Academic literature on the topic 'Meningitis; Influenza virus'

The concentration of total neopterin in serum and cerebrospinal fluid (CSF) was measured in cases of febrile convulsion, aseptic meningitis and influenza encephalopathy. In febrile convulsion except for exanthem subitum, the concentrations of CSF neopterin (26± 11, Mean±SD, n=6) were all within normal range while those of serum neopterin (66± 20, n=8) were significantly higher (p < 0.05). In aseptic meningitis, on the other hand, the concentrations of CSF neopterin (194± 130, n=13) were significantly higher than those of serum (33±23, n=11, p < 0.05). In influenza encephalopathy, both concentrations of serum neopterin (329±478, n=13) and CSF neopterin(179±131, n=11) were much higher than the control range. Our results indicate that the primary immunoreacting site is the central nervous system (CNS) for aseptic meningitis, the periphery for febrile convulsion except for exanthem subitum and both the periphery and the CNS for influenza encephalopathy. Measurements of neopterin concentrations in CSF as well as in serum may thus constitute an immediate aid for early differentiation of CNS infection from peripheral infection as well as for early detection of viral encephalopathy caused by viruses such as the influenza virus or the human herpes virus 6.

Pneumococcus is an important human pathogen, highly antibiotic resistant and a major cause of bacterial meningitis worldwide. Better prevention requires understanding the drivers of pneumococcal infection incidence and antibiotic susceptibility. Although respiratory viruses (including influenza) have been suggested to influence pneumococcal infections, the underlying mechanisms are still unknown, and viruses are rarely considered when studying pneumococcus epidemiology. Here, we propose a novel mathematical model to examine hypothetical relationships between Streptococcus pneumoniae meningitis incidence (SPMI), acute viral respiratory infections (AVRIs) and antibiotic exposure. French time series of SPMI, AVRI and penicillin consumption over 2001–2004 are analysed and used to assess four distinct virus–bacteria interaction submodels, ascribing the interaction on pneumococcus transmissibility and/or pathogenicity. The statistical analysis reveals strong associations between time series: SPMI increases shortly after AVRI incidence and decreases overall as the antibiotic-prescription rate rises. Model simulations require a combined impact of AVRI on both pneumococcal transmissibility (up to 1.3-fold increase at the population level) and pathogenicity (up to threefold increase) to reproduce the data accurately, along with diminished epidemic fitness of resistant pneumococcal strains causing meningitis (0.97 (0.96–0.97)). Overall, our findings suggest that AVRI and antibiotics strongly influence SPMI trends. Consequently, vaccination protecting against respiratory virus could have unexpected benefits to limit invasive pneumococcal infections.

ABSTRACTInfluenza A virus (IAV) predisposes individuals to secondary infections with the bacteriumStreptococcus pneumoniae(the pneumococcus). Infections may manifest as pneumonia, sepsis, meningitis, or otitis media (OM). It remains controversial as to whether secondary pneumococcal disease is due to the induction of an aberrant immune response or IAV-induced immunosuppression. Moreover, as the majority of studies have been performed in the context of pneumococcal pneumonia, it remains unclear how far these findings can be extrapolated to other pneumococcal disease phenotypes such as OM. Here, we used an infant mouse model, human middle ear epithelial cells, and a series of reverse-engineered influenza viruses to investigate how IAV promotes bacterial OM. Our data suggest that the influenza virus HA facilitates disease by inducing a proinflammatory response in the middle ear cavity in a replication-dependent manner. Importantly, our findings suggest that it is the inflammatory response to IAV infection that mediates pneumococcal replication. This study thus provides the first evidence that inflammation drives pneumococcal replication in the middle ear cavity, which may have important implications for the treatment of pneumococcal OM.

Research into Haemophilus influenzae, a commensal and pathogen of humans, has resulted in major scientific contributions to biology. The first endonucleases (restriction enzymes), which paved the way for the new genetics, and the DNA used to obtain the first complete genome sequence of a free-living organism were obtained from H. influenzae. Prevention of invasive bacterial infections of infants, such as meningitis, has been achieved using a novel class of vaccines, of which the glycoconjugates of H. influenzae were the first to be licensed. Originally fallaciously proposed to be the aetiological agent of epidemic influenza, now known to be caused by a virus, H. influenzae is a pathogen of global public health importance. Research into the pathogenesis of the infections it causes (for example, meningitis, septicaemia, pneumonia and otitis media) are case studies in understanding the molecular basis of the variation in gene expression and gene sequences that are critical to its commensal and virulence behaviour and for the strategies that can be pursued to prevent H. influenzae diseases through vaccines.

Abstract Background The aim of the study was to evaluate the incidence and characteristics of influenza associated neurologic complications (IANCs) in hospitalized pediatric patients in Korea. Methods We performed retrospective review of hospitalized cases of confirmed influenza infection from October 2010 to April 2017. Patient’s data were collected from three referral hospitals in different regions of the country. Results A total 2,002 laboratory confirmed influenza cases were identified. The median age was 3.3 years old (range 0.0–18.9 years) and 1,003 patients were male (54%). Influenza A was diagnosed in 1,357 cases (68%), influenza B in 624 (31%) and both influenza A and B in 21 (1%). Other combined respiratory virus infection was detected in 104 (5.2%) cases. Out of 2,002 cases, IANCs were identified in 167 cases (8.3%); influenza virus A was detected in 116 (69.4%), B in 50 (29.9%) and both A and B in one case (0.6%). Of 167 cases with IANCs, 25 patients (15%) had underlying neurologic diseases. Eleven patients (11/167, 6.5%) had combined respiratory viral infection (Rhinovirus = 5; respiratory syncytial virus = 3; coronavirus = 2; and bocavirus = 1). The most common diagnosis was a simple febrile seizure (112/167, 67.1%), followed by other seizures (26/167, 15.6%), encephalopathy/encephalitis (17/167, 10.2%), meningitis (7/167, 4.2%), meningism (4/167, 2.4%) and acute ataxia (1/167, 0.6%). In two patients with encephalitis/meningitis, one patient had influenza A and the other patient had influenza B detected by PCR in cerebrospinal fluid. Most of the patients were fully recovered (162/167, 97%) and no neurologic complication occurred in patients who had only initial manifestation of simple febrile seizure. Ten patients (10/167, 6.0%) required hospitalization in intensive care unit. Three patients (3/167, 1.8%) died of encephalopathy (n = 1) and combined encephalopathy/myocarditis (n = 2). Pre-existing neurologic disease was a risk factor of IANCs with an odds ratio of 3.94 (95% confidence interval 2.37 to 6.56, P &lt; 0.0001). Conclusion IANCs is not rare and may cause serious outcome including death. Clinicians should be aware of the increased risk for IANCs in certain patients with neurologic diseases. Disclosures All authors: No reported disclosures.

Abstract We examined serum amyloid protein A (SAA) and C-reactive protein (CRP) as inflammatory markers of viral and bacterial infections. Both acute-phase reactants increased in the acute stage and thereafter decreased in the convalescent stage. In viral infections, the mean serum concentrations of SAA during the acute stage were 141 mg/L in infections with adenovirus, 77 mg/L with measles virus, 63 mg/L with influenza virus, 55 mg/L with parainfluenza virus, 31 mg/L with respiratory syncytial virus, and 31 mg/L in aseptic meningitis. The mean serum concentration of CRP was 19 mg/L for adenovirus infection and &lt; 7 mg/L in all other viral infections. The SAA concentrations were 5- to 11-fold greater than the CRP concentrations. Both the SAA and the CRP concentrations were higher in bacterial infections than in viral infections. Changes in the concentrations of serum SAA paralleled those in serum CRP in bacterial infection; during the course of viral infection, however, serum SAA tended to disappear more quickly than CRP did. SAA appears to be a clinically useful marker of inflammation in acute viral infections, with or without significant changes in the CRP concentration.

Background: While the rise of antimicrobial resistance (AMR) has been recognised as a major public health problem, the value of vaccines to control AMR is poorly defined. This expert survey was launched with the aim of informing the 2018 Vaccine Investment Strategy through which Gavi, the Vaccine Alliance prioritises future vaccine funding. This exercise focused on both vaccines currently supported by Gavi and under consideration for future funding. Methods: The relative importance of pre-defined criteria as drivers of overall value of vaccines as a tool/ intervention to control AMR was assessed by 18 experts: prevention of mortality and morbidity due to resistant pathogens, antibiotic use prevented, societal impact, ethical importance and sense of urgency. For each vaccine, experts attributed scores reflecting the estimated value for each criterion, and overall value relative to AMR was derived from the value assigned to each criterion and their relative importance for each vaccine. Results: Mortality, morbidity due to targeted resistant pathogens, and antibiotic use prevented were considered the most important determinants of overall value. Pneumococcal, typhoid and malaria vaccines were assigned highest value relative to antimicrobial resistance. Intermediate value was estimated for specific rotavirus, cholera, respiratory syncytial virus (RSV), influenza, dengue, measles, meningitis and Haemophilus influenza type b- (Hib-) containing pentavalent vaccines. Lowest value relative to AMR was estimated for Japanese encephalitis, hepatitis A, yellow fever, rabies and human papilloma virus vaccine. Conclusions: In the future, more evidence-based, data-driven, robust methodologies should be developed to guide coordinated, rational decision making on priority actions aimed at strengthening the use of vaccines against AMR.

The sandfly-borne Toscana phlebovirus (TOSV), a close relative of the sandfly fever Sicilian phlebovirus (SFSV), is one of the most common causes of acute meningitis or meningoencephalitis in humans in the Mediterranean Basin. However, most of human phlebovirus infections in endemic areas either are asymptomatic or cause mild influenza-like illness. To date, a vertebrate reservoir for sandfly-borne phleboviruses has not been identified. Dogs are a prime target for blood-feeding phlebotomines and are the primary reservoir of human sandfly-borne Leishmania infantum. However, there are no definitive studies to assess whether dogs play a significant role as a reservoir host for human phlebovirus survival in the environment. Here, we have evaluated the susceptibility of domestic dogs to infection by TOSV and SFSV following the direct inoculation of the infectious virus. After experimental infection, the presence of viral RNA was investigated in plasma, urine, saliva, conjunctiva, faeces, semen, and bone marrow samples from 0 to 91 days postinoculation (dpi), as well as in plasma, saliva, and tears samples at 760 dpi. None of the challenged dogs developed clinical signs of infection with either TOSV or SFSV. SFSV RNA was never detected. TOSV RNA was not in any of the specimen types, except for plasma samples that showed low viral loads, although irregularly. None of the dogs developed detectable neutralizing antibodies after a single challenge dose of either TOSV or SFSV. However, a second challenge dose of virus given 56 days later elicited neutralizing antibodies, implying that the first inoculation of virus primed the animals for an anamnestic response following the second challenge. These results demonstrated that healthy domestic dogs are not highly susceptible to infection by TOSV or SFSV and do not develop significant viremia or excrete virus following infection. Consequently, dogs are unlikely natural reservoir hosts of infection and do not appear to play a significant role in phlebovirus transmission cycles.

Over the past several years, new vaccines have become available to prevent serious illnesses and conditions in the adolescent population. Several have already been approved by the FDA for use in this age group; others are still in development. Recently, significant public attention has been focused on the availability of vaccines for several strains of HPV, to prevent both cervical cancer and genital warts. Prior to that, the vaccine for Hepatitis B was approved and recommended for the adolescent age group. Others currently available and recommended include vaccines for pertussis, meningitis, and influenza. In the future, additional vaccines are expected to become available for sexually transmitted and communicable diseases such as herpes simplex virus and HIV. Unfortunately, financial limitations and consent requirements can impede adolescents’ access to the vaccines that are recommended for their age group. However, a variety of policy options exist for overcoming the barriers and expanding access. These policy options are grounded both in international principles of human rights and in the existing framework of laws in the United States, and can be enhanced by attending to variations in age and developmental status among adolescents.

The Tick-borne encephalitis virus (TBEV) causes different disease symptoms varying from asymptomatic infection to severe encephalitis and meningitis suggesting a crucial role of the human host immune system in determining the fate of the infection. There is a need to understand the mechanisms underpinning TBEV-host interactions leading to protective immunity. To this aim, we studied the response of human peripheral blood mononuclear cells (PBMC) to the whole formaldehyde inactivated TBEV (I-TBEV), the drug substance of Encepur, one of the five commercially available vaccine. Immunophenotyping, transcriptome and cytokine profiling of PBMC revealed that I-TBEV generates differentiation of a sub-population of plasmacytoid dendritic cells (pDC) that is specialized in type I interferon (IFN) production. In contrast, likely due to the presence of aluminum hydroxide, Encepur vaccine was a poor pDC stimulus. We demonstrated I-TBEV-induced type I IFN together with Interleukin 6 and BAFF to be critical for B cell differentiation to plasmablasts as measured by immunophenotyping and immunoglobulin production. Robust type I IFN secretion was induced by pDC with the concerted action of both viral E glycoprotein and RNA mirroring previous data on dual stimulation of pDC by both S. aureus and influenza virus protein and nucleic acid that leads to a type I IFN-mediated sustained immune response. E glycoprotein neutralization or high temperature denaturation and inhibition of Toll-like receptor 7 signalling confirmed the importance of preserving the functional integrity of these key viral molecules during the inactivation procedure and manufacturing process to produce a vaccine able to stimulate strong immune responses.

Longtemps décrit comme un simple tissu de réserve énergétique, le tissu adipeux blanc est, depuis l’identification de la leptine en 1994, considéré comme un véritable organe endocrine. En effet, ce tissu secrète de nombreuses hormones et cytokines agissant de manière paracrine et endocrine pour contrôler le métabolisme énergétique. Par ailleurs, en plus des préadipocytes et des adipocytes, le tissu adipeux blanc contient également des cellules immunes innées et adaptatives ; lui conférant ainsi un rôle important dans le développement et le contrôle de l’immunité. Cependant, le rôle joué par le tissu adipeux blanc dans les infections - notamment pulmonaires - reste encore peu étudié. C’est dans ce cadre général que s’est inscrit ce travail de Thèse. La susceptibilité accrue des individus obèses (expansion du tissu adipeux blanc) à l’infection par le virus de la grippe (influenza) est largement étayée dans la littérature. Nous avons évalué l’impact de l’infection par le virus influenza sur le tissu adipeux blanc, chez des souris minces et des souris obèses. Nos résultats montrent que, de manière inattendue, le virus est détecté dans les tissus adipeux, sous-cutané (inguinal) et viscéral (périgonadique), de souris infectées par voie intra-nasale (détection du génome viral par RT-qPCR). La présence de virus dans le tissu adipeux est associée à l’augmentation de la sécrétion de cytokines pro- et anti-inflammatoires, à la diminution de l’expression de gènes impliqués dans la lipolyse et la lipogénèse, et à l’augmentation de l’expression des gènes impliqués dans l’induction d’une réponse immune anti-virale. De manière intéressante, l’infection par le virus influenza est associée au brunissement du tissu adipeux sous-cutané chez les souris minces. Chez les souris obèses, l’infection par le virus de la grippe n’induit pas l’effet dépôt spécifique observé chez la souris mince et ne montre pas de brûnissement au niveau du tissu adipeux sous-cutané 7 jours p.i. In vitro, nous montrons que le virus influenza peut infecter les préadipocytes et les adipocytes (lignée murine et cellules primaires humaines). Cependant, alors que le virus effectue la totalité de son cycle dans l’adipocyte, le préadipocyte libère très peu, voire pas, de nouveaux virions infectieux (PCR, transcriptomique, technique de plages de lyse, microscopie confocale et électronique). Ainsi nos résultats, très originaux, identifient le tissu adipeux blanc comme un nouveau tissu cible de l’infection par le virus de la grippe, in vivo. Au sein de ce tissu, les préadipocytes et les adipocytes sont potentiellement infectés par le virus, comme le montrent nos données in vitro, les adipocytes seuls permettant la production de nouvelles particules infectieuses.Contrairement à l’infection grippale, les données épidémiologiques et/ou expérimentales concernant la susceptibilité des obèses à l’infection par la bactérie Streptococcus pneumoniae sont contradictoires, du fait de l’utilisation de différents modèles d’obésité d’origine génétique et de sérotypes de pneumocoques. Dans ce projet, nous avons utilisé un modèle d’obésité d’origine nutritionnelle ; le modèle de souris nourries par un régime enrichi en lipides. Nous montrons que les souris obèses infectées (sérotype Sp1) développent un syndrome de type méningite, mortel, tandis que les souris minces contrôlent l’infection. Si les réponses pulmonaires à l’infection sont comparables entre les souris minces et obèses (dénombrement des colonies bactériennes, histologie, PCR, ELISA, cytométrie en flux), le nombre de bactéries dans le cerveau est significativement plus élevé chez les souris obèses, associé à une altération de la perméabilité de la barrière hématoencéphalique [...]
Since the identification of leptin in 1994, the white adipose tissue (WAT) is no longer considered to solely be an inert tissue storing fat. As an endocrine organ, the adipose tissue synthesizes and secretes several hormones and cytokines involved in the control of whole-body metabolism. In addition, besides preadipocytes and adipocytes, WAT also contains innate and adaptive immune cells; thereby contributing to the development and control of immunity. However, the role played by the adipose tissue during infections - notably during pulmonary infections, such as those resulting from influenza virus or Streptococcus pneumoniae infections - has barely been investigated. This defines the general scope of this work. Epidemiological and experimental data convincingly report that obese individuals are more susceptible to influenza infection. During this project, we therefore questioned whether influenza infection may impact on adipose tissues, both subcutaneous (inguinal, SCAT) and visceral (perigonadal, EWAT) depots, in lean and high-fat diet-induced obese mice. We unexpectedly showed that influenza virus is detected in SCAT and EWAT (quantification of the viral genome by RtqPCR) and that this was associated with drastic changes in the tissue such as: increased secretion of pro- and anti-inflammatory cytokines, decreased expression of genes involved in lipogenesis and lipolysis, as well as increased expression of genes related to the induction of anti-viral immunity. Interestingly enough, influenza infection was associated with the development of brown-like adipocytes in the SCAT, only in lean animals. Moreover, we demonstrated in vitro that preadipocytes and adipocytes (murine cell-line and human primary cells) are permissive to infection, yet with different outcomes. Indeed, only adipocytes allowed the release of new infectious particles (RtqPCR, transcriptomics, quantification of infectious particules on MDCK cells, confocal and transmission electron microscopy). Altogether, our findings revealed, for the first time, that the white adipose tissue, an organ at the crossroads of metabolism and immunity, is deeply affected by influenza infection and might thus be undervalued in influenza pathophysiology.In opposite to influenza infection, the impact of obesity on the outcome of Streptococcus pneumoniae (S.p.) infection remains uncertain, due to the different models (genetically-based obesity, and bacterial strains) used. During this work, we investigated S. pneumoniae (Sp1 strain, sublethal dose) infection in lean and high-fat diet-induced obese mice. We showed that obese mice died from sublethal S. pneumoniae infection, compared to lean animals. The increased mortality induced by infection did not result from impaired pulmonary response but rather from the development of a meningitis-like syndrom likely resulting from an increased bacterial dissemination through the bloodbrain barrier into the brain. We propose that the model of dietary obesity induced by consumption of fat-enriched diet, may be envisaged as a novel and valuable experimental model of memingitis to study Streptococcus pneumoniae travel through the blood-brain barrier and the subsequent immune consequences

La neuraminidase (NA) est l'une des 2 glycoprotéines de surface des virus influenza A et B. Son activité sialidase est nécessaire pour la libération des virions néoformés. Cette enzyme est la cible des principaux anti-viraux disponibles contre les virus influenza : le zanamivir et l'oseltamivir (OC). Nous avons étudié la sensibilité aux anti-NA de virus H5N1 et de virus H1N1 saisonniers. La comparaison de la sensibilité à TOC de la N1 des virus H5N1 de 2005 à celle des virus H5N1 antérieurs ou des virus H1N1 saisonniers par détermination des IC50 et des contantes d'inhibition montrent que la N1 des virus H5N1 de 2005 est 10 fois plus sensible à l'OC. Durant l'hiver 2007-08, différents pays ont rapporté la circulation de virus H1N1 naturellement résistants à l'OC. La comparaison des Km de N1 de ces virus à celles de virus antérieurs montrent une augmentation de l'affinité pour le substrat des N1 des virus récents qui compense l'effet de la mutation H275Y, ce qui pourrait expliquer la capacité de diffusion des virus résistants. Les résultats obtenus sur les virus H5N1 ou H1N1 soulignent l'impact potentiel de la dérive génétique de la NA sur son affinité pour son substrat et ses inhibiteurs en l'absence de pression de sélection. Des données cliniques et épidémiologiques indiquent une corrélation entre les pics d'épidémie grippale et l'incidence des infections invasives à Neisseria meningitidis. Nos observations suggèrent que l'hydrolyse partielle de la capsule des Nm par la NA grippale favorise l'adhésion des bactéries aux cellules épithéliales in vitro, et pourrait faciliter in vivo la colonisation de l'épithélium du rhinopharynx et le passage de la barrière épithéliale
Neuraminidase is a major surface glycoprotein of influenza A viruses, which possesses critical enzymatic activity allowing elution of progeny virus particles from infected cells. Neuraminidase inhibitors : zanamivir and oseltamivir (OC), are the major drugs available against influenza viruses. We studied the sensitivity to NA inhibitors of influenza H5N1 and H1N1 viruses. Our data show that sensitivity to OC of the NA of H5N1 viruses isolated in 2004-05, when determined by IC50 and Ki calculation, is about 10-fold higher as compared to earlier H5N1 viruses or to currently circulating H1N1 viruses. During 2007-08 winter surveillance of the antiviral susceptibility of influenza viruses in Europe revealed thé émergence of H1N1 viruses naturally resistant to OC. When compared to previously circulating H1N1 viruses, OC sensitive H1N1 viruses from the 2007-08 season were found to have significantly reduced Km value for the substrate. Thus, affinity for the substrate of the H275Y mutated N1 is comparable to that of previously circulating sensitive viruses, which may contribute to their overall fitness and transmissibility. These observations on H5N1 or H1N1 viruses underline the natural variability of NA enzymatic properties and its potential consequences in terms of antiviral sensitivity. Epidemiological and clinical data repeatedly report a coincidence between influenza infections and secondary meningococcal disease. Our data suggest that partial hydrolysis of neisserial capsule favour bacterial adhesion on epithelial cells in vitro, and could promote nasopharyngeal tract colonisation in vivo leading in some case to invasive infection

For decades, scientists puzzled over which influenza virus was actually responsible for the Russian pandemic. Finally, in 2014, phylogenetic techniques (examining evolutionary patterns of the virus genes) and seroarcheologic techniques (measuring antibodies likely present in people at various points in time) were applied to the question of which virus caused the Russian flu of 1889–1892. Thus, Pfeiffer’s proclamation that his bacillus caused influenza was finally proven wrong. His identification of Bacillus influenzae in the respiratory tract, however, was a major contribution to the scientific understanding of bacterial infections and moved the field of bacteriology forward in allowing other investigators to unearth its full potential as an important human pathogen. Further, in the course of his studies of B. influenzae, Pfeiffer pioneered the field of nutritional requirements of bacteria. Finally, Pfeiffer’s identification of Haemophilus influenzae launched subsequent studies of the causes of bacterial meningitis and initiated in-depth explorations of bacterial meningitis-causing pathogens that ground our concepts of pathogenesis, and guide our management, of the infection.

This chapter in the Oxford Handbook of Emergency Medicine discusses infectious diseases in the emergency department (ED). It starts by examining the general subjects of incubation periods, notifiable infectious diseases, and childhood diseases. It goes on to explore specific diseases, including meningitis, acute encephalitis, herpes simplex virus, herpes varicella-zoster, Zika virus, gastroenteritis/food poisoning, fish poisoning, infestations, tuberculosis, anthrax, streptococcal infections, staphylococcal infections, tetanus, gas gangrene, botulism, sexually transmitted infections, hepatitis, leptospirosis (Weil’s disease), and human immunodeficiency virus (HIV). It discusses imported infectious diseases, such as malaria, typhoid and paratyphoid (enteric fever), dengue, poliomyelitis, rabies, viral haemorrhagic fevers, and severe acute respiratory syndrome, before looking at influenza pandemics, avian flu, and swine flu.

The vaccines included in the current UK Immunisation Schedule offer protection against the following pathogens: A. Viruses ● Measles ● Mumps ● Rubella ● Polio ● Human Papilloma Virus (certain serotypes) ● Rotavirus ● Influenza virus (flu A and B) ● Varicella zoster virus (shingles) ● Hepatitis B virus B. Bacteria ● Corynebacterium diphtheriae (Diphtheria) ● Clostridium tetani (Tetanus) ● Bordetella pertussis (Pertussis) ● Haemophilus influenzae type B (Hib) ● Neisseria meningitidis (Meningococcal disease—certain serotypes) ● Streptococcus pneumoniae (Pneumococcal disease—certain serotypes) The UK Immunisation Schedule has evolved over several decades and reflects changes in vaccine development and commercial availability, national and sometimes international disease epidemiology, and the latest expert opinion. It is designed to offer optimal protection against infectious diseases of childhood to infants and children at the most appropriate age. The most up-to-date information about the UK Immunisation Schedule is available on the online version of the Department of Health publication commonly known as the ‘Green Book’: Immunisation Against Infectious Disease Handbook (see Further reading. Various chapters of the online version are updated at regular intervals; thus, it is very important to refer to the online version of the Green Book on the website for current guidance. Changes to the UK Immunisation Schedule are made on the recommendation of the independent Joint Committee on Vaccines and Immunisation (JCVI). Several of the UK Immunisation Schedule vaccines are combined vaccines: ● Measles, mumps, and rubella (MMR). ● Hexavalent diphtheria, tetanus, acellular pertussis, inactivated polio virus, Haemophilus influenza type b, hepatitis B (DTaP/IPV/Hib/HepB). ● Diphtheria, tetanus, acellular pertussis, inactivated polio, and Haemophilus influenzae (DTaP/IPV/Hib). ● Diphtheria, tetanus, acellular pertussis, inactivated polio (DTaP/IPV). ● Tetanus, diphtheria, and inactivated polio (Td/IPV). ● Inactivated influenza vaccine: influenza A H1N1, H3N2, influenza B. ● Live attenuated intranasal influenza vaccine: influenza A H1N1, H3N2, influenza B. In the UK, vaccines against single pathogens covered by the MMR vaccine are not recommended and not available in the National Health Service (NHS). There has been some limited demand for single-target vaccines, e.g. measles, due to misguided and unfounded concerns about the alleged risks of autism following MMR.