Tuberculosis

MTB, or TB (short for tubercle bacillus) is a common, and in many cases lethal, infectious disease caused by various strains ofmycobacteria, usually Mycobacterium tuberculosis.[1] 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.[2] Most infections areasymptomatic 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 bloodtinged sputum, fever, night sweats, and weight loss (the latter giving rise to the formerly prevalent term "consumption"). 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 thetuberculin 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.

Causes
The main cause of TB is Mycobacterium tuberculosis, a small, aerobic, nonmotile bacillus.[9] The high lipid content of this pathogen accounts for many of its unique clinical characteristics.[15] It divides every 16 to 20 hours, which is an extremely slow rate compared with other bacteria, which usually divide in less than an hour. [16] Mycobacteria have an outer membrane lipid bilayer.[17] If a Gram stain is performed, MTB either stains very weakly "Gram-positive" or does not retain dye as a result of the high lipid and mycolic acid content of its cell wall.[18] MTB can withstand weak disinfectantsand survive in a dry state for weeks. In nature, the bacterium can grow only within the cells of a host organism, but M. tuberculosis can be cultured in the laboratory.[19] Using histological stains on expectorated samples from phlegm (also called "sputum"), scientists can identify MTB under a regular (light) microscope. Since MTB retains certain stains even after being treated with acidic solution, it is classified as an acid-fast bacillus (AFB).[1][18] The most common acid-fast staining techniques are the ZiehlNeelsen stain, which dyes AFBs a bright red that stands out clearly against a blue background,[20] and theauramine-rhodamine stain followed by fluorescence microscopy.[21] The M. tuberculosis complex (MTBC) includes four other TB-causing mycobacteria: M. bovis, M. africanum, M. canetti, and M. microti.[22] M. africanumis not widespread, but it is a significant cause of tuberculosis in parts of Africa.[23][24] M. bovis was once a common cause of tuberculosis, but the introduction of pasteurized milk has largely eliminated this as a public health problem in developed countries.[1][25] M. canetti is rare and seems to be limited to the Horn of Africa, although a few cases have been seen in African emigrants.[26][27] M. microti is also rare and is mostly seen in immunodeficient people, although the prevalence of this pathogen has possibly been significantly underestimated. [28] Other known pathogenic mycobacteria include M. leprae, M. avium, and M. kansasii. The latter two species are classified as "nontuberculous mycobacteria" (NTM). NTM cause neither TB norleprosy, but they do cause pulmonary diseases that resemble TB.[29]

Risk factors
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.[5] This is a particular problem insub-Saharan Africa, where rates of HIV are high.[30][31] Tuberculosis is closely linked to both overcrowding and malnutrition, making it one of the principal diseases of poverty.[6] 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.[32] Chronic lung disease is another significant risk factor with silicosis increasing the risk about 30-fold.[33] Those who smoke cigarettes have nearly twice the risk of TB than nonsmokers.[34] Other disease states can also increase the risk of developing tuberculosis, including alcoholism[6] and diabetes mellitus (threefold increase).[35] Certain medications, such as corticosteroids and infliximab (an anti-TNF monoclonal antibody) are becoming increasingly important risk factors, especially in the developed world.[6] There is also a genetic susceptibility[36] for which overall importance is still undefined.[6]

TREATMENT
A person with a positive skin test, a normal chest X-ray, and no symptoms most likely has only a few TB germs in an inactive state and is not contagious. Nevertheless, treatment with an antibiotic may be recommended for this person to prevent the TB from turning into an active infection. The antibiotic used for this purpose is called isoniazid (INH). If taken for six to 12 months, it will prevent the TB from becoming active in the future. In fact, if a person with a positive skin test does not take INH, there is a 5%-10% lifelong risk that the TB will become active. Taking isoniazid can be inadvisable (contraindicated) during pregnancy or for those suffering from alcoholism or liver disease. Also, isoniazid can have side effects. The side effects occur infrequently, but a rash can develop, and the individual can feel tired or irritable. Liver damage from isoniazid is a rare occurrence and typically reverses once the drug is stopped. Very rarely, however, especially in older people, the liver damage (INH hepatitis) can even be fatal. It is important therefore, for the doctor to monitor a patient's liver by periodically ordering blood tests called "liver function tests" during the course of INH therapy. Another side effect of INH is a decreased sensation in the extremities referred to as a peripheral neuropathy. This can be avoided by taking vitamin B6 (pyridoxine), and this is often prescribed along with INH. A person with a positive skin test along with an abnormal chest X-ray and sputum evidencing TB bacteria has active TB and is contagious. As already mentioned, active TB usually is accompanied by symptoms, such as a cough, fever, weight loss, and fatigue. Active TB is treated with a combination of medications along with isoniazid.Rifampin (Rifadin), ethambutol (Myambutol), and pyrazinamide are the drugs commonly used to treat active TB in conjunction with isoniazid (INH). Four drugs are often taken for the first two months of therapy to help kill any potentially resistant strains of bacteria. Then the number is usually reduced to two drugs for the remainder

of the treatment based on drug-sensitivity testing that is usually available by this time in the course. Streptomycin, a drug that is given by injection, may be used as well, particularly when the disease is extensive and/or the patients do not take their oral medications reliably (termed "poor compliance"). Treatment usually lasts for many months and sometimes for years. Successful treatment of TB is dependent largely on the compliance of the patient. Indeed, the failure of a patient to take the medications as prescribed is the most important cause of failure to cure the TB infection. In some locations, the health department demands direct monitoring of patient compliance with therapy. Surgery on the lungs may be indicated to help cure TB when medication has failed, but in this day and age, surgery for TB is unusual. Treatment with appropriate antibiotics will usually cure the TB. Without treatment, however, tuberculosis can be a lethal infection. Therefore, early diagnosis is important. Those individuals who have been exposed to a person with TB, or suspect that they have been, should be examined by a doctor for signs of TB and screened with a TB skin test.

SYPHILIS
Syphilis is a sexually transmitted infection caused by the spirochete bacterium Treponema pallidum subspecies pallidum. The primary route of transmission is through sexual contact; it may also be transmitted from mother to fetus during pregnancy or at birth, resulting in congenital syphilis. Other human diseases caused by related Treponema pallidum include yaws (subspecies pertenue), pinta (subspecies carateum), and bejel(subspecies endemicum). The signs and symptoms of syphilis vary depending in which of the four stages it presents (primary, secondary, latent, and tertiary). The primary stage classically presents with a single chancre (a firm, painless, non-itchy skin ulceration), secondary syphilis with a diffuse rash which frequently involves the palms of the hands and soles of the feet, latent syphilis with little to no symptoms, and tertiary syphilis with gummas, neurological, or cardiac symptoms. It has, however, been known as "the great imitator" due to its frequent atypical presentations. Diagnosis is usually via blood tests; however, the bacteria can also be visualized under a microscope. Syphilis can be effectively treated with antibiotics, specifically the preferred intramuscular penicillin G (given intravenously for neurosyphilis), or else ceftriaxone, and in those who have a severe pencillin allergy, oral doxycyclineor azithromycin. Syphilis is believed to have infected 12 million people worldwide in 1999, with greater than 90% of cases in the developing world. After decreasing dramatically since the widespread availability of penicillin in the 1940s, rates of infection have increased since the turn of the millennium in many countries, often in combination with human immunodeficiency virus (HIV). This has been attributed partly to unsafe sexual practices among men who have sex with men, increased promiscuity, prostitution, and decreasing use of barrier protection.

CAUSES
Bacteriology
Treponema pallidum subspecies pallidum is a spiral-shaped, Gram-negative, highly mobile [8][13] bacterium. Three other human diseases are caused by related Treponema pallidum, including yaws (subspecies pertenue), pinta (subspecies carateum)

and bejel (subspecies endemicum). neurological disease.

[12]

[4]

Unlike subtypepallidum, they do not cause

Humans are the only known natural reservoir for

subspecies pallidum. It is unable to survive without a host for more than a few days. This is due to its small genome (1.14 MDa) failing to encode the metabolic pathways necessary to make most of its macronutrients. It has a slow doubling time of greater than 30 hours.

Transmission
Syphilis is transmitted primarily by sexual contact or during pregnancy from a mother to her fetus; the spirochaete is able to pass through intact mucous membranes or compromised skin.[4][5] It is thus transmissible by kissing near a lesion, as well as oral, vaginal, and anal sex.[4] Approximately 30 to 60% of those exposed to primary or secondary syphilis will get the disease.[11] Its infectivity is exemplified by the fact that an individual inoculated with only 57 organisms has a 50% chance of being infected. [8] Most (60%) of new cases in the United States occur in men who have sex with men. It can be transmitted via blood products. However, it is tested for in many countries and thus the risk is low. The risk of transmission from sharing needlesappears limited.[4] Syphilis cannot be contracted through toilet seats, daily activities, hot tubs, or sharing eating utensils or clothing

PREVENTION
As of 2010, there is no vaccine effective for prevention.[5] Abstinence from intimate physical contact with an infected person is effective at reducing the transmission of syphilis, as is the proper use of a latex condom. Condom use, however, does not completely eliminate the risk.[16][14] Thus, the Centers for Disease Control and Preventionrecommends a long-term, mutually monogamous relationship with an uninfected partner and the avoidance of substances such as alcohol and other drugs that increase risky sexual behavior.[14] Congenital syphilis in the newborn can be prevented by screening mothers during early pregnancy and treating those who are infected.[17] The United States Preventive Services Task Force(USPSTF) strongly recommends universal screening of all pregnant women,[18] while the World Health Organization recommends all women be tested at their first antenatal visit and again in thethird trimester.[19] If they are positive, they recommend their partners also be treated.[19] Congenital syphilis is, however, still common in the developing world, as many women do not receiveantenatal care at all, and the antenatal care others do receive does not include screening,[17] and it still occasionally occurs in the developed world, as those most likely to acquire syphilis (through drug use, etc.) are least likely to receive care during pregnancy.[17] A number of measures to increase access to testing appear effective at reducing rates of congenital syphilis in low- to middle-income countries.[19] Syphilis is a notifiable disease in many countries, including Canada[20] the European Union,[21] and the United States.[22] This means health care providers are required to notify public healthauthorities, which will then ideally provide partner notification to the person's partners. [23] Physicians may also encourage patients to send their partners to seek care.[24] The CDC recommends sexually active men who have sex with men are tested at least yearly.[

TREATMENT
Early infections
The first-choice treatment for uncomplicated syphilis remains a single dose of intramuscular penicillin G or a single dose of

oral azithromycin.[26] Doxycycline and tetracycline are alternative choices; however, due to the risk of birth defects these are not recommended for pregnant women. Antibiotic resistance has developed to a number of agents, including macrolides, clindamycin, and rifampin.[5] Ceftriaxone, a third-generation cephalosporin antibiotic, may be as effective as penicillin-based treatment.[4]

Late infections
For neurosyphilis, due to the poor penetration of penicillin G into the central nervous system, those affected are recommended to be given large doses of intravenous penicillin for a minimum of 10 days.[4][5] If a person is allergic, ceftriaxone may be used or penicillin desensitization attempted. Other late presentations may be treated with once-weekly intramuscular penicillin G for three weeks. If allergic, as in the case of early disease, doxycycline or tetracycline may be used, albeit for a longer duration. Treatment at this stage limits further progression, but has only slight effect on damage which has already occurred.[4]

Jarisch-Herxheimer reaction
One of the potential side effects of treatment is the Jarisch-Herxheimer reaction. It frequently starts within one hour and lasts for 24 hours, with symptoms of fever, muscles pains, headache, andtachycardia.[4] It is caused by cytokines released by the immune system in response to lipoproteins released from rupturing syphilis bacteria.

MALARIA
Malaria is a mosquito-borne infectious disease of humans and other animals caused by protists (a type of microorganism) of the genus Plasmodium. The protists first infect the liver, then act as parasites within red blood cells, causing symptoms that typically include fever and headache, in severe cases progressing to coma or death. The disease is widespread in tropical and subtropical regions in a broad band around the equator, including much of Sub-Saharan Africa, Asia, and the Americas. Five species of Plasmodium can infect and be transmitted by humans. The vast majority of deaths are caused by P. falciparum while P. vivax,P. ovale, and P. malariae cause a generally milder form of malaria that is rarely fatal. The zoonotic species P. knowlesi, prevalent in Southeast Asia, causes malaria in macaques but can also cause severe infections in humans. Malaria is prevalent in tropical regions because the significant amounts of rainfall, consistently high temperatures and high humidity, along with stagnant waters in which mosquito larvae readily mature, provide them with the environment they need for continuous breeding. Disease transmission can be reduced by preventing mosquito bites by distribution of mosquito nets and insect repellents, or with mosquito-control measures such as spraying insecticides and draining standing water. The World Health Organization has estimated that in 2010, there were 216 million documented cases of malaria. Around 655,000 people died from the disease, many of whom were children under the age of five.[1] The actual number of deaths may be significantly higher, as precise statistics are unavailable in many rural areas, and many cases are undocumented. Malaria is commonly associated with poverty and is also a major hindrance toeconomic development. Despite a clear need, no vaccine offering a high level of protection currently exists. Efforts to develop one are ongoing. Several medications are available to prevent malaria in travelers to malaria-endemic countries (prophylaxis). A variety of antimalarial medications are available. Severe malaria is treated with intravenous or intramuscular quinine or, since the mid-2000s, the artemisinin derivative artesunate, which is superior to quinine in both children and

adults and is given in combination with a second anti-malarial such as mefloquine. Resistance has developed to several antimalarial drugs, most notably chloroquine and artemisini.

CAUSES
Malaria parasites are from the genus Plasmodium (phylum Apicomplexa). In humans, malaria is caused [11][12] by P. falciparum, P. malariae, P. ovale, P. vivax and P. knowlesi. Among those infected,P. falciparum is the most common species identified (~75%) followed [4] by P. vivax (~20%). P. falciparum accounts for the majority of [13] [14] deaths. P. vivax proportionally is more common outside of Africa. There have been documented human infections with several species of Plasmodium fromhigher apes; however, with the exception of P. knowlesia zoonotic species that causes malaria [12] inmacaques these are mostly of limited public health importance.

PREVENTIONS
.Methods used to prevent malaria include medications, mosquito eradication and the prevention of bites. The presence of malaria in an area requires a combination of high human population density, high mosquito population density and high rates of transmission from humans to mosquitoes and from mosquitoes to humans. If any of these is lowered sufficiently, the parasite will eventually disappear from that area, as happened in North America, Europe and much of the Middle East. However, unless the parasite is eliminated from the whole world, it could become re-established if conditions revert to a combination that favours the parasite's reproduction.[37] Many countries are seeing an increasing number of imported malaria cases owing to extensive travel and migration.[38] Many researchers argue that prevention of malaria may be more cost-effective than treatment of the disease in the long run, but the capital costsrequired are out of reach of many of the world's poorest people. There is a wide disparity in the costs of control (i.e. maintenance of low endemicity) and elimination programs between countries. For example, in Chinawhose government in 2010 announced a strategy to pursue malaria elimination in theChinese provincesthe required investment is a small proportion of public expenditure on health. In contrast, a similar program in Tanzania would cost an estimated one-fifth of the public health budget.

TREATMENT
The treatment of malaria depends on the severity of the disease; whether people can take oral drugs or must be admitted depends on the assessment and the experience of the clinician.

Uncomplicated malaria
Uncomplicated malaria may be treated with oral medications. The most effective strategy for P. falciparuminfection is the use of artemisinins in combination with other antimalarials (known as artemisinin-combination therapy).[60] This is done to reduce the risk of resistance against artemisinin.[60] These additional antimalarials include amodiaquine, lumefantrine, mefloquine or sulfadoxine/pyrimethamine.[36] Another

recommended combination is dihydroartemisinin and piperaquine.[36] In the 2000s (decade), malaria with partial resistance to artemisins emerged in Southeast Asia.

Severe malaria
Severe malaria requires the parenteral administration of antimalarial drugs. Until the mid2000s the most used treatment for severe malaria was quinine, but artesunate has been shown to be superior to quinine in both children[63] and adults.[64][65] Treatment of severe malaria also involves supportive measures that are optimally performed in a critical care unit, including management of high fevers (hyperpyrexia) and the subsequent seizures that may result from it, and monitoring for respiratory depression, hypoglycemia, and hypokalemia.[66]Infection with P. vivax, P. ovale or P. malariae is usually treated on an outpatient basis (while a person is at home). Treatment of P. vivax requires both treatment of blood stages (with chloroquine or ACT) as well as clearance of liver forms with primaquine.