HIV and AIDS: The Basics

What is HIV? HIV stands for Human Immunodeficiency Virus. The virus infects and gradually destroys the cells in the body that usually fight infections, leaving the body vulnerable to diseases it would normally be able to fight. Without treatment the immune system becomes weaker and weaker, and a person with HIV will begin to develop infections. As the immune system becomes too weak to fight infections, a person with HIV will begin to develop particularly serious infections. At this point the person is said to have developed AIDS (Acquired Immune Deficiency Syndrome).

How is HIV transmitted? HIV can only be passed on through infected blood, semen, vaginal fluids or breast milk. HIV is mainly transmitted through vaginal or anal intercourse without a condom or by sharing a needle or syringe with someone who is living with HIV. Other ways that HIV can be transmitted are: From a HIV positive mother to her baby during pregnancy, birth, or breastfeeding. From a needlestick injury in a healthcare setting. From a blood transfusion or blood products (blood is usually screened to prevent this but in some countries this may not happen so you need to check the protocol in your country of residence). By giving oral sex (although this is rare and will usually only occur if a person has cuts or sores in their mouth). It is IMPOSSIBLE to transmit HIV through saliva and HIV cannot be passed on through casual contact such as kissing, or sharing glasses or cutlery. HIV is a fragile virus that cannot survive outside the body.

Whos at risk of HIV? Anyone who is sexually active or shares needles and injecting equipment could be at risk of HIV. Many people living with HIV are undiagnosed so its important that you dont make assumptions about whether you or your partner has HIV.

HIV and AIDS: Symptoms and Treatment

Symptoms of early HIV infection Not everybody experiences symptoms when they are initially infected with HIV, but many people who acquire HIV do experience some early symptoms in the first few weeks after infection. These may feel like flu and the most common combination of symptoms are a fever, sore throat and perhaps also a rash. These symptoms get better on their own and may be the only symptoms a person with HIV experiences before becoming very ill with a damaged immune system several years later.

HIV Treatment Although there is no cure for HIV, extremely effective treatment called antiretroviral therapy (ART) is available which can keep the virus under control and allow someone with HIV to lead an active, healthy life. Treatment is most effective if started early and its important HIV positive people take their drugs exactly as prescribed in order to stay well. Someone with HIV who is diagnosed early and responds well to treatment can have a near normal life expectancy.

HIV and AIDS: HIV Testing

What should I do if I think I may have HIV? If youre worried you might have contracted HIV, its important to get tested. If you think youve put yourself at risk of HIV, visit a clinic as soon as possible to get advice on testing. Most clinics will test for HIV antibodies which are only present in sufficient numbers up to 12 weeks after infection. Therefore most rapid HIV tests cannot tell you if you are HIV positive within the first 12 weeks. There are other more expensive tests that can test for the virus itself from 4 weeks after infection, but these are not so easily available.

Routine HIV testing Because of the benefits of early HIV treatment and the risk of passing on HIV if youre undiagnosed and untreated, its important that youre aware of your HIV status. If youre sexually active its a good idea to have a regular HIV test as part of maintaining good sexual health.

HIV/AIDS
Human immunodeficiency virus infection / acquired immunodeficiency syndrome (HIV/AIDS) is a disease of the human immune system caused by the human immunodeficiency virus (HIV). During the initial infection a person may experience a brief period of influenza-like illness. This is typically followed by a prolonged period without symptoms. As the illness progresses it interferes more and more with the immune system, making people much more likely to get infections, including opportunistic infections, and tumors that do not usually affect people with working immune systems. HIV is transmitted primarily via unprotected sexual intercourse (including anal and even oral sex), contaminated blood transfusions and hypodermic needles, and from mother to child during pregnancy, delivery, or breastfeeding. Some bodily fluids, such as saliva and tears, do not transmit HIV. Prevention of HIV infection, primarily through safe sex and needle-exchange programs, is a key strategy to control the spread of the disease. There is no cure or vaccine; however, antiretroviral treatment can slow the course of the disease and may lead to a near-normal life expectancy. While antiretroviral treatment reduces the risk of death and complications from the disease, these medications are expensive and may be associated with side effects. Genetic research indicates that HIV originated in west-central Africa during the early twentieth century.[4] AIDS was first recognized by the Centers for Disease Control and Prevention (CDC) in 1981 and its causeHIV infectionwas identified in the early part of the decade.[5] Since its discovery, AIDS has caused nearly 30 million deaths (as of 2009).[6] As of 2010, approximately 34 million people have contracted HIV globally.[7] AIDS is considered a pandemica disease outbreak which is present over a large area and is actively spreading.[8] HIV/AIDS has had a great impact on society, both as an illness and as a source of discrimination. The disease also has significant economic impacts. There are many misconceptions about HIV/AIDS such as the belief that it can be transmitted by casual non-sexual contact. The disease has also become subject to many controversies involving religion.

Signs and symptoms

Main article: Signs and symptom of HIV/AIDS There are three main stages of HIV infection: acute infection, clinical latency and AIDS.
[9][10]

Acute infection

Main symptoms of acute HIV infection

The initial period following the contraction of HIV is called acute HIV, primary HIV or acute retroviral [9][11] syndrome. Many individuals develop an influenza-like illness or a mononucleosis-like illness 24 [12][13] weeks post exposure while others have no significant symptoms. Symptoms occur in 4090% of the cases and most commonly include fever, large tender lymph nodes, throat inflammation, a rash, [11][13] headache, and/or sores of the mouth and genitals. The rash, which occurs in 2050% of cases, [14] presents itself on the trunk and is classicallymaculopapular. Some people also develop opportunistic [11] infections at this stage. Gastrointestinal symptoms such as nausea, vomiting ordiarrhea may occur, as [13] may neurological symptoms of peripheral neuropathy or Guillain-Barre syndrome. The duration of the [13] symptoms varies, but is usually one or two weeks. Due to their nonspecific character, these symptoms are not often recognized as signs of HIV infection. Even cases that do get seen by a family doctor or a hospital are often misdiagnosed as one of the many common infectious diseases with overlapping symptoms. Thus, it is recommended that HIV be [13] considered in patients presenting an unexplained fever who may have risk factors for the infection.

Clinical latency
The initial symptoms are followed by a stage called clinical latency, asymptomatic HIV, or chronic [10] HIV. Without treatment, this second stage of the natural history of HIV infection can last from about [15] [16] [17] three years to over 20 years (on average, about eight years). While typically there are few or no symptoms at first, near the end of this stage many people experience fever, weight loss, gastrointestinal [10] problems and muscle pains. Between 50 and 70% of people also develop persistent generalized

lymphadenopathy, characterized by unexplained, non-painful enlargement of more than one group of [9] lymph nodes (other than in the groin) for over three to six months. Although most HIV-1 infected individuals have a detectable viral load and in the absence of treatment will + eventually progress to AIDS, a small proportion (about 5%) retain high levels of CD4 T cells (T helper [13][18] cells) without antiretroviral therapy for more than 5 years. These individuals are classified as HIV controllers or long-term nonprogressors (LTNP), and those who also maintain a low or undetectable viral [18] load without anti-retroviral treatment are known as "elite controllers" or "elite suppressors".

Acquired immunodeficiency syndrome

Main symptoms of AIDS.

Acquired immunodeficiency syndrome (AIDS) is defined in terms of either a CD4 T cell count below 200 [13] cells per L or the occurrence of specific diseases in association with an HIV infection. In the absence [13] of specific treatment, around half the people infected with HIV develop AIDS within ten years. The most common initial conditions that alert to the presence of AIDS are pneumocystis pneumonia (40%),cachexia in the form of HIV wasting syndrome (20%) and esophageal [13] [13] candidiasis. Other common signs include recurring respiratory tractinfections. Opportunistic infections may be caused by bacteria, viruses, fungi and parasites that are normally [19] controlled by the immune system. Which infections occur partly depends on what organisms are [13] [20] common in the person's environment. These infections may affect nearly every organ system. People with AIDS have an increased risk of developing various viral induced cancers including: Kaposi's [14] sarcoma, Burkitt's lymphoma, primary central nervous system lymphoma, and cervical cancer. Kaposi's [21] sarcoma is the most common cancer occurring in 10 to 20% of people with HIV. The second most common cancer is lymphoma which is the cause of death of nearly 16% of people with AIDS and is the

initial sign of AIDS in 3 to 4%. Both these cancers are associated with human herpesvirus 8. cancer occurs more frequently in those with AIDS due to its association with human [21] papillomavirus (HPV).

[21]

[21]

Cervical

Additionally, they frequently have systemic symptoms such as prolonged fevers, sweats (particularly at [22] night), swollen lymph nodes, chills, weakness, and weight loss. Diarrhea is another common symptom [23] present in about 90% of people with AIDS.

Transmission
Average per act risk of getting HIV by exposure route to an infected source

Exposure Route

Chance of infection

Blood Transfusion

90% [24]

Childbirth (to child)

25%[25]

Needle-sharing injection drug use

0.67%[24]

Percutaneous needle stick

0.30%[26]

Receptive anal intercourse*

0.043.0%[27]

Insertive anal intercourse*

0.03%[28]

Receptive penile-vaginal intercourse* 0.050.30%[27][29]

Insertive penile-vaginal intercourse*

0.010.38% [27][29]

Receptive oral intercourse*

00.04% [27]

Insertive oral intercourse*

00.005%[30]

assuming no condom use performed on a man

source refers to oral intercourse

HIV is transmitted by three main routes: sexual contact, exposure to infected body fluids or tissues, and from mother to child during pregnancy, delivery, or breastfeeding (known as vertical [2] transmission). There is no risk of acquiring HIV if exposed to feces, nasal secretions, saliva, sputum, [26] sweat, tears, urine, or vomit unless these are contaminated with blood. It is possible to be co[31] infectedby more than one strain of HIVa condition known as HIV superinfection.

Sexual
The most frequent mode of transmission of HIV is through sexual contact with an infected [2] person. Worldwide, the majority of cases of transmission occur through heterosexual contacts (i.e. [2] sexual contacts between people of the opposite sex). However, the pattern of transmission varies significantly between countries. In the United States, as of 2009, most sexual transmission occurred [2] [32] in men who have sex with men, with this population accounting for 64% of all new cases. As regards unprotected heterosexual contacts, estimates of the risk of HIV transmission per sexual act [33] appear to be four to ten times higher in low-income countries than in high-income countries. In lowincome countries, the risk of female-to-male transmission is estimated as 0.38% per act, and of male-tofemale transmission as 0.30% per act; the equivalent estimates for high-income countries are 0.04% per [33] act for female-to-male transmission, and 0.08% per act for male-to-female transmission. The risk of transmission from anal intercourse is especially high, estimated as 1.41.7% per act in heterosexual as [33][34] well as homosexual contacts. While the risk of transmission from oral sex is relatively low, it is still [35] [36] present. The risk from receiving oral sex has been described as "nearly nil" however a few cases [37] [38] have been reported. The per act risk is estimated at 00.04% for receptive oral intercourse. In settings involving commercial sex worldwide, risk of female-to-male transmission has been estimated as [33] 2.4% per act and male-to-female transmission as 0.08% per act. Risk of transmission increases in the presence of many sexually transmitted infections and genital [33] [33] ulcers. Genital ulcers appear to increase the risk approximately fivefold. Other sexually transmitted infections, such as gonorrhea, chlamydia,trichomoniasis, and bacterial vaginosis, are associated with [38] somewhat smaller increases in risk of transmission. The viral load of an infected person is an important risk factor in sexual as well as mother-to-child [40] transmission. During the first 2.5 months of an HIV infection a person's infectiousness is twelve times [38] higher due to this high viral load. If the person is in the late stages of infection, rates of transmission are [33] approximately eightfold greater. Rough sex can be a factor associated with an increased risk of transmission. Sexual assault is also believed to carry an increased risk of HIV transmission as condoms are rarely worn, physical trauma to the vagina or rectum is likely, and there may be a greater risk of concurrent sexually transmitted [42] infections.
[41] [39]

Body fluids

CDC poster from 1989 highlighting the threat of AIDS associated with drug use

The second most frequent mode of HIV transmission is via blood and blood products. Blood-borne transmission can be through needle-sharing during intravenous drug use, needle stick injury, transfusion of contaminated blood or blood product, or medical injections with unsterilised equipment. The risk from [43] sharing a needle during drug injection is between 0.63 and 2.4% per act, with an average of 0.8%. The risk of acquiring HIV from a needle stick from an HIV-infected person is estimated as 0.3% (about 1 in 333) per act and the risk following mucus membrane exposure to infected blood as 0.09% (about 1 in [26] 1000) per act. In the United States intravenous drug users made up 12% of all new cases of HIV in [32] [2] 2009, and in some areas more than 80% of people who inject drugs are HIV positive. Blood transfusions with infected blood result in transmission of infection in about 93% of cases. In developed countries the risk of acquiring HIV from a blood transfusion is extremely low (less than one in [2] half a million) where improved donor selection and HIV screening is performed. In the UK the risk is [44] reported at one in five million. However, in low income countries only half of the blood used for [45] transfusions may be appropriately screened (as of 2008). It is estimated that up to 15% of HIV infections in these areas come from transfusion of infected blood and blood products, representing [2][46] between 5% and 10% of global infections. Unsafe medical injections play a significant role in HIV spread in sub-Saharan Africa. In 2007, between [47] 12 and 17% of infections in this region were attributed to medical syringe use. The World Health Organisation estimates the risk of transmission as a result of a medical injection in Africa at [47] 1.2%. Significant risks are also associated with invasive procedures, assisted delivery, and dental care [47] in this area of the world.
[43]

[2]

People giving or receiving tattoos, piercings, and scarification are theoretically at risk of infection but no [48] confirmed cases have been documented. It is not possible for mosquitoes or other insects to transmit [49] HIV.

Mother-to-child
HIV can be transmitted from mother to child during pregnancy, during delivery, or through breast [50][51] [2] milk. This is the third most common way way in which HIV is transmitted globally. In the absence of treatment, the risk of transmission before or during birth is around 20% and in those who also breastfeed [50] [50] 35%. As of 2008, vertical transmission accounted for about 90% of cases of HIV in children. With [50] appropriate treatment the risk of mother-to-child infection can be reduced to about 1%. Preventive treatment involves the mother taking antiretroviral during pregnancy and delivery, an elective caesarean [52] section, avoiding breastfeeding, and administering antiretroviral drugs to the newborn. Many of these [52] measures are however not available in the developing world. If blood contaminates food during pre[48] chewing it may pose a risk of transmission.

Virology
Main article: HIV

A diagram showing the structure of HIV virus

HIV is the cause of the spectrum of disease known as HIV/AIDS. HIV is a retrovirus that primarily infects + components of the human immune systemsuch as CD4 T cells, macrophages and dendritic cells. It + [53] directly and indirectly destroys CD4 T cells. HIV is a member of the genus Lentivirus, part of the family of Retroviridae. Lentiviruses share many morphological and biological characteristics. Many species of mammals are infected by lentiviruses, which are characteristically responsible for long-duration illnesses with a long incubation [56] period. Lentiviruses are transmitted as single-stranded, positive-sense, enveloped RNA viruses. Upon entry into the target cell, the viral RNA genomeis converted (reverse transcribed) into doublestranded DNA by a virally encoded reverse transcriptase that is transported along with the viral genome in the virus particle. The resulting viral DNA is then imported into the cell nucleus and integrated into the [57] cellular DNA by a virally encoded integrase and host co-factors. Once integrated, the virus may become latent, allowing the virus and its host cell to avoid detection by the immune
[54] [55]

system. Alternatively, the virus may be transcribed, producing new RNA genomes and viral proteins that [59] are packaged and released from the cell as new virus particles that begin the replication cycle anew. Two types of HIV have been characterized: HIV-1 and HIV-2. HIV-1 is the virus that was originally [60] discovered (and initially referred to also as LAV or HTLV-III). It is more virulent, more infective, and is the cause of the majority of HIV infections globally. The lower infectivity of HIV-2 as compared with HIV-1 implies that fewer people exposed to HIV-2 will be infected per exposure. Because of its relatively poor [61] capacity for transmission, HIV-2 is largely confined to West Africa.

[58]

Pathophysiology
Main article: Pathophysiology of HIV/AIDS

Scanning electron micrograph of HIV-1, colored green, budding from a culturedlymphocyte.

After the virus enters the body there is a period of rapid viral replication, leading to an abundance of virus in the peripheral blood. During primary infection, the level of HIV may reach several million virus particles [62] per milliliter of blood. This response is accompanied by a marked drop in the number of circulating + + CD4 T cells. The acute viremia is almost invariably associated with activation of CD8 T cells, which kill + HIV-infected cells, and subsequently with antibody production, or seroconversion. The CD8 T cell + response is thought to be important in controlling virus levels, which peak and then decline, as the CD4 T + cell counts recover. A good CD8 T cell response has been linked to slower disease progression and a [63] better prognosis, though it does not eliminate the virus. The pathophysiology of AIDS is complex. Ultimately, HIV causes AIDS by depleting CD4 T cells. This weakens the immune system and allowsopportunistic infections. T cells are essential to the immune response and without them, the body cannot fight infections or kill cancerous cells. The mechanism of + [65] CD4 T cell depletion differs in the acute and chronic phases. During the acute phase, HIV-induced cell + lysis and killing of infected cells by cytotoxic T cells accounts for CD4 T cell depletion, although apoptosis may also be a factor. During the chronic phase, the consequences of generalized immune activation coupled with the gradual loss of the ability of the immune system to generate new T + [66] cells appear to account for the slow decline in CD4 T cell numbers. Although the symptoms of immune deficiency characteristic of AIDS do not appear for years after a + person is infected, the bulk of CD4 T cell loss occurs during the first weeks of infection, especially in the [67] intestinal mucosa, which harbors the majority of the lymphocytes found in the body. The reason for the + + preferential loss of mucosal CD4 T cells is that the majority of mucosal CD4 T cells express
[64] +

the CCR5 protein which HIV uses as a co-receptor to gain access to the cells, whereas only a small + [68] fraction of CD4 T cells in the bloodstream do so. HIV seeks out and destroys CCR5 expressing CD4 T cells during acute infection. A vigorous immune + response eventually controls the infection and initiates the clinically latent phase. CD4 T cells in mucosal [69] tissues remain particularly affected. Continuous HIV replication results in a state of generalized [70] immune activation persisting throughout the chronic phase. Immune activation, which is reflected by the increased activation state of immune cells and release of pro-inflammatory cytokines, results from the activity of several HIV gene products and the immune response to ongoing HIV replication. It is also linked to the breakdown of the immune surveillance system of the gastrointestinal mucosal barrier caused + [71] by the depletion of mucosal CD4 T cells during the acute phase of disease.
+ [69]

Diagnosis
Main article: Diagnosis of HIV/AIDS

A generalized graph of the relationship between HIV copies (viral load) and CD4 + T cell counts over the average course of untreated HIV infection.
CD4+ T Lymphocyte count (cells/mm) HIV RNA copies per mL of plasma

HIV/AIDS is diagnosed via laboratory testing and then staged based on the presence of certain signs or [11] symptoms. HIV testing is recommended for all those at high risk, which includes anyone diagnosed [14] with a sexually transmitted illness. In many areas of the world a third of HIV carriers only discover they are infected at an advanced stage of the disease when AIDS or severe immunodeficiency has become [14] apparent.

HIV testing
Most people infected with HIV develop specific antibodies (i.e. seroconvert) within three to twelve weeks [13] of the initial infection. Diagnosis of primary HIV before seroconversion is done by measuring HIV[13] RNA or p24 antigen. Positive results obtained by antibody orPCR testing are confirmed either by a [11] different antibody or by PCR. Antibody tests in children younger than 18 months are typically inaccurate due to the continued presence [72] of maternal antibodies. Thus HIV infection can only be diagnosed by PCR testing for HIV RNA or DNA, [11] or via testing for the p24 antigen. Much of the world lacks access to reliable PCR testing and many places simply wait until either symptoms develop or the child is old enough for accurate antibody [72] testing. In sub-Saharan Africa as of 20072009 between 3070% of the population was aware of their

HIV status. In 2009 between four and 42% of the population was tested. [73] substantial increases from ten years previous.

[73]

[73]

These figures represent

Classifications of HIV infection

Two main clinical staging systems are used to classify HIV and HIV-related disease [11] for surveillance purposes: the WHO disease staging system for HIV infection and disease, and [74] the CDC classification system for HIV infection. The CDC's classification system is more frequently adopted in developed countries. Since the WHO's staging system does not require laboratory tests, it is suited to the resource-restricted conditions encountered in developing countries, where it can also be used to help guide clinical management. Despite their differences, the two systems allow comparison for [9][11][74] statistical purposes. The World Health Organization first proposed a definition for AIDS in 1986. Since then, the WHO classification has been updated and expanded several times, with the most recent version being [11] published in 2007. The WHO system uses the following categories: Primary HIV infection: May be either asymptomatic or associated with acute retroviral syndrome.
+ [11] [11]

Stage I: HIV infection is asymptomatic with a CD4 T cell count (also known as CD4 count) greater [11] [11] than 500/uL. May include generalized lymph node enlargement. Stage II: Mild symptoms which may include minor mucocutaneous manifestations and [11] recurrent upper respiratory tract infections. A CD4 count of less than 500/uL. Stage III: Advanced symptoms which may include unexplained chronic diarrhea for longer than a month, severe bacterial infections including tuberculosis of the lung as well as a CD4 count of less [11] than 350/uL. Stage IV or AIDS: severe symptoms which includes toxoplasmosis of the brain, candidiasis of [11] the esophagus, trachea, bronchi or lungs and Kaposi's sarcoma. A CD4 count of less than 200/uL.

The United States Center for Disease Control and Prevention also created a classification system for HIV, [74] and updated it in 2008. In this system HIV infections are classified based on CD4 count and clinical [74] symptoms, and describes the infection in three stages: Stage 1: CD4 count 500 cells/uL and no AIDS defining conditions Stage 2: CD4 count 200 to 500 cells/uL and no AIDS defining conditions Stage 3: CD4 count 200 cells/uL or AIDS defining conditions Unknown: if insufficient information is available to make any of the above classifications
+

For surveillance purposes, the AIDS diagnosis still stands even if, after treatment, the CD4 T cell count [9] rises to above 200 per L of blood or other AIDS-defining illnesses are cured.

Prevention
Main article: Prevention of HIV/AIDS

AIDS Clinic, McLeod Ganj, Himachel Pradesh, India, 2010

Sexual contact
Consistent condom use reduces the risk of HIV transmission by approximately 80% over the long [75] term. When one partner of a couple is infected, consistent condom use results in rates of HIV infection [76] for the uninfected person of below 1% per year. There is some evidence to suggest thatfemale [77] condoms may provide an equivalent level of protection. Application of a vaginal gel containing tenofovir (a reverse transcriptase inhibitor) immediately before sex seems to reduce infection [78] rates by approximately 40% among African women. By contrast, use of the spermicide nonoxynol9 may increase the risk of transmission due to its tendency to cause vaginal and rectal [79] irritation. Circumcision in Sub-Saharan Africa "reduces the acquisition of HIV by heterosexual men by [80] between 38% and 66% over 24 months". Based on these studies, the World Health Organization and UNAIDS both recommended male circumcision as a method of preventing female-to-male HIV [81] [82][83] transmission in 2007. Whether it protects against male-to-female transmission is disputed and whether it is of benefit in developed countries and among men who have sex with men is [84][85][86] undetermined. Some experts fear that a lower perception of vulnerability among circumcised men [87] may result in more sexual risk-taking behavior, thus negating its preventive effects. Women who have [88] undergone female genital cutting have an increased risk of HIV. Programs encouraging sexual abstinence do not appear to affect subsequent HIV risk. Evidence for a [90] benefit from peer education is equally poor. Comprehensive sexual education provided at school may [91] decrease high risk behavior. A substantial minority of young people continues to engage in high-risk practices despite knowing about HIV/AIDS, underestimating their own risk of becoming infected with [92] [39] HIV. It is not known if treating other sexually transmitted infections is effective in preventing HIV.
[89]

Pre exposure
Early treatment of HIV-infected people with antiretrovirals protected 96% of partners from [93][94] infection. Pre-exposure prophylaxis with a daily dose of the medications tenofovir with or

withoutemtricitabine is effective in a number of groups including: men who have sex with men, couples [78] where one is HIV positive, and young heterosexuals in Africa. Universal precautions within the health care environment are believed to be effective in decreasing the [95] risk of HIV. Intravenous drug use is an important risk factor and harm reduction strategies such as needle-exchange programmes and opioid substitution therapy appear effective in decreasing this [96][97] risk.

Post exposure
A course of antiretrovirals administered within 48 to 72 hours after exposure to HIV positive blood or [98] genital secretions is referred to as post-exposure prophylaxis. The use of the single agentzidovudine reduces the risk of subsequent HIV infection fivefold following a needle stick [98] injury. Treatment is recommended after sexual assault when the perpetrator is known to be HIV [99] positive but is controversial when their HIV status is unknown. Current treatment regimes typically use lopinavir/ritonavir and lamivudine/zidovudine or emtricitabine/tenofovir and may decrease the risk [98] [100] further. The duration of treatment is usually four weeks and is frequently associated with adverse effects (with zidovudine in about 70% of cases, including nausea in 24%, fatigue in 22%, emotional [26] distress in 13%, and headaches in 9%).

Mother-to-child
Programs to prevent the transmission of HIV from mothers to children can reduce rates of transmission by [50][96] 9299%. This primarily involves the use of a combination of antivirals during pregnancy and after [50][101] birth in the infant but also potentially includes bottle feeding rather than breastfeeding. If replacement feeding is acceptable, feasible, affordable, sustainable and safe, mothers should avoid breast-feeding their infants, however exclusive breast-feeding is recommended during the first months of [102] life if this is not the case. If exclusive breast feeding is carried out, the provision of extended [103] antiretroviral prophylaxis to the infant decreases the risk of transmission.

Vaccination
As of 2012 there is no effective vaccine for HIV or AIDS. A single trial of the vaccine RV 144 published in 2009 found a partial reduction in the risk of transmission of roughly 30%, stimulating some hope in the [105] research community of developing a truly effective vaccine. Further trials of the RV 144 vaccine are [106][107] ongoing.
[104]

Management
Main article: Management of HIV/AIDS There is currently no cure or effective HIV vaccine. Treatment consists of high active antiretroviral therapy [108] (HAART) which slows progression of the disease and as of 2010 more than 6.6 million people were [7] taking them in low and middle income countries. Treatment also includes preventative and active treatment of opportunistic infections.

Antiviral therapy

Abacavir a nucleoside analog reverse transcriptase inhibitor (NARTI or NRTI)

Current HAART options are combinations (or "cocktails") consisting of at least three medications [109] belonging to at least two types, or "classes," ofantiretroviral agents. Initially treatment is typically a non-nucleoside reverse transcriptase inhibitor (NNRTI) plus two nucleoside analogue reverse [109] transcriptase inhibitors (NRTIs). Typical NRTIs include: zidovudine (AZT) or tenofovir (TDF) [109] and lamivudine (3TC) or emtricitabine (FTC). Combinations of agents which include a protease [109] inhibitors (PI) are used if the above regime loses effectiveness. When to start antiretroviral therapy is subject to debate. Both the World Health Organization, European guidelines and the United States recommends antiretrovirals in all adolescents, adults and pregnant women with a CD4 count less than 350/uL or those with symptoms regardless of CD4 [14][109] count. This is supported by the fact that beginning treatment at this level reduces the risk of [111] death. The United States in addition recommends them for all HIV-infected people regardless of CD4 count or symptoms, however makes this recommendation with less confidence for those with higher [112] counts. While the WHO also recommends treatment in those who are co-infected with tuberculosis [109] and those with chronic activehepatitis B. Once treatment is begun it is recommended that it is [14] continued without breaks or "holidays". Many people are diagnosed only after the moment treatment [14] ideally should have begun. The desired outcome of treatment is a long term plasma HIV-RNA count [14] below 50 copies/mL. Levels to determine if treatment is effective are initially recommended after four weeks and once levels fall below 50 copies/mL checks every three to six months are typically [14] [14] adequate. Inadequate control is deemed to be greater than 400 copies/mL. Based on these criteria [14] treatment is effective in more than 95% of people during the first year. Benefits of treatment include a decreased risk of progression to AIDS and a decreased risk of [113] [114] death. In the developing world treatment also improves physical and mental health. With treatment [109] there is a 70% reduced risk of acquiring tuberculosis. Additional benefits include a decreased risk of [109] transmission of the disease to sexual partners and a decrease in mother-to-child transmission. The [14] effectiveness of treatment depends to a large part on compliance. Reasons for non-adherence include: [115] [116] poor access to medical care, inadequate social supports, mental illness and drug abuse. As well the complexity of treatment regimens (due to pill numbers and dosing frequency) and adverse effectsmay
[14][110]

create intentional non-adherence. [118] countries.

[117]

Adherence is however just as good in low income as high income

[119]

Specific adverse events are related to the agent taken. Some relatively common ones include: lipodystrophy syndrome, dyslipidemia, and diabetes mellitus especially with protease [9] [119][120] inhibitors. Other common symptoms include: diarrhea, and an increased risk of cardiovascular [121] [14] disease. Adverse effects are however less with some of the newer recommended treatments. Cost [122] may be an issue with some medications being expensive however as of 2010, 47% of those who [7] needed them were taking them in low and middle income countries. Certain medications may be [14] associated with birth defects and thus not suitable for women hoping to have children. Treatment recommendations for children are slightly different from those for adults. In the developing [123] world, as of 2010, 23% of children who were in need of treatment had access. Both the World Health Organization and the United States recommend treatment for all children less than twelve months of [124][125] age. The United States recommends in those between one year and five years of age treatment in those with HIV RNA counts of greater than 100,000 copies/mL, and in those more than five years [124] treatments when CD4 counts are less than 500/ul.

Opportunistic infections
Measures to prevent opportunistic infections are effective in many people with HIV/AIDS. Treatment with antivirals often improves current, as well as decreases the risk of future, opportunistic [119] infections. Vaccination against hepatitis A and B is advised for all people at risk of HIV before they become infected however may also be given after [126] infection. Trimethoprim/sulfamethoxazole prophylaxis between four to six weeks of age and finishing [123] breastfeeding in infants born to HIV positive mothers is recommended in resource limited settings. It is also recommended to prevent PCP when peoples' CD4 count is below 200 cells/uL and in those who [127] have or have previously had PCP. People with substantial immunosuppression are also advised to [128] receive prophylactic therapy for toxoplasmosis and Cryptococcus meningitis. Appropriate preventive [129] measures have reduced the rate of these infections by 50% between 1992 and 1997.

Alternative medicine
In the US, approximately 60% of people with HIV use various forms of complementary or alternative [130] [131] medicine. The effectiveness of most of these therapies however has not been established. With respect to dietary advice and AIDS some evidence has shown a benefit [132] from micronutrient supplements. Evidence for supplementation with selenium is mixed with some [133] tentative evidence of benefit. There is some evidence that vitamin A supplementation in children [132] reduces mortality and improves growth. In Africa in nutritionally compromised pregnant and lactating [132] women a multivitamin supplementation has improved outcomes for both mothers and children. Dietary intake of micronutrients at RDA levels by HIV-infected adults is recommended by the World Health [134][135] Organization. The WHO further states that several studies indicate that supplementation of vitamin [135] A, zinc, and iron can produce adverse effects in HIV positive adults. There is not enough evidence to [136] support the use of herbal medicines.

Prognosis

Disability-adjusted life year for HIV and AIDS per 100,000 inhabitants as of 2004.
no data 10 1025 2550 50100 100500 5001000 10002500 25005000 50007500 7500-10000 10000-50000 50000

HIV/AIDS has become a chronic rather than an acutely fatal disease in many areas of the [137] world. Prognosis varies between people, and both the CD4 count and viral load are useful for [13] predicted outcomes. Without treatment, average survival time after infection with HIV is estimated to be [138] 9 to 11 years, depending on the HIV subtype. After the diagnosis of AIDS, if treatment is not available, [139][140] survival ranges between 6 and 19 months. HAART and appropriate prevention of opportunistic infections reduces the death rate by 80%, and raises the life expectancy for a newly diagnosed young [137][141][142] [141] adult to 2050 years. This is between two thirds and nearly that of the general [14][143] [14] population. If treatment is started late in the infection prognosis is not as good, for example if [14][137] treatment is begun following the diagnosis of AIDS life expectancy is ~1040 years. Half of infants [123] born with HIV die before two years of age without treatment. The primary causes of death from HIV/AIDS are opportunistic infections and cancer, both of which are [129][144] frequently the result of the progressive failure of the immune system. Risk of cancer appears to [14] increase once the CD 4 count gets below 500/uL. The rate of clinical disease progression varies widely between individuals and has been shown to be affected by a number of factors such as a person's [145] susceptibility and immune function; their access to health care and the presence of co[139][146] [147][148] infections; as well as the particular strain (or strains) of the virus involved. Tuberculosis co-infection is one of the leading causes of sickness and death in those with HIV/AIDS [149] being present in a third of all HIV infected people and resulting in 25% of HIV related deaths. HIV is [150] also the most important risk factors for tuberculosis. Hepatitis C is another very common co-infection [151] where each disease increases the progression of the other. The two most common cancers [144] associated with HIV/AIDS are Kaposi's sarcoma and AIDS-related non-Hodgkin's lymphoma. Even with anti-retroviral treatment, over the long term HIV-infected people may experience neurocognitive [152] [153] [154] [155][156] [157] disorders, osteoporosis, neuropathy, cancers, nephropathy, and cardiovascular

disease. It is not clear whether these conditions result from the HIV infection itself or are adverse effects of treatment.

[120]

Epidemiology
Main article: Epidemiology of HIV/AIDS

Estimated prevalence of HIV among young adults (1549) per country as of 2009.[158]

HIV/AIDS is a global pandemic. As of 2010 approximately 34 million people have HIV worldwide. Of [7] these approximately 16.8 million are women and 3.4 million are less than 15 years old. It resulted in [7] about 1.8 million death in 2010, down from 3.1 million in 2001. Sub-Saharan Africa is the region most affected. In 2010, an estimated 68% (22.9 million) of all HIV cases [160] and 66% of all deaths (1.2 million) occurred in this region. This means that about 5% of the adult [161] [162] population is infected and it is believed to be the cause of 10% of all deaths in children. Here in [160] contrast to other regions women compose nearly 60% of cases. South Africa has the largest [160] population of people with HIV of any country in the world at 5.9 million. Life expectancy has fallen in the worst-affected countries due to HIV/AIDS; for example, in 2006 it was estimated that it had dropped [8] from 65 to 35 years in Botswana. South & South East Asia is the second most affected; in 2010 this region contained an estimated 4 million [161] cases or 12% of all people living with HIV resulting in approximately 250,000 deaths. Approximately [160] 2.4 million of these cases are in India. Prevalence is lowest in Western and Central Europe at 0.2% [161] and East Asia at 0.1%. In 2008 in the United States approximately 1.2 million people were living with HIV, resulting in about 17,500 deaths. The Centre for Disease Control and Prevention estimated that in 2008 20% of infected [163] Americans were unaware of their infection. In the United Kingdom as of 2009 there where [164] approximately 86,500 cases which resulted in 516 deaths. In Canada as of 2008 there were about [165] 65,000 cases which results in 53 deaths. Between the first recognition of AIDS in 1981 and 2009 it has [6] led to nearly 30 million deaths.

[159]

[7]

History
Main article: History of HIV/AIDS

Discovery
AIDS was first clinically observed in 1981 in the United States. The initial cases were a cluster of injecting drug users and homosexual men with no known cause of impaired immunity who showed
[21]

symptoms of Pneumocystis carinii pneumonia (PCP), a rare opportunistic infection that was known to [166] occur in people with very compromised immune systems. Soon thereafter, an unexpected number of [167][168] gay men developed a previously rare skin cancer called Kaposi's sarcoma (KS). Many more cases of PCP and KS emerged, alerting U.S. Centers for Disease Control and Prevention (CDC) and a CDC [169] task force was formed to monitor the outbreak. In the early days, the CDC did not have an official name for the disease, often referring to it by way of the diseases that were associated with it, for example, lymphadenopathy, the disease after which the [170][171] discoverers of HIV originally named the virus. They also used Kaposi's Sarcoma and Opportunistic [172] Infections, the name by which a task force had been set up in 1981. At one point, the CDC coined the phrase "the 4H disease", since the syndrome seemed to affect Haitians, homosexuals, hemophiliacs, and [173] heroin users. In the general press, the term "GRID", which stood for gay-related immune deficiency, [174] [172] had been coined. However, after determining that AIDS was not isolated to the gay community, it was realized that the term GRID was misleading and the term AIDS was introduced at a meeting in July [175] [176] 1982. By September 1982 the CDC started referring to the disease as AIDS.

Robert Gallo, co-discoverer of HIV in the early eighties among (from left to right) Sandra Eva, Sandra Colombini, and Ersell Richardson.

In 1983, two separate research groups led by Robert Gallo and Luc Montagnier independently declared that a novel retrovirus may have been infecting AIDS patients, and published their findings in the same [177][178] issue of the journal Science. Gallo claimed that a virus his group had isolated from an AIDS patient was strikingly similar in shape to other human T-lymphotropic viruses (HTLVs) his group had been the first to isolate. Gallo's group called their newly isolated virus HTLV-III. At the same time, Montagnier's group isolated a virus from a patient presenting with swelling of the lymph nodes of the neck and physical weakness, two characteristic symptoms of AIDS. Contradicting the report from Gallo's group, Montagnier and his colleagues showed that core proteins of this virus were immunologically different from those of [169] HTLV-I. Montagnier's group named their isolated virus lymphadenopathy-associated virus (LAV). As [179] these two viruses turned out to be the same, in 1986, LAV and HTLV-III were renamed HIV.

Origins
Both HIV-1 and HIV-2 are believed to have originated in non-human primates in West-central Africa and [4] were transferred to humans in the early 20th century. HIV-1 appears to have originated in southern Cameroon through the evolution of SIV(cpz), a simian immunodeficiency virus (SIV) that infects wild chimpanzees (HIV-1 descends from the SIVcpz endemic in the chimpanzee subspecies Pan [180][181] troglodytes troglodytes). The closest relative of HIV-2 is SIV(smm), a virus of the sooty

mangabey (Cercocebus atys atys), an Old World monkey living in litoral West Africa (from [61] southern Senegalto western Cte d'Ivoire). New World monkeys such as the owl monkey are resistant [182] to HIV-1 infection, possibly because of a genomic fusion of two viral resistance genes. HIV-1 is thought to have jumped the species barrier on at least three separate occasions, giving rise to the three [183] groups of the virus, M, N, and O. There is evidence that humans who participate in bushmeat activities, either as hunters or as bushmeat [184] vendors, commonly acquire SIV. However, SIV is a weak virus which is typically suppressed by the human immune system within weeks of infection. It is thought that several transmissions of the virus from individual to individual in quick succession are necessary to allow it enough time to mutate into [185] HIV. Furthermore, due to its relatively low person-to-person transmission rate, SIV can only spread throughout the population in the presence of one or more of high-risk transmission channels, which are thought to have been absent in Africa prior to the 20th century. Specific proposed high-risk transmission channels, allowing the virus to adapt to humans and spread throughout the society, depend on the proposed timing of the animal-to-human crossing. Genetic studies of the virus suggest that the most recent common ancestor of the HIV-1 M group dates back to circa [186] 1910. Proponents of this dating link the HIV epidemic with the emergence of colonialism and growth of large colonial African cities, leading to social changes, including a higher degree of sexual promiscuity, the spread of prostitution, and the accompanying high frequency of genital ulcer diseases (such [187] as syphilis) in nascent colonial cities. While transmission rates of HIV during vaginal intercourse, are low under regular circumstances, they are increased many fold if one of the partners suffers from an sexually transmitted infection resulting in genital ulcers. Early 1900s colonial cities were notable due to their high prevalence of prostitution and genital ulcers, to the degree that, as of 1928, as many as 45% of female residents of eastern Kinshasa were thought to have been prostitutes, and, as of 1933, around [187] 15% of all residents of the same city were infected by one of the forms of syphilis. An alternative view holds that unsafe medical practices in Africa during years following World War II, such as unsterile reuse of single use syringes during mass vaccination, antibiotic and anti-malaria treatment [185][188][189] campaigns, were the initial vector that allowed the virus to adapt to humans and spread. The earliest well documented case of HIV in a human dates back to 1959 in the Congo. The virus may [191] have been present in the United States as early as 1966, but the vast majority of infections occurring outside sub-Saharan Africa (including the U.S.) can be traced back to a single unknown individual who got infected with HIV in Haiti and then brought the infection to the United States some time around [192] 1969. The epidemic then rapidly spread among high-risk groups (initially, sexually promiscuous men who have sex with men). By 1978, the prevalence of HIV-1 among gay male residents of New York and San Francisco was estimated at 5%, suggesting that several thousand individuals in the country [192] had been infected.
[190]

Society and culture

Stigma

Ryan White became a poster child for HIV after being expelled from school because he was infected.

Main article: Discrimination against people with HIV/AIDS AIDS stigma exists around the world in a variety of ways, including ostracism, rejection, discrimination and avoidance of HIV infected people; compulsory HIV testing without prior consent or protection of confidentiality; violence against HIV infected individuals or people who are perceived to be infected [193] with HIV; and thequarantine of HIV infected individuals. Stigma-related violence or the fear of violence prevents many people from seeking HIV testing, returning for their results, or securing treatment, possibly turning what could be a manageable chronic illness into a death sentence and perpetuating the spread of [194] HIV. AIDS stigma has been further divided into the following three categories: Instrumental AIDS stigmaa reflection of the fear and apprehension that are likely to be associated [195] with any deadly and transmissible illness. Symbolic AIDS stigmathe use of HIV/AIDS to express attitudes toward the social groups or [195] lifestyles perceived to be associated with the disease. Courtesy AIDS stigmastigmatization of people connected to the issue of HIV/AIDS or HIV- positive [196] people.

Often, AIDS stigma is expressed in conjunction with one or more other stigmas, particularly those [197] associated with homosexuality, bisexuality, promiscuity, prostitution, and intravenous drug use. In many developed countries, there is an association between AIDS and homosexuality or bisexuality, and this association is correlated with higher levels of sexual prejudice such as anti[198] homosexual/bisexual attitudes. There is also a perceived association between AIDS and all male-male [195] sexual behavior, including sex between uninfected men. However, the dominant mode of spread [199] worldwide for HIV remains heterosexual transmission.

Economic impact
Main articles: Economic impact of HIV/AIDS and Cost of HIV treatment

Changes in life expectancy in some hard-hit African countries.

Africa Uganda

Botswana

Zimbabwe

Kenya

South

HIV/AIDS affects the economics of both individuals and countries. The gross domestic product of the [162][200] most affected countries have decreased due to the lack of human capital. Without proper nutrition, health care and medicine, large numbers of people die from AIDS-related complications. They will not only be unable to work, but will also require significant medical care. It is estimated that as of 2007 there [162] [201] where 12 million AIDS orphans. Many are cared for by elderly grandparents. By affecting mainly young adults, AIDS reduces the taxable population, in turn reducing the resources available for public expenditures such as education and health services not related to AIDS resulting in increasing pressure for the state's finances and slower growth of the economy. This results in a slower growth of the tax base, an effect that is reinforced if there are growing expenditures on treating the sick, training (to replace sick workers), sick pay and caring for AIDS orphans. This is especially true if the sharp increase in adult mortality shifts the responsibility and blame from the family to the government in caring [201] for these orphans. At the household level, AIDS results in both the loss of income but also increased spending on healthcare. A study in Cte d'Ivoire showed that households with an HIV/AIDS patient, spent twice as much on medical expenses as other households. This additional expenditure also leaves less income to [202] spend on education and other personal or family investment.

[162]

Religion and AIDS

Main article: Religion and HIV/AIDS The topic of religion and AIDS has become highly controversial in the past twenty years, primarily because some religious authorities have publicly declared their opposition to the use of [203][204] condoms. The religious approach to prevent the spread of AIDS according to a report by American health expert Matthew Hanley titled The Catholic Church and the Global Aids Crisis argues that cultural changes are needed including a re-emphasis on fidelity within marriage and sexual abstinence outside of [204] it. Some religious organisations have claimed that prayer can cure HIV/AIDS. In 2011, the BBC reported that some churches in London were claiming that prayer would cure AIDS, and the Hackney-based Centre for the Study of Sexual Health and HIV reported that several people stopped taking their medication, sometimes on the direct advice of their pastor, leading to a number of

deaths. The Synagogue Church Of All Nations advertise an "anointing water" to promote God's [205] healing, although the group deny advising people to stop taking medication.

[205]

Media portrayal
Main article: Media portrayal of HIV/AIDS One of the first high profile cases of AIDS was the American Rock Hudson, a gay actor who had been married and divorced earlier in life, who died on 2 October 1985 having announced that he was suffering [206] from the virus on 25 July that year. He had been diagnosed during 1984. A notable British casualty of AIDS that year was Nicholas Eden, a gay politician and son of the late prime minister Anthony [207] Eden. On November 24, 1991, the virus claimed the life of British rock star Freddie Mercury, lead singer of the band Queen, died from an AIDS related illness having only revealed the diagnosis on the [208] [209] previous day. However he had been diagnosed as HIV positive during 1987. One of the first high profile heterosexual cases of the virus was Arthur Ashe, the American tennis player. He was diagnosed as HIV positive on 31 August 1988, having contracted the virus from blood transfusions during heart surgery earlier in the 1980s. Further tests within 24 hours of the initial diagnosis revealed that Ashe had [210] AIDS, but he did not tell the public about his diagnosis until April 1992. He died, aged 49, as a result [211] on 6 February 1993. Therese Frare's photograph of gay activist David Kirby, as he lay dying from AIDS while surrounded by family, was taken in April 1990. LIFE magazine said the photo became the one image "most powerfully identified with the HIV/AIDS epidemic." The photo was displayed in LIFE magazine, was the winner of the World Press Photo, and acquired worldwide notoriety after being used in aUnited Colors of [212] Benetton advertising campaign in 1992.

Denial, conspiracies, and misconceptions

Main articles: AIDS denialism and Misconceptions about HIV/AIDS A small group of individuals continue to dispute the connection between HIV and AIDS, the existence [214][215] of HIV itself, or the validity of HIV testing and treatment methods. These claims, known as AIDS [216] denialism, have been examined and rejected by the scientific community. However, they have had a significant political impact, particularly in South Africa, where the government's official embrace of AIDS denialism was responsible for its ineffective response to that country's AIDS epidemic, and has been [217][218][219] blamed for hundreds of thousands of avoidable deaths and HIV infections. Operation INFEKTION was a worldwide Soviet active measures operation to spread information that the United States had created HIV/AIDS. Surveys show that a significant number of people believed and continue [220] to believe in such claims. There are many misconceptions about HIV and AIDS. Three of the most common are that AIDS can spread through casual contact, that sexual intercourse with a virgin will cure AIDS, and that HIV can infect only homosexual men and drug users. Other misconceptions are that any act of anal intercourse between two uninfected gay men can lead to HIV infection, and that open discussion of homosexuality and HIV in [221][222] schools will lead to increased rates of homosexuality and AIDS.
[213]

Research
"AIDS research" redirects here. For the journal formerly known as AIDS Research, see AIDS Research and Human Retroviruses.

Research to improve current treatments includes decreasing side effects of current drugs, further simplifying drug regimens to improve adherence, and determining better sequences of regimens to manage drug resistance. However, only a vaccine is thought to be able to halt the pandemic. This is because a vaccine would cost less, thus being affordable for developing countries, and would not require [223] daily treatment. However, after over 20 years of research, HIV-1 remains a difficult target for a [223][224] vaccine, and there is as yet no cure.

Stem cell transplantation

In 2007, Timothy Ray Brown, a 40-year-old HIV-positive man, also known as "the Berlin Patient", was [226] given a stem cell transplant as part of his treatment for acute myeloid leukemia(AML). A second transplant was made a year later after a relapse. The donor was chosen not only for genetic compatibility but also for being homozygous for a CCR5-32 mutation that confers resistance to HIV [227][228] infection. After 20 months without antiretroviral drug treatment, it was reported that HIV levels in [228] Brown's blood, bone marrow, and bowel were below the limit of detection. The virus remained [226] undetectable over three years after the first transplant. Although the researchers and some commentators have characterized this result as a cure, others suggest that the virus may remain hidden [229] [230] in tissues such as the brain (which acts as a viral reservoir). Stem cell treatment remains investigational because of its anecdotal nature, the disease and mortality risk associated with [229][231] stem cell transplants, and the difficulty of finding suitable donors.
[225]

Immunomodulatory agents
Complementing efforts to control viral replication, immunotherapies that may assist in the recovery of the [232] immune system have been explored in past and ongoing trials, including IL-2 and IL-7. The failure of vaccine candidates to protect against HIV infection and progression to AIDS has led to a renewed focus on the biological mechanisms responsible for HIV latency. A limited period of therapy combining anti-retrovirals with drugs targeting the latent reservoir may one day allow for total eradication [233] of HIV infection. Researchers have discovered an abzyme that can destroy the protein gp120 CD4 binding site. This protein is common to all HIV variants as it is the attachment point for B lymphocytes and [234 subsequent compromising of the immune system.

Tuberculosis

Tuberculosis, MTB, or TB (short for tubercle bacillus) is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Tuberculosis typically attacks the lungs, but can also affect other parts of the body. It is spread through the air when people who have an active TB infection cough, sneeze, or otherwise transmit their saliva through the air. Most infections area symptomatic and latent, but about one in ten latent infections eventually progresses to active disease which, if left untreated, kills more than 50% of those so infected. The classic symptoms of active TB infection are a chronic cough with blood-tinged sputum, fever, night sweats, and weight loss . Infection of other organs causes a wide range of symptoms. Diagnosis of active TB relies on radiology, commonly chest X-rays as well as microscopic examination and microbiological culture of body fluids. Diagnosis of latent TB relies on the tuberculin skin test (TST) and/or blood tests. Treatment is difficult and requires administration of multiple antibiotics over a long period of time. Social contacts are also screened and treated if necessary. Antibiotic resistance is a growing problem in multiple drug-resistant tuberculosis (MDR-TB) infections. Prevention relies on screening programs and vaccination with the bacillus CalmetteGurin vaccine.
]

Signs and symptoms

Tuberculosis may infect any part of the body, but most commonly occurs in the lungs (known as pulmonary tuberculosis). Extrapulmonary TB occurs when tuberculosis develops outside of the lungs. Extrapulmonary TB may coexist with pulmonary TB as well. General signs and symptoms include fever, chills, night sweats, loss of appetite, weight loss, and fatigue, and significant finger clubbing may also occur. Pulmonary If a tuberculosis infection does become active, it most commonly involves the lungs (in about 90% of cases). Symptoms may include chest pain and a prolonged cough producing sputum. About 25% of people may not have any symptoms (i.e. they remain "asymptomatic"). Occasionally, people may cough up blood in small amounts, and in very rare cases, the infection may erode into the pulmonary artery, resulting in massive bleeding (Rasmussen's aneurysm). Tuberculosis may become a chronic illness and cause extensive scarring in the upper lobes of the lungs. The upper lung lobes are more frequently affected by tuberculosis than the lower ones. Extrapulmonary In 1520% of active cases, the infection spreads outside the respiratory organs, causing other kinds of TB. These are collectively denoted as "extrapulmonary tuberculosis". commonly in immunosuppressed persons and young children.
[12] ]

Extrapulmonary TB occurs more

Causes
Mycobacteria

The main cause of TB is Mycobacterium tuberculosis, a small, aerobic, non motile bacillus. high lipid content of this pathogen accounts for many of its unique clinical characteristics. Risk factors

[9]

The

A number of factors make people more susceptible to TB infections. The most important risk factor globally is HIV; 13% of all TB cases are infected by the virus. This is a particular problem insub-Saharan Africa, where rates of HIV are high. Tuberculosis is closely linked to both overcrowding and malnutrition, making it one of the principal diseases of poverty. Those at high risk thus include: people who inject illicit drugs, inhabitants and employees of locales where vulnerable people gather (e.g. prisons and homeless shelters), medically underprivileged and resource-poor communities, high-risk ethnic minorities, children in close contact with high-risk category patients and health care providers serving these clients. Those who smoke cigarettes have nearly twice the risk of TB than nonsmokers. Other disease states can also increase the risk of developing tuberculosis, including alcoholism and diabetes mellitus (threefold increase). There is also a genetic susceptibility for which overall importance is still undefined.
] [6]

Prevention
Vaccines The only currently available vaccine as of 2011 is bacillus CalmetteGurin (BCG) which, while it is effective against disseminated disease in childhood, confers inconsistent protection against contracting pulmonary TB. Nevertheless, it is the most widely used vaccine worldwide, with more than 90% of all children being vaccinated. However, the immunity it induces decreases after about ten years. Public health The World Health Organization declared TB a "global health emergency" in 1993 and in 2006, the Stop TB Partnership developed a Global Plan to Stop Tuberculosis that aims to save 14 million lives between its launch and 2015. A number of targets they have set are not likely to be achieved by 2015, mostly due to the increase in HIV-associated tuberculosis and the emergence of multiple drug-resistant tuberculosis (MDR-TB). A tuberculosis classification system developed by the American Thoracic Society is used primarily in public health programs.
[69]

Hepatitis B

Hepatitis B is an infectious inflammatory illness of the liver caused by the hepatitis B virus (HBV) that affects hominoidea, including humans. Originally known as "serum hepatitis . The virus is transmitted by exposure to infectious blood or body fluids such as semen and vaginal fluids, while viral DNA has been detected in the saliva, tears, and urine of chronic carriers. Perinatal infection is a major route of infection in endemic, mainly developing countries. Other risk factors for developing HBV infection include working in a healthcare setting, transfusions, dialysis, acupuncture, tattooing, extended overseas travel, and residence in an institution. However, Hepatitis B viruses cannot be spread by holding hands, sharing eating utensils or drinking glasses, kissing, hugging, coughing, sneezing, or breastfeeding. The acute illness causes liver inflammation, vomiting, jaundice and, rarely, death. Chronic hepatitis B may eventually cause cirrhosis and liver cancera disease with poor response to all but a few current therapies. The infection is preventable by vaccination.
[11]

Hepatitis B virus is an hepadnavirushepa from hepatotropic (attracted to the liver) and dna because it is a DNA virus
[12]

and it has a circulargenome of partially double-stranded DNA. The

viruses replicate through an RNA intermediate form by reverse transcription, which in practice relates them to retroviruses. Although replication takes place in the liver, the virus spreads to the blood where viral proteins and antibodies against them are found in infected people. The hepatitis B virus is 50 to 100 times more infectious than HIV.

Signs and symptoms

. Signs and symptoms of hepatitis B usually appear about three months after you've been infected and can range from mild to severe. Signs and symptoms of hepatitis B may include: Abdominal pain Dark urine Fever Joint pain Loss of appetite Nausea and vomiting Weakness and fatigue Yellowing of your skin and the whites of your eyes (jaundice) Most infants and children with hepatitis B never develop signs and symptoms. The same is true for some adults.

Prevention
Several vaccines have been developed for the prevention of hepatitis B virus infection. These rely on the use of one of the viral envelope proteins (hepatitis B surface antigen or HBsAg). The vaccine was originally prepared from plasma obtained from people who had long-standing hepatitis B virus infection. However, it is made using a synthetic recombinant DNA technology that does not contain blood products. One cannot be infected with hepatitis B from this vaccine. Consider the hepatitis B vaccine The hepatitis B vaccine is typically given as a series of three or four injections over a period of six months. You can't get hepatitis B from the vaccine. The hepatitis B vaccine is recommended for: All infants, beginning at birth All children and adolescents who weren't vaccinated at birth Anyone being treated for a sexually transmitted infection Developmentally disabled people who live in an institutional setting Health care workers, emergency workers and other people who come into contact with blood on the job Anyone infected with HIV Men who have sex with men People who have multiple sexual partners People with chronic liver disease People who inject illicit drugs People who live with someone who has hepatitis B People with end-stage kidney disease Sexual partners of someone who has hepatitis B Travelers planning to go to an area of the world with a high hepatitis B infection rate
[55]

Take precautions to avoid HBV Other ways to reduce your risk of HBV include: Know the HBV status of any sexual partner. Don't engage in unprotected sex unless you're absolutely certain your partner isn't infected with HBV or any other sexually transmitted infection. Use a new latex or polyurethane condom every time you have sex. If you don't know the health status of your partner, use a new latex condom every time you have sexual contact. Remember that although condoms can reduce your risk of contracting HBV, they don't eliminate the risk entirely. Condoms can break or develop small tears, and people don't always use them properly. Stop using illicit drugs. If you use illicit drugs, get help to stop. If you can't stop, use a sterile needle each time you inject illicit drugs. Never share needles. Be cautious about body piercing and tattooing. If you choose to undergo piercing or tattooing, look for a reputable shop. Ask questions beforehand about how the equipment is cleaned. Make sure the employees use sterile needles. If the staff won't answer your questions, look for another shop. Ask about the hepatitis B vaccine before you travel. If you're planning an extended trip to a region where hepatitis B is more common, ask your doctor about the hepatitis B vaccine well in advance. It's usually given in a series of three injections over a six-month period.

Treatment
Screening healthy people for hepatitis B Doctors sometimes test certain healthy people for hepatitis B infection. This is recommended because hepatitis B infection often begins damaging the liver before it causes signs and symptoms. Testing for hepatitis B infection in people who have a high risk of coming in contact with the virus may help doctors begin treatment or recommend lifestyle changes that may slow liver damage. People who may want to talk to their doctors about screening for hepatitis B infection include: Anyone who lives with a person who has hepatitis B infection Anyone who has had sex with a person who has hepatitis B infection Anyone with an unexplained, abnormal liver enzyme test Anyone infected with HIV Immigrants, including internationally adopted children, from areas of the world where hepatitis B is more common, including Asia, the Pacific Islands, Africa and Eastern Europe People who inject drugs Inmates Men who have sex with men People who have one or both parents from an area of the world where hepatitis B is more common People who receive kidney dialysis People who take medications that suppress the immune system, such as anti-rejection medications used after an organ transplant Pregnant women

Blood tests to detect hepatitis B infection Blood tests used to diagnose hepatitis B infection include: A test to determine whether you can easily pass HBV to others.The hepatitis B surface antigen (HBsAg) test looks for hepatitis B surface antigen part of the outer surface of the virus. Testing positive for this antigen means you have an active hepatitis B infection and can easily pass the virus to others. A negative test means you're probably not currently infected. A test to determine whether you're immune to HBV. The antibody to hepatitis B surface antigen (antiHBs) test determines if you have antibodies to HBV. Having antibodies can be due to a prior HBV infection from which you've recovered. Or, it can mean you may already have been vaccinated. In either case, a positive anti-HBs test means you can't infect others or become infected yourself because you're protected by the vaccine or your own natural immunity. A test to determine whether you have had or currently have a hepatitis B infection. The antibody to hepatitis B core antigen (anti-HBc) test identifies people who have an HBV infection. If you test positive for hepatitis B core antibodies, you may have a chronic infection that you can transmit to others. A positive result may also mean you're recovering from an acute infection or have a slight immunity to HBV that can't otherwise be detected. How this test is interpreted often depends on the results of the other two tests. Additional tests to gauge liver health and infection severity If you receive a diagnosis of hepatitis B, your doctor may perform tests to check the severity of the HBV infection as well as the health of your liver. These tests include: A test to determine how likely you are to spread HBV to others.The E antigen blood test looks for the presence of a protein secreted by HBV-infected cells. A positive result means you have high levels of the virus in your blood and can easily infect others. If the test is negative, you have lower blood levels of HBV and are less likely to spread the infection. A test to determine how much HBV DNA is in your blood. The hepatitis B DNA test detects parts of HBV DNA in your blood, indicating how much virus is present (viral load). Assessing your viral load can help monitor how well antiviral therapy is working. Tests to measure liver function. Liver function tests may gauge the amount of damage that has occurred in your liver cells. Removing a sample of liver tissue for testing During a liver biopsy, your doctor inserts a thin needle through your skin and into your liver. A small sample of liver tissue is removed for laboratory analysis. A biopsy may show the extent of any liver damage and may help determine the best treatment for you.

Diphtheria

Diphtheria is an upper respiratory tract illness caused by Corynebacterium diphtheriae, afacultative anaerobic, Gram-positive bacterium. It is characterized by sore throat, low fever, and an adherent membrane (a pseudomembrane) on the tonsils, pharynx, and/or nasal cavity. Diphtheria is a contagious disease spread by direct physical contact or breathing the aerosolized secretions of infected individuals.

Signs and symptoms

The symptoms of diphtheria usually begin two to seven days after infection. Symptoms of diphtheria include fever of 38C (100.4F) or above, chills, fatigue, bluish skin coloration, sore throat, hoarseness, cough, headache, difficulty swallowing, painful swallowing, difficulty breathing, rapid breathing, foulsmelling bloodstained nasal discharge and lymphadenopathy. Symptoms can also include cardiac arrhythmias, myocarditis, and cranial and peripheral nerve palsies.
[citation needed]

Treatment
The disease may remain manageable, but in more severe cases, lymph nodes in the neck may swell, and breathing and swallowing will be more difficult. People in this stage should seek immediate medical attention, as obstruction in the throat may require intubation or a tracheotomy. Abnormal cardiac rhythms can occur early in the course of the illness or weeks later, and can lead to heart failure. Diphtheria can also cause paralysis in the eye, neck, throat, or respiratory muscles. Patients with severe cases will be put in a hospital intensive care unit and be given a diphtheria antitoxin. Since antitoxin does not neutralize toxin that is already bound to tissues, delaying its administration is associated with an increase in mortality risk. Therefore, the decision to administer diphtheria antitoxin is based on clinical diagnosis, and should not await laboratory confirmation. Antibiotics have not been demonstrated to affect healing of local infection in diphtheria patients treated with antitoxin. Antibiotics are used in patients or carriers to eradicate C. diphtheriae and prevent its transmission to others. The CDC recommends
[12]

either:

In cases that progress beyond a throat infection, diphtheria toxin spreads through the blood and can lead to potentially life-threatening complications that affect other organs, such as the heart and kidneys. The toxin can cause damage to the heart that affects its ability to pump blood or the kidneys' ability to clear wastes. It can also cause nerve damage, eventually leading to paralysis. About 40% to 50% of those left untreated can die.

Tetanus

. Tetanus is a medical condition characterized by a prolonged contraction of skeletal muscle fibers. The primary symptoms are caused by tetanospasmin, a neurotoxin produced by the Gram-positive, rodshaped, obligate anaerobic bacterium Clostridium tetani. Infection generally occurs through wound contamination and often involves a cut or deep puncture wound. As the infection progresses, muscle spasms develop in the jaw (thus the name "lockjaw") and elsewhere in the body. Infection can be prevented by proper immunization and by post-exposure prophylaxis.

Signs and symptoms

Tetanus often begins with mild spasms in the jaw muscles (lockjaw). The spasms can also affect the chest, neck, back, and abdominal muscles. Back muscle spasms often cause arching, called opisthotonos. Sometimes the spasms affect muscles that help with breathing, which can lead to breathing problems.
[3]

Prolonged muscular action causes sudden, powerful, and painful contractions of muscle groups. This is called tetany. These episodes can cause fractures and muscle tears. Other symptoms include drooling, excessive sweating, fever, hand or foot spasms, irritability, swallowing difficulty, uncontrolled urination or defecation. Tetanus affects skeletal muscle, a type of striated muscle used in voluntary movement. The other type of striated muscle, cardiac or heart muscle, cannot be tetanized because of its intrinsic electrical properties.

Prevention
Unlike many infectious diseases, recovery from naturally acquired tetanus does not usually result in immunity to tetanus. This is due to the extreme potency of the tetanospasmin toxin; even a lethal dose of tetanospasmin is insufficient to provoke an immune response. Tetanus can be prevented by vaccination with tetanus toxoid. The CDC recommends that adults receive a booster vaccine every ten years and standard care practice in many places is to give the booster to any patient with a puncture wound who is uncertain of when he or she was last vaccinated, or if he or she has had fewer than three lifetime doses of the vaccine. The booster may not prevent a potentially fatal case of tetanus from the current wound, however, as it can take up to two weeks for tetanus antibodies to form. In children under the age of seven, the tetanus vaccine is often administered as a combined vaccine, DPT/DTaP vaccine, which also includes vaccines against diphtheria and pertussis. For adults and children over seven, the Td vaccine (tetanus and diphtheria) or Tdap (tetanus, diphtheria, and acellular pertussis) is commonly used.

Pertussis

Pertussis commonly called whooping cough which is a highly contagious bacterial disease caused by Bordetella pertussis. In some countries, this disease is called the 100 days' cough or cough of 100 days. Symptoms are initially mild, and then develop into severe coughing fits, which produce the namesake high-pitched "whoop" sound in infected babies and children when they inhale air after coughing. The coughing stage lasts approximately six weeks before subsiding. Prevention by vaccination is of primary importance given the seriousness of the disease in children.
[3]

Although treatment is of little direct benefit to the person infected, antibiotics are recommended

because they shorten the duration of infectiousness.

Signs and symptoms

Once you become infected with whooping cough, it can take one to three weeks for signs and symptoms to appear. They're usually mild at first and resemble those of a common cold: Runny nose Nasal congestion Sneezing Red, watery eyes A mild fever Dry cough After a week or two, signs and symptoms worsen. Thick mucus accumulates inside your airways, causing uncontrollable coughing. Severe and prolonged coughing attacks may: Provoke vomiting Result in a red or blue face Cause extreme fatigue End with a high-pitched "whoop" sound during the next breath of air However, many people don't develop the characteristic whoop. Sometimes, a persistent hacking cough is the only sign that an adolescent or adult has whooping cough. When to see a doctor Call your doctor if prolonged coughing spells cause you or your child to: Vomit Turn red or blue Inhale with a whooping sound

Diagnosis

Gram stain of the bacteria Bordetella pertussis Diagnosing whooping cough in its early stages can be difficult because the signs and symptoms resemble those of other common respiratory illnesses, such as a cold, the flu or bronchitis. Sometimes, doctors can diagnose whooping cough simply by asking about symptoms and listening to the cough. Medical tests may be needed to confirm the diagnosis. Such tests may include: A nose or throat culture and test. Your doctor takes a nose or throat swab or suction sample. The sample is then checked for evidence of the presence of whooping cough bacteria. Blood tests. A blood sample may be drawn and sent to a lab to check for a high white blood cell count. White blood cells help the body fight infections, such as whooping cough. A high white blood cell count typically indicates the presence of infection or inflammation. This is a general test and not specific for whooping cough. A chest X-ray. Your doctor may order an X-ray to check for the presence of inflammation or fluid in the lungs, which can occur when pneumonia complicates whooping cough and other respiratory infections.

Prevention
The best way to prevent whooping cough is with the pertussis vaccine, which doctors often give in combination with vaccines against two other serious diseases diphtheria and tetanus. Doctors recommend beginning vaccination during infancy. The vaccine consists of a series of five injections, typically given to children at these ages: 2 months 4 months 6 months 15 to 18 months 4 to 6 years Vaccine side effects Side effects of the vaccine may include fever, crankiness or soreness at the site of the injection. In rare cases, severe side effects may occur, including: Persistent crying, lasting more than three hours High fever Seizures, shock or coma Booster shots Adolescents. Because immunity from the pertussis vaccine tends to wane by age 11, doctors recommend a booster shot at that age to protect against whooping cough (pertussis), diphtheria and tetanus. Adults. Some varieties of the every-10-year tetanus and diphtheria vaccine also include protection against whooping cough (pertussis). In addition to protecting you against whooping cough, this vaccine will also reduce the risk of your transmitting whooping cough to infants. Pregnant women. The Centers for Disease Control and Prevention now recommends that pregnant women receive the pertussis vaccine after 20 weeks gestation. This may also give some protection to the infant during the first few months of life.

Poliomyelitis
From Wikipedia, the free encyclopedia

"Polio" redirects here. For the virus, see Poliovirus. Not to be confused with poliosis, a condition of the hair being or becoming white or grey.

Poliomyelitis

Classification and external resources

A man with an atrophied right leg due to poliomyelitis

ICD-10

A80, B91

ICD-9

045, 138

DiseasesDB

10209

MedlinePlus

001402

eMedicine

ped/1843 pmr/6

MeSH

C02.182.600.700

Poliomyelitis (plee--m--ltiss), often called polio or infantile paralysis, is an acute, viral, infectious disease spread from person to person, primarily via the fecal-oral route.[1] The term derives from the Greek polis (), meaning "grey", myels ( marrow), referring to the grey matter of the spinal cord, and the suffix -itis, which denotes inflammation.,[2] i.e., inflammation of the spinal cords grey matter, although a severe infection can extend into the brainstem and even higher structures, resulting in polioencephalitis, producing apnea that requires mechanical assistance such as an iron lung. Although approximately 90% of polio infections cause no symptoms at all, affected individuals can exhibit a range of symptoms if the virus enters theblood stream.[3] In about 1% of cases, the virus enters the central nervous system, preferentially infecting and destroying motor neurons, leading tomuscle weakness and acute flaccid paralysis. Different types of paralysis may occur, depending on the nerves involved. Spinal polio is the most common form, characterized by asymmetric paralysis that most often involves the legs. Bulbar polio leads to weakness of muscles innervated bycranial nerves. Bulbospinal polio is a combination of bulbar and spinal paralysis.[4] Poliomyelitis was first recognized as a distinct condition by Jakob Heine in 1840.[5] Its causative agent, poliovirus, was identified in 1908 by Karl Landsteiner.[5] Although major polio epidemics were unknown before the late 19th century, polio was one of the most dreaded childhood diseases of the 20th century. Polio epidemics have crippled thousands of people, mostly young children; the disease has caused paralysis and death for much ofhuman history. Polio had existed for thousands of years quietly as an endemic pathogen until the 1880s, when major epidemics began to occur in Europe; soon after, widespread epidemics appeared in the United States.[6] By 1910, much of the world experienced a dramatic increase in polio cases and epidemics became regular events, primarily in cities during the summer months. These epidemics which left thousands of children and adults paralyzed provided the impetus for a "Great Race" towards the development of a vaccine. Developed in the 1950s, polio vaccines have reduced the global number of polio cases per year from many hundreds of thousands to under a thousand today.[7] Enhanced vaccination efforts led by Rotary International, the World Health Organization, and UNICEF should result in global eradication of the disease.[8][9]
Contents
[hide]

1 Classification 2 Cause

2.1 Transmission

3 Pathophysiology

3.1 Paralytic polio

4 Diagnosis 5 Prevention

o o

5.1 Passive immunization 5.2 Vaccine

6 Treatment 7 Prognosis

o o o

7.1 Recovery 7.2 Complications 7.3 Post-polio syndrome

8 Epidemiology 9 History 10 See also 11 Notes and references 12 Further reading 13 External links

[edit]Classification

Outcomes of poliovirus infection

Outcome

Proportion of cases

[4]

Asymptomatic

9095%

Minor illness

48%

Nonparalytic aseptic

12%

meningitis

Paralytic poliomyelitis

0.10.5%

Spinal polio

79% of paralytic cases

Bulbospinal polio

19% of paralytic cases

Bulbar polio

2% of paralytic cases

The term "poliomyelitis" is used to identify the disease caused by any of the three serotypes of poliovirus. Two basic patterns of polio infection are described: a minor illness which does not involve the central nervous system (CNS), sometimes called abortive poliomyelitis, and a major illness involving the CNS, which may be paralytic or nonparalytic.[10] In most people with a normal immune system, a poliovirus infection is asymptomatic. Rarely, the infection produces minor symptoms; these may include upper respiratory tract infection (sore throat and fever), gastrointestinaldisturbances (nausea, vomiting, abdominal pain, constipation or, rarely, diarrhea), and influenza-like illness.[4] The virus enters the central nervous system in about 3% of infections. Most patients with CNS involvement develop nonparalytic aseptic meningitis, with symptoms of headache, neck, back, abdominal and extremity pain, fever, vomiting, lethargy, and irritability.[2][11] About one to five in 1000 cases progress to paralytic disease, in which the muscles become weak, floppy and poorly controlled, and, finally, completely paralyzed; this condition is known as acute flaccid paralysis.[12] Depending on the site of paralysis, paralytic poliomyelitis is classified as spinal, bulbar, or bulbospinal. Encephalitis, an infection of the brain tissue itself, can occur in rare cases, and is usually restricted to infants. It is characterized by confusion, changes in mental status, headaches, fever, and, less commonly, seizures and spastic paralysis.[13]

[edit]Cause
Main article: Poliovirus

A TEM micrograph of poliovirus

Poliomyelitis is caused by infection with a member of the genus Enterovirus known as poliovirus (PV). This group of RNA viruses colonize thegastrointestinal tract[1] specifically the oropharynx and the intestine. The incubation time (to the first signs and symptoms) ranges from three to 35 days, with a more common span of six to 20 days.[4] PV infects and causes disease in humans alone.[3] Its structure is very simple, composed of a single (+) sense RNA genome enclosed in a protein shell called a capsid.[3] In addition to protecting the viruss genetic material, the capsid proteins enable poliovirus to infect certain types of cells. Three serotypes of poliovirus have been identifiedpoliovirus type 1 (PV1), type 2 (PV2), and type 3 (PV3)each with a slightly different capsid protein.[14] All three are extremely virulent and produce the same disease symptoms.[3] PV1 is the most commonly encountered form, and the one most closely associated with paralysis. [15] Individuals who are exposed to the virus, either through infection or by immunization with polio vaccine, develop immunity. In immune individuals, IgAantibodies against poliovirus are present in the tonsils and gastrointestinal tract, and are able to block virus replication; IgG and IgM antibodies against PV can prevent the spread of the virus to motor neurons of the central nervous system.[16] Infection or vaccination with one serotype of poliovirus does not provide immunity against the other serotypes, and full immunity requires exposure to each serotype.[16] A rare condition with a similar presentation, nonpoliovirus poliomyelitis, may result from infections with nonpoliovirus enteroviruses.[17]

[edit]Transmission
Poliomyelitis is highly contagious via the oral-oral (oropharyngeal source) and fecal-oral (intestinal source) routes.[16] In endemic areas, wild polioviruses can infect virtually the entire human population.[18] It is seasonal in temperate climates, with peak transmission occurring in summer and autumn.[16]These seasonal differences are far less pronounced in tropical areas.[18] The time between first exposure and first symptoms, known as the incubation period, is usually six to 20 days, with a maximum range of three to 35 days.[19] Virus particles are excreted in the feces for several weeks following initial infection.[19] The disease is transmitted primarily via the fecal-oral route, by ingesting contaminated food or water. It is occasionally transmitted via the oral-oral route,[15] a mode especially visible in areas with good sanitation and hygiene.[16] Polio is most infectious between seven and 10 days before and after the appearance of symptoms, but transmission is possible as long as the virus remains in the saliva or feces.[15] Factors that increase the risk of polio infection or affect the severity of the disease include immune deficiency,[20] malnutrition,[21] tonsillectomy,[22] physical activity immediately following the onset of paralysis,[23] skeletal muscle injury due to injection of vaccines or therapeutic agents,[24] and pregnancy.[25] Although the virus can cross the placenta during pregnancy, the fetus does not appear to be affected by either maternal infection or polio vaccination.[26] Maternal antibodies also cross the placenta, providing passive immunity that protects the infant from polio infection during the first few months of life.[27] As a precaution against infection, public swimming pools were often closed in affected areas during poliomyelitis epidemics.

[edit]Pathophysiology

A blockage of the lumbar anterior spinal cord artery due to polio (PV3)

Poliovirus enters the body through the mouth, infecting the first cells with which it comes in contact the pharynx and intestinal mucosa. It gains entry by binding to an immunoglobulin-like receptor, known as the poliovirus receptor or CD155, on the cell membrane.[28] The virus then hijacks the host cell's own machinery,

and begins to replicate. Poliovirus divides within gastrointestinal cells for about a week, from where it spreads to the tonsils(specifically the follicular dendritic cells residing within the tonsilar germinal centers), the intestinal lymphoid tissue including the M cells of Peyer's patches, and the deep cervical and mesenteric lymph nodes, where it multiplies abundantly. The virus is subsequently absorbed into the bloodstream. [29] Known as viremia, the presence of virus in the bloodstream enables it to be widely distributed throughout the body. Poliovirus can survive and multiply within the blood and lymphatics for long periods of time, sometimes as long as 17 weeks.[30] In a small percentage of cases, it can spread and replicate in other sites, such as brown fat, the reticuloendothelial tissues, and muscle.[31] This sustained replication causes a major viremia, and leads to the development of minor influenza-like symptoms. Rarely, this may progress and the virus may invade the central nervous system, provoking a localinflammatory response. In most cases, this causes a selflimiting inflammation of the meninges, the layers of tissue surrounding the brain, which is known as nonparalytic aseptic meningitis.[2] Penetration of the CNS provides no known benefit to the virus, and is quite possibly an incidental deviation of a normal gastrointestinal infection. [32] The mechanisms by which poliovirus spreads to the CNS are poorly understood, but it appears to be primarily a chance eventlargely independent of the age, gender, or socioeconomic position of the individual.[32]

[edit]Paralytic

polio

Denervation of skeletal muscle tissue secondary to poliovirus infection can lead to paralysis.

In around 1% of infections, poliovirus spreads along certain nerve fiber pathways, preferentially replicating in and destroying motor neurons within thespinal cord, brain stem, or motor cortex. This leads to the development of paralytic poliomyelitis, the various forms of which (spinal, bulbar, and bulbospinal) vary only with the amount of neuronal damage and inflammation that occurs, and the region of the CNS affected. The destruction of neuronal cells produces lesions within the spinal ganglia; these may also occur in the reticular formation, vestibular nuclei, cerebellar vermis, and deep cerebellar nuclei.[32] Inflammation associated with nerve cell destruction often alters the color and appearance of the gray matter in thespinal column, causing it to appear reddish and swollen.[2] Other destructive changes associated with paralytic

disease occur in the forebrain region, specifically the hypothalamus and thalamus.[32] The molecular mechanisms by which poliovirus causes paralytic disease are poorly understood. Early symptoms of paralytic polio include high fever, headache, stiffness in the back and neck, asymmetrical weakness of various muscles, sensitivity to touch, difficulty swallowing, muscle pain, loss of superficial and deep reflexes, paresthesia (pins and needles), irritability, constipation, or difficulty urinating. Paralysis generally develops one to ten days after early symptoms begin, progresses for two to three days, and is usually complete by the time the fever breaks.[33] The likelihood of developing paralytic polio increases with age, as does the extent of paralysis. In children, nonparalytic meningitis is the most likely consequence of CNS involvement, and paralysis occurs in only one in 1000 cases. In adults, paralysis occurs in one in 75 cases.[34] In children under five years of age, paralysis of one leg is most common; in adults, extensive paralysis of the chest and abdomen also affecting all four limbs quadriplegia is more likely.[35] Paralysis rates also vary depending on the serotype of the infecting poliovirus; the highest rates of paralysis (one in 200) are associated with poliovirus type 1, the lowest rates (one in 2,000) are associated with type 2.[36]

[edit]Spinal polio

The location of motor neurons in theanterior horn cells of the spinal column

Spinal polio, the most common form of paralytic poliomyelitis, results from viral invasion of the motor neurons of the anterior horn cells, or the ventral(front) grey matter section in the spinal column, which are responsible for movement of the muscles, including those of the trunk, limbs, and theintercostal muscles.[12] Virus invasion causes inflammation of the nerve cells, leading to damage or destruction of motor neuron ganglia. When spinal neurons die, Wallerian degeneration takes place, leading to weakness of those muscles formerly innervated by the now-dead neurons.[37] With the destruction of nerve cells, the muscles no longer receive signals from the brain or spinal cord; without nerve stimulation, the muscles atrophy, becoming weak, floppy and poorly controlled, and finally completely paralyzed.[12] Progression to maximum paralysis is rapid (two to four days),

and is usually associated with fever and muscle pain.[37] Deep tendon reflexes are also affected, and are usually absent or diminished; sensation (the ability to feel) in the paralyzed limbs, however, is not affected.[37] The extent of spinal paralysis depends on the region of the cord affected, which may be cervical, thoracic, or lumbar.[38] The virus may affect muscles on both sides of the body, but more often the paralysis is asymmetrical.[29] Any limb or combination of limbs may be affectedone leg, one arm, or both legs and both arms. Paralysis is often more severe proximally (where the limb joins the body) than distally (the fingertips and toes).[29]

[edit]Bulbar polio

The location and anatomy of the bulbar region (in orange)

Making up about 2% of cases of paralytic polio, bulbar polio occurs when poliovirus invades and destroys nerves within the bulbar region of the brain stem.[4] The bulbar region is a white matter pathway that connects the cerebral cortex to the brain stem. The destruction of these nerves weakens the muscles supplied by the cranial nerves, producing symptoms of encephalitis, and causes difficulty breathing, speaking and swallowing.[11] Critical nerves affected are the glossopharyngeal nerve (which partially controls swallowing and functions in the throat, tongue movement, and taste), the vagus nerve (which sends signals to the heart, intestines, and lungs), and the accessory nerve (which controls upper neck movement). Due to the effect on swallowing, secretions of mucus may build up in the airway, causing suffocation.[33] Other signs and symptoms include facial weakness (caused by destruction of the trigeminal nerve and facial nerve, which innervate the cheeks, tear ducts, gums, and muscles of the face, among other structures),double vision, difficulty in chewing, and abnormal respiratory rate, depth, and rhythm (which may lead to respiratory arrest). Pulmonary edema andshock are also possible and may be fatal.[38]

[edit]Bulbospinal polio

Approximately 19% of all paralytic polio cases have both bulbar and spinal symptoms; this subtype is called respiratory or bulbospinal polio.[4] Here, the virus affects the upper part of the cervical spinal cord (cervical vertebrae C3 through C5), and paralysis of the diaphragm occurs. The critical nerves affected are the phrenic nerve (which drives the diaphragm to inflate the lungs) and those that drive the muscles needed for swallowing. By destroying these nerves, this form of polio affects breathing, making it difficult or impossible for the patient to breathe without the support of a ventilator. It can lead to paralysis of the arms and legs and may also affect swallowing and heart functions.[39]

[edit]Diagnosis
Paralytic poliomyelitis may be clinically suspected in individuals experiencing acute onset of flaccid paralysis in one or more limbs with decreased or absent tendon reflexes in the affected limbs that cannot be attributed to another apparent cause, and without sensory or cognitive loss.[40] A laboratory diagnosis is usually made based on recovery of poliovirus from a stool sample or a swab of the pharynx. Antibodies to poliovirus can be diagnostic, and are generally detected in the blood of infected patients early in the course of infection.[4] Analysis of the patient's cerebrospinal fluid (CSF), which is collected by a lumbar puncture ("spinal tap"), reveals an increased number of white blood cells (primarily lymphocytes) and a mildly elevated protein level. Detection of virus in the CSF is diagnostic of paralytic polio, but rarely occurs.[4] If poliovirus is isolated from a patient experiencing acute flaccid paralysis, it is further tested through oligonucleotide mapping (genetic fingerprinting), or more recently by PCR amplification, to determine whether it is "wild type" (that is, the virus encountered in nature) or "vaccine type" (derived from a strain of poliovirus used to produce polio vaccine).[41] It is important to determine the source of the virus because for each reported case of paralytic polio caused by wild poliovirus, an estimated another 200 to 3,000 contagious asymptomatic carriers exist.[42]

[edit]Prevention [edit]Passive

immunization

In 1950, William Hammon at the University of Pittsburgh purified the gamma globulin component of the blood plasma of polio survivors.[43] Hammon proposed the gamma globulin, which contained antibodies to poliovirus, could be used to halt poliovirus infection, prevent disease, and reduce the severity of disease in other patients who had contracted polio. The results of a large clinical trialwere promising; the gamma globulin was shown to be about 80% effective in preventing the development of paralytic poliomyelitis.[44] It was also shown to reduce the severity of the disease in patients who developed polio.[43] The gamma globulin approach was later deemed impractical for widespread use, however, due in large part to the limited supply of blood plasma, so the medical community turned its focus to the development of a polio vaccine.[45]

[edit]Vaccine
Main article: Polio vaccine

A child receiving an oral polio vaccine

Two types of vaccine are used throughout the world to combat polio. Both types induce immunity to polio, efficiently blocking person-to-person transmission of wild poliovirus, thereby protecting both individual vaccine recipients and the wider community (so-called herd immunity).[46] The first candidate polio vaccine, based on one serotype of a live but attenuated (weakened) virus, was developed by the virologist Hilary Koprowski. Koprowski's prototype vaccine was given to an eight-year-old boy on February 27, 1950.[47] Koprowski continued to work on the vaccine throughout the 1950s, leading to largescale trials in the then Belgian Congo and the vaccination of seven million children in Poland against serotypes PV1 and PV3 between 1958 and 1960.[48] The second inactivated virus vaccine was developed in 1952 by Jonas Salk at the University of Pittsburgh, and announced to the world on April 12, 1955.[49] The Salk vaccine, or inactivated poliovirus vaccine (IPV), is based on poliovirus grown in a type of monkey kidney tissue culture (vero cell line), which is chemically inactivated with formalin.[16] After two doses of IPV (given by injection), 90% or more of individuals develop protective antibody to all three serotypes of poliovirus, and at least 99% are immune to poliovirus following three doses.[4] Subsequently, Albert Sabin developed another live, oral polio vaccine (OPV). It was produced by the repeated passage of the virus through nonhuman cells at subphysiological temperatures.[50] The attenuated poliovirus in the Sabin vaccine replicates very efficiently in the gut, the primary site of wild poliovirus infection and replication, but the vaccine strain is unable to replicate efficiently within nervous system tissue.[51] A single dose of Sabin's oral polio vaccine produces immunity to all three poliovirus serotypes in about 50% of recipients.

Three doses of live-attenuated OPV produce protective antibody to all three poliovirus types in more than 95% of recipients.[4] Human trials of Sabin's vaccine began in 1957,[52] and in 1958 it was selected, in competition with the live vaccines of Koprowski and other researchers, by the US National Institutes of Health.[48] Licensed in 1962,[52] it rapidly became the only polio vaccine used worldwide.[48] Because OPV is inexpensive, easy to administer, and produces excellent immunity in the intestine (which helps prevent infection with wild virus in areas where it is endemic), it has been the vaccine of choice for controlling poliomyelitis in many countries.[53] On very rare occasions (about one case per 750,000 vaccine recipients), the attenuated virus in OPV reverts into a form that can paralyze.[19] Most industrialized countries have switched to IPV, which cannot revert, either as the sole vaccine against poliomyelitis or in combination with oral polio vaccine.[54]

[edit]Treatment
There is no cure for polio. The focus of modern treatment has been on providing relief of symptoms, speeding recovery and preventing complications. Supportive measures include antibiotics to prevent infections in weakened muscles, analgesics for pain, moderate exercise and a nutritious diet.[55] Treatment of polio often requires long-term rehabilitation, including occupational therapy,physical therapy, braces, corrective shoes and, in some cases, orthopedic surgery.[38] Portable ventilators may be required to support breathing. Historically, a noninvasive, negative-pressure ventilator, more commonly called an iron lung, was used to artificially maintain respiration during an acute polio infection until a person could breathe independently (generally about one to two weeks). Today, many polio survivors with permanent respiratory paralysis use modern jacket-type negative-pressure ventilators worn over the chest and abdomen.[56] Other historical treatments for polio include hydrotherapy, electrotherapy, massage and passive motion exercises, and surgical treatments, such as tendon lengthening and nerve grafting. [12]Devices such as rigid braces and body castswhich tended to cause muscle atrophy due to the limited movement of the user were also touted as effective treatments.[57]

[edit]Prognosis
Patients with abortive polio infections recover completely. In those who develop only aseptic meningitis, the symptoms can be expected to persist for two to ten days, followed by complete recovery.[58] In cases of spinal polio, if the affected nerve cells are completely destroyed, paralysis will be permanent; cells that are not destroyed, but lose function temporarily, may recover within four to six weeks after onset.[58] Half the patients with spinal polio recover fully; one-quarter recover with mild disability, and the remaining quarter are left with severe disability.[59] The degree of both acute paralysis and residual paralysis is likely to be proportional to the degree of viremia, and inversely proportional to the degree of immunity.[32] Spinal polio is rarely fatal.[33]

A child with a deformity of her right leg due to polio

Without respiratory support, consequences of poliomyelitis with respiratory involvement include suffocation or pneumonia from aspiration of secretions.[56] Overall, 510% of patients with paralytic polio die due to the paralysis of muscles used for breathing. The mortality rate varies by age: 25% of children and up to 1530% of adults die.[4] Bulbar polio often causes death if respiratory support is not provided;[39] with support, its mortality rate ranges from 25 to 75%, depending on the age of the patient.[4][60] When positive pressure ventilators are available, the mortality can be reduced to 15%.[61]

[edit]Recovery
Many cases of poliomyelitis result in only temporary paralysis.[12] Nerve impulses return to the formerly paralyzed muscle within a month, and recovery is usually complete in six to eight months.[58] The neurophysiological processes involved in recovery following acute paralytic poliomyelitis are quite effective; muscles are able to retain normal strength even if half the original motor neurons have been lost.[62] Paralysis remaining after one year is likely to be permanent, although modest recoveries of muscle strength are possible 12 to 18 months after infection.[58] One mechanism involved in recovery is nerve terminal sprouting, in which remaining brainstem and spinal cord motor neurons develop new branches, or axonal sprouts.[63] These sprouts can reinnervate orphaned muscle fibers that have been denervated by acute polio infection,[64] restoring the fibers' capacity to contract and improving strength.[65] Terminal sprouting may generate a few significantly enlarged motor neurons doing work

previously performed by as many as four or five units:[34] a single motor neuron that once controlled 200 muscle cells might control 800 to 1000 cells. Other mechanisms that occur during the rehabilitation phase, and contribute to muscle strength restoration, include myofiber hypertrophyenlargement of muscle fibers through exercise and activityand transformation of type II muscle fibers to type I muscle fibers.[64][66] In addition to these physiological processes, the body possesses a number of compensatory mechanisms to maintain function in the presence of residual paralysis. These include the use of weaker muscles at a higher than usual intensity relative to the muscle's maximal capacity, enhancing athletic development of previously little-used muscles, and using ligaments for stability, which enables greater mobility.[66]

[edit]Complications
Residual complications of paralytic polio often occur following the initial recovery process.[11] Muscle paresis and paralysis can sometimes result in skeletal deformities, tightening of the joints and movement disability. Once the muscles in the limb become flaccid, they may interfere with the function of other muscles. A typical manifestation of this problem is equinus foot (similar to club foot). This deformity develops when the muscles that pull the toes downward are working, but those that pull it upward are not, and the foot naturally tends to drop toward the ground. If the problem is left untreated, the Achilles tendons at the back of the foot retract and the foot cannot take on a normal position. Polio victims that develop equinus foot cannot walk properly because they cannot put their heel on the ground. A similar situation can develop if the arms become paralyzed.[67] In some cases the growth of an affected leg is slowed by polio, while the other leg continues to grow normally. The result is that one leg is shorter than the other and the person limps and leans to one side, in turn leading to deformities of the spine (such as scoliosis).[67] Osteoporosis and increased likelihood of bone fractures may occur. An intervention to prevent or lessen length disparity can be to perform an epiphysiodesis on the distal femoral and proximal tibial/fibular condyles, so that limb's growth is artificially stunted, and by the time of epiphyseal (growth) plate closure, the legs are more equal in length. Other surgery to re-balance muscular agonist/antagonist imbalances may also be helpful. Extended use of braces or wheelchairs may cause compression neuropathy, as well as a loss of proper function of the veins in the legs, due to pooling of blood in paralyzed lower limbs.[39][68] Complications from prolonged immobility involving the lungs, kidneys and heart include pulmonary edema, aspiration pneumonia, urinary tract infections, kidney stones, paralytic ileus, myocarditis and cor pulmonale.[39][68]

[edit]Post-polio

syndrome

Main article: Post-polio syndrome Between 25% and 50% of individuals who survive paralytic polio in childhood develop additional symptoms decades after recovering from the acute infection,[69] notably new muscle weakness and extreme fatigue. This condition is known as post-polio syndrome (PPS) or post-polio sequelae.[70] The symptoms of PPS are thought

to involve a failure of the over-sized motor units created during recovery from paralytic disease.[71][72] Factors that increase the risk of PPS include the length of time since acute poliovirus infection, the presence of permanent residual impairment after recovery from the acute illness, and both overuse and disuse of neurons.[70] Post-polio syndrome is not an infectious process, and persons experiencing the syndrome do not shed poliovirus.[4]

Meningitis
From Wikipedia, the free encyclopedia

Meningitis

Classification and external resources

Meninges of the central nervous system: dura mater, arachnoid, and pia mater.

ICD-10

G00G03

ICD-9

320322

DiseasesDB

22543

MedlinePlus

000680

eMedicine

med/2613 emerg/309emerg/390

MeSH

D008581

Meningitis is inflammation of the protective membranes covering the brain and spinal cord, known collectively as the meninges.[1] The inflammation may be caused by infection with viruses, bacteria, or other microorganisms, and less commonly by certain drugs.[2] Meningitis can be life-threatening because of the inflammation's proximity to the brain and spinal cord; therefore the condition is classified as a medical emergency.[1][3]

The most common symptoms of meningitis are headache and neck stiffness associated with fever, confusion or altered consciousness, vomiting, and an inability to tolerate light (photophobia) or loud noises (phonophobia). Children often exhibit only nonspecific symptoms, such as irritability and drowsiness. If a rash is present, it may indicate a particular cause of meningitis; for instance, meningitis caused by meningococcal bacteria may be accompanied by a characteristic rash.[1][4] A lumbar puncture diagnoses or excludes meningitis. A needle is inserted into the spinal canal to extract a sample of cerebrospinal fluid (CSF), that envelops the brain and spinal cord. The CSF is examined in a medical laboratory.[3] The first treatment in acute meningitis consists of promptly administered antibiotics and sometimes antiviral drugs. Corticosteroids can also be used to prevent complications from excessive inflammation.[3][4]Meningitis can lead to serious long-term consequences such as deafness, epilepsy, hydrocephalus and cognitive deficits, especially if not treated quickly.[1][4] Some forms of meningitis (such as those associated with meningococci, Haemophilus influenzae type B, pneumococci or mumps virusinfections) may be prevented by immunization.[1]
Contents
[hide]

1 Signs and symptoms

o o

1.1 Clinical features 1.2 Early complications

2 Causes

o o o o o

2.1 Bacterial 2.2 Viral 2.3 Fungal 2.4 Parasitic 2.5 Non-infectious

3 Mechanism 4 Diagnosis

o o o

4.1 Blood tests and imaging 4.2 Lumbar puncture 4.3 Postmortem

5 Prevention

o o

5.1 Behavioral 5.2 Vaccination

5.3 Antibiotics

6 Management

o o o

6.1 Bacterial meningitis 6.2 Viral meningitis 6.3 Fungal meningitis

7 Prognosis 8 Epidemiology 9 History 10 References 11 External links

[edit]Signs

and symptoms
features

[edit]Clinical

Neck stiffness, Texas meningitis epidemic of 191112.

In adults, the most common symptom of meningitis is a severe headache, occurring in almost 90% of cases of bacterial meningitis, followed by nuchal rigidity (the inability to flex the neck forward passively due to increased neck muscle tone and stiffness).[5] The classic triad of diagnostic signs consists of nuchal rigidity, sudden high fever, and altered mental status; however, all three features are present in only 4446% of bacterial meningitis cases.[5][6]If none of the three signs is present, meningitis is extremely unlikely.[6] Other signs commonly associated with meningitis include photophobia(intolerance to bright light) and phonophobia (intolerance to loud noises). Small children often do not exhibit the aforementioned symptoms, and may only be irritable and look unwell.[1] The fontanelle (the soft spot on the top of a baby's head) can bulge in infants aged up to 6 months. Other features that distinguish meningitis from less severe illnesses in young children are leg pain, cold extremities, and an abnormal skin color.[7][8]

Nuchal rigidity occurs in 70% of bacterial meningitis in adults.[6] Other signs of meningism include the presence of positive Kernig's sign or Brudziski sign. Kernig's sign is assessed with the person lying supine, with the hip and knee flexed to 90 degrees. In a person with a positive Kernig's sign, pain limits passive extension of the knee. A positive Brudzinski's sign occurs when flexion of the neck causes involuntary flexion of the knee and hip. Although Kernig's sign and Brudzinski's sign are both commonly used to screen for meningitis, the sensitivity of these tests is limited.[6][9] They do, however, have very good specificity for meningitis: the signs rarely occur in other diseases.[6] Another test, known as the "jolt accentuation maneuver" helps determine whether meningitis is present in those reporting fever and headache. A person is asked to rapidly rotate the head horizontally; if this does not make the headache worse, meningitis is unlikely.[6] Meningitis caused by the bacterium Neisseria meningitidis (known as "meningococcal meningitis") can be differentiated from meningitis with other causes by a rapidly spreading petechial rash, which may precede other symptoms.[7] The rash consists of numerous small, irregular purple or red spots ("petechiae") on the trunk, lower extremities, mucous membranes, conjuctiva, and (occasionally) the palms of the hands or soles of the feet. The rash is typically non-blanching; the redness does not disappear when pressed with a finger or a glass tumbler. Although this rash is not necessarily present in meningococcal meningitis, it is relatively specific for the disease; it does, however, occasionally occur in meningitis due to other bacteria.[1] Other clues on the cause of meningitis may be the skin signs of hand, foot and mouth disease and genital herpes, both of which are associated with various forms of viral meningitis.[10]

[edit]Early

complications

Charlotte Cleverley-Bismandeveloped severe meningococcal meningitis as a young child; in her case, the petechial rash progressed togangrene and required amputation of all limbs. She survived the disease and became a poster child for a meningitis vaccination campaign in New Zealand.

Additional problems may occur in the early stage of the illness. These may require specific treatment, and sometimes indicate severe illness or worse prognosis. The infection may trigger sepsis, a systemic inflammatory response syndrome of falling blood pressure, fast heart rate, high or abnormally low temperature, and rapid breathing. Very low blood pressure may occur at an early stage, especially but not exclusively in

meningococcal meningitis; this may lead to insufficient blood supply to other organs.[1] Disseminated intravascular coagulation, the excessive activation of blood clotting, may obstructblood flow to organs and paradoxically increase the bleeding risk. Gangrene of limbs can occur in meningococcal disease.[1] Severe meningococcal and pneumococcal infections may result in hemorrhaging of the adrenal glands, leading to Waterhouse-Friderichsen syndrome, which is often fatal.[11] The brain tissue may swell, pressure inside the skull may increase and the swollen brain may herniate through the skull base. This may be noticed by a decreasing level of consciousness, loss of the pupillary light reflex, and abnormal posturing.[4] The inflammation of the brain tissue may also obstruct the normal flow of CSF around the brain (hydrocephalus).[4] Seizures may occur for various reasons; in children, seizures are common in the early stages of meningitis (in 30% of cases) and do not necessarily indicate an underlying cause.[3] Seizures may result from increased pressure and from areas of inflammation in the brain tissue.[4] Focal seizures (seizures that involve one limb or part of the body), persistent seizures, late-onset seizures and those that are difficult to control with medication indicate a poorer long-term outcome.[1] Inflammation of the meninges may lead to abnormalities of the cranial nerves, a group of nerves arising from the brain stem that supply the head and neck area and which control, among other functions, eye movement, facial muscles, and hearing.[1][6] Visual symptoms and hearing loss may persist after an episode of meningitis.[1] Inflammation of the brain (encephalitis) or its blood vessels (cerebral vasculitis), as well as the formation of blood clots in the veins (cerebral venous thrombosis), may all lead to weakness, loss of sensation, or abnormal movement or function of the part of the body supplied by the affected area of the brain. [1][4]

[edit]Causes
Meningitis is typically caused by an infection with microorganisms. Most infections are due to viruses,[6] with bacteria, fungi, and protozoa being the next most common causes.[2] It may also result from various non-infectious causes.[2] The term aseptic meningitis refers to cases of meningitis in which no bacterial infection can be demonstrated. This type of meningitis is usually caused by viruses, but it may be due to bacterial infection that has already been partially treated, when bacteria disappear from the meninges, or pathogens infect a space adjacent to the meninges (e.g.sinusitis). Endocarditis (an infection of the heart valves which spreads small clusters of bacteria through the bloodstream) may cause aseptic meningitis. Aseptic meningitis may also result from infection with spirochetes, a type of bacteria that includes Treponema pallidum (the cause of syphilis) and Borrelia burgdorferi (known for causing Lyme disease). Meningitis may be encountered in cerebral malaria (malaria infecting the brain) or amoebic meningitis, meningitis due to infection with amoebae such as Naegleria fowleri, contracted from freshwater sources.[2]

[edit]Bacterial
The types of bacteria that cause bacterial meningitis vary according to the infected individual's age group.

In premature babies and newborns up to three months old, common causes are group B streptococci (subtypes III which normally inhabit the vagina and are mainly a cause during the first week of life) and bacteria that normally inhabit the digestive tract such as Escherichia coli (carrying the K1 antigen). Listeria monocytogenes (serotype IVb) may affect the newborn and occurs in epidemics.

Older children are more commonly affected by Neisseria meningitidis (meningococcus) and Streptococcus pneumoniae (serotypes 6, 9, 14, 18 and 23) and those under five by Haemophilus influenzae type B (in countries that do not offer vaccination).[1][3]

In adults, Neisseria meningitidis and Streptococcus pneumoniae together cause 80% of bacterial meningitis cases. Risk of infection with Listeria monocytogenes is increased in persons over 50 years old.[3][4] The introduction of pneumococcal vaccine has lowered rates of pneumococcal meningitis in both children and adults.[12]

Recent skull trauma potentially allows nasal cavity bacteria to enter the meningeal space. Similarly, devices in the brain and meninges, such as cerebral shunts, extraventricular drains orOmmaya reservoirs, carry an increased risk of meningitis. In these cases, the persons are more likely to be infected with Staphylococci, Pseudomonas, and other Gram-negative bacteria.[3]These pathogens are also associated with meningitis in people with an impaired immune system.[1] An infection in the head and neck area, such as otitis media or mastoiditis, can lead to meningitis in a small proportion of people.[3] Recipients of cochlear implants for hearing loss risk more a pneumococcal meningitis.[13] Tuberculous meningitis, which is meningitis caused by Mycobacterium tuberculosis, is more common in people from countries where tuberculosis is endemic, but is also encountered in persons with immune problems, such as AIDS.[14] Recurrent bacterial meningitis may be caused by persisting anatomical defects, either congenital or acquired, or by disorders of the immune system.[15] Anatomical defects allow continuity between the external environment and the nervous system. The most common cause of recurrent meningitis is a skull fracture,[15] particularly fractures that affect the base of the skull or extend towards the sinuses and petrous pyramids.[15] Approximately 59% of recurrent meningitis cases are due to such anatomical abnormalities, 36% are due to immune deficiencies (such ascomplement deficiency, which predisposes especially to recurrent meningococcal meningitis), and 5% are due to ongoing infections in areas adjacent to the meninges.[15]

[edit]Viral
Viruses that cause meningitis include enteroviruses, Herpes simplex virus type 2 (and less commonly type 1), Varicella zoster virus (known for causing chickenpox and shingles), mumps virus,HIV, and LCMV.[10]

[edit]Fungal
There are a number of risk factors for fungal meningitis, including the use of immunosuppressants (such as after organ transplantation), HIV/AIDS,[16] and the loss of immunity associated with aging.[17] It is uncommon in those with a normal immune system[18] but has occurred with medication contamination.[19] Symptom onset is typically more gradual, with headaches and fever being present for at least a couple of weeks before diagnosis.[17] The most common fungal meningitis is cryptococcal meningitis due to Cryptococcus neoformans.[20] In Africa, cryptococcal meningitis is estimated to be the most common cause of meningitis [21] and it accounts for 2025% of AIDS-related deaths in Africa.[22] Other common fungal agents include Histoplasma capsulatum,Coccidioides immitis, Blastomyces dermatitidis, and Candida species.[17]

[edit]Parasitic
A parasitic cause is often assumed when there is a predominance of eosinophils (a type of white blood cell) in the CSF. The most common parasites implicated are Angiostrongylus cantonensis,Gnathostoma spinigerum, Schistosoma, as well as the conditions cysticercosis, toxocariasis, baylisascariasis, paragonimiasis, and a number of rarer infections and noninfective conditions.[23]

[edit]Non-infectious
Meningitis may occur as the result of several non-infectious causes: spread of cancer to the meninges (malignant or neoplastic meningitis)[24] and certain drugs (mainly non-steroidal anti-inflammatory drugs, antibiotics and intravenous immunoglobulins).[25] It may also be caused by several inflammatory conditions, such as sarcoidosis (which is then called neurosarcoidosis), connective tissue disorders such as systemic lupus erythematosus, and certain forms of vasculitis (inflammatory conditions of the blood vessel wall), such as Behet's disease.[2] Epidermoid cysts and dermoid cysts may cause meningitis by releasing irritant matter into the subarachnoid space.[2][15] Mollaret's meningitis is a syndrome of recurring episodes of aseptic meningitis; it is thought to be caused by herpes simplex virus type 2. Rarely, migraine may cause meningitis, but this diagnosis is usually only made when other causes have been eliminated. [2]

[edit]Mechanism
The meninges comprise three membranes that, together with the cerebrospinal fluid, enclose and protect the brain and spinal cord (the central nervous system). The pia mater is a very delicate impermeable membrane that firmly adheres to the surface of the brain, following all the minor contours. The arachnoid mater (so named because of its spider-web-like appearance) is a loosely fitting sac on top of the pia mater. The subarachnoid space separates the arachnoid and pia mater membranes and is filled with cerebrospinal fluid. The outermost membrane, the dura mater, is a thick durable membrane, which is attached to both the arachnoid membrane and the skull.

In bacterial meningitis, bacteria reach the meninges by one of two main routes: through the bloodstream or through direct contact between the meninges and either the nasal cavity or the skin. In most cases, meningitis follows invasion of the bloodstream by organisms that live upon mucous surfaces such as the nasal cavity. This is often in turn preceded by viral infections, which break down the normal barrier provided by the mucous surfaces. Once bacteria have entered the bloodstream, they enter the subarachnoid space in places where the bloodbrain barrier is vulnerablesuch as the choroid plexus. Meningitis occurs in 25% of newborns with bloodstream infections due to group B streptococci; this phenomenon is less common in adults.[1] Direct contamination of the cerebrospinal fluid may arise from indwelling devices, skull fractures, or infections of the nasopharynx or the nasal sinuses that have formed a tract with the subarachnoid space (see above); occasionally, congenital defects of the dura mater can be identified.[1] The large-scale inflammation that occurs in the subarachnoid space during meningitis is not a direct result of bacterial infection but can rather largely be attributed to the response of the immune system to the entry of bacteria into the central nervous system. When components of the bacterial cell membrane are identified by the immune cells of the brain (astrocytes and microglia), they respond by releasing large amounts of cytokines, hormone-like mediators that recruit other immune cells and stimulate other tissues to participate in an immune response. The bloodbrain barrier becomes more permeable, leading to "vasogenic" cerebral edema (swelling of the brain due to fluid leakage from blood vessels). Large numbers of white blood cells enter the CSF, causing inflammation of the meninges and leading to "interstitial" edema (swelling due to fluid between the cells). In addition, the walls of the blood vessels themselves become inflamed (cerebral vasculitis), which leads to decreased blood flow and a third type of edema, "cytotoxic" edema. The three forms of cerebral edema all lead to increased intracranial pressure; together with the lowered blood pressure often encountered in acute infection, this means that it is harder for blood to enter the brain, consequently brain cells are deprived of oxygen and undergo apoptosis(automated cell death).[1] It is recognized that administration of antibiotics may initially worsen the process outlined above, by increasing the amount of bacterial cell membrane products released through the destruction of bacteria. Particular treatments, such as the use of corticosteroids, are aimed at dampening the immune system's response to this phenomenon.[1][4]

[edit]Diagnosis
CSF findings in different forms of meningitis[26]

Type of meningitis

Glucose

Protein

Cells

Acute bacterial

low

high

PMNs, often > 300/mm

Acute viral

normal

normal or high

mononuclear, < 300/mm

Tuberculous

low

high

mononuclear and PMNs, < 300/mm

Fungal

low

high

< 300/mm

Malignant

low

high

usually mononuclear

[edit]Blood

tests and imaging

In someone suspected of having meningitis, blood tests are performed for markers of inflammation (e.g. Creactive protein, complete blood count), as well as blood cultures.[3][27] The most important test in identifying or ruling out meningitis is analysis of the cerebrospinal fluid through lumbar puncture (LP, spinal tap).[28] However, lumbar puncture is contraindicated if there is a mass in the brain (tumor or abscess) or the intracranial pressure(ICP) is elevated, as it may lead to brain herniation. If someone is at risk for either a mass or raised ICP (recent head injury, a known immune system problem, localizing neurological signs, or evidence on examination of a raised ICP), a CT or MRI scan is recommended prior to the lumbar puncture.[3][27][29] This applies in 45% of all adult cases.[4] If a CT or MRI is required before LP, or if LP proves difficult, professional guidelines suggest that antibiotics should be administered first to prevent delay in treatment,[3]especially if this may be longer than 30 minutes.[27][29] Often, CT or MRI scans are performed at a later stage to assess for complications of meningitis.[1] In severe forms of meningitis, monitoring of blood electrolytes may be important; for example, hyponatremia is common in bacterial meningitis, due to a combination of factors, including dehydration, the inappropriate excretion of the antidiuretic hormone (SIADH), or overly aggressive intravenous fluid administration.[4][30]

[edit]Lumbar

puncture

Gram stain of meningococci from a culture showing Gram negative (pink) bacteria, often in pairs

A lumbar puncture is done by positioning the person, usually lying on the side, applying local anesthetic, and inserting a needle into the dural sac (a sac around the spinal cord) to collect cerebrospinal fluid (CSF). When this has been achieved, the "opening pressure" of the CSF is measured using amanometer. The pressure is normally between 6 and 18 cm water (cmH2O);[28] in bacterial meningitis the pressure is usually elevated.[3][27] Incryptococcal meningitis, intracranial pressure is markedly elevated.[31] The initial appearance of the fluid may prove an indication of the nature of the infection: cloudy CSF indicates higher levels of protein, white and red blood cells and/or bacteria, and therefore may suggest bacterial meningitis. [3] The CSF sample is examined for presence and types of white blood cells, red blood cells, protein content and glucose level.[3] Gram staining of the sample may demonstrate bacteria in bacterial meningitis, but absence of bacteria does not exclude bacterial meningitis as they are only seen in 60% of cases; this figure is reduced by a further 20% if antibiotics were administered before the sample was taken. Gram staining is also less reliable in particular infections such as listeriosis. Microbiological culture of the sample is more sensitive (it identifies the organism in 7085% of cases) but results can take up to 48 hours to become available.[3] The type of white blood cell predominantly present (see table) indicates whether meningitis is bacterial (usually neutrophil-predominant) or viral (usually lymphocyte-predominant),[3] although at the beginning of the disease this is not always a reliable indicator. Less commonly, eosinophils predominate, suggesting parasitic or fungal etiology, among others.[23] The concentration of glucose in CSF is normally above 40% of that in blood. In bacterial meningitis it is typically lower; the CSF glucose level is therefore divided by the blood glucose (CSF glucose to serum glucose ratio). A ratio 0.4 is indicative of bacterial meningitis;[28] in the newborn, glucose levels in CSF are normally higher, and a ratio below 0.6 (60%) is therefore considered abnormal.[3] High levels of lactate in CSF indicate a higher likelihood of bacterial meningitis, as does a higher white blood cell count. [28] If lactate levels are less than 35 mg/dl and the person has not previously received antibiotics then this may rule out bacterial meningitis. [32]

Various other specialized tests may be used to distinguish between different types of meningitis. A latex agglutination test may be positive in meningitis caused by Streptococcus pneumoniae,Neisseria meningitidis, Haemophilus influenzae, Escherichia coli and group B streptococci; its routine use is not encouraged as it rarely leads to changes in treatment, but it may be used if other tests are not diagnostic. Similarly, the limulus lysate test may be positive in meningitis caused by Gram-negative bacteria, but it is of limited use unless other tests have been unhelpful.[3]Polymerase chain reaction (PCR) is a technique used to amplify small traces of bacterial DNA in order to detect the presence of bacterial or viral DNA in cerebrospinal fluid; it is a highly sensitive and specific test since only trace amounts of the infecting agent's DNA is required. It may identify bacteria in bacterial meningitis and may assist in distinguishing the various causes of viral meningitis (enterovirus, herpes simplex virus 2 and mumps in those not vaccinated for this).[10] Serology (identification of antibodies to viruses) may be useful in viral meningitis. [10] If tuberculous meningitis is suspected, the sample is processed for Ziehl-Neelsen stain, which has a low sensitivity, and tuberculosis culture, which takes a long time to process; PCR is being used increasingly. [14] Diagnosis of cryptococcal meningitis can be made at low cost using an India ink stain of the CSF; however, testing for cryptococcal antigen in blood or CSF is more sensitive, particularly in people with AIDS.[33][34] A diagnostic and therapeutic difficulty is "partially treated meningitis", where there are meningitis symptoms after receiving antibiotics (such as for presumptive sinusitis). When this happens, CSF findings may resemble those of viral meningitis, but antibiotic treatment may need to be continued until there is definitive positive evidence of a viral cause (e.g. a positive enterovirus PCR).[10]

[edit]Postmortem

Histopathology of bacterial meningitis: autopsy case of a person with pneumococcal meningitis showing inflammatory infiltrates of the pia materconsisting of neutrophil granulocytes (inset, higher magnification).

Meningitis can be diagnosed after death has occurred. The findings from a post mortem are usually a widespread inflammation of the pia mater andarachnoid layers of the meninges. Neutrophil granulocytes tend

to have migrated to the cerebrospinal fluid and the base of the brain, along with cranial nerves and the spinal cord, may be surrounded with pus as may the meningeal vessels.[35]

[edit]Prevention
For some causes of meningitis, protection can be provided in the long term through vaccination, or in the short term with antibiotics. Some behavioral measures may also be effective.

[edit]Behavioral
Bacterial and viral meningitis are contagious; however, neither are as contagious as the common cold or flu.[36] Both can be transmitted through droplets of respiratory secretions during close contact such as kissing, sneezing or coughing on someone, but cannot be spread by only breathing the air where a person with meningitis has been.[36] Viral meningitis is typically caused by enteroviruses, and is most commonly spread through fecal contamination.[36] The risk of infection can be decreased by changing the behavior that led to transmission.

[edit]Vaccination
Since the 1980s, many countries have included immunization against Haemophilus influenzae type B in their routine childhood vaccination schemes. This has practically eliminated this pathogen as a cause of meningitis in young children in those countries. In the countries where the disease burden is highest, however, the vaccine is still too expensive.[37][38] Similarly, immunization against mumps has led to a sharp fall in the number of cases of mumps meningitis, which prior to vaccination occurred in 15% of all cases of mumps. [10] Meningococcus vaccines exist against groups A, C, W135 and Y.[39] In countries where the vaccine for meningococcus group C was introduced, cases caused by this pathogen have decreased substantially. [37] A quadrivalent vaccine now exists, which combines all four vaccines. Immunization with the ACW135Y vaccine against four strains is now a visa requirement for taking part inHajj.[40] Development of a vaccine against group B meningococci has proved much more difficult, as its surface proteins (which would normally be used to make a vaccine) only elicit a weakresponse from the immune system, or cross-react with normal human proteins.[37][39] Still, some countries (New Zealand, Cuba, Norway and Chile) have developed vaccines against local strains of group B meningococci; some have shown good results and are used in local immunization schedules.[39] In Africa, until recently, the approach for prevention and control of meningococcal epidemics was based on early detection of the disease and emergency reactive mass vaccination of the at-risk population with bivalent A/C or trivalent A/C/W135 polysaccharide vaccines,[41]though the introduction of MenAfriVac (meningococcus group A vaccine) has demonstrated effectiveness in young people and has been described as a model for product development partnerships in resource-limited settings.[42][43] Routine vaccination against Streptococcus pneumoniae with the pneumococcal conjugate vaccine (PCV), which is active against seven common serotypes of this pathogen, significantly reduces the incidence of

pneumococcal meningitis.[37][44] The pneumococcal polysaccharide vaccine, which covers 23 strains, is only administered to certain groups (e.g. those who have had asplenectomy, the surgical removal of the spleen); it does not elicit a significant immune response in all recipients, e.g. small children.[44] Childhood vaccination with Bacillus Calmette-Gurin has been reported to significantly reduce the rate of tuberculous meningitis, but its waning effectiveness in adulthood has prompted a search for a better vaccine.[37]

[edit]Antibiotics
Short-term antibiotic prophylaxis is another method of prevention, particularly of meningococcal meningitis. In cases of meningococcal meningitis, prophylactic treatment of close contacts with antibiotics (e.g. rifampicin, ciprofloxacin or ceftriaxone) can reduce their risk of contracting the condition, but does not protect against future infections.[27][45] Resistance to rifampicin has been noted to increase after use, which has caused some to recommend considering other agents.[45] While antibiotics are frequently used in an attempt to prevent meningitis in those with a basilar skull fracture there is insufficient evidence to determine whether this is beneficial or harmful.[46] This applies to those with or without a CSF leak.[46]

[edit]Management
Meningitis is potentially life-threatening and has a high mortality rate if untreated;[3] delay in treatment has been associated with a poorer outcome.[4] Thus, treatment with wide-spectrum antibiotics should not be delayed while confirmatory tests are being conducted.[29] If meningococcal disease is suspected in primary care, guidelines recommend that benzylpenicillin be administered before transfer to hospital.[7] Intravenous fluids should be administered if hypotension (low blood pressure) or shock are present.[29] Given that meningitis can cause a number of early severe complications, regular medical review is recommended to identify these complications early[29] and to admit the person to an intensive care unit if deemed necessary.[4] Mechanical ventilation may be needed if the level of consciousness is very low, or if there is evidence of respiratory failure. If there are signs of raised intracranial pressure, measures to monitor the pressure may be taken; this would allow the optimization of the cerebral perfusion pressure and various treatments to decrease the intracranial pressure with medication (e.g. mannitol).[4]Seizures are treated with anticonvulsants.[4] Hydrocephalus (obstructed flow of CSF) may require insertion of a temporary or longterm drainage device, such as a cerebral shunt.[4]

[edit]Bacterial

meningitis

[edit]Antibiotics

Structural formula of ceftriaxone, one of the third-generation cefalosporin antibiotics recommended for the initial treatment of bacterial meningitis.

Empiric antibiotics (treatment without exact diagnosis) should be started immediately, even before the results of the lumbar puncture and CSF analysis are known. The choice of initial treatment depends largely on the kind of bacteria that cause meningitis in a particular place and population. For instance, in the United Kingdom empirical treatment consists of a third-generation cefalosporin such as cefotaxime or ceftriaxone.[27][29] In the USA, where resistance to cefalosporins is increasingly found in streptococci, addition of vancomycin to the initial treatment is recommended.[3][4][27]Chloramphenicol, either alone or in combination with ampicillin, however, appears to work equally well.[47] Empirical therapy may be chosen on the basis of the person's age, whether the infection was preceded by a head injury, whether the person has undergone recent neurosurgery and whether or not a cerebral shunt is present.[3] In young children and those over 50 years of age, as well as those who are immunocompromised, the addition of ampicillin is recommended to cover Listeria monocytogenes.[3][27] Once the Gram stain results become available, and the broad type of bacterial cause is known, it may be possible to change the antibiotics to those likely to deal with the presumed group of pathogens.[3] The results of the CSF culture generally take longer to become available (2448 hours). Once they do, empiric therapy may be switched to specific antibiotic therapy targeted to the specific causative organism and its sensitivities to antibiotics. [3] For an antibiotic to be effective in meningitis it must not only be active against the pathogenic bacterium but also reach the meninges in adequate quantities; some antibiotics have inadequate penetrance and therefore have little use in meningitis. Most of the antibiotics used in meningitis have not been tested directly on people with meningitis in clinical trials. Rather, the relevant knowledge has mostly derived from laboratory studies in rabbits.[3] Tuberculous meningitis requires prolonged treatment with antibiotics. While tuberculosis of the lungs is typically treated for six months, those with tuberculous meningitis are typically treated for a year or longer.[14]

[edit]Steroids
Adjuvant treatment with corticosteroids (usually dexamethasone) has shown some benefits, such as a reduction of hearing loss,[48] and better short term neurological outcomes[49] in adolescents and adults from high income countries with low rates of HIV.[50] Some research has found reduced rates of death[50] while other

research has not.[49] They also appear to be beneficial in those with tuberculosis meningitis, at least in those who are HIV negative.[51] Professional guidelines therefore recommend the commencement of dexamethasone or a similar corticosteroid just before the first dose of antibiotics is given, and continued for four days.[27][29]Given that most of the benefit of the treatment is confined to those with pneumococcal meningitis, some guidelines suggest that dexamethasone be discontinued if another cause for meningitis is identified. [3][27] The likely mechanism is suppression of overactive inflammation.[52] Adjuvant corticosteroids have a different role in children than in adults. Though the benefit of corticosteroids has been demonstrated in adults as well as in children from high-income countries, their use in children from low-income countries is not supported by the evidence; the reason for this discrepancy is not clear.[49] Even in high-income countries, the benefit of corticosteroids is only seen when they are given prior to the first dose of antibiotics, and is greatest in cases of H. influenzae meningitis,[3][53] the incidence of which has decreased dramatically since the introduction of the Hib vaccine. Thus, corticosteroids are recommended in the treatment of pediatric meningitis if the cause is H. influenzae, and only if given prior to the first dose of antibiotics; other uses are controversial.[3]

[edit]Viral

meningitis

Viral meningitis typically only requires supportive therapy; most viruses responsible for causing meningitis are not amenable to specific treatment. Viral meningitis tends to run a more benign course than bacterial meningitis. Herpes simplex virus and varicella zoster virus may respond to treatment with antiviral drugs such as aciclovir, but there are no clinical trials that have specifically addressed whether this treatment is effective.[10] Mild cases of viral meningitis can be treated at home with conservative measures such as fluid, bedrest, and analgesics.[54]

[edit]Fungal

meningitis

Fungal meningitis, such as cryptococcal meningitis, is treated with long courses of high dose antifungals, such as amphotericin B and flucytosine.[33][55] Raised intracranial pressure is common in fungal meningitis, and frequent (ideally daily) lumbar punctures to relieve the pressure are recommended,[33] or alternatively a lumbar drain.[31]

[edit]Prognosis

Disability-adjusted life year for meningitis per 100,000 inhabitants in 2004.[56] no data <10 10-25 25-50 50-75 75-100 100-200 200-300 300-400 400-500 500-750 7501000 >1000

Untreated, bacterial meningitis is almost always fatal. Viral meningitis, in contrast, tends to resolve spontaneously and is rarely fatal. With treatment,mortality (risk of death) from bacterial meningitis depends on the age of the person and the underlying cause. Of newborns, 2030% may die from an episode of bacterial meningitis. This risk is much lower in older children, whose mortality is about 2%, but rises again to about 19 37% in adults.[1][4]Risk of death is predicted by various factors apart from age, such as the pathogen and the time it takes for the pathogen to be cleared from the cerebrospinal fluid,[1] the severity of the generalized illness, a decreased level of consciousness or an abnormally low count of white blood cells in the CSF. [4] Meningitis caused by H. influenzae and meningococci has a better prognosis than cases caused by group B streptococci, coliforms and S. pneumonia.[1] In adults, too, meningococcal meningitis has a lower mortality (37%) than pneumococcal disease.[4] In children there are several potential disabilities which may result from damage to the nervous system, including sensorineural hearing loss, epilepsy,learning and behavioral difficulties, as well as decreased intelligence.[1] These occur in about 15% of survivors.[1] Some of the hearing loss may be reversible.[57] In adults, 66% of all cases emerge without disability. The main problems are deafness (in 14%) and cognitive impairment (in 10%).

Measles
Measles is a serious and highly contagious viral disease which causes fever, runny nose, cough and sore red eyes, followed by a rash. Measles can sometimes lead to dangerous complications such as pneumonia. About one person in 2,000 who contracts measles will develop inflammation of the brain. For every 10 people who become affected in this way, one will die and four will have permanent brain damage. Measles still causes deaths in Australia. A rare condition called SSPE can develop several years after a measles infection. SSPE rapidly destroys the brain and is always fatal. Measles can be caught through coughs and sneezes from an infected person before that person realises they are sick.

Mumps
Mumps causes fever, headache and inflammation of the salivary glands. Occasionally it causes an infection of the membrane covering the brain, but permanent side effects are rare. The disease can also cause permanent deafness. About one in five adolescent or adult males who contracts mumps develops a painful inflammation and swelling of the testicles. Males with this condition generally recover completely, but on rare occasions it may cause infertility. Mumps can be caught through coughs and sneezes from an infected person before that person realises they are sick.

Rubella
This is a mild childhood disease but it can also affect teenagers and adults. The disease causes swollen glands, joint pains and a rash on the face and neck which lasts two to three days. Recovery is always speedy and complete. Rubella is most dangerous when a woman catches it in the first 20 weeks of pregnancy. This can result in serious abnormalities in the newborn baby. Deafness, blindness, heart defects and intellectual disabilities can occur. Rubella can be caught through coughs and sneezes from an infected person before that person realises they are sick. Rubella is highly contagious and the best way to protect expectant mothers and their babies is to ensure that women are immunised before they become pregnant. *Pregnancy should be avoided for one month following immunisation.

Measles/mumps/rubella (MMR) vaccine

The MMR vaccine contains small amounts of each of the viruses at a reduced strength, a small amount of the antibiotic neomycin and a stabiliser.

Who should be immunised?

The vaccine protects children against all three diseases and is given at 12 months of age. A booster dose of the vaccine is given at four years of age. All people born during or since 1966 should check their immunisation status to ensure they have had two doses of a measles containing vaccine. If people in this age group do not have documentation (either written or by a blood test showing immunity) of two measles containing vaccines, they should be vaccinated. Women of child bearing age, especially those considering pregnancy, should see their doctor and have a blood test for rubella. The blood test will show if another MMR immunisation is needed. If you do require another MMR immunisation, a further blood test should be done after immunisation to ensure that the vaccine has provided protection. Women should not have the vaccine if they are already pregnant or might become pregnant within one month. It is important that women have a rubella blood test before each pregnancy to check that the level of protection is still adequate.

Possible side-effects of MMR

Reactions to MMR vaccine are much less frequent than the complications of the diseases. Common side effects Seen five to 12 days after vaccination: high fever over 39 C faint red rash (not infectious) head cold and/or runny nose cough and/or puffy eyes drowsiness or tiredness swelling of the salivary glands a temporary small lump at the injection site
o

Serious side effects: encephalitis (inflammation of the brain) at a rate of one in one million thrombocytopenia (bruising or bleeding) at a rate of one in 30,500 doses

Extremely rare side effect: severe allergic reaction

If mild reactions do occur, they may last two to three days. The side-effects can be reduced by: drinking extra fluids and not overdressing if the person has a fever placing a cold wet cloth on the sore injection site taking (or giving your child) paracetamol to reduce any discomfort (note the recommended dose for the age of your child)

If reactions are severe or persistent, or if you are worried, contact your doctor or hospital.

Pre-immunisation checklist
Before you or your child is immunised, tell the doctor or nurse if any of the following apply: Have had a vaccine containing live viruses within the last month (such as chickenpox or BCG). Are unwell on the day of immunisation (temperature over 38.5C). Have had a severe reaction to a previous MMR vaccine. Have had a severe allergy to any vaccine component, for example, neomycin. Are taking steroids of any sort other than inhaled asthma sprays or steroid creams (for example, cortisone or prednisone). Have had immunoglobulin or a blood product in the last year. Have a disease or are having treatment which causes low immunity (for example, leukaemia, cancer, HIV/AIDS, radiotherapy or chemotherapy). Are pregnant or planning to become pregnant within one month of immunisation

About Chickenpox
Caused by the varicella-zoster virus (VZV), chickenpox used to be a common illness among kids in the United States (particularly among those under age 12). An itchy rash of spots that look like blisters can appear all over the body and be accompanied by flu-like symptoms. Chickenpox is very contagious, so an infected child should stay home and rest until the rash is gone.

Kids can be protected from VZV by getting the chickenpox (varicella) vaccine. The vaccine significantly reduces the chances of getting chickenpox. Vaccinated kids who do get chickenpox tend to have milder cases and quicker recoveries compared to those who contract the virus and aren't immunized.

Symptoms
Chickenpox often starts with a fever, headache, sore throat, or stomachache. These symptoms may last for a few days, with fever in the 101-102F (38.3-38.8C) range.

Chickenpox causes a red, itchy skin rash that usually appears first on the abdomen or back and face, and then spreads to almost everywhere else on the body, including the scalp, mouth, arms, legs, and genitals.

The rash begins as multiple small red bumps that look like pimples or insect bites, usually less than a quarter of an inch wide. They appear in crops over 2 to 4 days and develop into thin-walled blisters filled with fluid. The blister walls break, leaving open sores, which finally crust over to become dry, brown scabs. The rash is very itchy, and cool baths or calamine lotion may help to manage the itching.

A hallmark of chickenpox is that all stages (red bumps, blisters, and scabs) can appear on the body at the same time. The rash may be more extensive or severe in kids who have skin disorders like eczema, or weak immune systems. Young kids tend to have a mild illness with fewer blisters than older children or adults.

In rare cases, serious bacterial infections involving the skin, lungs, bones, joints, and the brain can occur.

Risk of Shingles
Anyone who has had chickenpox is at risk for developing a skin condition called shingles (herpes zoster) later in life. That's because after an infection, VZV remains inactive in nerve cells near the spinal cord and reactivates later as shingles, which can cause tingling, itching, or pain in one area of the body, followed by a rash with red bumps and blisters. Fortunately, this is a rare occurrence in kids and teens who have healthy immune systems. It's also uncommon for someone who's been vaccinated against chickenpox to develop singles later in life. When it does happen, the case of shingles is usually milder and less likely to cause complications than in a person who wasn't immunized.

Contagiousness
The chickenpox virus spreads both through the air (by coughing and sneezing), and by direct contact with mucus, saliva, or fluid from blisters. Chickenpox is contagious from about 2 days before the rash appears until all the blisters are crusted over. A child with chickenpox should be kept out of school until all blisters have dried, usually about 1 week. If you're unsure about whether your child is ready to return to school, ask your doctor.

Chickenpox is very contagious most kids with a sibling who's been infected will get it as well (if they haven't already had the disease or the vaccine), showing symptoms about 2 weeks after the first child does. To help keep it from spreading, make sure your kids wash their hands frequently, particularly before eating and after using the bathroom. And keep a child with chickenpox away from unvaccinated siblings as much as possible.

People who haven't had chickenpox or the vaccine also can catch it from someone with shingles, but they cannot catch shingles itself. That's because shingles can only develop from a reactivation of VZV in someone who has previously had chickenpox.

High-Risk Groups
Certain groups of people are more at risk for complications from chickenpox, including pregnant women and anyone with immune system problems. These groups should avoid others who have chickenpox.

If a pregnant woman who hasn't had chickenpox in the past contracts it (especially in the first 20 weeks of pregnancy), the fetus is at risk for birth defects and the mother is at risk for more health complications than if she'd been infected when she wasn't pregnant. If she develops chickenpox just before or after the child is born, the newborn is at risk for serious health complications. There is no risk to a developing baby if the mother develops shingles during pregnancy.

If a pregnant woman has had chickenpox before the pregnancy, the baby will be protected from infection for the first few months of life, since the mother's immunity gets passed on to the baby through the placenta and breast milk.

Those at risk for severe disease or serious complications such as newborns whose mothers had chickenpox at the time of delivery, patients with leukemia or immune deficiencies, and kids receiving drugs that suppress the immune system may be given a medication after exposure to chickenpox to reduce its severity.

Prevention
The chickenpox vaccine is 99% effective at preventing the VZV infection in kids. Doctors recommend that kids receive the chickenpox vaccine twice when they're 12 to 15 months old, with a booster shot at 4 to 6 years old.

People 13 years of age and older who have never had chickenpox or haven't gotten the vaccine should receive two doses of the vaccine at least 28 days apart to be protected. While few people who've been vaccinated actually develop chickenpox, those who do tend to develop very mild cases of the condition and recover quickly.

Healthy kids who have had chickenpox do not need the vaccine they usually have lifelong protection against the illness.

Treatment
Since a virus causes chickenpox, doctors won't prescribe antibiotics to treat it. However, antibiotics may be required if the sores become infected by bacteria. This is pretty common among kids because they often scratch and pick at the blisters.

An antiviral medicine might be prescribed for people with chickenpox who are at risk for complications. The decision to use this will depend on a child's age and health, the extent of the infection, and the timing of the treatment. Your doctor can tell you if the medication is right for your child.

Dealing With Discomfort

To help relieve the itchiness, fever, and discomfort of chickenpox:

Use cool wet compresses or give baths in cool or lukewarm water every 3 to 4 hours for the first few days. Oatmeal bath products, available at supermarkets and drugstores, can help to relieve itching. (Baths do not spread the rash.)

Pat (don't rub) the body dry.

Put calamine lotion on itchy areas (but don't use it on the face, especially near the eyes).

Serve foods that are cold, soft, and bland because chickenpox in the mouth can make drinking or eating difficult. Avoid feeding your child anything highly acidic or especially salty, like orange juice or pretzels.

Ask your doctor or pharmacist about pain-relieving creams to apply to sores in the genital area.

Give your child acetaminophen regularly to help relieve pain if your child has mouth blisters.

Ask the doctor about using over-the-counter medication for itching.

Never use aspirin to reduce pain or fever in kids with chickenpox because aspirin has been associated with the serious diseaseReye syndrome, which can lead to liver failure and even death. As much as possible, discourage kids from scratching. This can be difficult for them, so consider putting mittens or socks on your child's hands to prevent scratching during sleep. In addition, trim fingernails and keep them clean to help lessen the effects of scratching, including broken blisters and infection.

Most chickenpox infections require no special medical treatment. But sometimes, there are problems. Call the doctor if your child:

has fever that lasts for more than 4 days or rises above 102F (38.8C) has a severe cough or trouble breathing has an area of rash that leaks pus (thick, yellowish fluid) or becomes red, warm, swollen, or sore has a severe headache is unusually drowsy or has trouble waking up has trouble looking at bright lights has difficulty walking seems confused seems very ill or is vomiting has a stiff neck

Call your doctor if you think your child has chickenpox and you have a question or are concerned about a possible complication. The doctor can guide you in watching for complications and in choosing medication to relieve itching.

If you take your child to the doctor, let the office know in advance that your child might have chickenpox. It's important to try to avoid exposing other kids in the office for some of them, a chickenpox infection could cause severe complications.