NorovirusNorovirusesarea genetically diverse group of single-stranded RNA, non-envelopedvirusesin theCaliciviridaefamily.[1]Theviruses are transmitted byfecally-contaminatedfood or water; by person-to-person contact;[2]andviaaerosolizationof the virus and subsequentcontamination of surfaces.[3]Noroviruses are the most common causeof viralgastroenteritisin humans,[4]andaffect people of all ages.[4]Norovirus infection is characterized bynausea, forceful vomiting, watery diarrhea, and abdominal pain, and in somecases, loss of taste. General lethargy, weakness, muscle aches, headache,coughs, and low-grade fever may occur. The disease is usually self-limiting,and severe illness is rare. A small number of people die, mostly the veryyoung, the elderly, and persons with weakened immune systems.Winter vomiting bugis acommon term for noroviruses in the UK, because the virus tends to causevomiting and to spread more easily in winter, when people tend to spend moretime indoors and near to each other.[5]Afterinfection,immunityto norovirus is usually incomplete andtemporary.[6]Outbreaksof norovirus infection often occur in closed or semiclosed communities, such aslong-term care facilities, overnight camps, hospitals, prisons, dormitories,and cruise ships, where the infection spreads very rapidly either byperson-to-person transmission or through contaminated food.[7]Manynorovirus outbreaks have been traced to food that was handled by one infectedperson.[8]Norovirus is rapidly inactivated by eithersufficient heating or bychlorine-based disinfectants,but the virus is less susceptible to alcohols and detergents, as it does nothave alipidenvelope.[9]The genus nameNorovirusis derived from Norwalk virus, whichcauses approximately 90% ofepidemicnonbacterial outbreaks ofgastroenteritisaround the world,[10]andmay be responsible for 50% of all foodborne outbreaks of gastroenteritis in theUnited States.[11][12]DiagnosisSpecific diagnosis of norovirus is routinelymade bypolymerase chainreaction(PCR)assaysorreal-timePCRassays, which giveresults within a few hours. These assays are very sensitive and can detect asfew as 10 virus particles.[13]Tests such asELISAthat useantibodiesagainsta mixture of norovirus strains are available commercially, but lackspecificityandsensitivity.[14]VirologyTransmissionNoroviruses are transmitted directly fromperson to person and indirectly via contaminated water and food. They arehighly contagious, and fewer than twenty virus particles can cause aninfection.[4]Transmissionoccurs through ingesting contaminated food and water and by person-to-personspread. Transmission through fecal-oral can beaerosolizedwhenthose stricken with the illness vomit, and can be aerosolized by a toilet flushwhen vomit or diarrhea is present; infection can follow eating food orbreathing air near an episode of vomiting, even if cleaned up.[15]Theviruses continue to be shed after symptoms have subsided and shedding can stillbe detected many weeks after infection.[16]Vomiting, in particular, transmits infectioneffectively. In one incident, a person who vomited spread infection rightacross a restaurant, suggesting that many unexplained cases of food poisoningmay have their source in vomit. 126 people were dining at six tables inDecember 1998; one woman vomited. Staff quickly cleaned up, and peoplecontinued eating. Three days later others started falling ill; 52 peoplereported a range of symptoms, from fever and nausea to vomiting and diarrhoea.The cause was not immediately identified. Researchers plotted the seatingarrangement: more than 90% of the people at the same table as the sick womanlater reported becoming ill. There was a direct correlation between the risk ofinfection of people at other tables and how close they were to the sick woman.More than 70% of the diners at an adjacent table fell ill; at a table on theother side of the restaurant, the rate was still 25%. The outbreak is beingblamed on a Norwalk-like virus (norovirus). Other cases of transmission byvomit were later identified.In one outbreak at an international scoutjamboree in the Netherlands, each person with gastroenteritis infected anaverage of 14 people before increased hygiene measures were put in place. Evenafter these new measures were enacted, an ill person still infected an averageof 2.1 other people.[17]ACDCstudy of 11 outbreaks inNew York Statelists the suspectedmode oftransmissionasperson-to-person in seven outbreaks, foodborne in two, waterborne in one, andone unknown. The source of waterborne outbreaks may include water frommunicipal supplies, wells, recreational lakes, swimming pools and ice machines.[18]Shellfishandsalad ingredients are the foods most often implicated in norovirus outbreaks.Ingestion of shellfish that have not been sufficiently heated poses a high riskfor norovirus infection.[19]Foodsother than shellfish may be contaminated by infected food handlers.[20]ClassificationNoroviruses (NoV) are a genetically diversegroup of single-stranded RNA, non-envelopedvirusesbelonging to theCaliciviridaefamily.[21]Accordingto the International Committee on Taxonomy of Viruses, thegenusNorovirushas one species, whichis calledNorwalk virus.[1]Serotypes,strains and isolates include:[22]·Norwalk virus;·Hawaii virus;·Snow Mountain virus;·Mexico virus;·Desert Shield virus;·Southampton virus;·Lordsdale virus;·Wilkinson Virus.[23]Noroviruses commonly isolated in cases ofacute gastroenteritis belong to two genogroups: genogroup I (GI) includesNorwalk virus, Desert Shield virus and Southampton virus; and II (GII), whichincludes Bristol virus, Lordsdale virus, Toronto virus, Mexico virus, Hawaiivirus and Snow Mountain virus.[21]Noroviruses can genetically be classifiedinto five different genogroups (GI, GII, GIII, GIV, and GV), which can befurther divided into different genetic clusters orgenotypes. For example, genogroup II, the mostprevalent human genogroup, presently contains 19 genotypes. Genogroups I, IIand IV infect humans, whereas genogroup III infectsbovine species, and genogroup V has recentlybeen isolated in mice.[23]Most noroviruses that infect humans belong togenogroups GI and GII.[24]Norovirusesfrom Genogroup II, genotype 4 (abbreviated as GII.4) account for the majorityof adult outbreaks ofgastroenteritisand often sweep across the globe.[25]Recentexamples include US95/96-US strain, associated with global outbreaks in themid- to late-1990s;Farmington Hillsvirus associated with outbreaks inEuropeandthe United States in 2002 and in 2004; and Hunter virus which was associatedwith outbreaks in Europe, Japan and Australasia. In 2006, there was anotherlarge increase in NoV infection around the globe.[26]Reportshave shown a link between the expression of human histo-blood group antigens(HBGAs) and the susceptibility to norovirus infection. Studies have suggestedthe viral capsid of noroviruses may have evolved from selective pressure ofhuman HBGAs.[27]A 2008 study suggests the proteinMDA-5may be the primary immune sensor thatdetects the presence of noroviruses in the body.[28]Interestingly,some people have common variations of the MDA-5 gene that could make them moresusceptible to norovirus infection.[29]A 2010 study suggested a specific geneticversion of norovirus (which would not be distinguishable from other types ofthe virus using standard viral antibody tests) interacts with a specificmutation in theATG16L1geneto help trigger symptomaticCrohn's diseasein mice that have been subjected to achemical that causes intestinal injury similar to the process in humans (thereare other similar ways for such diseases to happen like this, and this study initself does not prove norovirus causes Crohn's in humans).StructureNoroviruses contain apositive-senseRNAgenomeofapproximately 7.5kbp, encoding a majorstructuralprotein(VP1) of about 58~60kDaand a minorcapsidprotein(VP2).[30]Thevirus particles demonstrate an amorphous surface structure when visualizedusingelectron microscopyand are between 27-38nmin size.[31]Themost variable region of the viral capsid is the P2 domain, which containsantigen-presenting sites and carbohydrate-receptor binding regions.[32][33][34]The estimated mutation rate (1.21 x 102to 1.41 x 102substitutions per site per year) inthis virus is high even compared with other RNA viruses.[35]PathophysiologyWhen a person becomes infected with norovirus,the virus begins toreplicatewithinthesmall intestine. After approximately one totwo days, norovirus symptoms can appear. The principal symptom is acutegastroenteritisthat develops between 24 and 48 hoursafter exposure, and lasts for 24–60 hours.[12]Thedisease is usuallyself-limiting,and characterized by nausea, forceful vomiting, waterydiarrhea, and abdominal pain, and in somecases, loss of taste. General lethargy, weakness, muscle aches, headache,coughs, and low-grade fever may occur.Severe illness is rare: although people arefrequently treated at the emergency ward, they are rarely admitted to thehospital. The number of deaths from norovirusin the United States is estimated to be around 300 each year, with most ofthese occurring in the very young, the elderly, and persons with weakenedimmune systems. Symptoms may become life-threatening in these groups ifdehydrationisignored or not treated.[2]PreventionHand washing with soap and water is aneffective method for reducing the transmission of noroviruspathogens. Alcohol rubs (≥62% ethanol) may be used as an adjunct, but are less effective thanhand-washing, as norovirus lacks alipidviral envelope. Surfaces where norovirusparticles may be present can be sanitised with a solution of 1.5% to 7.5% ofhousehold bleach in water, or other disinfectant effective against norovirus.[36][37][38]In health-care environments, the preventionofnosocomial infectionsinvolves routine andterminal cleaning.Nonflammablealcohol vapor in CO2systems are used in health careenvironments where medical electronics would be adversely affected byaerosolized chlorine or other caustic compounds.[39]Ligocyte announced in 2007 that it wasworking on a vaccine and had started phase 1 trials.[40]Asof 2011a monovalent nasalvaccine had completed phase I/II trials, while bivalent intramuscular and nasalvaccines were at earlier stages of development.[41]PersistenceThe norovirus can survive for long periodsoutside a human host depending on the surface and temperature conditions: 12hours on hard surfaces, and up to 12 days on contaminated fabrics,[42]andit can survive for months, maybe even years in contaminated still water.[43]Astudy done in 2006 found the virus on several surfaces used for foodpreparation 7 days after contamination.[44]Detection in foodsRoutine protocols to detect norovirus(norovirus RNA) in clams and oysters byreverse transcription polymerase chain reactionare being employed by governmentallaboratories such as the FDA in the USA.[45]EpidemiologyEpidemiological data from developingcountries about the importance of norovirus in pediatric diarrhea are limited.Recently, in Nicaragua, it has been observed that norovirus is responsible for11% of the diarrhea cases occurring in children less than five years of age atcommunity level and 15% of the moderate to severe cases requiring intravenousrehydration.[47]In theGuangdongprovinceof the People's Republic of China, the Provincial Health Department said onDecember 17, 2010, that it had confirmed 429 cases of norovirus infection inthe November 2010 outbreak inConghua,Guangzhou, but no one died from it.[48]Human geneticsA non functionalfucosyltransferaseFUT2 provides high protection from themost common norovirus GII.4.[49]Functional FUT2 fucosyltransferasetransfers a fucose sugar to the end of the Histo-blood groupABO(H)precursor in gastrointestinal cells and saliva glands. The ABH antigen producedis thought to act as receptors for human norovirus. Homozygous carriers of anynonsense mutation in the FUT2 gene are called non-secretors, as no ABH antigenis produced. Approximately 20% of Caucasians are non-secretors due to the G428Aand C571T nonsense mutations in FUT2 and therefore have strong although notabsolute protection from the norovirus GII.4.[50]Non-secretorscan still produce ABH antigens in erythrocytes, as the precursor is formed byFUT1.[51]Somenorovirus genotypes (GI.3) can infect non-secretors.[52]Of individuals who are secretor positive,those with blood type O were more likely to be infected and B less likely.[53][54][55]HistoryThe norovirus was originally named the"Norwalk agent" afterNorwalk, Ohio, in the United States, where anoutbreak of acute gastroenteritis occurred among children at BronsonElementary Schoolin November 1968. In 1972, electronmicroscopy on storedhuman stoolsamplesidentified a virus, which was given the name "Norwalk virus." Numerous outbreaks withsimilar symptoms have been reported since. Thecloningandsequencingofthe Norwalk virus genome showed that these viruses have a genomic organizationconsistent with viruses belonging to the familyCaliciviridae.[56]Thename was shortened to "norovirus" after being identified in anumber of outbreaks oncruise shipsandreceiving attention throughout the United States. The name"norovirus" (Norovirusforthe genus) was approved by theInternationalCommittee on Taxonomy of Viruses(ICTV)in 2002.[57]In2011, however, a press release and a newsletter[58]werepublished by ICTV, which strongly encourage the media, national healthauthorities and the scientific community to use the virus nameNorwalk virus, rather than the genus nameNorovirus, when referring to outbreaks of the disease. This is also a publicstatement of ICTV to the request from an individual in Japan to rename thegenus Norovirus because of the possibility of negative associations for peoplein Japan and elsewhere who have the family name "Noro". Before thisposition of ICTV was made public, ICTV consulted widely with members of theCaliciviridae Study Group and carefully discussed the case.In addition to "Norwalk agent" and"Norwalk virus," the virus previously has been called"Norwalk-like virus," "small, round-structured viruses"(SRSVs), and "Snow Mountain virus."[59]Commonnames of the illness caused by noroviruses still in use include "wintervomiting disease,"[60]"wintervomiting bug,"[61][62]"viralgastroenteritis," and "acute nonbacterial gastroenteritis."[2]Italso colloquially is known as "stomach flu," but this actually is abroad name that refers to gastric inflammation caused by a range of viruses andbacteria.
The 2009 flu pandemic or swine flu was an influenza pandemic, and the second of the two pandemics involving H1N1 influenza virus (the first of them was the 1918 flu pandemic), albeit in a new version. First described in April 2009, the virus appeared to be a new strain of H1N1 which resulted when a previous triplereassortment of bird, swine and human flu viruses further combined with a Eurasian pig flu virus,[2] leading to the term "swine flu" to be used for this pandemic.[3] Unlike most strains of influenza, H1N1 does not disproportionately infect adults older than 60 years; this was an unusual and characteristic feature of the H1N1 pandemic.[4] Even in the case of previously very healthy persons, a small percentage will developpneumonia or acute respiratory distress syndrome (ARDS). This manifests itself as increased breathing difficulty and typically occurs 3–6 days after initial onset of flu symptoms.[5][6] The pneumonia caused by flu can be either direct viral pneumonia or a secondary bacterial pneumonia. In fact, a November 2009 New England Journal of Medicine article recommends that flu patients whose chest X-ray indicates pneumonia receive both antivirals and antibiotics.[7] In particular, it is a warning sign if a child (and presumably an adult) seems to be getting better and then relapses with high fever, as this relapse may be bacterial pneumonia.[8]Initially coined an "outbreak", the stint began in the state of Veracruz, Mexico, with evidence that there had been an ongoing epidemic for months before it was officially recognized as such.[9] The Mexican government closed most of Mexico City's public and private facilities in an attempt to contain the spread of the virus; however, it continued to spread globally, and clinics in some areas were overwhelmed by infected people. In June, the World Health Organization (WHO) and the U.S. CDC stopped counting cases and declared the outbreak a pandemic.[10]Despite being informally called "swine flu", the H1N1 flu virus cannot be spread by eating pork or pork products;[11][12] similar to other influenza viruses, it is typically contracted by person to person transmission through respiratory droplets.[13] Symptoms usually last 4–6 days.[14] Antivirals (oseltamivir orzanamivir) were recommended for those with more severe symptoms or those in an at-risk group.[15]The pandemic began to taper off in November 2009,[16] and by May 2010, the number of cases was in steep decline.[17][18][19][20] On 10 August 2010, the Director-General of the World Health Organization, Margaret Chan, announced the end of the H1N1 pandemic,[21] and announced that the H1N1 influenza event has moved into the post-pandemic period.[22]According to the latest WHO statistics (July 2010), the virus has killed more than 18,000 people since it appeared in April 2009, however they state that the total mortality (including deaths unconfirmed or unreported) from the H1N1 strain is "unquestionably higher".[17][23] Critics claimed the WHO had exaggerated the danger, spreading "fear and confusion" rather than "immediate information".[24] The WHO began an investigation to determine[25] whether it had "frightened people unnecessarily".[26] A flu followup study done in September 2010, found that "the risk of most serious complications was not elevated in adults or children."[27] In an 5 August 2011 PLoS ONE article, researchers estimated that the 2009 H1N1 global infection rate was 11% to 21%, lower than what was previously expected.[28] However, by 2012, a study showed that as many as 579,000 people could have been killed by the disease, as only those fatalities confirmed by laboratory testing were included in the original number, and meant that many of those without access to health facilities went uncounted. The majority of these deaths occurred in Africa and Southeast Asia. Experts agreed that an estimated 294,500 people were killed by the disease.[29][30] The World Health Organization also said that the initial death toll could be much higher.[31]ClassificationThe initial outbreak was called the "H1N1 influenza", or "Swine Flu" by American media. It is called pandemic H1N1/09 virus by the World Health Organization,[32] while the U.S. Centers for Disease Control and Prevention refer to it as "novel influenza A (H1N1)" or "2009 H1N1 flu".[33] In theNetherlands, it was originally called "Pig Flu", but is now called "New Influenza A (H1N1)" by the national health institute, although the media and general population use the name "Mexican Flu". South Korea and Israel briefly considered calling it the "Mexican virus".[34] Later, the South Korean press used "SI", short for "swine influenza". Taiwan suggested the names "H1N1 flu" or "new flu", which most local media adopted.[35] The World Organization for Animal Health proposed the name "North American influenza".[36] The European Commission adopted the term "novel flu virus".[37]Signs and symptomsThe symptoms of H1N1 flu are similar to those of other influenzas, and may include fever, cough (typically a "dry cough"), headache, muscle or jointpain, sore throat, chills, fatigue, and runny nose. Diarrhea, vomiting, and neurological problems have also been reported in some cases.[38][39]People at higher risk of serious complications include those aged over 65, children younger than 5, children with neurodevelopmental conditions, pregnant women (especially during the third trimester),[5][40] and those of any age with underlying medical conditions, such as asthma, diabetes, obesity, heart disease, or a weakened immune system (e.g., taking immunosuppressive medications or infected with HIV).[41] More than 70% of hospitalizations in the U.S. have been people with such underlying conditions, according to the CDC.[42]In September 2009, the CDC reported that the H1N1 flu "seems to be taking a heavier toll among chronically ill children than the seasonal flu usually does."[8] Through 8 August 2009, the CDC had received 36 reports of paediatric deaths with associated influenza symptoms and laboratory-confirmed pandemic H1N1 from state and local health authorities within the United States, with 22 of these children having neurodevelopmental conditions such as cerebral palsy, muscular dystrophy, or developmental delays.[43] "Children with nerve and muscle problems may be at especially high risk for complications because they cannot cough hard enough to clear their airways".[8] From 26 April 2009, to 13 February 2010, the CDC had received reports of the deaths of 277 children with laboratory-confirmed 2009 influenza A (H1N1) within the United States.[44]Symptoms in severe casesThe World Health Organization reports that the clinical picture in severe cases is strikingly different from the disease pattern seen during epidemics of seasonal influenza. While people with certain underlying medical conditions are known to be at increased risk, many severe cases occur in previously healthy people. In severe cases, patients generally begin to deteriorate around three to five days after symptom onset. Deterioration is rapid, with many patients progressing to respiratory failure within 24 hours, requiring immediate admission to an intensive care unit. Upon admission, most patients need immediate respiratory support with mechanical ventilation.[45]A November 2009 CDC recommendation stated that the following constitute "emergency warning signs" and advised seeking immediate care if a person experiences any one of these signs:[46]In adults:· Difficulty breathing or shortness of breath· Pain or pressure in the chest or abdomen· Sudden dizziness· Confusion· Severe or persistent vomiting· Low temperatureIn children:· Fast breathing or working hard to breathe· Bluish skin color· Not drinking enough fluids· Not waking up or not interacting· Being so irritable that the child does not want to be held· Flu-like symptoms which improve but then return with fever and worse cough· Fever with a rash· Being unable to eat· Having no tears when cryingResearch later indicated that the severe flu effects in healthy young and middle-aged adults are caused by an excessive immune response.[47]ComplicationsMost complications have occurred among previously healthy individuals, with obesity and respiratory disease as the strongest risk factors. Pulmonarycomplications are common. Primary influenza pneumonia occurs most commonly in adults and may progress rapidly to acute lung injury requiringmechanical ventilation. Secondary bacterial infection is more common in children. Staphylococcus aureus, including methicillin-resistant strains, is an important cause of secondary bacterial pneumonia with a high mortality rate. Neuromuscular and cardiac complications are unusual but may occur.[48]A United Kingdom investigation of risk factors for hospitalisation and poor outcome with pandemic A/H1N1 influenza looked at 631 patients from 55 hospitals admitted with confirmed infection from May through September 2009. 13% were admitted to a high dependency or intensive care unit and 5% died; 36% were aged <16 years and 5% were aged ≥65 years. Non-white and pregnant patients were over-represented. 45% of patients had at least one underlying condition, mainly asthma, and 13% received antiviral drugs before admission. Of 349 with documented chest x-rays on admission, 29% had evidence of pneumonia, but bacterial co-infection was uncommon. Multivariate analyses showed that physician-recorded obesity on admission and pulmonary conditions other than asthma or chronic obstructive pulmonary disease (COPD) were associated with a severe outcome, as were radiologically confirmed pneumonia and a raised C-reactive protein (CRP) level (≥100 mg/l). 59% of all in-hospital deaths occurred in previously healthy people.[49]Fulminant (sudden-onset) myocarditis has been linked to infection with H1N1, with at least four cases of myocarditis confirmed in patients also infected with A/H1N1. Three out of the four cases of H1N1-associated myocarditis were classified as fulminant, and one of the patients died.[50]Also, there appears to be a link between severe A/H1N1 influenza infection and pulmonary embolism. In one report, five out of 14 patients admitted to the intensive care unit with severe A/H1N1 infection were found to have pulmonary emboli.[51]An article published in JAMA in September 2010[52] challenged previous reports and stated that children infected in the 2009 flu pandemic were no more likely to be hospitalised with complications or get pneumonia than those who catch seasonal strains. Researchers found that about 1.5% of children with the H1N1 swine flu strain were hospitalised within 30 days, compared with 3.7% of those sick with a seasonal strain of H1N1 and 3.1% with an H3N2 virus.[27]DiagnosisConfirmed diagnosis of pandemic H1N1 flu requires testing of a nasopharyngeal, nasal or oropharyngeal tissue swab from the patient.[53] Real-time RT-PCR is the recommended test as others are unable to differentiate between pandemic H1N1 and regular seasonal flu.[53] However, most people with flu symptoms do not need a test for pandemic H1N1 flu specifically, because the test results usually do not affect the recommended course of treatment.[54] The U.S. CDC recommend testing only for people who are hospitalised with suspected flu, pregnant women and people with weakened immune systems.[54] For the mere diagnosis of influenza and not pandemic H1N1 flu specifically, more widely available tests include rapid influenza diagnostic tests (RIDT), which yield results in about 30 minutes, and direct and indirect immunofluorescence assays (DFA and IFA), which take 2–4 hours.[55] Due to the high rate of RIDT false negatives, the CDC advises that patients with illnesses compatible with novel influenza A (H1N1) virus infection but with negative RIDT results should be treated empirically based on the level of clinical suspicion, underlying medical conditions, severity of illness and risk for complications, and if a more definitive determination of infection with influenza virus is required, testing with rRT-PCR or virus isolation should be performed.[56] Dr. Rhonda Medows of the Georgia Department of Community Health states that the rapid tests are incorrect anywhere from 30% to 90% of the time and warns doctors in her state not to use them because they are wrong so often.[57] The use of RIDTs has also been questioned by researcher Paul Schreckenberger of the Loyola University Health System, who suggests that rapid tests may actually pose a dangerous public health risk.[58] Dr. Nikki Shindo of the WHO has expressed regret at reports of treatment being delayed by waiting for H1N1 test results and suggests, "[D]octors should not wait for the laboratory confirmation but make diagnosis based on clinical and epidemiological backgrounds and start treatment early".[59]On 22 June 2010, the CDC announced a new test called the "CDC Influenza 2009 A (H1N1)pdm Real-Time RT-PCR Panel (IVD)". It uses a molecular biology technique to detect influenza A viruses and specifically the 2009 H1N1 virus. The new test will replace the previous real-time RT-PCR diagnostic test used during the 2009 H1N1 pandemic, which received an emergency use authorisation from the U.S. Food and Drug Administration in April 2009. Tests results are available in four hours and are 96% accurate.[60]TransmissionSpread of the H1N1 virus is thought to occur in the same way that seasonal flu spreads. Flu viruses are spread mainly from person to person through coughing or sneezing by people with influenza. Sometimes people may become infected by touching something – such as a surface or object – with flu viruses on it and then touching their face. "Avoid touching your eyes, nose or mouth. Germs spread this way".[11]The basic reproduction number (the average number of other individuals whom each infected individual will infect, in a population which has no immunity to the disease) for the 2009 novel H1N1 is estimated to be 1.75.[69] A December 2009 study found that the transmissibility of the H1N1 influenza virus in households is lower than that seen in past pandemics. Most transmissions occur soon before or after the onset of symptoms.[70]The H1N1 virus has been transmitted to animals, including swine, turkeys, ferrets, household cats, at least one dog and a cheetah.[71][72][73][74]PreventionThe H1N1 vaccine was initially in short supply and in the U.S., the CDC recommended that initial doses should go to priority groups such as pregnant women, people who live with or care for babies under six months old, children six months to four years old and health-care workers.[75] In the UK, the NHS recommended vaccine priority go to people over six months old who were clinically at risk for seasonal flu, pregnant women and households of people with compromised immunity.[76]Although it was initially thought that two injections would be required, clinical trials showed that the new vaccine protected adults "with only one dose instead of two", and so the limited vaccine supplies would go twice as far as had been predicted.[77][78] Health officials worldwide were also concerned because the virus was new and could easily mutate and become more virulent, even though most flu symptoms were mild and lasted only a few days without treatment. Officials also urged communities, businesses and individuals to make contingency plans for possible school closures, multiple employee absences for illness, surges of patients in hospitals and other effects of potentially widespread outbreaks.[79]In February 2010, the CDC's Advisory Committee on Immunization Practices voted for "universal" flu vaccination in the U.S. to include all people over six months of age. The 2010–2011 vaccine will protect against the 2009 H1N1 pandemic virus and two other flu viruses.[80]VaccinesAs of 19 November 2009, over 65 million doses of vaccine had been administered in over 16 countries; the vaccine seems safe and effective, producing a strong immune response that should protect against infection.[88] Whereas the 2009 trivalent seasonal influenza vaccine neither increases nor decreases the risk of infection with H1N1, the vaccines rushed to combat the new strain are effective against H1N1,[89][90] although they are manufactured similarly. Overall the safety profile of the new H1N1 vaccine is similar to that of the seasonal flu vaccine, and as of November 2009 fewer than a dozen cases of Guillain-Barre syndrome had been reported post-vaccination.[91]Only a few of these were suspected to be actually related to the H1N1 vaccination, and only temporary illness had been observed.[91] This is in strong contrast to the 1976 swine flu outbreak, when mass vaccinations in the United States caused over 500 cases of Guillain-Barre syndrome and led to 25 deaths.[92] Although the vaccines were effective, many industrialised nations were giving away, selling, canceling orders for and destroying excess doses of the vaccine.[93][94]There are safety concerns for people who are allergic to eggs because the viruses for the vaccine are grown in chicken-egg-based cultures. People with egg allergies may be able to receive the vaccine, after consultation with their physician, in graded doses in a careful and controlled environment.[95] A vaccine manufactured by Baxter is made without using eggs, but requires two doses three weeks apart to produce immunity.[96]As of late November 2009, in Canada there had been 24 confirmed cases of anaphylactic shock following vaccination, including one death. The estimated rate is one anaphylactic reaction per 312,000 persons receiving the vaccine; however, six persons had suffered anaphylaxis out of 157,000 doses given from one batch of vaccine. Dr. David Butler-Jones, Canada's chief public health officer, stated that even though this was an adjuvantedvaccine, that did not appear to be the cause of this severe allergic reaction in these six patients.[97][98]Infection controlTravel precautionsOn 7 May 2009, the WHO stated that containment was not feasible and that countries should focus on mitigating the effect of the virus. They did not recommend closing borders or restricting travel.[107] On 26 April 2009, theChinese government announced that visitors returning from flu-affected areas who experienced flu-like symptoms within two weeks would be quarantined.[108]U.S. airlines had made no major changes as of the beginning of June 2009, but continued standing practices which include looking for passengers with symptoms of flu, measles or other infections, and relying on in-flight air filters to ensure that aircraft were sanitised.[109] Masks were not generally provided by airlines and the CDC did not recommend that airline crews wear them.[109] Some non-U.S. airlines, mostly Asian, including Singapore Airlines, China Eastern Airlines, China Southern Airlines, Cathay Pacific and Mexicana Airlines, took measures such as stepping up cabin cleaning, installing state-of-the-art air filters and allowing in-flight staff to wear face masks.[109]SchoolsU.S. government officials have been especially concerned about schools because the H1N1 flu virus appears to disproportionately affect young and school-age people, between six months and 24 years of age.[110] The H1N1 outbreak led to numerous precautionary school closures in some areas. Rather than closing schools, the CDC recommended that students and school workers with flu symptoms should stay home for either seven days total, or until 24 hours after symptoms subsided, whichever was longer.[111] The CDC also recommended that colleges should consider suspending fall 2009 classes if the virus began to cause severe illness in a significantly larger share of students than the previous spring. They also urged schools to suspend rules, such as penalties for late papers or missed classes or requirements for a doctor's note, to enforce "self-isolation" and prevent students from venturing out while ill;[112] schools were advised to set aside a room for people developing flu-like symptoms while they waited to go home and to have ill students or staff and those caring for them use face masks.[113]In California, school districts and universities were on alert and working with health officials to launch education campaigns. Many planned to stockpile medical supplies and discuss worst-case scenarios, including plans to provide lessons and meals for low-income children in case elementary and secondary schools closed.[114]University of California campuses stockpiled supplies, from paper masks and hand sanitizer to food and water.[114] To help prepare for contingencies, University of Maryland School of Medicine professor of pediatricsJames C. King Jr. suggested that every county should create an "influenza action team" to be run by the localhealth department, parents and school administrators.[115] As of 28 October 2009, about 600 schools in the United States had been temporarily closed, affecting over 126,000 students in 19 states.[116]WorkplaceFearing a worst-case scenario, the U.S. Department of Health and Human Services (HHS), the Centers for Disease Control and Prevention and theDepartment of Homeland Security (DHS) developed updated guidance[117] and a video for employers to use as they developed plans to respond to the H1N1 outbreak. The guidance suggested that employers consider and communicate their objectives, such as reducing transmission among staff, protecting people who are at increased risk of influenza-related complications from becoming infected, maintaining business operations, and minimising adverse effects on other entities in their supply chains.[117]The CDC estimated that as much as 40% of the workforce might be unable to work at the peak of the pandemic due to the need for many healthy adults to stay home and care for an ill family member,[118] and advised that individuals should have steps in place should a workplace close down or a situation arise that requires working from home.[119] The CDC further advised that persons in the workplace should stay home sick for seven days after getting the flu, or 24 hours after symptoms end, whichever is longer.[111]In the UK, the Health and Safety Executive (HSE) also issued general guidance for employers.[120]Facial masksThe U.S. CDC does not recommend use of face masks or respirators in non-health care settings, such as schools, workplaces, or public places, with a few exceptions: people who are ill with the virus when around other people, and people who are at risk for severe illness while caring for someone with the flu.[121] There has been some disagreement about the value of wearing facial masks, some experts fearing that masks may give people a false sense of security and should not replace other standard precautions.[122] Masks may benefit people in close contact with infected persons, but it is unknown whether they prevent H1N1 flu infection.[122] Yukihiro Nishiyama, professor of virology at Nagoya University's School of Medicine, commented that the masks are "better than nothing, but it's hard to completely block out an airborne virus since it can easily slip through the gaps".[123]According to mask manufacturer 3M, masks will filter out particles in industrial settings, but "there are no established exposure limits for biological agents such as swine flu virus".[122] However, despite the lack of evidence of effectiveness, the use of such masks is common in Asia.[123][124] They are particularly popular in Japan, where cleanliness and hygiene are highly valued and where etiquette obligates those who are sick to wear masks to avoid spreading disease.[123]Pigs and food safetyThe pandemic virus is a type of swine influenza, derived originally from a strain which lived in pigs, and this origin gave rise to the common name of "swine flu". This term is widely used by mass media. The virus has been found in American hogs,[133] and Canadian[134] as well as in hogs in Northern Ireland, Argentina, and Norway.[135] Leading health agencies and the United States Secretary of Agriculture have stressed that eating properly cooked pork or other food products derived from pigs will not cause flu.[136][137] Nevertheless, on 27 April, Azerbaijan imposed a ban on the importation of animal husbandry products from America.[138] The Indonesian government also halted the importation of pigs and initiated the examination of 9 million pigs in Indonesia.[139] The Egyptian government ordered the slaughter of all pigs in Egypt on 29 April 2009.[140]TreatmentFurther information: Influenza treatmentA number of methods have been recommended to help ease symptoms, including adequate liquid intake and rest.[141] Over-the-counter pain medications such as acetaminophen and ibuprofen do not kill the virus; however, they may be useful to reduce symptoms.[142] Aspirin and other salicylate products should not be used by people under 19 with any flu-type symptoms because of the risk of developing Reye's Syndrome.[143]If the fever is mild and there are no other complications, fever medication is not recommended.[142] Most people recover without medical attention, although those with pre-existing or underlying medical conditions are more prone to complications and may benefit from further treatments.[46]People in at-risk groups should be treated with antivirals (oseltamivir or zanamivir) as soon as possible when they first experience flu symptoms. The at-risk groups include pregnant and post partum women, children under two years old, and people with underlying conditions such as respiratory problems.[15] People who are not in an at-risk group who have persistent or rapidly worsening symptoms should also be treated with antivirals. People who have developed pneumonia should be given both antivirals and antibiotics, as in many severe cases of H1N1-caused illness, bacterial infection develops.[59] Antivirals are most useful if given within 48 hours of the start of symptoms and may improve outcomes in hospitalised patients.[144] In those beyond 48 hours who are moderately or severely ill, antivirals may still be beneficial.[13] If oseltamivir (Tamiflu) is unavailable or cannot be used, zanamivir (Relenza) is recommended as a substitute.[15][145] Peramivir is an experimental antiviral drug approved for hospitalised patients in cases where the other available methods of treatment are ineffective or unavailable.[146]To help avoid shortages of these drugs, the U.S. CDC recommended oseltamivir treatment primarily for people hospitalised with pandemic flu; people at risk of serious flu complications due to underlying medical conditions; and patients at risk of serious flu complications. The CDC warned that the indiscriminate use of antiviral medications to prevent and treat influenza could ease the way for drug-resistant strains to emerge, which would make the fight against the pandemic that much harder. In addition, a British report found that people often failed to complete a full course of the drug or took the medication when not needed.[147]Side effectsBoth medications have known side effects, including lightheadedness, chills, nausea, vomiting, loss of appetite and trouble breathing. Children were reported to be at increased risk of self-injury and confusion after taking oseltamivir.[141] The WHO warn against buying antiviral medications from online sources, and estimate that half the drugs sold by online pharmacies without a physical address are counterfeit.[148]ResistanceAs of December 2010, the World Health Organization (WHO) reported 314 samples of the 2009 pandemic H1N1 flu tested worldwide have shown resistance to oseltamivir (Tamiflu).[149] This is not totally unexpected as 99.6% of the seasonal H1N1 flu strains tested have developed resistance to oseltamivir.[150] No circulating flu has yet shown any resistance to zanamivir (Relenza), the other available anti-viral.[151]Effectiveness of antivirals questionedOn 8 December 2009, the Cochrane Collaboration, which reviews medical evidence, announced in a review published in BMJ that it had reversed its previous findings that the antiviral drugs oseltamivir (Tamiflu) and zanamivir (Relenza) can ward off pneumonia and other serious conditions linked to influenza. They reported that an analysis of 20 studies showed oseltamivir offered mild benefits for healthy adults if taken within 24 hours of onset of symptoms, but found no clear evidence it prevented lower respiratory tract infections or other complications of influenza.[152][153] Their published finding relates only to its use in healthy adults with influenza; they say nothing about its use in patients judged to be at high risk of complications (pregnant women, children under five and those with underlying medical conditions), and uncertainty over its role in reducing complications in healthy adults may still leave it as a useful drug for reducing the duration of symptoms. The drugs might eventually be demonstrated to be effective against flu-related complications; in general, the Cochrane Collaboration concluded "Paucity of good data".[153][154]Some specific results from the BMJ article include: "The efficacy of oral oseltamivir against symptomatic laboratory confirmed influenza was 61% (risk ratio 0.39, 95% confidence interval 0.18 to 0.85) at 75 mg daily ... The remaining evidence suggests oseltamivir did not reduce influenza related lower respiratory tract complications (risk ratio 0.55, 95% confidence interval 0.22 to 1.35)".[153] Notice especially the wide range for this second result.
发热发烧(也被称为热病)是最常见的医学体征之一,其特征是体温升高超过正常范围36.5-37.5 ℃(98-100°F),是由于体温调节设定点的提高所致。体温调节设定点触发点的提高增加了肌肉紧张度并且(颤抖)寒战。温度的升高,一般而言,会有一种寒冷的感觉,尽管体温是升高了。一旦达到新的温度,会有一种热的感觉。从发烧的开始,到有潜在危险性的发烧,发烧会由许许多多不同的条件引起。发烧是否有用,这个问题存在争议,有赞成的,也有反对的。除了非常高的温度,降温治疗常常是不必要的。然而,解热药物可以有效地降低温度,可能会改善受影响的人的舒适度。发热不同于不受控制的高烧,高烧是由于过度产热和/或体温调节的不足,体温升高超过人体的体温调节设定点。定义人们已经发现了一个宽泛的正常温度范围。如果升高的体温由抬高的设定点所致,便常被认定存在发热,且肛温(直肠/直肠的)处于或超过37.5-38.3°C(99.5-100.9°F)口温(口部的)处于或超过37.7 ℃(99.9°F)臂下温度(腋窝的)或耳内(耳部的)温度处于或超过37.2 ℃(99.0°F)在健康的成年男性和女性中,正常的,健康的口腔温度温度范围为33.2-38.2 °C (91.8-100.8°F),直肠为34.4-37.8°C(93.9-100°F),鼓膜(耳鼓)是35.4-37.8℃(95.7-100°F),腋温(腋下)是35.5-37.0℃(95.9-98.6°F)。哈里森内科教科书定义发烧为,早晨温度大于37.2 °C(98.9°F)或晚上温度> 37.7°C(99.9°F),而一般的日常温度变化一般为0.5°C(0.9°F)。正常的身体温度变化取决于许多因素,包括年龄,性别,一天中的时间,环境温度,活动水平,和更多。体温升高并不总是发烧。例如,一个健康的人,当他或她锻炼时,温度上升,但这不被认为是发烧,因为(体温)设定点是正常的。另一方面,可能一个“正常”的温度或许就是发热——如果一个温度对一个人而言,异乎寻常的高。例如,年老体弱者产生身体热量能力下降,所以“正常”的温度37.3°C(99.1°F)可能对他们而言就是一种临床上显著的发热。类型温度的变化模式可能暗示诊断:持续发热:温度一整天持续高于正常,24小时波动不超过1°C,例如:大叶性肺炎,伤寒,泌尿道感染,布氏杆菌病,或斑疹伤寒。伤寒热可以表现出一种特殊的发热模式(伤寒热文德利希曲线),温度缓慢逐级上升达到与一个高温的稳定阶段。(退烧药所致降温除外)。间歇性发热:只有在某一段时间表现出温度升高,之后回于正常,如疟疾,黑热病,脓血症,败血症等。以下是它的类型:——每日热,24小时的周期性的,典型的恶性疟原虫或诺尔斯疟原虫。——间日热(48小时周期),典型的间日(单细胞动物)疟原虫和卵形疟原虫疟疾。——四日热(72小时周期),典型的三日疟原虫疟疾。时好时坏发热(驰张热):温度一整天都高于正常,24小时内波动超过1 °C,如感染性心内膜炎。佩-埃热:与霍奇金淋巴瘤有关的一种特殊类型的发热,表现为一个星期的发烧,下一个星期体温降下,等等。然而,这种模式是否真的存在存有争议。中性粒细胞减少性发热,也被称为发热性中性粒细胞减少,是一种缺乏正常免疫系统功能的发热。由于缺乏抗感染中性粒细胞,细菌感染可迅速蔓延,这种发热,通常认为需要紧急就医。与正常人相比,这种发热更常见于接受免疫抑制化疗的人。轻热病是指低热的一个古老词汇,尤其是病因不明,没有表现出其他症状,病人不到一个星期就完全恢复。高热高热是体温极度升高大于或等于41.5°C(106.7°F)。如此高的温度被认为是医疗紧急情况,因为它可能表明有严重的、潜在的情况,或有重大的副作用。最常见的原因是颅内出血。 其他可能的原因包括败血症,川崎综合征,抗精神病药物恶性综合征,药物作用,五羟色胺(血清素)综合征,甲状腺危象。感染是最常见的发烧原因,然而随着温度的升高,其他原因变得更常见。感染通常与高烧相关,包括:红疹(玫瑰疹),麻疹,肠病毒感染。立即积极降温到低于38.9 °C(102.0 °F )已被发现可以提高存活率。高热不同于过高热,在于高热时身体的温度调节机制设置体温高于正常的温度,之后产生热量以达到此温度,而过高热是因外源性因素使身体体温升高超过体温设定点。(如中暑等)。过高热过高热是高温一个例子,它不是发烧。它有许多原因,包括中暑,抗精神病药物恶性症候群,恶性高热,兴奋剂如安非他明和可卡因,特异的药物反应,和五羟色胺综合征。征象发烧通常伴有病态的行为,包括倦怠,抑郁,厌食,嗜睡,痛觉过敏,注意力不集中。鉴别诊断发热是许多身体疾病的常见症状:感染性疾病,如流感,HIV,疟疾,传染性单核细胞增多症,或肠胃炎各种皮肤炎症,如疖,或脓肿免疫学疾病,例如红斑狼疮,结节病,炎症性肠疾病,川崎病组织破坏,可发生溶血,手术,血栓形成,挤压综合征,横纹肌溶解症,脑出血等。不兼容的血液制品反应癌症,最常见于肾癌和白血病和淋巴瘤代谢性疾病,如痛风或卟啉症血栓栓塞的过程,例如,肺栓塞或深静脉血栓形成经过反复常规的临床查询后无法解释的持续发热,被称为不明原因发热病理生理学体温最终在下丘脑调节。发烧的起因,即致热原,导致前列腺素E2 (PGE2)的释放。 PGE2之后反作用于下丘脑,后者产生全身反应返回到身体其他部位,造成产热效果以配合新的体温水平。在许多方面,下丘脑起着恒温器的作用。当设定点升高,人体通过主动产生热量和保持热量,增加其温度。血管收缩,能减少热量通过皮肤损失,也造成人感到寒冷。如果这些措施不足以令大脑中的血液温度适应下丘脑新的设定,便开始寒战,以使肌肉运动,产生更多的热量。发烧停止时,下丘脑的体温设定点设置较低,与发热过程相反(血管舒张,寒战和非寒战产热的结束)和出汗,使得体温冷却到新的、较低的体温设定。而过高热,正常体温设定没有变化,身体过热是由于多余热量或过量产热令人厌烦地保留。过高热通常是极度热环境(中暑)或药物不良反应的结果。通过周围的境况以及对解热药物的反应,能够鉴别发热与过高热。热原质热原质是引起发热的一种物质,可以是身体内部的(内生的、内源性)亦或外部的(外生的、外源性)。细菌物质脂多糖(LPS),存在于一些细菌的细胞壁中,是外源性热原质的一个例子。热原能够变化:在极端的例子中,一些细菌致热原,被称作超抗原,会导致快速而危险的发烧。去热源法,可以通过过滤,蒸馏,色谱法,钝化(失活)这些方法实现。内生的在本质上,所有的内源性热原都是细胞因子,分子学是先天免疫系统的一部分,由吞噬细胞产生,导致下丘脑的体温调节设定点的升高。主要内源性热原质是白细胞介素1(α和β),白细胞介素6(IL-6),肿瘤坏死因子-α。次要的内源性热原包括白细胞介素8 ,肿瘤坏死因子-α ,肿瘤坏死因子-β ,巨噬细胞炎性蛋白-α,巨噬细胞炎性蛋白-β ,以及干扰素-α,干扰素-β ,和γ-干扰素。这些细胞因子被释放到全身循环中,并迁移到更易吸收它们的脑室周围结构,因为血-脑屏障在那里减少了过滤。细胞因子然后与血管壁的内皮细胞上的受体结合,或与该处的小胶质细胞相互作用。当这些细胞因子结合时,花生四烯酸途径随即得到激活。外生的外源性热原引起发烧的机制的一个类型包括脂多糖(LPS),是革兰阴性细菌的细胞壁成分。免疫蛋白结合LPS 被称为脂多糖结合蛋白(LBP)。之后,LBP-LPS复合物结合邻近巨噬细胞的CD14受体。这种结合导致各种内源性细胞因子,如白细胞介素1(IL-1),白细胞介素6(IL-6),和肿瘤坏死因子-α的合成与释放。换句话说,外源性因素引起内源性因素释放,这反过来,激活花生四烯酸途径。释放前列腺素E2PGE2释放来自花生四烯酸途径。这条通路(它涉及到发热),由磷脂酶A2(PLA2),环氧合酶-2(COX-2)和前列腺素E2合成酶介导。最终这些酶介导前列腺素E2(PGE2)的合成和释放。PGE2是发热反应最终的调解物质。身体的设定点温度将继续升高直到PGE2不再存在。 PGE2通过前列腺素E受体3(EP3)作用于视前区(POA)的神经元。 EP3表达POA的神经元刺激下丘脑背内侧核(DMH),延髓头端中缝苍白核(rRPa),下丘脑室旁核(PVN)。发烧信号发送到DMH和rRPa,刺激交感神经输出系统,它唤起非颤抖生热作用产生体热,和皮肤血管收缩,以减少从身体表面的热损失。据推测,从POA到PVN的神经分布,通过垂体和各种内分泌器官途径,介导神经内分泌影响的发热。下丘脑通过自主(植物性)神经系统,大脑最终编排热效应机制。这些可能是:靠肌张力增高,颤抖(寒战)和如肾上腺素的激素增加产热防止热损失,如血管收缩在婴幼儿,自主(植物性)神经系统也可以激活褐色脂肪组织产生热量(非运动相关的生热,也被称为非颤抖性产热)。发热时增加心率和血管收缩,导致血压增高。有用性发烧是否有用,这个问题存在争议,有赞成的,也有反对的。一些提议说,发热使人从感染或危重病中恢复得更快,后有使用热血脊椎动物和人类的活体研究。芬兰的一项研究表明出现发热降低了细菌感染的死亡率。从理论上讲,发热可以帮助宿主的防御。一定是有一些重要的免疫反应由于发热而加快, 有严格的温度偏好的一些病原体受到干扰。研究表明,发热有助于愈合过程的几个重要方面:增加粒细胞流动性增强粒细胞的吞噬作用内毒素影响的减少增加T细胞的增殖管理发烧不一定要治疗。大多数人未经特殊的医药治疗而痊愈。虽然它不太舒服,发热很少上升到一个危险水平,即时未经治疗。对大脑的损害一般不会发生,除非温度达到42 °C (107.6 °F),但未经治疗的发烧超过41°C(105°F)是及其罕见的。一些有限的证据支持给发烧的孩子用温水擦身或洗浴。使用风扇或空调可能会有所降低温度和增加舒适度。如果温度达到非常高的高烧,需要积极的降温。在一般情况下,建议应保持充足的水分。是否增加液体的摄入量改善症状,或是缩短呼吸系统疾病,如普通感冒病程,目前尚不清楚。药物降温的药物被称为退热药。退热药布洛芬在儿童中用于降温是有效的,它比对乙酰氨基酚(扑热息痛)更有效。布洛芬和对乙酰氨基酚都可安全地用于孩子发烧。对乙酰氨基酚单独用于孩子发烧受到质疑。对于孩子发烧,布洛芬是优于阿司匹林。此外,阿司匹林不建议在儿童和青壮年(16岁或19岁以下,因国家而异)使用,因有瑞氏综合征的风险。流行病学看急诊的人中,大约有5%发烧。历史到希波克拉底时代,人们已经认识到了发热的几种模式:包括间日热(每48小时)和四日热(每72小时)是由疟疾引起的发烧。在随后的几个世纪中形成普遍共识:发烧怎样形成,发烧作为一个症状和发烧作为一种疾病的差别,多种类型发热的详尽的分类方案,发热原因的假设,诊断和治疗发烧的不同的方法。在10世纪,波斯医生Akhawaynī创造发烧曲线的概念——发热对应时间,作为诊断的辅助手段。社会文化发热恐怖症发烧恐惧症是医学专家针对患儿家长对发烧的误解给出的名称。其中,很多家长错误地认为,发热是一种疾病,而不知道它是一个医学体征,认为低烧是有害的,还认为即使是短时间略高于很简单的温度计上标记的“正常”的数字,是临床上显着的发热。他们也害怕无害的副作用,如热病猝发和夸张性高估典型的发烧所致的长期损害的可能性。儿科教授Barton D. Schmitt 指出,根本的问题,是“作为父母,我们往往怀疑我们的孩子的大脑可能会熔化。“由于这些误解的结果,父母都急迫地给孩子退烧药物,即时当温度在技术上是正常或仅轻度增高,并且为让孩子保持正常睡眠,给孩子更多的药品。词源发热源自希腊PYR,是火的意思。发热词源拉丁词febris,意思是发烧,古体被称为疟疾。其他动物的发热发烧是驯养动物疾病诊断中的一个重要特征。动物的体温,采于直肠,物种间是不同的。例如,据说马发烧是体温超过101.0°F(38.3°C)。允许身体有一个宽范围“正常”温度的物种,如骆驼,有时是难以确定发热阶段。
FeverFever (also known as pyrexia[1]) is one of the most common medical signs and is characterized by an elevation of body temperature above the normal range of 36.5–37.5 °C (98–100 °F) due to an increase in the temperature regulatory set-point.[2] This increase in set-point triggers increased muscle tone andshivering.As a person's temperature increases, there is, in general, a feeling of cold despite an increasing body temperature. Once the new temperature is reached, there is a feeling of warmth. A fever can be caused by many different conditions ranging from benign to potentially serious. There are arguments for and against the usefulness of fever, and the issue is controversial. With the exception of very high temperatures, treatment to reduce fever is often not necessary; however, antipyretic medications can be effective at lowering the temperature, which may improve the affected person's comfort.Fever differs from uncontrolled hyperthermia,[1] in that hyperthermia is an increase in body temperature over the body's thermoregulatory set-point, due to excessive heat production and/or insufficient thermoregulation.DefinitionA wide range for normal temperatures has been found.[4] Fever is generally agreed to be present if the elevated temperature is caused by a raised set point and:· Temperature in the anus (rectum/rectal) is at or over 37.5–38.3 °C (99.5–100.9 °F)[1][4]· Temperature in the mouth (oral) is at or over 37.7 °C (99.9 °F)[7]· Temperature under the arm (axillary) or in the ear (otic) is at or over 37.2 °C(99.0 °F)In healthy adult men and women, the range of normal, healthy temperatures for oral temperature is 33.2–38.2 °C (91.8–100.8 °F), for rectal it is 34.4–37.8 °C (93.9–100 °F), for tympanic membrane (the ear drum) it is 35.4–37.8 °C (95.7–100 °F), and for axillary (the armpit) it is 35.5–37.0 °C (95.9–98.6 °F).[8]Harrison's textbook of internal medicine defines a fever as a morning temperature of >37.2°C (>98.9°F) or an evening temperature of >37.7°C (>99.9°F) while the normal daily temperature variation is typically 0.5°C (0.9°F).[9]Normal body temperatures vary depending on many factors, including age, sex, time of day, ambient temperature, activity level, and more. A raised temperature is not always a fever. For example, the temperature of a healthy person rises when he or she exercises, but this is not considered a fever, as the set-point is normal. On the other hand, a "normal" temperature may be a fever, if it is unusually high for that person. For example,medically frail elderly people have a decreased ability to generate body heat, so a "normal" temperature of 37.3 °C (99.1 °F) may represent a clinically significant fever.TypesThe pattern of temperature changes may occasionally hint at the diagnosis:· Continuous fever: Temperature remains above normal throughout the day and does not fluctuate more than 1 °Cin 24 hours, e.g. lobar pneumonia, typhoid, urinary tract infection, brucellosis, or typhus. Typhoid fever may show a specific fever pattern (Wunderlich curve of typhoid fever), with a slow stepwise increase and a high plateau. (Drops due to fever-reducing drugs are excluded.)· Intermittent fever: The temperature elevation is present only for a certain period, later cycling back to normal, e.g. malaria, kala-azar, pyaemia, or septicemia. Following are its types [10]· Quotidian fever, with a periodicity of 24 hours, typical of Plasmodium falciparum or Plasmodium knowlesimalaria· Tertian fever (48 hour periodicity), typical of Plasmodium vivax or Plasmodium ovale malaria· Quartan fever (72 hour periodicity), typical of Plasmodium malariae malaria.· Remittent fever: Temperature remains above normal throughout the day and fluctuates more than 1 °C in 24 hours, e.g., infective endocarditis.· Pel-Ebstein fever: A specific kind of fever associated with Hodgkin's lymphoma, being high for one week and low for the next week and so on. However, there is some debate as to whether this pattern truly exists.[11]A neutropenic fever, also called febrile neutropenia, is a fever in the absence of normal immune system function. Because of the lack of infection-fighting neutrophils, a bacterial infection can spread rapidly; this fever is, therefore, usually considered to require urgent medical attention. This kind of fever is more commonly seen in people receiving immune-suppressing chemotherapy than in apparently healthy people.Febricula is an old term for a low-grade fever, especially if the cause is unknown, no other symptoms are present, and the patient recovers fully in less than a week.[12]HyperpyrexiaHyperpyrexia is a fever with an extreme elevation of body temperature greater than or equal to 41.5 °C (106.7 °F).[13] Such a high temperature is considered a medical emergency as it may indicate a serious underlying condition or lead to significant side effects.[14] The most common cause is anintracranial hemorrhage.[13] Other possible causes include sepsis, Kawasaki syndrome,[15] neuroleptic malignant syndrome, drug effects, serotonin syndrome, and thyroid storm.[14] Infections are the most common cause of fevers, however as the temperature rises other causes become more common.[14] Infections commonly associated with hyperpyrexia include: roseola, rubeola and enteroviral infections.[15] Immediate aggressive cooling to less than 38.9 °C (102.0 °F) has been found to improve survival.[14] Hyperpyrexia differs from hyperthermia in that in hyperpyrexia the body's temperature regulation mechanism sets the body temperature above the normal temperature, then generates heat to achieve this temperature, while in hyperthermia the body temperature rises above its set point due to an outside source.[13]HyperthermiaHyperthermia is an example of a high temperature that is not a fever. It occurs from a number of causes including heatstroke, neuroleptic malignant syndrome, malignant hyperthermia, stimulants such as amphetamines and cocaine, idiosyncratic drug reactions, and serotonin syndrome.Signs and symptomsA fever is usually accompanied by sickness behavior, which consists of lethargy, depression, anorexia,sleepiness, hyperalgesia, and the inability to concentrate.[16][17][18]Differential diagnosisFever is a common symptom of many medical conditions:· Infectious disease, e.g., influenza, HIV, malaria, infectious mononucleosis, or gastroenteritis· Various skin inflammations, e.g., boils, or abscess· Immunological diseases, e.g., lupus erythematosus, sarcoidosis, inflammatory bowel diseases, Kawasaki disease· Tissue destruction, which can occur in hemolysis, surgery, infarction, crush syndrome, rhabdomyolysis,cerebral hemorrhage, etc.· Reaction to incompatible blood products· Cancers, most commonly kidney cancer and leukemia and lymphomas· Metabolic disorders, e.g., gout or porphyria· Thrombo-embolic processes, e.g., pulmonary embolism or deep venous thrombosisPersistent fever that cannot be explained after repeated routine clinical inquiries is called fever of unknown origin.PathophysiologyTemperature is ultimately regulated in the hypothalamus. A trigger of the fever, called a pyrogen, causes a release of prostaglandin E2 (PGE2). PGE2 then in turn acts on the hypothalamus, which generates a systemic response back to the rest of the body, causing heat-creating effects to match a new temperature level.In many respects, the hypothalamus works like a thermostat.[19] When the set point is raised, the body increases its temperature through both active generation of heat and retaining heat. Vasoconstriction both reduces heat loss through the skin and causes the person to feel cold. If these measures are insufficient to make the blood temperature in the brain match the new setting in the hypothalamus, then shivering begins in order to use muscle movements to produce more heat. When the fever stops, and the hypothalamic setting is set lower; the reverse of these processes (vasodilation, end of shivering and nonshivering heat production) and sweating are used to cool the body to the new, lower setting.This contrasts with hyperthermia, in which the normal setting remains, and the body overheats through undesirable retention of excess heat or over-production of heat.[19] Hyperthermia is usually the result of an excessively hot environment (heat stroke) or an adverse reaction to drugs. Fever can be differentiated from hyperthermia by the circumstances surrounding it and its response to anti-pyretic medications.PyrogensA pyrogen is a substance that induces fever. These can be either internal (endogenous) or external (exogenous) to the body. The bacterial substance lipopolysaccharide (LPS), present in the cell wall of some bacteria, is an example of an exogenous pyrogen. Pyrogenicity can vary: In extreme examples, some bacterial pyrogens known assuperantigens can cause rapid and dangerous fevers. Depyrogenation may be achieved through filtration,distillation, chromatography, or inactivation.EndogenousIn essence, all endogenous pyrogens are cytokines, molecules that are a part of the innate immune system. They are produced by phagocytic cells and cause the increase in the thermoregulatory set point in the hypothalamus. Major endogenous pyrogens are interleukin 1 (α and β),[20] interleukin 6 (IL-6) and tumor necrosis factor-alpha. Minor endogenous pyrogens include interleukin-8, tumor necrosis factor-α, tumor necrosis factor-β,macrophage inflammatory protein-α and macrophage inflammatory protein-β as well as interferon-α, interferon-β, and interferon-γ.[20]These cytokine factors are released into general circulation, where they migrate to the circumventricular organs of the brain due to easier absorption caused by the blood–brain barrier's reduced filtration action there. The cytokine factors then bind with endothelial receptors on vessel walls, or interact with local microglial cells. When these cytokine factors bind, the arachidonic acid pathway is then activated.ExogenousOne model for the mechanism of fever caused by exogenous pyrogens includes LPS, which is a cell wall component of gram-negative bacteria. An immunological protein called lipopolysaccharide-binding protein (LBP) binds to LPS. The LBP–LPS complex then binds to the CD14 receptor of a nearbymacrophage. This binding results in the synthesis and release of various endogenous cytokine factors, such as interleukin 1 (IL-1), interleukin 6 (IL-6), and the tumor necrosis factor-alpha. In other words, exogenous factors cause release of endogenous factors, which, in turn, activate the arachidonic acid pathway.PGE2 releasePGE2 release comes from the arachidonic acid pathway. This pathway (as it relates to fever), is mediated by the enzymes phospholipase A2 (PLA2),cyclooxygenase-2 (COX-2), and prostaglandin E2 synthase. These enzymes ultimately mediate the synthesis and release of PGE2.PGE2 is the ultimate mediator of the febrile response. The set point temperature of the body will remain elevated until PGE2 is no longer present. PGE2 acts on neurons in the preoptic area (POA) through the prostaglandin E receptor 3 (EP3). EP3-expressing neurons in the POA innervate thedorsomedial hypothalamus (DMH), the rostral raphe pallidus nucleus in the medulla oblongata (rRPa), and the paraventricular nucleus (PVN) of thehypothalamus . Fever signals sent to the DMH and rRPa lead to stimulation of the sympathetic output system, which evokes non-shivering thermogenesis to produce body heat and skin vasoconstriction to decrease heat loss from the body surface. It is presumed that the innervation from the POA to the PVN mediates the neuroendocrine effects of fever through the pathway involving pituitary gland and various endocrine organs.HypothalamusThe brain ultimately orchestrates heat effector mechanisms via the autonomic nervous system. These may be:· Increased heat production by increased muscle tone, shivering and hormones like epinephrine· Prevention of heat loss, such as vasoconstriction.In infants, the autonomic nervous system may also activate brown adipose tissue to produce heat (non-exercise-associated thermogenesis, also known as non-shivering thermogenesis). Increased heart rate and vasoconstriction contribute to increased blood pressure in fever.UsefulnessThere are arguments for and against the usefulness of fever, and the issue is controversial.[21][22] There are studies using warm-bloodedvertebrates[23] and humans[24] in vivo, with some suggesting that they recover more rapidly from infections or critical illness due to fever. A Finnish study suggested reduced mortality in bacterial infections when fever was present.[25]In theory, fever can aid in host defense.[21] There are certainly some important immunological reactions that are sped up by temperature, and somepathogens with strict temperature preferences could be hindered.[26]Research[27] has demonstrated that fever assists the healing process in several important ways:· Increased mobility of leukocytes· Enhanced leukocytes phagocytosis· Endotoxin effects decreased· Increased proliferation of T cells[28]ManagementFever should not necessarily be treated.[29] Most people recover without specific medical attention.[30] Although it is unpleasant, fever rarely rises to a dangerous level even if untreated. Damage to the brain generally does not occur until temperatures reach 42 °C (107.6 °F), and it is rare for an untreated fever to exceed 41 °C (105 °F).[29] Some limited evidence supports sponging or bathing feverish children with tepid water.[31] The use of a fan or air conditioning may somewhat reduce the temperature and increase comfort. If the temperature reaches the extremely high level of hyperpyrexia, aggressive cooling is required.[14] In general, people are advised to keep adequately hydrated.[32] Whether increased fluid intake improves symptoms or shortens respiratory illnesses such as the common cold is not known.[33]MedicationsMedications that lower fevers are called antipyretics. The antipyretic ibuprofen is effective in reducing fevers in children.[34] It is more effective than acetaminophen (paracetamol) in children. Ibuprofen and acetaminophen may be safely used together in children with fevers.[35][36] The efficacy of acetaminophen by itself in children with fevers has been questioned.[37] Ibuprofen is also superior to aspirin in children with fevers.[38] Additionally, aspirin is not recommended in children and young adults (those under the age of 16 or 19 depending on the country) due to the risk of Reye's syndrome.[39]EpidemiologyAbout 5% of people who go to an emergency room have a fever.[40]HistoryBy the time of Hippocrates several patterns of fever had been recognised: these included the tertian (every 48 hours) and quartan (every 72 hours) fevers caused by malaria.[41] Over the succeeding centuries a general consensus arose regarding what constitutes a fever, the distinction between fever as a symptom and fever as a disease, an elaborate classification scheme for multiple types of fever, hypotheses as to the causes of fever and various methods for diagnosing and treating fevers. In the 10th century the Persian physician Akhawaynī created the concept of a fever curve - fever against time as a diagnostic aid.Society and cultureFever phobiaFever phobia is the name given by medical experts to parents' misconceptions about fever in their children. Among them, many parents incorrectly believe that fever is a disease rather than a medical sign, that even low fevers are harmful, and that any temperature even briefly or slightly above the oversimplified "normal" number marked on a thermometer is a clinically significant fever.[42] They are also afraid of harmless side effects like febrile seizures and dramatically overestimate the likelihood of permanent damage from typical fevers.[42] The underlying problem, according to professor of pediatrics Barton D. Schmitt, is "as parents we tend to suspect that our children’s brains may melt."[43]As a result of these misconceptions parents are anxious, give the child fever-reducing medicine when the temperature is technically normal or only slightly elevated, and interfere with the child's sleep to give the child more medicine.[42]EtymologyPyrexia is from the Greek pyr meaning fire. Febrile is from the Latin word febris, meaning fever, and archaically known as ague.In other animalsFever is an important feature for the diagnosis of disease in domestic animals. The body temperature of animals, which is taken rectally, is different from one species to another. For example, a horse is said to have a fever above 101.0 °F (38.3 °C).[44]In species that allow the body to have a wide range of "normal" temperatures, such as camels,[45] it is sometimes difficult to determine a febrile stage.
细支气管炎细支气管炎是肺部最小的空气通道——细支气管的炎症。它多发于不到两岁的儿童,表现出咳嗽,喘息,气短。这种炎症通常是由呼吸道合胞病毒引起。治疗通常是支持性的,会用雾化吸入肾上腺素或高渗盐水。征象典型的病例,两岁以下的婴幼儿表现为一或两天多的咳嗽,喘息,呼吸急促。患儿可能好几天喘不过气来。急性疾病之后,气道通常保持数个星期敏感状态,造成反复发作的咳嗽和喘息。病因此病通常是指急性病毒性细支气管炎,是婴幼儿时期的常见疾病。最常见为呼吸道合胞病毒(RSV,也被称为人类的肺炎病毒)引起。还可能会导致这种疾病的其他病毒包括偏肺病毒、流感、副流感病毒、冠状病毒、腺病毒、和鼻病毒。有研究表明,自愿剖腹产和毛细支气管炎的患病率增加有联系。Perth'sTelethon儿童健康研究所最近的一项研究已经显示以这种方式出生的孩子患此病住院率增长了11%。诊断通常是由临床检查得出诊断。胸部X线检查排除肺炎时有用,但常规情况下用处不大。特定病毒检测可以做,但意义不大,因此不建议常规检查。RSV直接免疫荧光法检测鼻咽分泌物,检测的敏感性为61%,特异性为89%。鉴定呼吸道合胞病毒呈阳性群体可以帮助:疾病监测,在医院的病房分组集中( “集中隔离”),防止交叉感染,预测疾病的过程是否已经达到了顶峰,减少其他诊断程序需要(赋予确定疾病的信心)。两三个月岁之间的婴幼儿患有毛细支气管炎,同时被细菌二次感染(通常是尿道感染)的,小于6%。预防毛细支气管炎的预防措施,很大程度上依赖于减少引起呼吸道感染的病毒传播(即洗手,避免接触那些有呼吸道感染症状者)。除了良好的卫生习惯,改善免疫系统是强有力的预防手段。提高人体免疫系统的方法之一是母乳哺育,特别是在出生后第一个月。免疫接种,可用于满足一定条件的早产儿(有心脏和呼吸系统疾病),如呼吸道合胞病毒单抗(一种RSV单克隆抗体)。被动免疫治疗需要每到冬季时,每月注射。管控治疗和管控毛细支气管炎,通常集中在症状,而不是感染本身(支持疗法),因为感染会按常规发展,而症状会引发并发症。吸入肾上腺素雾化吸入肾上腺素(外消旋和左旋(1)-肾上腺素)已被证明能减少住院率。吸入高渗盐水吸入高渗盐水(3%)似乎可有效提高临床疗效,缩短住院时间。其他药物目前其他药物尚无证据以支持其使用。无效治疗利巴韦林是一种抗病毒药物,似乎无效于细支气管炎。有细菌感染的复杂性细支气管炎,给予抗生素治疗。但对潜在的病毒感染没有任何作用。皮质类固醇类,没有证据有益处,治疗细支气管炎,不建议使用。DNA酶无效。流行病学90 %的患者年龄介乎1个月到9个月大。细支气管炎是1岁前住院的最常见的原因。它在冬季流行。支气管炎支气管炎是支气管(输送气流从气管进入肺的通道)粘膜的炎症。支气管炎可分为两类,急性和慢性,各具病因、病理和治疗。急性支气管炎的特点是咳嗽,可有可无咳痰,咳出的粘液来自呼吸道。急性支气管炎常发生于急性病毒性疾病过程中,如普通感冒或流感。病毒导致约90%的急性支气管炎病例,而细菌所致的占不到10 % 。慢性支气管炎,慢性阻塞性肺疾病的一种类型,特点是排痰性咳嗽,每年持续3个月或以上,至少两年。慢性支气管炎最常见于吸入各种刺激物引起气道的反复损伤。吸烟是最常见的原因,其次是空气污染和职业接触刺激物。急性支气管炎急性支气管炎最常由感染支气管上皮的病毒引起,导致炎症和黏液的分泌增加。咳嗽,急性支气管炎的常见症状,试图排出肺中多余的粘液而表现出的症状。其他常见的症状包括喉咙痛,流鼻涕,鼻塞(鼻炎),低烧,胸膜炎,身体不适,咳痰。急性支气管炎常出现在上呼吸道感染,如普通感冒或流感期间(URI)。约有90%的急性支气管炎病例由病毒引起,包括鼻病毒,腺病毒,流感病毒。细菌,包括肺炎支原体,肺炎衣原体,百日咳杆菌,肺炎链球菌,流感嗜血杆菌,占约10%的病例。急性支气管炎的治疗主要是对症。可使用非甾体类抗炎药(NSAIDs),治疗发烧和咽喉疼痛。解充血药对鼻塞患者有用,祛痰剂用于松解粘液以增加排痰。尽管咳嗽有助于气道排痰,如果咳嗽影响睡眠,或者令人厌烦,可用止咳药。大多数情况下,即使没有治疗,急性支气管炎也会很快痊愈。只有约5%至10%的支气管炎是由细菌感染引起的。大多数情况下,支气管炎是由病毒感染引起的,是“自我限制”的,并在几个星期内自行好转。因是病毒所致,抗生素不常使用。在没有细菌感染的患者使用抗生素,将促进抗生素耐药细菌的出现,这可能会导致更大的发病率和死亡率。然而,即使是病毒性支气管炎病例,对某些患者,为了防止继发性细菌感染的发生,抗生素有使用的指证。慢性支气管炎慢性支气管炎,慢性阻塞性肺疾病的一种类型,定义排痰性咳嗽,每年持续3个月或以上,至少2年。其他症状包括喘息,气急,尤其劳累后。咳嗽往往是睡醒后不久加重,有痰,为黄色或绿色,或带血痕。反复损伤或刺激呼吸道支气管上皮细胞引起的慢性支气管炎,造成慢性炎症,水肿(肿胀) ,以及杯状细胞分泌的粘液增多。因为肿胀和支气管多余的黏液或者由于可逆的支气管痉挛,使得进出肺脏的气流部分受堵。多数情况下,慢性支气管炎是由吸烟或其他烟草相关因素造成。长期吸入刺激性气体或职业暴露于尘埃或者空气污染,也可能是病因。约5%的人口有慢性支气管炎,女性是男性的两倍。慢性支气管炎予对症治疗。吸入糖皮质激素,呼吸道上皮细胞的炎症和水肿可能会减少。减低支气管痉挛(支气管平滑肌收缩所致可逆性小支气管狭窄)来治疗喘息、气短,予支气管扩张剂,如吸入β-肾上腺素激动剂(如沙丁胺醇)和吸入抗胆碱能药物(如异丙托溴铵) 。低氧血症,血液中的氧太少,可以补充氧气治疗。然而,补充氧气,可能会导致呼吸驱动力下降,导致血液中的二氧化碳增加和随后的呼吸性酸中毒。预防慢性支气管炎和其他形式的慢性阻塞性肺病,最有效的方法是避免抽烟和其他形式的烟草因素。对肺的测试,支气管炎可能会出现FEV1和FEV1/FVC下降。然而,与其他常见的阻塞性疾病,如哮喘和肺气肿不同,支气管炎很少引起高残留量。这是因为支气管炎的气流阻塞是由于阻力增加所致,在一般情况下,不会引起气道过早溃塌致使气体困限于肺部。长时间的细菌性支气管炎长时间的细菌性支气管炎被定义为一种慢性湿咳,以使用抗生素、积极的支气管肺泡灌洗( BAL)治疗。它通常由肺炎链球菌,流感嗜血杆菌,卡他莫拉菌引起。
BronchiolitisBronchiolitis is inflammation of the bronchioles, the smallest air passages of the lungs. It usually occurs in children less than two years of age and presents with coughing, wheezing, and shortness of breath. This inflammation is usually caused by respiratory syncytial virus. Treatment is typically supportive and may involve the use of nebulized epinephrine or hypertonic saline.Signs and symptomsIn a typical case, an infant under two years of age develops cough, wheeze, and shortness of breath over one or two days. The infant may be breathless for several days. After the acute illness, it is common for the airways to remain sensitive for several weeks, leading to recurrent cough and wheeze.CausesThe term usually refers to acute viral bronchiolitis, a common disease in infancy. This is most commonly caused by respiratory syncytial virus[1](RSV, also known as human pneumovirus). Other viruses which may cause this illness include metapneumovirus, influenza, parainfluenza, coronavirus,adenovirus, and rhinovirus.Studies have shown there is a link between voluntary caesarean birth and an increased prevalence of bronchiolitis. A recent study by Perth'sTelethon Institute for Child Health Research has shown an 11% increase in hospital admissions for children delivered this way.[2]DiagnosisThe diagnosis is typically made by clinical examination. Chest X-ray is sometimes useful to exclude pneumonia, but not indicated in routine cases.[3]Testing for the specific viral cause can be done but has little effect on management and thus is not routinely recommended.[3] RSV testing by direct immunofluorescence testing on nasopharyngeal aspirate had a sensitivity of 61% and specificity of 89%.[4] Identification of those who are RSV-positive can help for: disease surveillance, grouping ("cohorting") people together in hospital wards to prevent cross infection, predicting whether the disease course has peaked yet, reducing the need for other diagnostic procedures (by providing confidence that a cause has been identified).Infant with bronchiolitis between the age of two and three months have a second infection by bacteria (usually a urinary tract infection) less than 6% of the time.[5]PreventionPrevention of bronchiolitis relies strongly on measures to reduce the spread of the viruses that cause respiratory infections (that is, handwashing, and avoiding exposure to those symptomatic with respiratory infections). In addition to good hygiene an improved immune system is a great tool for prevention. One way to improve the immune system is to feed the infant with breast milk, especially during the first month of life.[6] Immunizationsare available for premature infants who meet certain criteria (some cardiac and respiratory disorders) such as Palivizumab (a monoclonal antibodyagainst RSV). Passive immunization therapy requires monthly injections every winter.ManagementTreatment and management of bronchiolitis is usually focused on the symptoms instead of the infection itself (supportive therapies) since the infection will run its course and complications are typically from the symptoms themselves.[7]Inhaled epinephrineNebulized and inhaled epinephrine (both racemic and levo(1)-epinephrine) has been shown to decrease hospitalization rates.[8][9]Inhaled hypertonic salineInhaled hypertonic saline (3%) appears to be effective in improving clinical outcomes and shortening the duration of hospital stay.[3]Other medicationsCurrently other medications do not yet have evidence to support their use.[9]Non-effective treatmentsRibavirin is an antiviral drug which does not appear to be effective for bronchiolitis.[10] Antibiotics are often given in case of a bacterial infection complicating bronchiolitis, but have no effect on the underlying viral infection.[10] Corticosteroids have no proven benefit in bronchiolitis treatment and are not advised.[10] DNAse has not been found to be effective.[11]Epidemiology90% of the patients are aged between 1 and 9 months old. Bronchiolitis is the most common cause of hospitalization up to the first year of life. It is epidemic in winters.BronchitisBronchitis is inflammation of the mucous membranes of the bronchi, the airways that carry airflow from thetrachea into the lungs. Bronchitis can be divided into two categories, acute and chronic, each of which has two distinct etiologies, pathologies, and therapies.Acute bronchitis is characterized by the development of a cough, with or without the production of sputum,mucus that is expectorated (coughed up) from the respiratory tract. Acute bronchitis often occurs during the course of an acute viral illness such as the common cold or influenza. Viruses cause about 90% of cases of acute bronchitis, whereas bacteria account for fewer than 10%.[1]Chronic bronchitis, a type of chronic obstructive pulmonary disease, is characterized by the presence of a productive cough that lasts for three months or more per year for at least two years. Chronic bronchitis most often develops due to recurrent injury to the airways caused by inhaled irritants. Cigarette smoking is the most common cause, followed by air pollution and occupational exposure to irritants.[1]Acute bronchitisAcute bronchitis is most often caused by viruses that infect the epithelium of the bronchi, resulting in inflammation and increased secretion of mucus. Cough, a common symptom of acute bronchitis, develops in an attempt to expel the excess mucus from the lungs. Other common symptoms include sore throat, runny nose, nasal congestion (coryza), low-grade fever, pleurisy, malaise, and the production of sputum.[1]Acute bronchitis often develops during an upper respiratory infection (URI) such as the common cold or influenza.[1] About 90% of cases of acute bronchitis are caused by viruses, including rhinoviruses, adenoviruses, and influenza. Bacteria, including Mycoplasma pneumoniae, Chlamydophila pneumoniae, Bordetella pertussis, Streptococcus pneumoniae, and Haemophilus influenzae, account for about 10% of cases.[1]Treatment for acute bronchitis is primarily symptomatic. Non-steroidal anti-inflammatory drugs (NSAIDS) may be used to treat fever and sore throat.Decongestants can be useful in patients with nasal congestion, and expectorants may be used to loosen mucus and increase expulsion of sputum. Cough suppressants may be used if the cough interferes with sleep or is bothersome, although coughing may be useful in expelling sputum from the airways. Even with no treatment, most cases of acute bronchitis resolve quickly.[1]Only about 5–10% of bronchitis cases are caused by a bacterial infection. Most cases of bronchitis are caused by a viral infection and are "self-limiting" and resolve themselves in a few weeks.[2] As most cases of acute bronchitis are caused by viruses, antibiotics should not generally be used, since they are effective only against bacteria. Using antibiotics in patients without bacterial infections promotes the development ofantibiotic-resistant bacteria, which may lead to greater morbidity and mortality. However, even in cases of viral bronchitis, antibiotics may be indicated in certain patients in order to prevent the occurrence of secondary bacterial infections.Chronic bronchitisChronic bronchitis, a type of chronic obstructive pulmonary disease, is defined by a productive cough that lasts for 3 months or more per year for at least 2 years.[3] Other symptoms may include wheezing and shortness of breath, especially upon exertion. The cough is often worse soon after awakening, and the sputum produced may have a yellow or green color and may be streaked with blood.[1]Chronic bronchitis is caused by recurring injury or irritation to the respiratory epithelium of the bronchi, resulting in chronic inflammation,edema (swelling), and increased production of mucus by goblet cells.[1] Airflow into and out of the lungs is partly blocked because of the swelling and extra mucus in the bronchi or due to reversible bronchospasm.[4]Most cases of chronic bronchitis are caused by smoking cigarettes or other forms of tobacco. Chronic inhalation of irritating fumes or dust from occupational exposure or air pollution may also be causative. About 5% of the population has chronic bronchitis, and it is two times more common in females than in males.[1]Chronic bronchitis is treated symptomatically. Inflammation and edema of the respiratory epithelium may be reduced with inhaled corticosteroids. Wheezing and shortness of breath can be treated by reducing bronchospasm (reversible narrowing of smaller bronchi due to constriction of the smooth muscle) with bronchodilators such as inhaled β-Adrenergic agonists (e.g., salbutamol) and inhaled anticholinergics (e.g., ipratropium bromide).Hypoxemia, too little oxygen in the blood, can be treated with supplemental oxygen.[1] However, oxygen supplementation can result in decreased respiratory drive, leading to increased blood levels of carbon dioxide and subsequent respiratory acidosis.The most effective method of preventing chronic bronchitis and other forms of COPDis to avoid smoking cigarettes and other forms of tobacco.[1]On pulmonary tests, a bronchitic (bronchitis) may present a decreased FEV1 and FEV1/FVC. However, unlike the other common obstructive disorders, asthma and emphysema, bronchitis rarely causes a high residual volume. This is because the air flow obstruction found in bronchitis is due to increased resistance, which, in general, does not cause the airways to collapse prematurely and trap air in the lungs.[citation needed]Protracted bacterial bronchitisProtracted bacterial bronchitis is defined as a chronic wet cough, with a positive bronchoalveolar lavage (BAL), that resolves with antibiotics.[5]It is usually caused by Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis.[5]
布氏杆菌病布氏杆菌病,也叫班氏病(牛传染性流产),克里米亚发热,直布罗陀发热,马耳他热,马耳他发热,地中海热,岩石热,或波状热,是一种烈性人畜共患传染病,因食入未经消毒的、受感染动物的奶、肉或密切接触其分泌物而致病。从人到人之间的传播,也有可能通过性接触或母婴渠道,但极其少见。布鲁氏杆菌是小的、革兰氏阴性、非能动的、非孢子形成的杆状(球杆菌)细菌。他们是兼性寄生的细胞内寄生生物,引起慢性疾病,通常持续一生。症状包括大量出汗,关节和肌肉疼痛。自20世纪以来,布氏杆菌病已被确认为人畜共患疾病。历史与命名法名称为马耳他热的疾病,现在被称为布氏杆菌病。在19世纪50年代,在马耳他,克里米亚战争期间,首次引起英国医务人员的关注。David Bruce医生,于1887年,确定了生物体和疾病之间的因果关系。1897年,丹麦兽医Bernhard Bang 分离出流产胎布氏杆菌,班氏病因而得名。马耳他医生兼考古学家Themistocles Zammit 先生,因确定病原体的主要来源是未经高温消毒的奶液,在1905年获得了爵位,从此该病也被称为马耳他热。在牛类,这种病被称为传染性流产和感染性流产。通俗的名称波状热源于波状(或“波浪状”)的发烧,在未接受治疗的患者,发热升降多达数周。在20世纪,布氏杆菌病(布氏菌,以布鲁斯医生的名字命名),逐渐取代了19世纪命名的地中海热、马耳他热。1989年,沙特阿拉伯神经病学家发现了神经型布氏杆菌病,布鲁氏杆菌病牵涉入神经病学。以下过时的名字曾经被用于布氏杆菌病:布氏杆菌布鲁斯败血症Chumble(人名)热持续发烧克里米亚热塞浦路斯热波状热仁慈热山羊热布氏杆菌败血症牛奶病山热那不勒斯热撒旦发烧慢热苏格兰喜琼斯病动物布氏杆菌病感染家畜的是羊布氏杆菌(山羊和绵羊布氏杆菌),猪布氏杆菌(猪,猪布氏杆菌病),流产布氏杆菌(牛和野牛),卵布氏杆菌(绵羊),犬布氏杆菌(狗),流产布鲁氏菌在北美感染野牛和麋鹿,猪布氏杆菌在北美驯鹿流行,布氏菌在几种海洋哺乳类动物(鳍足类和鲸目动物)中也被分离出。牛布氏杆菌病流产布鲁氏菌是在牛布氏杆菌病的主要病因。围产犊或流产时,细菌脱落于受感染的动物,一旦暴露于细菌,动物被感染的可能性是个变量,取决于脱落细菌动物的年龄,妊娠状态,和被感动物的内在因素,以及暴露于动物的细菌量。最常见的牛布鲁氏菌感染牛的临床症状包括高发流产,关节炎及胎衣不下。在动物中,自然流产有两个主要原因。首先是由于赤丁四醇,它可促进胎儿和胎盘的感染。第二个是由于在羊水中缺乏抗布鲁氏菌的活性。雄性生殖道也能生存细菌,如精囊、壶腹、睾丸和附睾。狗布氏杆菌病犬布氏杆菌病的病原体是犬布氏菌。通过养育和接触流产的胎犬而在相互间传播。犬布氏杆菌病可发生于人类,主要是接触感染犬的流产组织或精液。狗的细菌通常感染生殖器和淋巴系统,但也能蔓延到眼、肾、椎间盘(导致脊椎炎) 。狗布氏杆菌病的症状包括雌犬流产及雄犬阴囊炎和睾丸炎(睾丸的炎症)。发烧不常见。眼睛感染可引起葡萄膜炎,椎间盘的感染可引起疼痛或虚弱。在配种前的狗的血液测试可以阻止这种疾病的传播。与人类一样,都以抗生素治疗,但难以治愈。人类布氏杆菌病人类布氏杆菌病通常是食用了未经高温消毒的受感染的动物奶和软奶酪,主要是布氏菌感染的山羊,还有职业暴露的实验室工作人员、兽医、屠宰场工人。有些疫苗用于牲畜,最受人关注的是流产布氏菌菌株19,如果意外注于人,也引起人类疾病。布氏杆菌病引起多变的发烧、发汗、虚弱、贫血、头痛、抑郁、肌肉和身体疼痛。症状症状与其他发热性疾病相似,但强调肌肉疼痛,出汗。病程可从几个星期到数月甚至数年不等。在疾病的第一阶段,会发生败血症,导致典型的三症状群:波状热,出汗(通常具有特有的气味,像干草受潮样),迁移性关节痛、肌痛。血液检查特征性显示白细胞减少症和贫血,显示AST和ALT有些升高,Bengal Rose反应和Huddleston反应阳性。这种综合征,至少在葡萄牙,被称作马耳他热。马耳他热发作期间,布氏菌血症(血液中有布氏菌)通常可以通过在蛋白胨培养基或阿尔比尼培养基血培养证实。如果不治疗,疾病可集中一些区域或成为慢性。布氏杆菌病集中焦点多见于骨骼、关节和腰椎间盘,同时伴有关节炎,是本病明显特征。男性常发生睾丸炎。布氏杆菌病的诊断依靠:1、证实病原菌:胰蛋白肉汤血培养,骨髓培养。布氏菌的生长非常缓慢(他们能花费近2个月生长)而且由于高度传染性,培养对实验室工作人员构成威胁。2、证实抗原产生的抗体,要么使用的经典Huddleson、Wright 和/或Bengal Rose反应,要么用ELISA法或2-巯基乙醇法检测与长期疾病相关的IgM抗体。3、组织学证据为肉芽肿性肝炎(肝活检)。4、受感染椎骨的影像学改变:Pedro Pons标记(先侵蚀腰椎的前上角)和显著的骨赘症可疑为布氏杆菌脊椎炎。本病的后遗症是充满变数,可能包括肉芽肿性肝炎,关节炎,脊椎炎,贫血,白细胞减少症,血小板减少症,脑膜炎,虹膜炎,视神经炎,感染性心内膜炎,以及被统称为神经型布氏杆菌病的各种神经系统疾病。治疗与预防对布氏杆菌有效的抗生素如四环素,利福平和氨基糖苷类链霉素和庆大霉素。要使用一种以上的抗生素治疗几个星期,因为细菌潜伏于细胞内。成人的金标准治疗为每日肌肉注射链霉素1克X14天,同时45天口服强力霉素,每天两次,每次100毫克。当链霉素不可用或者难以取得时,庆大霉素5毫克/公斤肌肉注射,每日一次共七天,是一个可以接受的替代选项。另一种被广泛使用的方案是强力霉素加利福平,每日两次,至少6个星期,这种治疗方案有口服给药的优点。三联疗法利福平和复方新诺明、强力霉素,已成功用于治疗神经型布氏杆菌病。强力霉素能够穿越血脑屏障,但需要另外两个其他药物,以防止复发。环丙沙星和复方新诺明治疗复发率高得令人无法接受。对布氏菌心内膜炎,需要手术治疗,以获得最佳的结果。即使使用最佳治疗方案,还是有5%至10%马耳他热的患者复发。预防布鲁氏杆菌病的主要方法是在生产原料奶产品过程中讲究卫生,或巴氏消毒法消毒所有人食用的奶制品,无论是原奶形式还是其衍生物,如奶酪。实验表明,复方新诺明和利福平用于治疗患布氏杆菌病的孕妇都是安全的药物。生物战争1954年,猪布氏杆菌,在美国阿肯色州的派恩布拉夫兵工厂首先被武器化。布氏菌物种气溶胶中生存良好而且抗干燥。美国武库中布氏菌及其余所有生物武器在1971-72年被摧毁,当时,美国的进攻性生物武器(BW)计划被中止。美国生物武器计划集中在三个布氏菌组:猪布氏杆菌病(US剂)牛布氏杆菌病(AB剂)山羊布鲁氏杆菌病(AM剂)二战结束前,US剂发展先进。当时美国空军(USAF)希望有生物战能力,化学陆战队提供有US剂的M114子母炸弹, 此武器以二战中成熟的4磅重的炭疽爆破炸弹为基础。虽然能力已达到,运行测试表明,武器不够理想,美国空军赋予其临时的功能,直到被一个更有效的生物武器所取代。带有US剂的M114主要缺点是不适用(美国空军想要“杀伤剂”),贮存稳定性太低,不允许存储在前方空军基地,后勤消除目标的需要远远高于原先预期,需要的后勤空中支援难以接受。US剂和AB剂中间感染剂量为500有机体/人,AM剂是300有机体/人。反应速率被认为是2周,反应持续时间数个月。杀伤力估计是基于流行病学资料,在1-2% 。AM剂一直被认为是一种更致命的疾病,预期死亡率3%。控制与消除努力美国在美国的存栏奶牛每年至少测试一次布氏菌乳环试验(BRT)。奶牛若被证实感染便杀掉。在美国,要求兽医须给所有年幼家畜接种疫苗,从而进一步减少动物传播机会。这种接种疫苗通常被称为幼犊期接种疫苗。大部分家畜在他们的耳朵上刺个纹身,作为它们的接种疫苗身份证明。纹身还包括他们出生年的最后一位数字。在美国,1934年开始,第一个州联邦合作组织,努力消除流产胎布氏菌引起的布氏杆菌病。大黄石区美国黄石地区(GYA)的野牛和麋鹿,是最后剩下的流产胎布氏菌载体。最近布氏杆菌病从麋鹿传播到牛,说明在爱达荷州和怀俄明州的GYA是美国最后剩余的流产胎布氏杆菌区。不利于畜牧产业。消除这个地区布氏杆菌病是一个挑战,如何管理患病的野生动物有许多观点。加拿大1985年9月19日,加拿大宣布他们的牛群无布鲁氏杆菌病。截至1999年4月1日止,布氏杆菌病环测试于牛奶和奶油,以及测试屠宰牛。继续通过拍卖市场的测试和标准的疾病报告机制来监控,并测试合格出口到美国以外的其他国家的牛。欧洲马耳他直到20世纪初,布氏杆菌病在马耳他呈地方性流行疾病,以致它被称为“马耳他热”。Temi Zammit确定了疾病和未经消毒的牛奶之间的联系。今天,感谢严格的产乳动物证明制度,和广泛使用巴氏杀菌法,疾病已经从马耳他根除。爱尔兰2009年7月1日,爱尔兰被宣布为无布氏杆菌病。这种疾病已经困扰该国的农民和兽医几十年。爱尔兰政府提交给欧洲委员会一份申请,经证实,爱尔兰已经无该病。 Brendan Smith,爱尔兰当时的农业,食品和海洋部长,说消灭布氏杆菌病是“在爱尔兰消灭疾病历史上的一个里程碑” 。根除疾病得到了证实,爱尔兰的农业,食品和海洋部,打算削减其布氏杆菌病根除计划。大洋洲澳大利亚澳大利亚目前无家畜布氏杆菌病,尽管它过去发生过。绵羊或山羊布氏杆菌病从未见报道。猪布氏杆菌病发生过。野猪是典型的人感染源。新西兰布氏杆菌病在新西兰限于羊(绵羊布氏菌)。该国没有其他种布氏菌。References1.^ "Brucellosis" in the American Heritage Dictionary2.^ Maltese Fever by wrongdiagnosis.com, last Update: 25 February 2009 (12:01), retrieved 2009-02-263.^ "Diagnosis and Management of Acute Brucellosis in Primary Care". Brucella Subgroup of the Northern Ireland Regional Zoonoses Group. August 2004.4.^ Wilkinson, Lise (1993). ""Brucellosis"". In Kiple, Kenneth F. (ed.). The Cambridge World History of Human Disease. Cambridge University Press).5.^ Brucellosis named after Sir David Bruce at Who Named It?6.^ Malhotra, Ravi (2004). "Saudi Arabia". Practical Neurology 4 (3): 184–185.doi:10.1111/j.1474-7766.2004.03-225.x.7.^ Al-Sous MW, Bohlega S, Al-Kawi MZ, Alwatban J, McLean DR (March 2004)."Neurobrucellosis: clinical and neuroimaging correlation". AJNR Am J Neuroradiol 25 (3): 395–401. PMID 15037461.8.^ Radostits, O.M., C.C. Gay, D.C. Blood, and K.W. Hinchcliff. 2000. Veterinary Medicine, A textbook of the Diseases of Cattle, Sheep, Pigs, Goats and Horses. Harcourt Publishers Limited, London, pp. 867–882.9.^ Ettinger, Stephen J; Feldman, Edward C. (1995). Textbook of Veterinary Internal Medicine (4th ed.). W.B. Saunders Company. ISBN 0-7216-4679-4.10.^ Hasanjani Roushan MR, Mohraz M, Hajiahmadi M, Ramzani A, Valayati AA (April 2006). "Efficacy of gentamicin plus doxycycline versus streptomycin plus doxycycline in the treatment of brucellosis in humans". Clin. Infect. Dis. 42(8): 1075–1080. doi:10.1086/501359. PMID 16575723.11.^ McLean DR, Russell N, Khan MY (October 1992). "Neurobrucellosis: clinical and therapeutic features". Clin. Infect. Dis. 15 (4): 582–90.doi:10.1093/clind/15.4.582. PMID 1420670.12.^ Woods, Lt Col Jon B. (ed.) (April 2005) (PDF). USAMRIID’s Medical Management of Biological Casualties Handbook (6th ed.). Fort Detrick, Maryland: U.S. Army Medical Institute of Infectious Diseases. p. 53.13.^ Hamilton AV, Hardy AV (March 1950). "The brucella ring test; its potential value in the control of brucellosis" (PDF). Am J Public Health Nations Health 40 (3): 321–323. doi:10.2105/AJPH.40.3.321. PMC 1528431.PMID 15405523.14.^ Vermont Beef Producers (PDF). How important is calfhood vaccination?.15.^ "Reportable Diseases". Accredited Veterinarian’s Manual. Canadian Food Inspection Agency. Retrieved 2007-03-18.16.^ Rizzo Naudi, John (2005). Brucellosis, The Malta Experience. Malta: Publishers Enterprises group (PEG) Ltd.. ISBN 99909-0-425-1.17.^ a b c "Ireland free of brucellosis". RT. 2009-07-01. Retrieved 2009-07-01.18.^ a b c d "Ireland declared free of brucellosis". The Irish Times. 2009-07-01. Retrieved 2009-07-01. "Michael F Sexton, president of Veterinary Ireland, which represents vets in practice said: "Many vets and farmers in particular suffered significantly with brucellosis in past decades and it is greatly welcomed by the veterinary profession that this debilitating disease is no longer the hazard that it once was.""19.^ "Queensland Health: Brucellosis". State of Queensland (Queensland Health). 2010-11-24. Retrieved 2011-06-06.20.^ Lehane,Robert (1996) Beating the Odds in a Big Country: The eradication of bovine brucellosis and tuberculosis in Australia, CSIRO PUBLISHING, ISBN 0-643-05814-1 ISBN 978-064305814921.^ "MAF Biosecurity New Zealand: Brucellosis". Ministry of Agriculture and Forestry of New Zealand. Retrieved 2011-06-06.
BrucellosisBrucellosis, also called Bang's disease, Crimean fever, Gibraltar fever, Malta fever, Maltese fever, Mediterranean fever, rock fever, or undulant fever,[1][2] is a highly contagious zoonosis caused by ingestion of unsterilized milk or meat from infected animals or close contact with their secretions. Transmission from human to human, through sexual contact or from mother to child, is rare but possible.[3]Brucella spp. are small, Gram-negative, non-motile, non-spore-forming, rod shaped (coccobacilli) bacteria. They function as facultative intracellular parasites causing chronic disease, which usually persists for life. Symptoms include profuse sweating and joint and muscle pain. Brucellosis has been recognized in animals including humans since the 20th century.History and nomenclatureUnder the name Malta fever, the disease now called brucellosis first came to the attention of British medical officers in the 1850s in Malta during the Crimean War. The causal relationship between organism and disease was first established in 1887 by Dr. David Bruce.[4][5]In 1897, Danish veterinarian Bernhard Bang isolated Brucella abortus as the agent; and the additional name Bang's disease was assigned.Maltese doctor and archaeologist Sir Themistocles Zammit earned a knighthood for identifying unpasteurized milk as the major source of the pathogen in 1905, and it has since become known as Malta Fever. In cattle, this disease is also known as contagious abortion and infectious abortion.The popular name undulant fever originates from the characteristic undulance (or "wave-like" nature) of the fever, which rises and falls over weeks in untreated patients. In the 20th century, this name, along with brucellosis (after Brucella, named for Dr. Bruce), gradually replaced the 19th century names Mediterranean fever and Malta fever.In 1989, neurologists in Saudi Arabia discovered neurobrucellosis, a neurological involvement in brucellosis.[6][7]The following obsolete names have previously been applied to brucellosis:§ Brucelliasis§ Bruce's septicemia§ Chumble fever§ continued fever§ Crimean fever§ Cyprus fever§ febris melitensis§ febris undulans§ Fist of mercy§ goat fever§ melitensis septicemia§ melitococcosis§ milk sickness§ mountain fever§ Neapolitan fever§ Satan's fever§ slow fever§ Scottish Delight§ Jones DiseaseBrucellosis in animalsSpecies infecting domestic livestock are B. melitensis (goats and sheep, see Brucella melitensis), B. suis (pigs, see Swine brucellosis), B. abortus(cattle and bison), B. ovis (sheep), and B. canis (dogs). B. abortus also infects bison and elk in North America and B. suis is endemic in caribou.Brucella species have also been isolated from several marine mammal species (pinnipeds and cetaceans).Brucellosis in cattleThe bacterium Brucella abortus is the principal cause of brucellosis in cattle. The bacteria are shed from an infected animal at or around the time of calving or abortion. Once exposed, the likelihood of an animal becoming infected is variable, depending on age, pregnancy status, and other intrinsic factors of the animal, as well as the amount of bacteria to which the animal was exposed.[8] The most common clinical signs of cattle infected with Brucella abortus are high incidences of abortions, arthritic joints and retained after-birth.There are two main causes for spontaneous abortion in animals. The first is due to erythritol, which can promote infections in the fetus and placenta. The second is due to the lack of anti-Brucella activity in the amniotic fluid. Males can also harbor the bacteria in their reproductive tracts, namely seminal vesicles, ampullae, testicles, and epididymes.Brucellosis in dogsThe causative agent of brucellosis in dogs is Brucella canis. It is transmitted to other dogs through breeding and contact with aborted fetuses. Brucellosis can occur in humans that come in contact with infected aborted tissue or semen. The bacteria in dogs normally infect the genitals andlymphatic system, but can also spread to the eye, kidney, and intervertebral disc (causing discospondylitis). Symptoms of brucellosis in dogs include abortion in female dogs and scrotal inflammation and orchitis (inflammation of the testicles) in males. Fever is uncommon. Infection of the eye can cause uveitis, and infection of the intervertebral disc can cause pain or weakness. Blood testing of the dogs prior to breeding can prevent the spread of this disease. It is treated with antibiotics, as with humans, but it is difficult to cure.[9]Brucellosis in humansBrucellosis in humans is usually associated with the consumption of unpasteurized milk and soft cheeses made from the milk of infected animals, primarily goats, infected with Brucella melitensis and with occupational exposure of laboratory workers, veterinarians, and slaughterhouse workers. Some vaccines used in livestock, most notably B. abortus strain 19, also cause disease in humans if accidentally injected. Brucellosis induces inconstant fevers, sweating, weakness, anaemia, headaches, depression, and muscular and bodily pain.SymptomsThe symptoms are like those associated with many other febrile diseases, but with emphasis on muscular pain and sweating. The duration of the disease can vary from a few weeks to many months or even years. In the first stage of the disease, septicaemia occurs and leads to the classic triad of undulant fevers, sweating (often with characteristic smell, likened to wet hay), and migratory arthralgia and myalgia. Blood tests characteristically reveal leukopenia and anemia, show some elevation of AST and ALT, and demonstrate positive Bengal Rose and Huddleston reactions.This complex is, at least in Portugal, known as Malta fever. During episodes of Malta fever, melitococcemia (presence of brucellae in blood) can usually be demonstrated by means of blood culture in tryptose medium or Albini medium. If untreated, the disease can give origin to focalizations or become chronic. The focalizations of brucellosis occur usually in bones and joints and spondylodiscitis of lumbar spine accompanied by sacroiliitisis very characteristic of this disease. Orchitis is also frequent in men.Diagnosis of brucellosis relies on:1. Demonstration of the agent: blood cultures in tryptose broth, bone marrow cultures. The growth of brucellae is extremely slow (they can take until 2 months to grow) and the culture poses a risk to laboratory personnel due to high infectivity of brucellae.2. Demonstration of antibodies against the agent either with the classic Huddleson, Wright and/or Bengal Rose reactions, either with ELISA or the 2-mercaptoethanol assay for IgM antibodies associated with chronic disease3. Histologic evidence of granulomatous hepatitis (hepatic biopsy)4. Radiologic alterations in infected vertebrae: the Pedro Pons sign (preferential erosion of antero-superior corner of lumbar vertebrae) and marked osteophytosis are suspicious of brucellic spondylitis.The disease's sequelae are highly variable and may include granulomatous hepatitis, arthritis, spondylitis, anaemia, leukopenia, thrombocytopenia,meningitis, uveitis, optic neuritis, endocarditis, and various neurological disorders collectively known as neurobrucellosis.Treatment and preventionAntibiotics like tetracyclines, rifampicin, and the aminoglycosides streptomycin and gentamicin are effective against Brucella bacteria. However, the use of more than one antibiotic is needed for several weeks, because the bacteria incubate within cells.The gold standard treatment for adults is daily intramuscular injections of streptomycin 1 g for 14 days and oral doxycycline 100 mg twice daily for 45 days (concurrently). Gentamicin 5 mg/kg by intramuscular injection once daily for seven days is an acceptable substitute when streptomycin is not available or difficult to obtain.[10] Another widely used regimen is doxycycline plus rifampin twice daily for at least six weeks. This regimen has the advantage of oral administration. A triple therapy of doxycycline, with rifampin and cotrimoxazole, has been used successfully to treat neurobrucellosis.[11]Doxycycline is able to cross the blood–brain barrier, but requires the addition of two other drugs to prevent relapse. Ciprofloxacin and cotrimoxazole therapy is associated with an unacceptably high rate of relapse. In brucellic endocarditis, surgery is required for an optimal outcome. Even with optimal antibrucellic therapy, relapses still occur in 5–10 percent of patients with Malta fever.The main way of preventing brucellosis is by using fastidious hygiene in producing raw milk products, or by pasteurizing all milk that is to be ingested by human beings, either in its unaltered form or as a derivate, such as cheese. Experiments have shown that cotrimoxazol and rifampin are both safe drugs to use in treatment of pregnant women who have brucellosis.[citation needed]Biological warfareIn 1954, B. suis became the first agent weaponized by the United States at its Pine Bluff Arsenal in Arkansas. Brucella species survive well in aerosols and resist drying. Brucella and all other remaining biological weapons in the U.S. arsenal were destroyed in 1971–72 when the U.S. offensive biological weapons (BW) program was discontinued.[12]The United States BW program focused on three agents of the Brucella group:§ Porcine Brucellosis (Agent US)§ Bovine Brucellosis (Agent AB)§ Caprine Brucellosis (Agent AM)Agent US was in advanced development by the end of World War II. When the U.S. Air Force (USAF) wanted a biological warfare capability, the Chemical Corps offered Agent US in the M114 bomblet, based after the 4-pound bursting bomblet developed for anthrax in World War II. Though the capability was developed, operational testing indicated that the weapon was less than desirable, and the USAF termed it an interim capability until replaced by a more effective biological weapon.The main drawbacks of the M114 with Agent US was that it was incapacitating (the USAF wanted "killer" agents), the storage stability was too low to allow for storing at forward air bases, and the logistical requirements to neutralize a target were far higher than originally anticipated, requiring unreasonable logistical air support.Agents US and AB had a median infective dose of 500 org/person, and AM was 300 org/person. The rate-of-action was believed to be 2 weeks, with a duration of action of several months. The lethality estimate was based on epidemiological information at 1–2%. AM was always believed to be a more virulent disease, and a 3% fatality rate was expected.Control and eradication effortsUnited StatesDairy herds in the USA are tested at least once a year with the Brucella Milk Ring Test (BRT).[13] Cows that are confirmed to be infected are often killed. In the United States, veterinarians are required to vaccinate all young stock, thereby further reducing the chance of zoonotic transmission. This vaccination is usually referred to as a "calfhood" vaccination. Most cattle receive a tattoo in their ear serving as proof of their vaccination status. This tattoo also includes the last digit of the year they were born.[14]The first state–federal cooperative efforts towards eradication of brucellosis caused by Brucella abortus in the U.S. began in 1934.Greater Yellowstone areaWild bison and elk in the Greater Yellowstone Area (GYA) are the last remaining reservoir of Brucella abortus in the U.S. The recent transmission of brucellosis from elk to cattle in Idaho and Wyoming illustrates how the GYA is the last remaining reservoir in the United States, adversely affecting the livestock industry. Eliminating brucellosis from this area is a challenge, as there are many viewpoints on how to manage diseased wildlife.CanadaCanada declared their cattle herd brucellosis-free on September 19, 1985. Brucellosis ring testing of milk and cream, as well as testing of slaughter cattle, ended April 1, 1999. Monitoring continues through auction market testing, standard disease reporting mechanisms, and testing of cattle being qualified for export to countries other than the USA.[15]EuropeMaltaUntil the early 20th century the disease was endemic in Malta to the point of it being referred to as "the Maltese fever". The link between the illness and unpasteurised milk was established by Temi Zammit. Today thanks to a strict regime of certification of milk animals and widespread use of pasteurisation the illness has been eradicated from Malta.[16]Republic of IrelandIreland was declared free of brucellosis on 1 July 2009. The disease had troubled the country's farmers and veterinarians for several decades.[17][18] The Irish government submitted an application to the European Commission, which verified that Ireland had been liberated.[18] Brendan Smith, Ireland's then Minister for Agriculture, Food and the Marine, said the elimination of brucellosis was "a landmark in the history of disease eradication in Ireland".[17][18] Ireland's Department of Agriculture, Food and the Marine intends to reduce its brucellosis eradication programme now that eradication has been confirmed.[17][18]OceaniaAustraliaAustralia is at present free of cattle brucelosis, although it occurred in the past. Brucellosis of sheep or goats has never been reported. Brucellosis of pigs does occur. Feral pigs are the typical source of human infections.[19] [20]New ZealandBrucellosis in New Zealand is limited to sheep (Brucella ovis). The country is free of all other species of Brucella.[21]
成年发病型斯蒂尔病是炎症性关节炎的一种罕见形式,由EGBywaters在1971年描述此特征。 根本原因未知,通常表现为高烧,关节和肌肉疼痛,橙红色皮疹和其他全身炎症症状。历史斯蒂尔病是以英国内科医生George Frederic Still先生的名字命名。流行病学成年患病型斯蒂尔病极其罕见,世界各地都有描述。患病率估计为每十万到百万人口中1.5例。发病呈双峰年龄分布,高发于15-25岁年龄段和36-46岁年龄段。病理生理学本病病理生理学原因不明:基本病因不清楚。征象本病典型表现为关节痛,发烧,橙红-粉红色的皮疹,淋巴结病。类风湿因子(RF)和抗核抗体(ANA)是一般是阴性,血清铁蛋白升高。经历本病的骤然发作的病例,常被报告有极度疲劳,淋巴腺肿大,不常见胸腔和心包积液。诊断诊断属临床诊断,而不是根据血清学检查。至少有七套已制定的诊断标准,山口标准最具灵敏度。诊断至少需要5个特征,其中至少有两个是主要的诊断标准。 主要标准 次要标准 至少39度体温并至少1周 咽喉疼痛 多关节痛或关节炎至少2周 淋巴结病 非瘙痒性橙红色皮疹(常遍及躯干或手足,与发烧同时) 肝肿大或脾肿大 白细胞增多(10000/微升或更多),粒细胞为主 肝功异常 抗核抗体和类风湿因子试验阴性 治疗1987年,美国风湿病学院《关节炎和风湿性关节炎》发表的一篇文章建议,本病患者可分为四种类型。有些病人经历单周期全身性疾病,有些经历多周期全身性疾病,有些病人经历慢性关节的单周期全身性疾病和其他的经历慢性关节的多周期全身性疾病。治疗效果可能取决于病人的疾病类型。本病以消炎药治疗。类固醇激素,如强的松是用来治疗严重的症状。其他常用的药物包括羟氯喹,青霉胺,硫唑嘌呤,氨甲喋呤,依那西普,阿那白滞素,环磷酰胺,阿达木单抗,利妥昔单抗和英夫利昔单抗。越来越多的案例研究都集中于阿那白滞素(或白滞素)治疗本病的疗效。发表在2005年《关节炎和风湿性关节炎》中的一篇文章报告,4例本病患者以阿那白滞素治疗而迅速改善。2012年的加拿大《风湿病学期刊》出版的一个随机,多中心研究报告,一组12例病人予阿那白滞素治疗,比在另一组10例患者服用其他缓解疾病的抗风湿药物,结果更好。2012年的《国际炎症期刊》上刊登的回顾性文章得出结论:越来越多的证据支持使用阿那白滞素治疗成年发病型斯蒂尔病。少年发病型斯蒂尔病的状况,现在通常归类入少年类风湿关节炎。证据表明,少年发病型斯提尔氏病与成年发病型斯提尔氏病密切相关。
Adult-onset Still's disease is a rare form of inflammatory arthritis that was characterized by EG Bywaters in 1971.[1] The underlying cause is unknown. It usually presents with high spiking fevers, joint and muscle pains, a salmon colored rash and other symptoms of systemic inflammation.HistoryStill's disease is named after English physician Sir George Frederic Still (1861–1941).[2][3]EpidemiologyAdult-onset Still's Disease is rare and has been described all over the world. Prevalence is estimated at 1.5 cases per 100,000-1,000,000 population. There is a bimodal age distribution with one peak incidence between ages 15–25 and a second peak between ages of 36–46 years.[4]PathophysiologyIts pathophysiology is cryptogenic: the underlying cause is unknown.Signs and symptomsThe disease typically presents with arthralgia, fever, a 'salmon-pink' rash, and lymphadenopathy. Rheumatoid factor (RF) and anti-nuclear antibody (ANA) are classically negative and serum ferritin is elevated. Patients experiencing a flare-up from Adult-onset Still's disease usually report extreme fatigue, swelling of the lymph glands, and less commonly fluid accumulation in the lungs and heart.DiagnosisThe diagnosis is clinical, not based upon serology.[5] At least seven sets of diagnostic criteria have been devised, however the Yamaguchi criteria have the highest sensitivity. Diagnosis requires at least five features, with at least two of these being major diagnostic criteria.[6]Major criteriaMinor criteriaFever of at least 39C for at least one weekSore throatArthralgias or arthritis for at least two weeksLymphadenopathyNonpruritic salmon colored rash (usually over trunk or extremities while febrile)Hepatomegaly or splenomegalyLeukocytosis ( 10,000/microL or greater), with granulocyte predominanceAbnormal liver function testsNegative tests for antinuclear antibody and rheumatoid factorTreatmentA 1987 article published in Arthritis & Rheumatism suggested that patients with Adult-onset Still's Disease can be differentiated into four types. Some patients experience monocyclic systemic disease, some experience polycyclic systemic disease, some experience chronic articular monocyclic systemic disease and others experience chronic articular polycyclic systemic disease.[7] Treatment efficacy may depend on the nature of the patient's disease.Adult-onset Still's disease is treated with anti-inflammatory drugs. Steroids such as prednisone are used to treat severe symptoms of Still's. Other commonly-used medications include hydroxychloroquine, penicillamine, azathioprine, methotrexate, etanercept, anakinra, cyclophosphamide, adalimumab,rituximab, and infliximab.A growing number of case studies have focused on the efficacy of Anakinra (or Kineret) in the treatment of Adult-onset Still's Disease. A 2005 article published in Arthritis & Rheumatism reported rapid improvement in four patients with Adult-onset Still's Disease who were treated with Anakinra.[8] A randomized, multicenter study published in the Journal of Rheumatology in 2012 reported better outcomes in a group of 12 patients treated with Anakinra than in a group of 10 patients taking other disease-modifying antirheumatic drugs.[9] Authors of a 2012 review article published in the International Journal of Inflammation concluded that "a growing number of evidences supports the the utilisation of Anakinra in Adult-onset Still's Disease".[10]The condition "juvenile-onset Still's disease" is now usually grouped under juvenile rheumatoid arthritis. However, there is some evidence that the two conditions are closely related.[11]