1. A controlled clinical trial was conducted to assess the effectiveness of a homoeopathic preparation in the treatment of influenza-like syndromes. 2. 237 cases received the test drug and 241 were assigned to placebo. Patients recorded their rectal temperature twice a day, and the presence or absence of five cardinal symptoms (headache, stiffness, lumbar and articular pain, shivers) along with cough, coryza and fatigue. 3. Recovery was defined as a rectal temperature less than 37.5 degrees C and complete resolution of the five cardinal symptoms. 4. The proportion of cases who recovered within 48 h of treatment was greater among the active drug group than among the placebo group (17.1% against 10.3%, P = 0.03). 5. The result cannot be explained given our present state of knowledge, but it calls for further rigorously designed clinical studies.

BACKGROUND:The 2014-2015 influenza season was distinguished by an epidemic of antigenically-drifted A(H3N2) viruses and vaccine components identical to 2013-2014. We report 2014-2015 vaccine effectiveness (VE) from Canada and explore contributing agent-host factors.

METHODS:VE against laboratory-confirmed influenza was derived using a test-negative design among outpatients with influenza-like illness. Sequencing identified amino acid mutations at key antigenic sites of the viral hemagglutinin protein.

RESULTS:Overall, 815/1930 (42%) patients tested influenza-positive: 590 (72%) influenza A and 226 (28%) influenza B. Most influenza A viruses with known subtype were A(H3N2) (570/577; 99%); 409/460 (89%) sequenced viruses belonged to genetic clade 3C.2a and 39/460 (8%) to clade 3C.3b. Dominant clade 3C.2a viruses bore the pivotal mutations F159Y (a cluster-transition position) and K160T (a predicted gain of glycosylation) compared to the mismatched clade 3C.1 vaccine. VE against A(H3N2) was -17% (95% confidence interval [CI], -50% to 9%) overall with clade-specific VE of -13% (95% CI, -51% to 15%) for clade 3C.2a but 52% (95% CI, -17% to 80%) for clade 3C.3b. VE against A(H3N2) was 53% (95% CI, 10% to 75%) for patients vaccinated in 2014-2015 only, significantly lower at -32% (95% CI, -75% to 0%) if also vaccinated in 2013-2014 and -54% (95% CI, -108% to -14%) if vaccinated each year since 2012-2013. VE against clade-mismatched B(Yamagata) viruses was 42% (95% CI, 10% to 62%) with less-pronounced reduction from prior vaccination compared to A(H3N2).

CONCLUSIONS:Variation in the viral genome and negative effects of serial vaccination likely contributed to poor influenza vaccine performance in 2014-2015.

Upper respiratory tract infections (URIs) are a common complaint in competitive swimmers and can adversely affect performance. No intervention has yet been shown to reduce URI incidence in intensively trained athletes. The University of Virginia varsity swim team received three weeks of training in qigong for the purpose of reducing stress and improving health. Our primary objective was to assess the relationship between qigong practice and symptoms of URI during a time when swimmers would be at high URI risk. Secondary objectives were to assess degree of compliance with a qigong practice regimen, to evaluate differences between qigong practitioners and non-practitioners, and to determine the response-rate and reliability of a newly developed internet-based, self-report survey. The design was observational, cross-sectional, and prospective. Weekly data on cold and flu symptoms, concurrent health problems and medication use, and qigong practice were gathered for seven weeks. Retrospective information on health and qigong training response was also collected. Participants were 27 of the 55 members of the University of Virginia Swim Team in the Virginia Athletic Department. Main outcomes were measures of aggregated cold/flu symptoms and Qigong practice. Survey completion was 100%, with no missing data, and reliability of the instrument was acceptable. Cold and flu symptoms showed a significant non-linear association with frequency of qigong practice (R(2) = 0.33, p<0.01), with a strong, inverse relationship between practice frequency and symptom scores in swimmers who practised qigong at least once per week (R(2) = 0.70, p<0.01). Qigong practitioners did not differ from non-practitioners in demographic or lifestyle characteristics, medical history, supplement or medication use, or belief in qigong. These preliminary findings suggest that qigong practice may be protective against URIs among elite swimmers who practice at least once per week.

OBJECTIVE:To report a case of Guillain-Barré syndrome (GBS) following a dose of influenza A (H1N1) vaccine (Arepanrix).

CASE SUMMARY:An 11-year-old boy was admitted to the hospital after presenting with facial diplegia; abdominal, forehead, and thigh pain; and acute cervical pain. He had received the Arepanrix H1N1 subcutaneous vaccine 13 days before symptom onset. The neurologic examination also revealed a symmetric bilateral paralysis of the VIIth cranial nerve and intense pain, proximal weakness of the shoulder girdles and pelvis, and preserved deep tendon reflexes. Cerebrospinal fluid analysis revealed an albuminocytologic dissociation. Therefore, a diagnosis of atypical GBS following vaccination against HINI influenza was made.

DISCUSSION:Based on the clinical evaluation, laboratory test results, neurologic features, and the exclusion of alternative diagnoses, the Naranjo probability scale revealed a probable relationship between the clinical manifestations of GBS and the vaccine against influenza A (H1N1) received by the patient. This is the first published case for the 2009 influenza pandemic in children.

CONCLUSIONS:While recent studies have found inconclusive results on the association between influenza vaccine and GBS, all suspected cases should be published for further evaluation.

BACKGROUND:Influenza is a highly infectious viral disease that is particularly common in the winter months. Conventional management options are limited to bed rest and treatment of complications such as secondary bacterial infections. Oscillococcinum is a patented, commercially available homoeopathic medicine. The rationale for its use in influenza comes from the homoeopathic principle of 'let like be cured by like'. The medicine is manufactured from wild duck heart and liver, a well-known reservoir for influenza viruses.

OBJECTIVES:To determine whether homoeopathic Oscillococcinum or similar medicines are more effective than placebo in the prevention and treatment of influenza and influenza-like syndromes.

SEARCH STRATEGY:The registry of randomised trials for the Cochrane Complementary Medicine Field was searched using the term "homeopathy" with "influenza", "respiratory tract", "infection", "cough", "virus" and "fever". The manufacturers of Oscillococcinum were contacted for information about other trials. Date of the most recent search: February 1999.

SELECTION CRITERIA:Placebo-controlled trials of Oscillococcinum or homeopath-prepared influenza virus, influenza vaccine or avian liver in the prevention and treatment of influenza and influenza-like syndromes.

DATA COLLECTION AND ANALYSIS:Two reviewers extracted data and assessed methodological quality independently.

MAIN RESULTS:Seven studies were included in the review, three prevention trials (n=2265) and four treatment trials (n=1194). Only for two studies was there sufficient information to complete data extraction fully. There was no evidence that ic treatment can prevent influenza-like syndrome (relative risk 0.64, 95% confidence interval 0.28 to 1.43). Oscillococcinum treatment reduced length of influenza illness by 0.28 days (95% confidence interval 0.50 to 0.06). Oscillococcinum also increased the chance of a patient considering treatment effective (relative risk 1.08; 95% CI 1.17, 1).

REVIEWER'S CONCLUSIONS:Oscillococcinum probably reduces the duration of illness in patients presenting with influenza symptoms. Though promising, the data are not strong enough to make a general recommendation to use Oscillococcinum for first-line treatment of influenza and influenza-like syndrome. Further research is warranted but required sample sizes are large. Current evidence does not support a preventative effect of homeopathy in influenza and influenza-like syndromes.

BACKGROUND: Observational studies report that influenza vaccination reduces winter mortality risk from any cause by 50% among the elderly. Influenza vaccination coverage among elderly persons (>or =65 years) in the United States increased from between 15% and 20% before 1980 to 65% in 2001. Unexpectedly, estimates of influenza-related mortality in this age group also increased during this period. We tried to reconcile these conflicting findings by adjusting excess mortality estimates for aging and increased circulation of influenza A(H3N2) viruses.

METHODS: We used a cyclical regression model to generate seasonal estimates of national influenza-related mortality (excess mortality) among the elderly in both pneumonia and influenza and all-cause deaths for the 33 seasons from 1968 to 2001. We stratified the data by 5-year age group and separated seasons dominated by A(H3N2) viruses from other seasons. RESULTS: For people aged 65 to 74 years, excess mortality rates in A(H3N2)-dominated seasons fell between 1968 and the early 1980s but remained approximately constant thereafter. For persons 85 years or older, the mortality rate remained flat throughout. Excess mortality in A(H1N1) and B seasons did not change. All-cause excess mortality for persons 65 years or older never exceeded 10% of all winter deaths.

CONCLUSIONS: We attribute the decline in influenza-related mortality among people aged 65 to 74 years in the decade after the 1968 pandemic to the acquisition of immunity to the emerging A(H3N2) virus. We could not correlate increasing vaccination coverage after 1980 with declining mortality rates in any age group. Because fewer than 10% of all winter deaths were attributable to influenza in any season, we conclude that observational studies substantially overestimate vaccination benefit.

BACKGROUND:Influenza infects 5-15% of the global population each year, and obesity has been shown to be an independent risk factor for increased influenza-related complications including hospitalization and death. However, the risk of developing influenza or ILI in a vaccinated obese adult population has not been addressed.

OBJECTIVE:This study evaluated whether obesity was associated with increased risk of influenza and influenza-like illness among vaccinated adults.

SUBJECTS AND METHODS:During the 2013-2014 and 2014-2015 influenza seasons, we recruited 1042 subjects to a prospective observational study of trivalent inactivated influenza vaccine (IIV3) in adults.1022 subjects completed the study. Assessments of relative risk for laboratory confirmed influenza and influenza-like illness were determined based on BMI. Seroconversion and seroprotection rates were determined using pre-vaccination and 26-35 days post-vaccination serum samples. Recruitment criteria for this study were adults 18 years of age and older receiving the seasonal trivalent inactivated influenza vaccine (IIV3) for the years 2013-2014 and 2014-2015. Exclusion criteria were immunosuppressive diseases, use of immunomodulatory or immunosuppressive drugs, acute febrile illness, history of Guillain-Barre syndrome, use of theophylline preparations, or use of warfarin.

RESULTS:Among obese, 9.8% had either confirmed influenza or influenza-like-illness compared with 5.1% of healthy weight participants. Compared with vaccinated healthy weight, obese participants had double the risk of developing influenza or influenza-like illness (relative risk=2.01, 95% CI 1.12, 3.60, P=0.020). Seroconversion or seroprotection rates were not different between healthy weight and obese adults with influenza or ILI.

CONCLUSIONS:Despite robust serological responses, vaccinated obese adults are twice as likely to develop influenza and influenza-like illness compared to healthy weight adults. This finding challenges the current standard for correlates of protection, suggesting use of antibody titers to determine vaccine effectiveness in an obese population may provide misleading information.International Journal of Obesity accepted article preview online, 06 June 2017. doi:10.1038/ijo.2017.131.

BACKGROUND:Influenza vaccine is moderately effective for preventing influenza illness. It is not known if vaccination reduces the risk of subsequent hospital admission among patients with vaccine failure and laboratory confirmed influenza illness.

METHODS:Patients in a community cohort presenting with acute respiratory illness were prospectively enrolled and tested for influenza during 8 seasons to estimate seasonal vaccine effectiveness. Hospital admissions within 14 days after illness onset were identified for all participants aged≥20 years with laboratory confirmed influenza. The association between vaccination and hospital admission was examined in a propensity score adjusted logistic regression model. The model was validated by examining the association between vaccination and hospital admission in participants without influenza.

RESULTS:Influenza was identified in 1393 (28%) of 4996 participants. Sixty-two (6%) of 1020 with influenza A and 17 (5%) of 369 with influenza B were hospitalized. Vaccination was not associated with a reduced risk of hospital admission among all participants with influenza [adjusted odds ratio (aOR)=1.08; 95% CI: 0.62, 1.88]; or among those with influenza A (aOR=1.35; 95% CI: 0.71, 2.57) or influenza B (aOR=0.67; 95% CI: 0.21, 2.15). Influenza vaccination was not associated with hospitalization after non-influenza respiratory illness (aOR=1.14; 95% CI: 0.84, 1.54).

CONCLUSIONS:Influenza vaccination did not reduce the risk of subsequent hospital admission among patients with vaccine failure. These findings do not support the hypothesis that vaccination mitigates influenza illness severity.

Influenza A virus (IAV) infection-associated morbidity and mortality are a key global health care concern, necessitating the identification of new therapies capable of reducing the severity of IAV infections. In this study, we show that the consumption of a low-carbohydrate, high-fat ketogenic diet (KD) protects mice from lethal IAV infection and disease. KD feeding resulted in an expansion ofγδ T cells in the lung that improved barrier functions, thereby enhancing antiviral resistance. Expansion of these protective γδ T cells required metabolic adaptation to a ketogenic diet because neither feeding mice a high-fat, high-carbohydrate diet nor providing chemical ketone body substratethat bypasses hepatic ketogenesis protected against infection. Therefore, KD-mediated immune-metabolic integration represents a viable avenue toward preventing or alleviating influenza disease.

During our ongoing investigation of neuraminidase inhibitors from medicinal fungi, we found that the fruiting bodies of Phellinus igniarius exhibited significant inhibitory activity against neuraminidase from recombinant H3N2 influenza viruses. Two active compounds were isolated from the methanolic extract of P. igniarius through solvent partitioning and Sephadex LH-20 column chromatography. The active compounds were identified as phelligridins E and G on proton nuclear magnetic resonance ((1)H NMR) and electrospray ionization mass measurements. These compounds inhibited neuraminidases from recombinant rvH1N1, H3N2, and H5N1 influenza viruses, with IC50 values in the range of 0.7~8.1µM.

Public health practices including handwashing and vaccinations help reduce the spread and impact of infections. Nevertheless, the global burden of infection is high, and additional measures are necessary. Acute respiratory tract infections, for example, were responsible for approximately 2.38 million deaths worldwide in 2016. The role nutrition plays in supporting the immune system is well-established. A wealth of mechanistic and clinical data show that vitamins, including vitamins A, B, B, C, D, E, and folate; trace elements, including zinc, iron, selenium, magnesium, and copper; and the omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid play important and complementary roles in supporting the immune system. Inadequate intake and status of these nutrients are widespread, leading to a decrease in resistance to infections and as a consequence an increase in disease burden. Against this background the following conclusions are made: (1) supplementation with the above micronutrients and omega-3 fatty acids is a safe, effective, and low-cost strategy to help support optimal immune function; (2) supplementation above the Recommended Dietary Allowance (RDA), but within recommended upper safety limits, for specific nutrients such as vitamins C and D is warranted; and (3) public health officials are encouraged to include nutritional strategies in their recommendations to improve public health.

Abstract Since the introduction of the H1N1 influenza vaccine in the wake of the 2009 H1N1 influenza pandemic, many serious and nonserious adverse events related to the vaccine have been reported. We describe a 59-year-old African-American man with severe chronic heart failure and chronic obstructive pulmonary disease who experienced a new-onset, generalized tonic-clonic seizure less than 1 hour after receiving the H1N1 vaccine. He had never experienced any reactions to previous seasonal influenza vaccines. His medical history, physical examination, and targeted investigations revealed no evidence of other potential etiologies for his seizure. After this event, the patient, who was discharged without anticonvulsant therapy, remained seizure free for the next 10 months. Use of the Naranjo adverse drug reaction probability scale indicated a possible relationship (score of 4) between the patient's seizure and the receipt of the H1N1 vaccine. This is the first case report, to our knowledge, to suggest a possible association between the H1N1 influenza vaccine and seizure. The mechanism of the association is unclear. Further case series may clarify the nature of the association.

In recent years viral respiratory tract infections, especially influenza viruses, have had a major impact on communities worldwide as a result of unavailability of effective treatment or vaccine. The frequent alterations in the antigenic structures of respiratory viruses, particularly for RNA viruses, pose difficulties in production of effective vaccines. The unavailability of optimal medication and shortage of effective vaccines suggests the requirement for alternative natural therapies. Several herbal remedies were used for prevention and treatment viral respiratory illnesses. Among those that were found effective included maoto, licorice roots, antiwei, North American ginseng, berries, Echinacea, plants extracted carnosic acid, pomegranate, guava tea, and Bai Shao. There is scientific evidence regarding the effectiveness of several complementary therapies for colds. Oral zinc may reduce the length and severity of a cold. Taking vitamin C supplements on a regular basis only slightly reduces the length and severity of colds. Probiotics were found better than placebo in reducing the number episodes of acute upper respiratory tract infections, the rate of episodes of acute upper respiratory tract infection and reducing antibiotic use. Alkaline diets or drinks might have antiviral properties as in vitro studies demonstrated inactivation effect of alkaline medium on respiratory virus. Earthing might have a natural anti-inflammatory effect for human body. It is now accepted that an overwhelming inflammatory response is the cause of human deaths from avian H5N1 influenza infection. Earthing accelerates immune response following vaccination, as demonstrated by increases of gamma globulin concentration. No in vivo or clinical studies were found that investigate the role of alkalization or earthing on respiratory viral infections. Thus, future studies are recommended to reveal any potential curative effects.

Pelargonium sidoides is a medical herb and respective extracts are used very frequently for the treatment of respiratory tract infections. However, the effects of Pelargonium sidoides and a special extract prepared from its roots (EPs 7630) on human immune cells are not fully understood. Here we demonstrate that EPs 7630 induced a rapid and dose-dependent production of TNF-α, IL-6, and IL-10 by human blood immune cells. This EPs 7630-induced cytokine profile was more pro-inflammatory in comparison with the profile induced by viral or bacterial infection-mimicking agents. The search for EPs 7630 target cells revealed that T-cells did not respond to EPs 7630 stimulation by production of TNF-α, IL-6, or IL-10. Furthermore, pretreatment of T-cells with EPs 7630 did not modulate their TNF-α, IL-6, and IL-10 secretion during subsequent activation. In contrast to lymphocytes, monocytes showed clear intracellular TNF-α staining after EPs 7630 treatment. Accordingly,EPs 7630 predominantly provoked activation of MAP kinases and inhibition of p38 strongly reduced the monocyte TNF-α production. The pretreatment of blood immune cells with EPs 7630 lowered their secretion of TNF-α and IL-10 and caused an IL-6 dominant response during second stimulation with viralor bacterial infection-mimicking agents. In summary, we demonstrate that EPs 7630 activates human monocytes, induces MAP kinase-dependent pro-inflammatory cytokines in these cells, and specifically modulates their production capacity of mediators known to lead to an increase of acute phase proteinproduction in the liver, neutrophil generation in the bone marrow, and the generation of adaptive Th17 and Th22 cells.

Pelargonium sidoides is a medical herb and respective extracts are used very frequently for the treatment of respiratory tract infections. However, the effects of Pelargonium sidoides and a special extract prepared from its roots (EPs 7630) on human immune cells are not fully understood. Here we demonstrate that EPs 7630 induced a rapid and dose-dependent production of TNF-α, IL-6, and IL-10 by human blood immune cells. This EPs 7630-induced cytokine profile was more pro-inflammatory in comparison with the profile induced by viral or bacterial infection-mimicking agents. The search for EPs 7630 target cells revealed that T-cells did not respond to EPs 7630 stimulation by production of TNF-α, IL-6, or IL-10. Furthermore, pretreatment of T-cells with EPs 7630 did not modulate their TNF-α, IL-6, and IL-10 secretion during subsequent activation. In contrast to lymphocytes, monocytes showed clear intracellular TNF-α staining after EPs 7630 treatment. Accordingly,EPs 7630 predominantly provoked activation of MAP kinases and inhibition of p38 strongly reduced the monocyte TNF-α production. The pretreatment of blood immune cells with EPs 7630 lowered their secretion of TNF-α and IL-10 and caused an IL-6 dominant response during second stimulation with viralor bacterial infection-mimicking agents. In summary, we demonstrate that EPs 7630 activates human monocytes, induces MAP kinase-dependent pro-inflammatory cytokines in these cells, and specifically modulates their production capacity of mediators known to lead to an increase of acute phase proteinproduction in the liver, neutrophil generation in the bone marrow, and the generation of adaptive Th17 and Th22 cells.

The effect of H2O2 on adenovirus types 3 and 6, adenoassociated virus type 4, rhinoviruses 1A, 1B, and type 7, myxoviruses, influenza A and B, respiratory syncytial virus, strain Long, and coronavirus strain 229E was studied in vitro, using different H2O2 concentration and timec of exposure. H2O2 in a 3 percent concentration inactivated all the viruses under study within 1--30 min. Coronavirus and influenza viruses were found to be most sensitive. Reoviruses, adenoviruses and adenoassociated virus were relatively stable. H2O2 is a convenient means for virus inactivation.