Echinacea reduces antibiotic usage in children through respiratory tract infection prevention: a randomized, blinded, controlled clinical trial.

BACKGROUND: In children, up to 30% of viral respiratory tract infections (RTIs) develop into bacterial complications associated with pneumonia, sinusitis or otitis media to trigger a tremendous need for antibiotics. This study investigated the efficacy of Echinacea for the prevention of viral RTIs, for the prevention of secondary bacterial complications and for reducing rates of antibiotic prescriptions in children. METHODS: Echinaforce® Junior tablets [400 mg freshly harvested Echinacea purpurea alcoholic extract] or vitamin C [50 mg] as control were given three times daily for prevention to children 4-12 years. Two × 2 months of prevention were separated by a 1-week treatment break. Parents assessed respiratory symptoms in children via e-diaries and collected nasopharyngeal secretions for screening of respiratory pathogens (Allplex® RT-PCR). RESULTS: Overall, 429 cold days occurred in NITT = 103 children with Echinacea in comparison to 602 days in NITT = 98 children with vitamin C (p < 0.001, Chi-square test). Echinacea prevented 32.5% of RTI episodes resulting in an odds ratio of OR = 0.52 [95% CI 0.30-0.91, p = 0.021]. Six children (5.8%) with Echinacea and 15 children (15.3%) with vitamin C required 6 and 24 courses of antibiotic treatment, respectively (reduction of 76.3%, p < 0.001). A total of 45 and 216 days of antibiotic therapy were reported in the two groups, respectively (reduction of 80.2% (p < 0.001). Eleven and 30 events of RTI complications (e.g., otitis media, sinusitis or pneumonia) occurred with Echinacea and vitamin C, respectively (p = 0.0030). Echinacea significantly prevented influenza (3 vs. 20 detections, p = 0.012) and enveloped virus infections (29 vs. 47 detections, p = 0.0038). Finally, 76 adverse events occurred with Echinacea and 105 events with vitamin C (p = 0.016), only three events were reported possibly related with Echinacea. CONCLUSIONS: Our results support the use of Echinacea for the prevention of RTIs and reduction of associated antibiotic usage in children. Trial registration clinicaltrials.gov, NCT02971384, 23th Nov 2016.

Traditional Chinese medicine for symptoms of upper respiratory tract of COVID-19: A protocol for systematic review and meta-analysis.

BACKGROUND: Assessing the effectiveness and safety of traditional Chinese medicine (TCM) for symptoms of upper respiratory tract of coronavirus disease 2019 is the main purpose of this systematic review protocol. METHODS: The following electronic databases will be searched from inception to Sep 2020: the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, Web of Science, TCM, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chinese Scientific Journal Database (VIP database), and Wan-Fang Database. Search dates: from inception dates to June 2020. Language: English. Publication period: from inception dates to June 2020. The primary outcome is the time and rate of appearance of main symptoms (including coughing, pharyngalgia, and nasal obstruction). The secondary outcome is the length of hospital stay. Two independent reviewers will conduct the study selection, data extraction and assessment. RevMan V.5.3 will be used for the assessment of risk of bias and data synthesis. RESULTS: The results will provide a high-quality synthesis of current evidence for researchers in this subject area. CONCLUSION: The conclusion of our study will provide an evidence to judge whether TCM is effective and safe for the patients with symptoms of upper respiratory tract of coronavirus disease 2019. ETHICS AND DISSEMINATION: This protocol will not evaluate individual patient information or affect patient rights and therefore does not require ethical approval. Results from this review will be disseminated through peer-reviewed journals and conference reports. PROSPERO REGISTRATION NUMBER: CRD42020187422.

Odoriferous Therapy: A Review Identifying Essential Oils against Pathogens of the Respiratory Tract.

This review explores the body of scientific information available on the antimicrobial properties of essential oils against pathogens responsible for respiratory infections and critically compares this to what is recommended in the Layman's aroma-therapeutic literature. Essential oils are predominantly indicated for the treatment of respiratory infections caused by bacteria or viruses (total 79.0 %), the efficacy of which has not been confirmed through clinical trials. When used in combination, they are often blended for presumed holistic synergistic effects. Of the essential oils recommended, all show some degree of antioxidant activity, 50.0 % demonstrate anti-inflammatory effects and 83.3 % of the essential oils showed antihistaminic activity. Of the essential oils reviewed, 43.8 % are considered non-toxic while the remaining essential oils are considered slightly to moderately toxic (43.7 %) or the toxicity is unknown (12.5 %). Recommendations are made for further research into essential oil combinations.

Greater Efficacy of Black Ginseng (CJ EnerG) over Red Ginseng against Lethal Influenza A Virus Infection.

Black ginseng (BG, CJ EnerG), prepared via nine repeated cycles of steaming and drying of fresh ginseng, contains more accessible acid polysaccharides and smaller and less polar ginsenosides than red ginseng (RG) processed only once. Because RG exhibits the ability to increase host protection against viral respiratory infections, we investigated the antiviral effects of BG. Mice were orally administered either BG or RG extract at 10 mg/kg bw daily for two weeks. Mice were then infected with a A(H1N1) pdm09 (A/California/04/2009) virus and fed extracts for an additional week. Untreated, infected mice were assigned to either the negative control, without treatments, or the positive control, treated with Tamiflu. Infected mice were monitored for 14 days to determine the survival rate. Lung tissues were evaluated for virus titer and by histological analyses. Cytokine levels were measured in bronchoalveolar lavage fluid. Mice treated with BG displayed a 100% survival rate against infection, while mice treated with RG had a 50% survival rate. Further, mice treated with BG had fewer accumulated inflammatory cells in bronchioles following viral infection than did mice treated with RG. BG also enhanced the levels of GM-CSF and IL-10 during the early and late stages of infection, respectively, compared to RG. Thus, BG may be useful as an alternative antiviral adjuvant to modulate immune responses to influenza A virus.

Increased risk of refeeding syndrome-like hypophosphatemia with high initial amino acid intake in small-for-gestational-age, extremely-low-birthweight infants.

BACKGROUND: Recent nutrition guidelines for extremely-low-birth-weight infants (ELBWIs) recommend implementation of high initial amino acid (AA) supplementation in parenteral nutrition. OBJECTIVE: We sought to evaluate the influence of AA intake on refeeding syndrome-like electrolyte disturbances including hypophosphatemia in ELBWIs. STUDY DESIGN: Medical records of 142 ELBWIs were reviewed. Demographic, nutritional, outcome, and electrolyte data were compared between ELBWIs with initial low (1.5 g/kg/day) and high (3 g/kg/day) AA intake. Multivariate analysis was conducted to determine the odds ratio of hypophosphatemia with high AA intake and small-for-gestational-age (SGA) ELBWIs. RESULTS: The incidence of hypophosphatemia and severe hypophosphatemia increased from 51% and 8% in period I to 59% and 20% in period II, respectively (p = 0.36 and < 0.01). Specifically, SGA ELBWIs showed higher incidence of hypophosphatemia than appropriate-for-gestational age (AGA) ELBWIs in period II, whereas there was no difference in period I. For severe hypophosphatemia, SGA ELBWIs presented a 27% incidence versus a 2% incidence in AGA ELBWIs, even with low initial AA intake. Despite no difference in phosphate intake between infants with and without hypophosphatemia, serum phosphate level reached a nadir at the sixth postnatal day and gradually recovered over the second week in infants with hypophosphatemia. In multivariate analyses, the odds ratios for severe hypophosphatemia were 3.6 and 6.6 with high AA intake and SGA status, respectively, with the highest being 18.0 with combined high AA intake and SGA status. CONCLUSIONS: In summary, high initial AA intake significantly increased the risk of refeeding syndrome-like electrolyte dysregulations including severe hypophosphatemia in ELBWIs. In SGA ELBWIs, the risk of electrolyte disturbance was significantly higher, even with low initial AA intake. Therefore, new tailored parenteral nutrition protocols starting with lower energy intake and a gradual increase over the first week may be warranted for application in high-risk SGA ELBWIs.

Bacterial Aetiologies of Lower Respiratory Tract Infections among Adults in Yaoundé, Cameroon.

Lower respiratory tract infections (LRTIs) remain a challenge in African healthcare settings and only few data are available on their aetiology in Cameroon. The purpose of this study was to access the bacterial cause of LRTIs in patients in Cameroon by two methods. Methods. Participants with LRTIs were enrolled in the referral centre for respiratory diseases in Yaoundé city and its surroundings. To detect bacteria, specimens were tested by conventional bacterial culture and a commercial reverse-transcriptase real-time polymerase chain reaction (RT-PCR) assay. One hundred forty-one adult patients with LRTIs were enrolled in the study. Among the participants, 46.8% were positive for at least one bacterium. Streptococcus pneumoniae and Haemophilus influenzae were the most detected bacteria with 14.2% (20/141) followed by Klebsiella pneumoniae, 9.2% (13/141), Staphylococcus aureus, 7.1% (10/141), and Moraxella catarrhalis, 4.3% (6/141). Bacterial coinfection accounted for 23% (14/61) with Haemophilus influenzae being implicated in 19.7% (12/61). The diagnostic performance of RT-PCR for bacteria detection (43.3%) was significantly different from that of culture (17.7%) (p< 0.001). Only Streptococcus pneumoniae detection was associated with empyema by RT-PCR (p<0.001). These findings enhance understanding of bacterial aetiologies in order to improve respiratory infection management and treatment. It also highlights the need to implement molecular tools as part of the diagnosis of LRTIs.

San Wu Huangqin Decoction, a Chinese Herbal Formula, Inhibits Influenza a/PR/8/34 (H1N1) Virus Infection In Vitro and In Vivo.

The San Wu Huangqin Decoction (SWHD), a traditional Chinese medicine formula, is used to treat colds caused by exposure to wind-pathogen, hyperpyrexia, infectious diseases and cancer; moreover, it is used for detoxification. The individual herbs of SWHD, such as Sophora flavescens and Scutellaria baicalensis, exhibit a wide spectrum of antiviral, anti-inflammatory, antibacterial, anticancer and other properties. The Chinese compound formula of SWHD is composed of S. flavescens, S. baicalensis and Rehmannia glutinosa. However, the effect of SWHD on the influenza virus (IFV) and its mechanism remain unknown. The aim of this study was to evaluate, for the first time, whether SWHD could be used to treat influenza. Results showed that SWHD could effectively inhibit influenza A/PR/8/34 (H1N1) virus at different stages of viral replication (confirmed through antiviral effect assay, penetration assay, attachment assay and internalization assay) in vitro. It could reduce the infection of the virus in a dose- and time-dependent manner, as confirmed by observing the cell cytopathic effect and calculating the cell viability (p < 0.05). SWHD demonstrated better antiviral activity than oseltamivir in the evaluation of antiviral prophylaxis on influenza (p < 0.05). The antiviral activity of SWHD may be related to its regulation ability on the immune system. Western blot, real-time polymerase chain reaction and indirect immunofluorescence assay showed that the expression of the four target viral proteins of the IFV (namely, haemagglutinin (HA), neuraminidase (NA), nucleoprotein (NP) and matrix-2 (M2)) reduced significantly (p < 0.05). Moreover, SWHD (23.40 and 11.70 g/kg) significantly alleviated the clinical signs, reduced the mortality and increased the survival time of infected mice (p < 0.05). The lung index, virus titres, pathological changes in lung tissues and the expression of key proteins of the IFV in mice also decreased (p < 0.05). In conclusion, SWHD possessed anti-influenza activity. This work provided a new view of complementary therapy and drug discovery for clinical treatment.

Activity of Meropenem-Vaborbactam in Mouse Models of Infection Due to KPC-Producing Carbapenem-Resistant Enterobacteriaceae.

Meropenem-vaborbactam (Vabomere) is highly active against Gram-negative pathogens, especially Klebsiella pneumoniae carbapenemase (KPC)-producing, carbapenem-resistant Enterobacteriaceae The objective of these studies was to evaluate the efficacy of meropenem alone and in combination with vaborbactam in mouse thigh and lung infection models. Thighs or lungs of neutropenic mice were infected with KPC-producing carbapenem-resistant Enterobacteriaceae, with meropenem MICs ranging from ≤0.06 to 8 mg/liter in the presence of 8 mg/liter vaborbactam. Mice were treated with meropenem alone or meropenem in combination with vaborbactam every 2 h for 24 h to provide exposures comparable to 2-g doses of each component in humans. Meropenem administered in combination with vaborbactam produced bacterial killing in all strains tested, while treatment with meropenem alone either produced less than 0.5 log CFU/tissue of bacterial killing or none at all. In the thigh model, 11 strains were treated with the combination of meropenem plus vaborbactam (300 plus 50 mg/kg of body weight). This combination produced from 0.8 to 2.89 logs of bacterial killing compared to untreated controls at the start of treatment. In the lung infection model, two strains were treated with the same dosage regimen of meropenem and vaborbactam. The combination produced more than 1.83 logs of bacterial killing against both strains tested compared to untreated controls at the start of treatment. Overall, these data suggest that meropenem-vaborbactam may have utility in the treatment of infections due to KPC-producing carbapenem-resistant Enterobacteriaceae.

Clinical Characteristics of Macrolide-Resistant Mycoplasma pneumoniae from Children in Jeju.

Mycoplasma pneumoniae is the major pathogen of community-acquired pneumonia in children. The prevalence of macrolide-resistant M. pneumoniae (MRMP) is important owing to the limited alternative therapies for children. We analyzed 111 M. pneumoniae obtained from 107 children admitted for lower respiratory tract infection at Jeju National University Hospital between 2010 and 2015. Macrolide resistance of M. pneumoniae was searched for using polymerase chain reaction (PCR) and sequencing. Of 107 clinical M. pneumoniae, 11 (10.3%) carried macrolide resistance mutations in the 23S rRNA gene. All macrolide resistance mutations were A2063G transitions. We found an acquired A2063G mutation of M. pneumoniae from a patient during macrolide treatment. Patients' characteristics and clinical severity did not differ between those with MRMP and macrolide-sensitive M. pneumoniae, with the exception of frequent pleural effusion in the MRMP group. The prevalence of MRMP (10.3%) in Jeju Island was relatively lower than those of surrounding countries in East Asia. Previous antimicrobial usage and timing of diagnostic test should be considered when determining of macrolide resistance of M. pneumoniae.

Patho-bacteriological investigation of an outbreak of Mycoplasma bovis infection in calves - Emerging stealth assault.

Mycoplasma bovis (M. bovis) is an important bacterium, causing severe respiratory infection, and arthritis in dairy animals worldwide. This study is based on 50 suckling calves among which 15 showed respiratory distress, lameness and swollen joints and died later. M. bovis was isolated and identified from all dead (n = 15) and live (17.14%; 06 out of 35) calves on the basis of bacteriological examination. In morbid calves, the carpus and stifle joints were severely affected, while necropsy revealed multiple well-circumscribed calcified abscesses and caseous exudates in cranio-ventral and diaphragmatic lobes of lungs. Suppurative polyarthritis, fibrino-suppurative, teno-synovitis and otitis media were the common and striking lesion observed at postmortem examination. Histopathological examination revealed broncho-interstitial pneumonia and necrotic fibrino-purulent broncho-pneumonia in lungs. Similarly, synovial membranes and joints revealed presence of multiple foci of liquefactive necrosis surrounded by lymphocytes, plasma cells, macrophages and peripheral fibroplasia. In the bacteriological investigations, the characteristic fried egg colonies of M. bovis further confirmed this infection in all suspected cases. In conclusion, the current clinico-histo-pathological features are the depictive picture, and is the first report of M. bovis infection in calves in Pakistan.

The Vitamin D Assessment (ViDA) Study: design of a randomized controlled trial of vitamin D supplementation for the prevention of cardiovascular disease, acute respiratory infection, falls and non-vertebral fractures.

Observational studies have shown that low vitamin D status is associated with an increased risk of cardiovascular disease, acute respiratory infection, falls and non-vertebral fractures. We recruited 5110 Auckland adults, aged 50-84 years, into a randomized, double-blind, placebo-controlled trial to test whether vitamin D supplementation protects against these four major outcomes. The intervention is a monthly cholecalciferol dose of 100,000IU (2.5mg) for an estimated median 3.3 years (range 2.5-4.2) during 2011-2015. Participants were recruited primarily from family practices, plus community groups with a high proportion of Maori, Pacific, or South Asian individuals. The baseline evaluation included medical history, lifestyle, physical measurements (e.g. blood pressure, arterial waveform, lung function, muscle function), and a blood sample (stored at -80°C for later testing). Capsules are being mailed to home addresses with a questionnaire to collect data on non-hospitalized outcomes and to monitor adherence and potential adverse effects. Other data sources include New Zealand Ministry of Health data on mortality, hospitalization, cancer registrations and dispensed pharmaceuticals. A random sample of 438 participants returned for annual collection of blood samples to monitor adherence and safety (hypercalcemia), including repeat physical measurements at 12 months follow-up. The trial will allow testing of a priori hypotheses on several other endpoints including: weight, blood pressure, arterial waveform parameters, heart rate variability, lung function, muscle strength, gait and balance, mood, psoriasis, bone density, and chronic pain.

Natural history and epidemiology of respiratory syncytial virus infection in the Middle East: Hospital surveillance for children under age two in Jordan.

UNLABELLED: Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and viral pneumonia in infants and young children worldwide. In the Middle East and Arab countries, the burden of RSV-associated hospitalizations is not well characterized. We sought to determine the burden and clinical/epidemiological characteristics of RSV hospitalization in young children in Amman, Jordan. We investigated risk factors for severity including vitamin D levels. METHODS: We conducted viral surveillance with clinical and demographic data in children <2 years admitted with respiratory symptoms and/or fever at the Al-Bashir Government Hospital from March16, 2010 to March 31, 2013. Nasal/throat swabs were obtained and placed into lysis buffer, and frozen at -80°C until testing by real-time RT-PCR for 11 respiratory viruses. Heel stick blood or sera samples for 25-hydroxyvitamin D [25(OH)D] levels were obtained and sent to a central laboratory for mass spectrometry. RESULTS: Of the 3168 children, >80% testing positive for one virus, with RSV the most common virus detected (44%). The RSV-associated hospitalization rate was highest in children <6 months with an annual range of 21.1-25.9 per 1000, compared to 6.0-8.0 in 6-11-month-olds and 1.6-2.5 in 12-23-month-olds. RSV-positive children compared with RSV-negative were more likely to be previously healthy without underlying medical conditions, less likely to be born prematurely, had a higher frequency of supplemental oxygen use, and had lower median vitamin D levels. Risk factors for oxygen use in RSV-positive children included underlying medical conditions, lack of breastfeeding, younger age, and higher viral load. CONCLUSION: RSV is a major cause of illness in hospitalized Jordanian children and is associated with increased severity compared to other respiratory viruses. Children with RSV in the Middle East would benefit from future RSV vaccines and antiviral therapy.

Nasal congestion in infants and children: a literature review on efficacy and safety of non-pharmacological treatments.

The most common causes of nasal obstruction and runny nose in infants and children are infections, mainly of viral origin, or allergies. In neonates and infants viral upper respiratory tract infections (URTI) are frequently observed during episodes of nasal obstruction. Saline irrigation of the nose is believed to alleviate URTI symptoms by helping to eliminate excess mucus, to reduce congestion and by contributing to improve breathing. Objective of the study was to review the efficacy and safety of non-pharmacological options for the treatment of nasal congestion and its sequelae, in infants and children, with a special focus on hypertonic and isotonic solutions and other medical devices, including nasal aspirators. Available data indicate that nasal symptoms in children with allergic rhinitis or acute sinusitis significantly improved following nasal saline irrigation. The use of medical devices is less documented. Nasal aspiration with a medical device, associated with an isotonic saline solution, during viral rhinitis, has been shown to lower the risk of developing acute otitis media and rhinosinusitis, in comparison with a group treated with physiological saline solution alone. Safety and tolerability have been evaluated and no serious adverse events have been reported. Literature data highlighted the good tolerability. The use of isotonic and hypertonic saline solutions to relief nasal congestion in infants and children is widespread; it is a safe and valuable therapeutic support, and can reduce the use of medications (antihistamines, decongestant, antibiotics, corticosteroids) during the treatment of URTIs.

Delivery of aerosolized liposomal amikacin as a novel approach for the treatment of nontuberculous mycobacteria in an experimental model of pulmonary infection.

Pulmonary infections caused by nontuberculous mycobacteria (NTM) are an increasing problem in individuals with chronic lung conditions and current therapies are lacking. We investigated the activity of liposomal amikacin for inhalation (LAI) against NTM in vitro as well as in a murine model of respiratory infection. Macrophage monolayers were infected with three strains of Mycobacterium avium, two strains of Mycobacterium abscessus, and exposed to LAI or free amikacin for 4 days before enumerating bacterial survival. Respiratory infection was established in mice by intranasal inoculation with M. avium and allowing three weeks for the infection to progress. Three different regimens of inhaled LAI were compared to inhaled saline and parenterally administered free amikacin over a 28 day period. Bacteria recovered from the mice were analyzed for acquired resistance to amikacin. In vitro, liposomal amikacin for inhalation was more effective than free amikacin in eliminating both intracellular M. avium and M. abscessus. In vivo, inhaled LAI demonstrated similar effectiveness to a ∼25% higher total dose of parenterally administered amikacin at reducing M. avium in the lungs when compared to inhaled saline. Additionally, there was no acquired resistance to amikacin observed after the treatment regimen. The data suggest that LAI has the potential to be an effective therapy against NTM respiratory infections in humans.

Effects of combined treatment with ambroxol and ciprofloxacin on catheter-associated Pseudomonas aeruginosa biofilms in a rat model.

BACKGROUND: Pseudomonas aeruginosa is an opportunistic pathogen that causes potentially devastating infections in immunocompromised patients. These infections are particularly difficult to treat if a biofilm forms, which is likely if foreign bodies are present. OBJECTIVE: This study aimed to investigate the effect of ambroxol combined with ciprofloxacin on P. aeruginosa biofilm in a rat model. METHODS: A rat model of acute lung infection was created by endotracheal (ET) intubation with a tube covered with a P. aeruginosa biofilm. The rats were treated with ciprofloxacin alone, ambroxol alone, or a combination of both for 7 days. The microstructure of the biofilm on the tube was assessed by scanning electron microscopy (SEM). The numbers of bacterial colonies in the lungs and on the ET tube were measured on agar plates. Pathological changes in the lungs were observed with hematoxylin and eosin staining. RESULTS: Changes in the microstructure of the biofilm after combined treatment were demonstrated by SEM. Ambroxol combined with ciprofloxacin significantly reduced the number of bacteria in the lungs and ET tube compared to the single treatments (p < 0.05). The pathological changes in the lungs were also mildest after the combined treatment. CONCLUSION: The combination treatment of ambroxol with ciprofloxacin has a high ability to eradicate P. aeruginosa biofilms in vivo. These initial results provide the basis of a new strategy for the treatment of P. aeruginosa infections.

Early child growth: how do nutrition and infection interact?

It is well known that the relationship between child nutrition and infection is bidirectional, i.e. frequent illness can impair nutritional status and poor nutrition can increase the risk of infection. What is less clear is whether infection reduces the effectiveness of nutrition interventions or, vice versa, whether malnutrition lessens the impact of infection control strategies. The objective of this paper is to review the evidence regarding this interaction between nutrition and infection with respect to child growth in low-income populations. Even when there are no obvious symptoms, physiological conditions associated with infections can impair growth by suppressing appetite, impairing absorption of nutrients, increasing nutrient losses and diverting nutrients away from growth. However, there is little direct evidence that nutrition interventions are less effective when infection is common; more research is needed on this question. On the other hand, evidence from four intervention trials suggests that the adverse effects of certain infections (e.g. diarrhoea) on growth can be reduced or eliminated by improving nutrition. Interventions that combine improved nutrition with prevention and control of infections are likely to be most effective for enhancing child growth and development.

Delivery with polycations extends the immunostimulant Ribomunyl into a potent antiviral Toll-like receptor 7/8 agonist.

BACKGROUND: Upper respiratory tract infection is a frequent cause of morbidity worldwide. Although the course of infection is usually mild, it is responsible for enormous social and economic costs. Immunostimulation with bacterial extracts consisting of ribosomal RNA and proteoglycans, such as Ribomunyl, was introduced into the clinic in the 1980s as a new treatment concept, but did not achieve widespread application. Ribomunyl has been proposed to activate innate immunity, but the contribution of its RNA content as well as its antiviral potential has not been studied. METHODS: Peripheral blood mononuclear cells from healthy donors and immune cells from adenoids were incubated with Ribomunyl either by itself or formulated in a complex with cationic polypeptides such as poly-l-arginine or protamine, and induction of cytokines was quantified by ELISA. RESULTS: Ribomunyl in complex with either poly-l-arginine or protamine, but not on its own, was able to strongly induce interferon-α (P<0.01) and interleukin-12 (P<0.01) in peripheral blood mononuclear cells, whereas induced tumour necrosis factor-α and interleukin-6 levels were independent of the formulation. Comparable results were obtained in immune cells from adenoids, suggesting efficacy also in virus-affected tissue. Cell sorting, RNase digests and selective receptor expression show that the RNA in Ribomunyl acts as an agonist of Toll-like receptor (TLR)7 and TLR8. CONCLUSIONS: Ribomunyl is, in principle, able to potently induce antiviral interferon-α and interleukin-12 via TLR7 and TLR8, respectively, but only when formulated in a complex with cationic polypeptides.

Ventilación no invasiva en infección respiratoria aguda fuera del área de cuidado intensivo / Non-invasive ventilation in patients with acute respiratory infection outside of intensive care units

Introduction: Acute Respiratory Infections (ARIs) in children constitute a Public Health issue. They represent the main cause of admission to hospitals and ICU use throughout the winter months. The benefit of noninvasive ventilation (NIV) in its treatment is not clearly defined. Objective: Describe the results of use of NIV in hospital, outside of ICU in children with severe ARIs. Patients and Methods: Population included all children < 2 y.o. with probable or confirmed viral AlRI with Tal score > 8 o > 6 without previous treatment response; all these seen between 8 June and 20 October, 2009. A management protocol was established, including monitoring and connection to NIV. A Vipap III (ResMed®) was used. Clinical characteristics and evolution of patients is described. Results: 113 patients were included, which amounted to 5.2 of all admissions for AlRI in that period. 80.5 percent (n = 91) showed a favorable evolution, with an average LOS of 76.1 hrs. The rest required conventional mechanical ventilation. No patient died. Conclusions: The use of NIV among these children is a valid and secure option. It can also be utilized outside of the ICU so long as it is limited to a restricted area, a management protocol, and trained staff.

Introducción: La infección respiratoria aguda (IRA) en niños constituye un problema de salud pública. Durante los meses de invierno representa la primera causa de ingreso hospitalario y de demanda de cuidado intensivo. El beneficio de la ventilación no invasiva (VNI) en su tratamiento no ha sido claramente definido. Objetivo: Describir los resultados de la aplicación de ventilación no invasiva fuera de la unidad de cuidado intensivo a niños con infección respiratoria aguda grave. Pacientes y Método: Se incluyeron niños < 2 años con IRA de etiología viral probable o confirmada y score de Tal > 8 o > 6 sin respuesta al tratamiento previo entre 8 de junio y 20 de octubre de 2009. Se estableció un protocolo de actuación, monitorización y conexión a VNI. Se utilizo un Vipap III (ResMed®). Se describen las características clínicas y evolutivas de los pacientes. Resultados: Se incluyeron 113 pacientes, el 5,2 por ciento de los ingresos hospitalarios por IRA en ese período. El 80,5 por ciento (n = 91) evolucionó favorablemente, con una estadía promedio de 76,1 horas. El resto requirió asistencia ventilatoria mecánica convencional. Ningún paciente falleció. Conclusiones: La aplicación de VNI en éste grupo de niños, constituyó una alternativa válida y segura. Su utilización puede ser extendida fuera del área de cuidado intensivo, siempre que se disponga de un área específica, protocolo de actuación y un equipo previamente capacitado.

Post-exposure therapy of inhalational anthrax in the common marmoset.

The aim of this study was to compare the pharmacokinetics and efficacy of ciprofloxacin as post-exposure therapy against inhalational anthrax in the common marmoset (Callithrix jacchus) with other non-human primate models in order to determine whether the marmoset is a suitable model to test post-exposure therapies for anthrax. Pharmacokinetic (PK) and efficacy studies with ciprofloxacin were performed in the marmoset. Ciprofloxacin plasma pharmacokinetics were determined in six animals in separate single-dose and multiple-dose studies and were analysed by high-performance liquid chromatography (HPLC). A separate group of marmosets was exposed to ca. 100× the 50% lethal dose (LD(50)) of Bacillus anthracis Ames strain by the airborne route. On Day 5 of a twice-daily dosing regimen of 17.5 mg/kg, the ciprofloxacin half-life (t(1/2)), maximum drug concentration (C(max)) and area under the concentration-time curve (AUC) in marmoset plasma were 1.9 h, 2.1 µg/mL and 7.9 µg/mL/h, respectively. Naïve untreated control animals succumbed to infection by Day 9. All animals treated with ciprofloxacin, started on the day of exposure and continued for 10 days, remained healthy during the treatment period. Two antibiotic-treated animals (33%) died after withdrawal of antibiotic therapy, attributed to the germination of residual spores. In conclusion, in many respects the marmoset appears to respond to B. anthracis in a similar way to the macaque, suggesting that this small non-human primate is an acceptable, practical alternative model for the evaluation of medical countermeasures against respiratory anthrax infection.

Paracetamol reduces influenza-induced immunopathology in a mouse model of infection without compromising virus clearance or the generation of protective immunity.

BACKGROUND: Seasonal influenza A infection affects a significant cohort of the global population annually, resulting in considerable morbidity and mortality. Therapeutic strategies are of limited efficacy, and during a pandemic outbreak would only be available to a minority of the global population. Over-the-counter medicines are routinely taken by individuals suffering from influenza, but few studies have been conducted to determine their effectiveness in reducing pulmonary immunopathology or the influence they exert upon the generation of protective immunity. METHODS: A mouse model of influenza infection was utilised to assess the efficacy of paracetamol (acetaminophen) in reducing influenza-induced pathology and to examine whether paracetamol affects generation of protective immunity. RESULTS: Administration (intraperitoneal) of paracetamol significantly decreased the infiltration of inflammatory cells into the airway spaces, reduced pulmonary immunopathology associated with acute infection and improved the overall lung function of mice, without adversely affecting the induction of virus-specific adaptive responses. Mice treated with paracetamol exhibited an ability to resist a second infection with heterologous virus comparable with that of untreated mice. CONCLUSIONS: Our results demonstrate that paracetamol dramatically reduces the morbidity associated with influenza but does not compromise the development of adaptive immune responses. Overall, these data support the utility of paracetamol for reducing the clinical symptoms associated with influenza virus infection.