatively every 3 months for 1 year, using the Ulcer Severity Score (USS). RESULTS: For all three treatment regimes, the mean USS decreased by about 30% in the first 3 months (p < 0.001). Further improvement was noted for up to 9 months. At the end of the study, the mean USS had improved by 50% from 34.9 ± 7.2 before treatment to 17.5 ± 8.9 after treatment (p < 0.001). Of included participants, 86% showed significant clinical improvement by the end of the study. There were no significant differences in outcomes between the three regimes (p < 0.05). CONCLUSIONS: This clinical trial has provided evidence for the efficacy of betamethasone mouthwash and for colchicine tablets in the treatment of RAS and has shown that at least six months of treatment may be required for optimum effect. CLINICAL TRIAL REGISTRATION NUMBER: ISRCTN3267716. Date of clinical trial registration: 15/04/2018.

Needs-led human resource planning for Sierra Leone in support of oral health.

BACKGROUND: In Sierra Leone (SL), a low-income country in West Africa, dental care is very limited, largely private, and with services focused in the capital Freetown. There is no formal dental education. Ten dentists supported by a similar number of dental care professionals (DCPs) serve a population of over 7.5 million people. The objective of this research was to estimate needs-led requirements for dental care and human resources for oral health to inform capacity building, based on a national survey of oral health in SL. METHODS: A dedicated operational research (OR) decision tool was constructed in Microsoft Excel to support this project. First, total treatment needs were estimated from our national epidemiological survey data for three key ages (6, 12 and 15 years), collected using the 'International Caries Classification and Management System (ICCMS)' tool. Second, oral health needs were extrapolated to whole population levels for each year-group, based on census demographic data. Third, full time equivalent (FTE) workforce capacity needs were estimated for mid-level providers in the form of Dental Therapists (DTs) and non-dental personnel based on current oral disease management approaches and clinical timings for treatment procedures. Fourth, informed by an expert panel, three oral disease management scenarios were explored for the national population: (1) Conventional care (CC): comprising oral health promotion (including prevention), restorations and tooth extraction; (2) Surgical and Preventive care (S5&6P and S6P): comprising oral health promotion (inc. prevention) and tooth extraction (D5 and D6 together, & at D6 level only); and (3) Prevention only (P): consisting of oral health promotion (inc. prevention). Fifth, the findings were extrapolated to the whole population based on demography, assuming similar levels of treatment need. RESULTS: To meet the needs of a single year-group of childrens' needs, an average of 163 DTs (range: 133-188) would be required to deliver Conventional care (CC); 39 DTs (range: 30-45) to deliver basic Surgical and Preventive care (S6P); 54 DTs for more extended Surgical and Preventive care (S5&6P) (range 38-68); and 27 DTs (range: 25-32) to deliver Prevention only (P). When scaled up to the total population, an estimated 6,147 DTs (range: 5,565-6,870) would be required to deliver Conventional care (CC); 1,413 DTs (range: 1255-1438 DTs) to deliver basic Surgical and Preventive care (S6P); 2,000 DTs (range 1590-2236) for more extended Surgical and Preventive care (S5&6P) (range 1590-2236); and 1,028 DTs to deliver Prevention only (P) (range: 1016-1046). Furthermore, if oral health promotion activities, including individualised prevention, could be delivered by non-dental personnel, then the remaining surgical care could be delivered by 385 DTs (range: 251-488) for the S6P scenario which was deemed as the minimum basic baseline service involving extracting all teeth with extensive caries into dentine. More realistically, 972 DTs (range: 586-1179) would be needed for the S5&6P scenario in which all teeth with distinctive and extensive caries into dentine are extracted. CONCLUSION: The study demonstrates the huge dental workforce needs required to deliver even minimal oral health care to the Sierra Leone population. The gap between the current workforce and the oral health needs of the population is stark and requires urgent action. The study also demonstrates the potential for contemporary epidemiological tools to predict dental treatment needs and inform workforce capacity building in a low-income country, exploring a range of solutions involving mid-level providers and non-dental personnel.

Global inequalities in HIV infection.

HIV infection continues to be one of the world's greatest pandemics, affecting nearly every country on the globe. By September 2018, it is estimated that 38 million people were living with HIV, 30 million people are aware of their status, and 23 million people are taking anti-retroviral therapy (8 million in 2010). Thus, currently 8 million people living with HIV are not aware that they are HIV-positive and 15 million persons are not being treated. There are nearly 15 million orphans (aged 0-17). There is widespread inequality both in the prevalence of HIV infection and in the access to therapy. However, although the number of people living with HIV continues to increase, the number of new infections shows a steady decrease over the last 9 years and in 2018 was 1.7 million. Deaths from AIDS in 2018 also decreased to 750,000 from 1.2 million in 2010. The world prevalence of HIV is about 0.23% but is over 0.3% in South-East Asia, Latin America, North America and Eastern Europe and with particularly high prevalence in the Caribbean (1.1%) and sub-Saharan Africa (5.5%). It is approximately 0.5% in Indonesia. There were approximately 5,000 new HIV infections (adults and children) a day during 2018. About 61% were in sub-Saharan Africa, nearly 50% were in females and 500 were in children. HIV therapy seems to have had a global impact, with AIDS-related deaths decreasing by 33% since 2010, and new infections decreasing by 16%. Nevertheless, the majority of the world's HIV is in low and middle resource countries and social determinants are strongly related. Many people living with HIV or at risk for HIV still do not have access to prevention, care and treatment, and there is still no cure.

HIV in Indonesia and in neighbouring countries and its social impact.

HIV incidence is still increasing in parts of Indonesia and in several Asian Countries. New cases of HIV in Indonesia have risen from 7,000 per year in 2006 to 48,000 per year in 2017. In spite of this increase, the number of newly diagnosed cases of AIDS has decreased from a peak of over 12,000 in 2013 to a little over 9,000 in 2017. The mean prevalence of HIV in Indonesia is 0.41% but there is a ten-fold difference in the prevalence in different regions with the highest in Papua (5%). Women represent over 35% of new infections per year and of the total (640,000) in Indonesia. Over 50% of HIV diagnoses are made when patients already have AIDS. Stigma and discrimination are still strong barriers in prevention and treatment but also there are considerable challenges in access to appropriate anti-retroviral therapy. There is a need for further investment in HIV Programs in Indonesia so that prevention can be enhanced, and diagnosis made at an earlier stage. Health Professionals including dentists should be readily willing to provide joint prevention efforts and care to people at risk and with HIV and other infectious diseases to help meet the WHO aims of 2030. Public health programmes are needed to make certain that the general public is aware of HIV testing and the role of dental healthcare workers in facilitating this, thereby further normalising attitudes to people living with HIV.

The impact of the world Workshops on oral health and disease in HIV and AIDS (1988-2020).

The first World Workshop on Oral AIDS was held in San Diego in 1988, organized by John and Deborah Greenspan who saw the need and advantages of getting together all those health workers globally who were interested in oral aspects of HIV with a common purpose of advancing the field collectively and collaboratively. Since that time and over the following 30 years, World Workshops on oral HIV have been held every four years or so. The aims of the first and all subsequent Workshops were to bring together clinicians and non-clinical scientists who have an interest in the oral manifestations of HIV disease, to share worldwide perspectives, knowledge and understanding of oral health and disease in HIV infection, to agree on global definitions and classifications of oral diseases and to identify research needs taking account of the worldwide perspectives and opportunities. Thus, there have been clinical science, social science and basic science aspects of each World Workshop. The Workshops have achieved their aims and have had impact in all three fields, leading to robust research agendas, changes in national HIV policies and international collaborations. They have led to policy declarations of access to oral care as a basic human right for both HIV-positive and HIV-negative individuals and advancing the rights of all HIV-positive healthcare workers to perform clinical practice.

Predictive value of ultrasound scoring in relation to clinical and histological parameters in xerostomia patients.

BACKGROUND: Salivary gland dysfunction is one of the main clinical features of Sjögren's syndrome (SS), manifested by xerostomia with subsequent complications and well-established effects on the person's quality of life. OBJECTIVES: To determine firstly whether selected tests of salivary gland function and structure, unstimulated whole salivary flow rate (UWSFR), parotid flow rate (PFR), clinical oral dryness score (CODS) and ultrasound score (USS), can discriminate SS from non-SS sicca patients and secondly whether these tests can differentiate between patients in different subgroups of SS. METHOD: Unstimulated whole salivary flow rate, PFR, CODS and USS were determined in 244 patients comprised of SS patients (n = 118), SS patients at higher risk of lymphoma (n = 30) or with lymphoma (n = 26), and non-SS sicca disease controls (n = 70). RESULTS: All assessments showed a significant difference between the overall SS group and the disease control group, attributed mainly to the lymphoma subgroups of SS (p < 0.0001 for all parameters). There was a significant correlation (Spearman r = 0.7, p value <0.0001) and 87.3% agreement between USS and the histology focus scores of 119 patients. CONCLUSION: The results suggest that salivary gland tests including USS can aid in differentiating between SS and non-SS dry mouth, especially the subgroups of SS with lymphoma or at higher risk of developing lymphoma.

Salivary S100A8/A9 in Sjögren's syndrome accompanied by lymphoma.

BACKGROUND: Sjögren's syndrome (SS) is an autoimmune inflammatory disease that affects the exocrine glands. The absence of early diagnostic markers contributes to delays in its diagnosis. Identification of changes in the protein profile of saliva is considered one of the promising strategies for the discovery of new biomarkers for SS. OBJECTIVE: To identify salivary protein biomarkers with potential for use in discriminating between different lymphoma risk subgroups of SS. METHOD: Parotid and whole mouth saliva samples were collected from patients with SS, including those in subgroups at higher risk of developing or with confirmed lymphoma, non-SS sicca disease controls and healthy subjects. An initial proteomics analysis by mass spectrometry (LCMSMS) identified S100A8/A9 as a biomarker and was followed by validation with an enzyme-linked immunosorbent assay (ELISA). RESULTS: Significant differences were found in levels of S100A8/A9 in parotid saliva but not whole mouth saliva between patients with SS compared with healthy and disease control subjects (P = 0.001 and 0.031, respectively). Subgroups of patients with SS based on lymphoma risk showed significant differences in salivary levels of S100A8/A9. CONCLUSION: The results suggest that salivary levels of S100A8/A9 can aid in differentiating between SS, disease control and healthy control subjects, especially the subgroups of SS with lymphoma or at higher risk of lymphoma.

Clinical assessment of disease severity in recurrent aphthous stomatitis.

BACKGROUND: Recurrent aphthous stomatitis (RAS) is one of the most common oral mucosal diseases in many parts of the world. However, there is very limited published clinical evidence for the therapies used in this condition. This could be partly due to the difficulty in evaluating the efficacy of oral ulcer treatment objectively. In this paper, we present a method for assessing and monitoring the severity of oral ulcers before and after treatment. METHODS: Six ulcer characteristics, number, size, duration, ulcer-free period, site and pain, were used to generate an ulcer severity score (USS). The scores for 223 RAS patients were determined, and 79 were scored again after 3-month therapy with topical betamethasone. RESULTS: The scores for the minor RAS group were between 18 and 43 (mean 29.2 ± 5.3). The mean score in the major ulcers group (range: 28-60, mean 39.9 ± 6.1) was significantly greater than in the minor group (P < 0.001). The herpetiform recurrent ulcers score range was wide (range: 18-57, mean 36.6 ± 8.4). The mean severity score decreased significantly after treatment (P < 0.001). CONCLUSIONS: The USS was indicative of the disease activity in recurrent oral ulceration. It helped in assessing the efficacy of therapy, as the change in the numerical score reflected the change in ulcer severity in response to treatment. This tool may well prove to be of value in clinical management, research and in clinical trials.

Implications in the quantification of SARS-CoV2 copies in concurrent nasopharyngeal swabs, whole mouth fluid and respiratory droplets.

OBJECTIVE: Association of SARS-CoV2 burden in the aerodigestive tract with the disease is sparsely understood. We propose to elucidate the implications of SARS-CoV2 copies in concurrent nasopharyngeal swab (NPS), whole mouth fluid (WMF) and respiratory droplet (RD) samples on disease pathogenesis/transmission. METHODS: SARS-CoV2 copies quantified by RT-PCR in concurrent NPS, WMF and RD samples from 80 suspected COVID-19 patients were analysed with demographics, immune response and disease severity. RESULTS: Among the 55/80 (69 %) NPS-positive patients, SARS-CoV2 was detected in 44/55 (80 %) WMF (concordance with NPS-84 %; p = 0.02) and 17/55 (31 %) RD samples. SARS-CoV2 copies were similar in NPS (median:8.74 × 10^5) and WMF (median:3.07 × 10^4), but lower in RD (median:3.60 × 10^2). The 25-75 % interquartile range of SARS-CoV2 copies in the NPS was significantly higher in patients who shed the virus in WMF (p = 0.0001) and RD (p = 0.01). Multivariate analyses showed that hospitalized patients shed significantly higher virus copies in the WMF (p = 0.01). Hospitalized patients with more severe disease (p = 0.03) and higher IL-6 values (p = 0.001) shed more SARS-CoV2 virus in the RD. CONCLUSIONS: WMF may be used reliably as a surrogate for diagnosis. High copy numbers in the NPS probably imply early disease onset, while in the WMF and RD may imply more severe disease and increased inflammation.

Protein and mucin retention on oral mucosal surfaces in dry mouth patients.

Oral homeostasis depends largely on proteins and mucins present in saliva that coat all oral surfaces. The present study compared the protein composition of residual fluid on mucosal surfaces in subjects with normal salivary flow with that of patients with dry mouth caused by salivary hypofunction. Samples of residual mucosal fluid were collected using paper strips and then analysed by protein electrophoresis and immunoblotting. In both patients and controls, residual fluids on mucosal surfaces (except the anterior tongue in control subjects) had higher protein concentrations than unstimulated whole-mouth saliva. High-molecular-weight mucin (MUC5B) was present in greater amounts on the anterior tongue than on other surfaces in control subjects. In dry mouth patients who were unable to provide a measurable saliva sample, MUC5B was often still present on all mucosal surfaces but in reduced amounts on the anterior tongue. The membrane-bound mucin, MUC1, was prominent on buccal and labial surfaces in patients and controls. Statherin was still present on surfaces that were dried to remove salivary fluid, suggesting that it may be adsorbed as a protein pellicle. It is concluded that oral mucosal surfaces in dry mouth patients can retain MUC5B and other salivary proteins, although the functional integrity of these proteins is uncertain.

Correction: Oral and Vaginal Epithelial Cell Lines Bind and Transfer Cell-Free Infectious HIV-1 to Permissive Cells but Are Not Productively Infected.

[This corrects the article DOI: 10.1371/journal.pone.0098077.].

Fortitude and resilience in service of the population: a case study of dental professionals striving for health in Sierra Leone.

OBJECTIVE: Sierra Leone (SL), with a population of over 7 million people, has a critical health workforce shortage. This research explores the views of key players on population oral health needs and demands, the challenges of oral and dental care delivery, and professional careers in dentistry, in order to inform future capacity building. MATERIALS AND METHODS: Semi-structured interviews were conducted with a purposive sample of key players in dentistry and healthcare, both in-country and externally. An interpretive phenomenological approach was used in exploring views of key-players on the oral needs and demands of population, challenges in the delivery of oral and dental care, professional careers of dental professionals in SL, and future workforce capacity building based on a topic guide drawn from the available literature. Interviews were audio-recorded, transcribed verbatim, anonymised and analysed using QSR NVivo 10 for data management and reported in accordance to the consolidated criteria for reporting qualitative research. RESULTS: Twenty-one informants, of whom 18 were male, 17 were in-country and 16 were dental professionals, participated in the research. Dental professionals reported clear consensus on a considerable level of unmet oral health needs, most notably dental caries and periodontal disease, together with life threatening oral conditions such as osteomyelitis, Ludwig's Angina and Burkitt's Lymphoma. Challenges associated with the delivery of dental care revolved around five themes: patients' predisposition for traditional remedies and urgent care; practical hindrances to the delivery of care; professional isolation and weak governance; and place with pressing local crises and lack of political will. An emerging typology of dental professionals included: demonstrating loyalty to their nation and family; exhibiting resilience in challenging circumstances; embracing opportunity most notably amongst expatriates; and striving to serve the needs of the population. There was support for innovative future capacity building developments. CONCLUSION: This paper provides important insights to the delivery of dental care in a low-income country with significant oral health needs and multiple challenges in the delivery of dental care, whilst also providing a vision for developing, building and retaining future human resources for oral health.

Candida albicans secreted aspartyl proteinases in virulence and pathogenesis.

Candida albicans is the most common fungal pathogen of humans and has developed an extensive repertoire of putative virulence mechanisms that allows successful colonization and infection of the host under suitable predisposing conditions. Extracellular proteolytic activity plays a central role in Candida pathogenicity and is produced by a family of 10 secreted aspartyl proteinases (Sap proteins). Although the consequences of proteinase secretion during human infections is not precisely known, in vitro, animal, and human studies have implicated the proteinases in C. albicans virulence in one of the following seven ways: (i) correlation between Sap production in vitro and Candida virulence, (ii) degradation of human proteins and structural analysis in determining Sap substrate specificity, (iii) association of Sap production with other virulence processes of C. albicans, (iv) Sap protein production and Sap immune responses in animal and human infections, (v) SAP gene expression during Candida infections, (vi) modulation of C. albicans virulence by aspartyl proteinase inhibitors, and (vii) the use of SAP-disrupted mutants to analyze C. albicans virulence. Sap proteins fulfill a number of specialized functions during the infective process, which include the simple role of digesting molecules for nutrient acquisition, digesting or distorting host cell membranes to facilitate adhesion and tissue invasion, and digesting cells and molecules of the host immune system to avoid or resist antimicrobial attack by the host. We have critically discussed the data relevant to each of these seven criteria, with specific emphasis on how this proteinase family could contribute to Candida virulence and pathogenesis.

Murine model of concurrent oral and vaginal Candida albicans colonization to study epithelial host-pathogen interactions.

We report the creation of a new low-estrogen murine model of concurrent oral and vaginal C. albicans colonization that resembles human candidal carriage at both mucosal sites. Weekly estrogen administration of 5 microg intramuscular and subcutaneously was optimal for enhancement of oral colonization and was essential for vaginal colonization. In BALB/c mice, a number of C. albicans clinical isolates (n=3) colonized both oral and/or vaginal sites, but only strain 529L colonized 100% of mice persistently for over 5 weeks. Laboratory strains SC5314 and NCPF 3153 did not colonize the model; however, NCPF 3156 showed vaginal colonization up to week 5. Prior passaging through mice enhanced subsequent colonization of SC5314. Intranasal immunization with a C. albicans virulence antigen (secreted aspartyl proteinase 2) significantly reduced or abolished the fungal burden orally and vaginally by week 2 and 7. Our concurrent model of mucosal colonization reduces the numbers of experimental mice by half, can be used to assess potential vaccine candidates, and permits the detailed analysis of host-fungal interactions during the natural state of Candida colonization.

Improvement in orofacial granulomatosis on a cinnamon- and benzoate-free diet.

BACKGROUND: Orofacial granulomatosis (OFG) is a chronic inflammatory disorder presenting characteristically with lip swelling but also affecting gingivae, buccal mucosa, floor of mouth, and a number of other sites in the oral cavity. Although the cause remains unknown, there is evidence for involvement of a dietary allergen. Patch testing has related responses to cinnamon and benzoate to the symptoms of OFG, with improvement obtained through exclusion diets. However, an objective assessment of the effect of a cinnamon- and benzoate-free diet (CB-free diet) as primary treatment for OFG has not previously been performed. Thus, this study was undertaken to investigate the benefits of a CB-free diet as first-line treatment of patients with OFG. MATERIALS AND METHODS: Thirty-two patients with a confirmed diagnosis of OFG were identified from a combined oral medicine/gastroenterology clinic. All had received a CB-free diet as primary treatment for a period of 8 weeks. Each patient underwent a standardized assessment of the oral cavity to characterize the number of sites affected and the type of inflammation involved before and after diet. RESULTS: There was a significant improvement in oral inflammation in patients on the diet after 8 weeks. Both global oral and lip inflammatory scores improved (P<0.001), and there was significant improvement in both lip and oral site and activity involvement. However, improvement in lip activity was less marked than oral activity. Response to a CB-free diet did not appear to be site specific. A history of OFG-associated gut involvement did not predict a response to the diet. CONCLUSIONS: The impact of dietary manipulation in patients with OFG can be significant, particularly with regard to oral inflammation. With the disease most prevalent in the younger population, a CB-free diet can be recommended as primary treatment. Subsequent topical or systemic immunomodulatory therapy may then be avoided or used as second line.

Candida albicans HWP1 gene expression and host antibody responses in colonization and disease.

In vivo expression of the developmentally regulated Candida albicans hyphal wall protein 1 (HWP1) gene was analysed in human subjects who were culture positive for C. albicans and had oral symptoms (n=40) or were asymptomatic (n=29), or had vaginal symptoms (n=40) or were asymptomatic (n=29). HWP1 mRNA was present regardless of symptoms, implicating hyphal and possibly pseudohyphal forms in mucosal carriage as well as disease. As expected, in control subjects without oral symptoms (n=10) and without vaginal symptoms (n=10) who were culture negative in oral and vaginal samples, HWP1 mRNA was not detected. However, exposure to Hwp1 in healthy culture-negative controls, as well as in oral candidiasis and asymptomatic mucosal infections, was shown by the existence of local salivary and systemic adaptive antibody responses to Hwp1. The results are consistent with a role for Hwp1 in gastrointestinal colonization as well as in mucosal symptomatic and asymptomatic infections. Overall, Hwp1 and hyphal growth forms appear to be important factors in benign and invasive interactions of C. albicans with human hosts.