Search

Typhoid and paratyphoid fevers have a high incidence worldwide and coexist in many geographical areas, especially in low-middle-income countries (LMIC) in South and Southeast Asia. There is extensive consensus on the urgent need for better and affordable vaccines against systemic Salmonella infections. Generalized modules for membrane antigens (GMMA), outer membrane exosomes shed by Salmonella bacteria genetically manipulated to increase blebbing, resemble the bacterial surface where protective antigens are displayed in their native environment. Here, we engineered S Paratyphi A using the pDC5-viaB plasmid to generate GMMA displaying the heterologous S Typhi Vi antigen together with the homologous O:2 O antigen. The presence of both Vi and O:2 was confirmed by flow cytometry on bacterial cells, and their amount was quantified on the resulting vesicles through a panel of analytical methods. When tested in mice, such GMMA induced a strong antibody response against both Vi and O:2, and these antibodies were functional in a serum bactericidal assay. Our approach yielded a bivalent vaccine candidate able to induce immune responses against different Salmonella serovars, which could benefit LMIC residents and travelers.

Supplemental material, sj-pdf-1-jdr-10.1177_00220345211049403 for Gas1 Regulates Patterning of the Murine and Human Dentitions through Sonic Hedgehog by M. Seppala, B. Thivichon-Prince, G.M. Xavier, N. Shaffie, I. Sangani, A.A. Birjandi, J. Rooney, J.N.S. Lau, R. Dhaliwal, O. Rossi, M.A. Riaz, D. Stonehouse-Smith, Y. Wang, S.N. Papageorgiou, L. Viriot and M.T. Cobourne in Journal of Dental Research

$\textbf{Objectives:}$ We determined the interactions between efficacy of antibiotic treatment, pathogen growth rates and between-organ spread during systemic $\textit{Salmonella}$ infections. $\textbf{Methods:}$ We infected mice with isogenic molecularly tagged subpopulations of either a fast-growing WT or a slow-growing $\Delta$$\textit{aroC Salmonella}$ strain. We monitored viable bacterial numbers and fluctuations in the proportions of each bacterial subpopulation in spleen, liver, blood and mesenteric lymph nodes (MLNs) before, during and after the cessation of treatment with ampicillin and ciprofloxacin. $\textbf{Results:}$ Both antimicrobials induced a reduction in viable bacterial numbers in the spleen, liver and blood. This reduction was biphasic in infections with fast-growing bacteria, with a rapid initial reduction followed by a phase of lower effect. Conversely, a slow and gradual reduction of the bacterial load was seen in infections with the slow-growing strain, indicating a positive correlation between bacterial net growth rates and the efficacy of ampicillin and ciprofloxacin. The viable numbers of either bacterial strain remained constant in MLNs throughout the treatment with a relapse of the infection with WT bacteria occurring after cessation of the treatment. The frequency of each tagged bacterial subpopulation was similar in the spleen and liver, but different from that of the MLNs before, during and after treatment. $\textbf{Conclusions:}$ In $\textit{Salmonella}$ infections, bacterial growth rates correlate with treatment efficacy. MLNs are a site with a bacterial population structure different to those of the spleen and liver and where the total viable bacterial load remains largely unaffected by antimicrobials, but can resume growth after cessation of treatment.

Both rapid and slow maxillary expansion protocols may produce different effects on the palatal suture, on the periodontium, and on alveolar anatomy such as lateral flexion of the alveolar processes, root resorption, bone fenestration and the anchorage teeth can show different degrees of inclination and dislocation. In order to reduce these side effects, maxillary expansion devices anchored to deciduous teeth or miniscrew-supported appliances should beconsidered.

Summary We performed a multicentre survey about the role of mobile apps in allergic respiratory diseases. The main objective was to investigate the current use and usefulness of mobile phone apps in the management of allergic respiratory disease. An original questionnaire including 12 multiple-choice questions was administered to 360 participants (153 male and 207 female subjects). Of notice, 290 subjects owned a smartphone, 120 a personal computer and 68 a tablet (multiple answers were possible). 123 subjects reported to be regular mobile-apps users, 209 were occasional users and 76 has never downloaded an app. Indeed, 259 subjects have never dealt with a medical or healthcare app, with only 8 subjects answering to often take advantage of such supportive tools. Data were even more discouraging when asking whether subjects had ever downloaded an app directly related to their own medical condition (allergy, asthma and rhinitis). 87.2% provided a negative answer. Among the few individuals who reported a previous experience with allergy/asthma apps only 2 subjects reported to regularly use the apps they had downloaded, even after months. The majority of subjects believed the apps would provide a relevant support, but only 25/360 participants found that the apps are "truly helpful", while 44 considered them of "help but not essential". Our data seem to show that the apps in the medical field, especially for allergic respiratory diseases, are welcome by patients, but their continued use and utility wane with the passage of time from the date of the download. In the future it will therefore be important to focus on the quality of the apps themselves and on the careful selection of the most suitable patients to use them. Finally, it will be important to make use of the fundamental contribution of healthcare professionals for the development of the apps.

Immunity can co-operate with antibiotics, but can also antagonize drug efficacy by segregating the bacteria to areas of the body that are less accessible to antimicrobials, and by selecting for subpopulations with low division rates that are often difficult to eradicate. We studied the effect of an anti-inflammatory/immunosuppressive anti-TNFα treatment, which accelerates bacterial growth in the tissues and inhibits or reverses the formation of granulomas, on the efficacy of ampicillin and ciprofloxacin during a systemic Salmonella enterica infection of the mouse. The anti-TNFα treatment neither precluded not enhanced the efficacy of antibiotic treatment. However, the anti-TNFα treatment rendered the animals susceptible to the rapid relapse of the infection seen after cessation of the antibiotic treatment. Reactivation of an established infection, due to late administration of anti-TNFα antibodies, could be successfully controlled by antibiotics, but full clearance of the bacterial load from the tissues was not achieved. We conclude that the lack of TNFα does not preclude the efficacy of antibiotic treatment and must be monitored with care due to post-treatment relapses. Combinations of anti-cytokine compounds and antibiotic molecules may not be the best way to treat persistent infections with intracellular bacteria like Salmonella.

As standard drug treatment of allergic rhinitis (AR) is not completely satisfactory, allergen immunotherapy (AIT) represents the only current treatment with the potential to modify the natural history. House dust mite (HDM) allergy is very common. The aim of the current experience was to describe the clinical profile of HDM-allergic patients with AR who received AIT in a real world model, such as allergy clinics. Globally, 239 patients (126 adults and 113 children; 107 females and 132 males; mean age 21 years, age range 6–56 years) were evaluated. AIT was prescribed in 59 patients (24.7%), 44 adults (35%) and 15 children (13.3%). The current findings deriving from this real world multicentre study are consistent with previous investigations on HDM-AIT and define some clinical characteristics of the eligible candidate to this treatment. In fact, severity of ocular-nasal symptoms and over-use of symptomatic medications may typify the ideal candidate to HDM-AIT and SLIT was the preferred choice.