Medmicro final

Hepatitis B

formerly known as serum hepatitis can cause acute or chronic infection - the hepatitis B virus (HBV) is transmitted through contact with body fluids Signs and symptoms: incubation period varies considerably 2 to 5 months depending upon the dose received - symptoms of hepatitis B are like those of other forms of hepatitis, ranging from asymptomatic to severe - the acute disease is rarely fatal, and the virus is usually cleared within weeks to month of initial symptoms - it can become chronic especially in infants and children - one in five people with a chronic infection develop cirrhosis (scarring of the liver), liver failure, liver cancer, and other chronic liver disease causative agent: HBV contains double stranded DNA (a portion is single stranded) and a lipid-containing outer envelope. Belongs to hepadnavirus family - remarkably resistant to environmental conditions - three important HBV Ags which serve as useful markers of infection 1. surface antigen (HBsAg) 2. core antigen (HBcAg) 3. e antigen (HBeAg) causative agent: HBsAg is produced during viral replication in far excess amounts than required for virus production - HBsAg appears in the blood stream days or weeks after infection, often long before signs of liver damage - HBsAg is a useful marker of infection and antibodies to HBsAg confer immunity - IgM antibodies against HBcAg indicate active viral replication - high levels of HBeAg correlate with increased risk of liver damage and spreading the disease - the complete hepatitis B virion is also referred as Dane particle Pathogenesis: following entry, HBV is carried to liver by the blood - HBsAg allows the virus to attach to and enter the host cell - liver damage is likely due to the cell-mediated immune response as cytotoxic T cells attack infected liver cells - the liver cell destruction leads to cirrhosis - many chronically infected people eventually die from cirrhosis of the liver, or liver cancer epidemiology: mainly spread by body fluids such as saliva, blood, blood products, and semen - infections may result from sharing of needles by drug abusers, unsterile tattooing and ear-piercing instruments - unprotected sexual intercourse (semen) is responsible for transmission in nearly half of hepatitis B cases in the US - persistent viremia in both symptomatic and non-symptomatic cases and virus may circulate in the blood for years - carriers are important in the spread of infection - more than 90% of infants who contact the virus from infected mothers at or shortly after birth develop a chronic infection - in contrast, 6 to 10% of individuals infected as older children or adults develop a chronic infection - about 19,000 new HBV infections occur each year and about one million people in the USA are chronically infected treatment and prevention: no curative antiviral treatment for hepatitis B, but post-exposure prophylaxis (PEP) with hyperimmune globulin (HBIG) and vaccine can over protection - in some chronic patients remarkable improvement can be achieved by using reverse transcriptase inhibitors along with the injections of genetically engineering interferon - first hepatitis B vaccine approved in early 1980s consisted of HBsAg obtained from the blood of chronic carriers - since 1986, a genetically engineered hepatitis B subunit vaccine containing HBsAg was produced in yeast and is used since that time - it is administered to all newborns before they leave the hospital and to infants - a combined hepatitis A and B vaccine can be used to complete the vaccination schedule - hepatitis B vaccination prevents the disease, and it also prevents millions of new liver cancers that occur each year - education of high risk groups help in prevention - people who are likely to be exposed to blood are taught to consider all blood to be infectious - teaching the importance and proper use of condoms helps in limiting the spread of infections - avoid alcohol and other hepatic toxins

gingivitis

gum inflammation

HIV progression

- CD4+ T cells fall initially, then slowly rise but does not reach the pre-infection level - symptoms of AIDS usually start appearing when CD4+ t-helper cell count falls bellow 200 cells per microliter (normal 1000 cell per microliter) - in AIDS, the levels of HIV virus as measured in circulating plasma (viral load) rises dramatically - as the viral load increases, the person develops detectable amounts of HIV specific antibodies and it is called seroconversion - the patient now beings experiencing a variety of opportunistic infections, including malignant tumors - half of the untreated process to AIDS within 9 to 10 days and others take longer

HIV pathogenesis

- CD4+ T-helper cells are the main target cells and CD4 is the receptor for HIV - monocytes, macrophages, and dendritic cells are CD4+ so are also target of HIV infection - HIV attachment process also requires a Co-receptor - most HIV strains use CCR5 as co-receptor, but some use CXCR4 and some strains use both - people who do not make normal amounts of CCR5 are less susceptible to HIV infection - HIV also causes infected cells to fuse with nearby cells, forming syncytia

cryptococcal meningoencephalitis

- Cryptococcal meningoencephalitis is an exception to this general pattern as about half the cases occur in apparently normal people, and can be cured by medication - cryptococcal meningoencephalitis was not a big health issue until the onset of the AIDS epidemic signs and symptoms: Headache, vomiting, confusion and weight loss; slight or no fever, symptoms may progress to seizures, paralysis coma and death incubation period: widely variable, few to many weeks causative agent: Cryptococcus neoformans, cryptococcus gattii (encapsulated yeast) pathogenesis: infection starts in lung; encapsulated organisms multiply, enter bloodstream, and are carried to various parts of the body; phagocytosis inhibited; meninges and adjacent brain tissue become infected epidemiology: inhalation of material contaminated with the fungus, other source; most people resistant to the disease treatment: antifungal medications prevention: none

Escherichia coli gastroenteritis

- Escherichia coli is a universal member of the normal intestinal flora of humans and some animals - although most strains are harmless, some strains of E. coli produce specific virulence factors that allow them to cause intestinal disease or gastroenteritis. - other stains with different virulence factors cause urinary tract infections, septicemia and meningitis Signs and symptoms: - incubation period is 2 hours to 6 days - some strain cause watery diarrhea and other cause dysentery - one group can cause hemolytic uremic syndrome Causative agent: - E. coli is a gram negative rod, closely related to shigella - Most E. coli strains ferment lactose, in contrast to most shigella and salmonella species - most of the diarrhea causing E. coli can be grouped into six pathovars (pathogenic varieties based on their array of virulence factors

3. mother to infant Epidemiology of HIV disease

- HIV can be transmitted vertically to the fetus in utero via the placenta, at childbirth, or breast feeding - breast feeding carries a significant risk of mother-infant transmission, especially when mother is acutely infected

HIV replication and pathogenesis

- HIV is genetically highly variable - the variablility is usually due to high rate of error when reverse transcriptase copies the viral genome into DNA - because the RT enzyme also lacks proofreading ability, these mistakes are left uncorrected - these changes allow HIV to evolve quickly, altering its antigens and thereby avoiding the immune response - antigenic variability of HIV enormously complicates the task of developing an effective vaccine against the virus - the variant issues show differences in their preferred host cell, rates of replication, response to host immunity, and other characteristics - replication of mature virion in T helper lymphocytes results in lysis of these cells and release of infectious HIV - macrophages and dendritic cells, on the other hand, usually release infectious virus over long period of time without death of cells - macrophages and dendritic cells along with memory T-helper cells become reservoirs for replicating HIV, protecting it from rest of the immune system and providing a continuous source of infectious virus - although infected macrophages and dendritic cells do survive, they show impaired chemotaxis, phagocytosis and antigen presentation which further weakens the immune response - eventually, the immune system becomes so weakened it can no longer respond to infections or cancers

preventing transmission via sexual contract (HIV)

- HIV is not very contagious, the risk of contracting and spreading HIV can be eliminated or reduced by avoiding the activities that might transmit it - using latex condoms and other safer sex practices during sex significantly reduces HIV transmission - circumcision can reduce HIV transmission - circumcision can reduce HIV acquisition by up to 60% and should be included in prevention strategies - the most recent addition of preventing HIV infection in high-risk adults is called PrEP (preexposure prophylaxis) - a single pill, taken daily, contains a fixed dose of two reverse transcriptase inhibitors and it interferes with HIV replication cycle - PrEP is not 100% effective so it should be used in combination with other prevention methods

Epidemiology of HIV disease

- HIV is present in blood, semen and vaginal secretions. Its common modes of transmission are: 1. sexual contact 2. blood and blood product 3. vertical transmission from mother to fetus or infant

Epidemiology of Shigellosis

- Shigellosis is almost exclusively a disease of humans - transmission by fecal-oral route - unlike V. cholerae, Shigella cells are not killed by stomach acid, so that the infectious dose is small and even 10 organisms can initiate the infection - transmission occurs most readily in overcrowded populations with poor sanitation such as in refugee camps and daycare centers - people who engage in anal intercourse are also prone to contract the disease - fecally contaminated food and water have caused numerous shigellosis outbreaks

Additional common mechanisms of pathogenesis of enteric lower digestive system

- Toxin production 2 types: 1) enterotoxins (cause water and electrolytes to flow from intestinal cells) 2) cytotoxins (cause cell death and some can be absorbed into blood, resulting in systemic effects - Alterations in the host cells: many pathogens activate type III secretion system to deliver effector proteins to cells. eg. certain strains of E. coli cause pedestal formation and attaching and effacing (A/E) lesions - cell invasion: some pathogens use type III secretion system to deliver effectors that induce the enterocytes to engulf the bacteria

HIV disease

- acquired immunodeficiency syndrome (AIDS) caused by human immunodeficiency virus (HIV) was first recognized in 1981 in homosexual and bisexual men in the US - AIDS is unquestionably the most important sexually transmitted infection of the past century - Drs. Luc Montagnier and Francouise Barre-Sinoussi (France) together were awarded Nobel prize in Medicine in 2008 for the discovery of HIV - since 1981, an enormous number of Americans died from AIDS and by 1994 it was one of the leading cause of death among those 25 to 44 years of age - Microbes like Pneumocystis jiroveci (formerly P. carinii) are common but are of very low virulence. They cause disease only in individuals with immnodeficiencies - in USA, unusual large number of cases of P. jiroveci pneumonia in previously healthy homosexual men in 1981 first led to the recognition of AIDS - acronym AIDS for acquired immunodeficiency syndrome was first used by CDC for diseaes that indicated a defect in cellular immunity in subjects with no apparent cause for low resistance to the diseases - the various opportunistic infections became as AIDS defining conditions - diseases that indicate a person AIDS - they help physicians in diagnosing AIDS - worldwide more than 35 million people have died of AIDS during the last three decade - over 37 million are currently living with AIDS - more people have died of AIDS than were killed by Plaque or Black death in Europe - sub-Saharan Africa is currently the most affected region, with 1 in 20 adults living with HIV - billions of dollars have been spent for the control of AIDS pandemic and the disease still cannot be cured and is far from conquered

HIV signs and symptoms

- almost everybody who gets infected with HIV develops HIV disease which is marked by slow destruction of the immune system which eventually ends in AIDS - first symptoms appear after an IP of 6 days to 6 weeks. - they are referred as to fluelike and include fever, headache, sore throat, muscle aches, and enlarged lymph nodes - some people develop a generalized rash - these symptoms constitute the acute retroviral syndrome (ARS), and coincide with high level of virus replication - these symptoms are often mild and subside within a month - many people with HIV disease never develop ARS or are asymptomatic - following acute illness, virus levels drop, and the disease enters an asymptomatic period that usually lasts for years. This is often referred to as clinical latency - during this time period virus continues to replicate, infecting and destroying helper T cells and macrophages - the concentration of virions in the bloodstream during this time remains relatively stable and is referred to as the HIV (Viral) set point - this set point, which is measured as HIV RNA in plasma, is important as it serves as predictor of disease progression - the higher the viral set point in an infected person, the more quickly he or she is likely to develop AIDS.

Hepatitis A

- also called infectious hepatitis is endemic around the world - introduction of an effective vaccine in 1995 significantly lowered the incidence of the disease Symptoms: acute illness with no known chronic form or carrier state - older children and adults with the disease develop jaundice, fever, fatigue, clay colored feces and vomiting after an incubation period of about 1 month - most young children of less than six years old and many older children (ages 6 to 14) are asymptomatic - about one in five infected adults requires hospitalization - most patients recover within 2 months, but some require up to 6 month for recovery Causative agent: Hepatitis A virus (HAV), naked, single stranded RNA virus of the picornaviridae - also called hepatoviral and there is only one serotype Pathogenesis: the liver is the main site of replication and only tissue known to be damaged by the infection - the virus is released into the bile and eliminated with the feces epidemiology: spreads by fecal-oral route mainly through contamination of hands, food or water - many outbreaks have been traced to resturants where infected food handlers failed to wash their hands - eating raw shellfish is a common source of infection - a high percentage occurs in low socioeconomic groups of people because of crowding and poor sanitary conditions - groups which are at risk include day care centers, nursing homes residents, international travelers and individuals having sexual contact with an infected person - because of long incubation period, HAV can spread widely through a population before being detected treatment and prevention: no antiviral treatment but post-exposure prophylaxis (PEP) can prevent the disease from developing if given within two weeks of exposure to the virus - two PEP options are: A passive immunization with immune globulin and active immunity with a vaccine - passive immunization gives immediate but short term protection; however, vaccination provides long term protection - effective inactivated virus vaccine is available since 1995 - CDC recommends vaccination for all children between 1 and 2 years of age, and several high-risk groups such as people travelling to developing countries or in occupations that put them at high risk of exposure

Acute Necrotizing Ulcerative Gingivitis (ANUG)

- also known as Vincent's disease or trench mouth - it is a severe acute condition - red swollen gingiva - spirochete and rod shaped bacteria - signs and symptoms: pain, bleeding gums, abscessed and broken teeth, bone loss, and extremely bad breath - incubation period: undetermined - causative agent: probably a spirochete of the genus Treponema actin with other anaerobes - pathogenesis: the spirochetes and certain other anaerobes act synergistically to destroy tissues. The spirochetes invade tissue, causing necrosis and ulceration (disease was present among soldiers living in trenches in world war I and thus its name trench mouth) - epidemiology: associated with poor oral hygiene, malnutrition, immunodeficiency, or methamphetamine use (meth mouth). All ages are susceptible - treatment: local treatment with possible antibiotic therapy, followed by removal of plaque and tartar - prevention: avoid buildup of plaque

Treatment and prevention of shigellosis

- antibacterial medications are useful for treatment as they shorten duration of symptoms and time shigellas are excreated - however, many strains are resistant to antibacterial medications as they often have R plasmids that encode resistance to several antibacterial drugs - the spread of Shigella is controlled by using sanitary measures to avoid fecal contamination of food and water - two specimen of feces should be negative after medication before a person is allowed to return to a day care or food-handling job - shigellosis cases can be tracked through PulseNet, making it easier to detect outbreaks - currently no vaccine is available

Pathogenesis of CDI

- antibiotic treatment is the primary risk factor for CDI - two important toxins: toxin a and toxin b Antibiotic treatment -> reduced gut microbiome -> C. difficile infection -> Flagyl (metronidazole) or Vancomycin --> cure (75%) OR Recurrance (25%) -> back to antibiotics

blood and lymphatic infections

- the cardiovascular system is composed of heart, blood vessels and blood - the lymphatic system consists of lymph, lymph vessels, lymph nodes and lymphoid organs (tonsils, appendix, and spleen) - both systems are normally sterile - blood and lymphatic systems allow physiological regulation of temperature, nutrients and oxygen to the tissues - carry away the waste products from tissues - may be sued to permit systemic spread of microbes and their toxins and that can have desvastating effects - different blood infections are known as bacteremia, viremia and fungemia - when illness results due to a circulating agent or its toxin, it is referred to as sepsis, septicemia, or blood poisoning - in septicemia, blood pressure falls to such a low level that blood flow to vital organs is insufficient to maintain their functioning and the condition is called septic shock

treatment and prevention of HIV disease

- as scientists learned more about HIV, treatment and preventions options have improved dramatically - improved anti-HIV therapy, as well as better treatment and prevention of opportunistic infections, has significantly slowed the progression of HIV disease - the treatments have also prolonged life once AIDS develops, decreasing the number of deaths due to AIDS - anti-HIV medications used to treat HIV infections are called antiretroviral (ARVs) - ARVs are designed to block replication of the virus, but do not affect viral nucleic acid (provirus) already integrated in the genome of the host cells - the most commonly used ARVs are entry inhibitors, reverse transcriptase inhibitors, integrase inhibitors and protease inhibitors - reverse transcriptase inhibitors include nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). - unfortunately, a significant problem with ARVs is that HIV quickly develops resistance to the medications

viral disease of the lower digestive system - liver

- at least five different hepatitis viruses ( a,b,c,d, and e) cause hepatitis (inflammation of liver) but A, B and C viruses are responsible for most viral hepatitis. - the hepatitis viruses are unrelated to each other, but all damage the liver and cause similar signs and symptoms during an acute infection - the most noticeable sign in all hepatitis is jaundice- yellowing of the skin and the whites of the eye - the hepatitis patients should avoid alcohol, acetaminophen and other chemicals known to damage the liver - some disease including yellow fever and infectious mononucleosis can also damage the liver.

Infective Endocarditis (IE)

- bacterial disease of the blood and lymphatic system - endocarditis: infection/inflammation of the heart valves or inner surfaces of the heart - predisposing factors include use of indwelling catheters, underlying heart defects or injected drug abuse - some types of IE progress gradually and referred as sub-acute bacterial endocarditis (SBE) - other types of IE have a more rapid progression and referred to as acute bacterial endocarditis - acute bacterial endocarditis starts abruptly with fever and usually an infection such as pneumonia is present - virulent species of Staphylococcus aureus and Streptococcus pneumoniae are usually the cause - they produce a rapidly progressive disease often with valve destruction and formation of abscesses in the heart muscle, leading to heart failure - septicemia is caused by both gram negative and gram positive bacteria dn other infectious agents - organisms with little virulence usually cause subacute bacterial endocarditis and it has more protracted course signs and symptoms: fever, loss of energy over a period of weeks or months; sometimes a stroke incubation period: poorly defined, usually weeks causative agent: staphylococcus aureus or S. epidermidis, enterococci, streptococci including oral viridans streptococci (normal flora) pathogenesis: normal microbiota or organisms from an infected body site enter bloodstream; turbulent blood flow causes formation of a thin clot that traps circulating organism; a biofilm forms, protecting the organisms from phagocytes pieces of clot break off, blocking blood vessels, leading to tissue death epidemiology: people at risk are mainly those with heart abnormalities, including artificial valves or damage from rheumatic fever, may develop after dental procedure or other situations that cause bacteremia, injected drug abuse. treatment: a combination of antibiotics prevention: in certain cases, administration of antibiotic immediately before anticipated bacteremia, such as before dental work.

Clostridium difficile infection (CDI)

- caused by endospore forming, gram positive bacillus clostridium difficile that is an obligate anaerobe - C. difficile produces exotoxins that are pathogenetic to a variety of mammalian hosts - C. difficile infection ranges in severity from mild diarrhea to fulminant colitis (inflammation of colon) and death - sometime C. difficile infection causes patchy area on the colon called pseudomembrane - antimicrobial use is the primary risk factor for development of CDI because it disrupts normal bowel flora and promotes C. difficile overgrowth

Enterotoxigenic E. coli (ETEC) strains epidemiology

- common cause of infants diarrhea in developing countries and traveler's diarrhea in visitors - infectious dose is relatively high, so they typically do not spread by direct contact - ETEC are species-specific and those that infect animals cause significant mortality in young livestock (cattle and pigs)

bacterial diseases of the lower digestive system

- diarrhea can be copious and water (the runs) with infections of the small intestine, or in smaller amounts (the squirts) containing mucus, pus and sometime blood when large intestine is involved - Dysentery: diarrheal illnesses when pus and blood are present in the feces - some intestinal bacterial pathogens first established an intestinal infection then spread systemically. This causes enteric fever, characterized by systemic signs such as shock - enteric fever is generally seen with certain strains of Salmonella eg. Typhoid fever

symptoms of gastroenteritis

- diarrhea, loss of appetite, nausea and vomiting, and sometimes fever or any combination of these symptoms - diarrhea, dysentery, vomiting, abdominal pain

digestive system infections

- digestive system compasses two general components - the digestive tract - accessory organs (salivary glands, liver and pancreas) - most microbes that inhibit the digestive tract live in harmony with the host as normal flora, but the balance in this complex ecosystem is delicate - the mucus membrane only a single layer thick separates the microbial population from the underlying tissues - the damage of mucous membrane allows penetration of resident microbes - ingested pathogens often have mechanism to breach intact barriers - the digestive system is one of the major routes for invading microbial pathogens to enter the body - the upper digestive system includes the mouth, salivary glands, esophagus and stomach

anatomy and physiology of blood and lymphatic system

- infections of the heart valves, muscle and pericardium, although not very common, may be severe in nature as they affect the vital function of blood circulation - infections of the arteries is unusual - aorta may be severely weakened by the syphilis infection - atherosclerosis: hardening and narrowing of arteries. possible role of bacteria and viruses - the lymphatics take up foreign materials (microbes, toxins and other Ags) from tissues and transport them to lymph nodes - the foreign material and pathogens are trapped in lymph nodes and immune responses are mounted against them - sometime when a hand or foot is infected, a streak of red color becomes visible and may spread up the limb from the infection site - the streak represents the course of inflamed lymphatic vessels in response to the infectious agent - infection of lymphatics is called lymphangitis - spleen cleanse the blood as lymph nodes cleanse the lymph and provides an immune response to microbial invaders - phagocytes present in the spleen remove aging or damaged RBCs, bacteria and other foreign material from the blood - other functions of spleen are to mount immune response to microbes and produce new blood cells in certain situations - spleen enlarges in a number of infectious diseases, such as infectious mononucleosis and malaria

Oral Herpes Simplex

- extremely widespread disease with many manifestations - disease in its most common form begins in the mouth and throat - esophagus involvement suggests AIDS or other immunodeficiency - the infection persists for life and a virus is transmissible with saliva - it is usually insignificant but in some cases has tragic consequences especially in newborn infants or people with immunodeficiency - recurrent disease is called herpes simplex labialis, also known as cold sores or fever blisters - so painful that it is difficult to eat and drink - signs and symptoms: initial infection- fever, ulcerations of the mouth and throat. Recurrences- itching, tingling, or pain usually on the lip, then blisters that break, leaving a painful sore. - incubation period: 2 to 20 days - causative agent: herpes simplex virus (HSV), usually type 1 (enveloped double-stranded DNA virus) - pathogenesis: virus multiples in the epithelium and destroys the cells. An immune response limits the infection, but HSV DNA persists in sensory nerves. This DNA becomes the source of infectious virions that are carried to the skin or mucous membranes, usually of the lip, causing recurrent sores. * multinucleated giant cells * intranuclear inclusion bodies * stresses include mentation, sunburn and illnesses with fever - epidemiology: widespread distribution; transmitted by close physical contact. Blisters contain large umbers of infectious virions. Saliva of asymptomatic people can be infectious (one in three Americans suffers from cold sores. the initial infection with HSV typically occurs during childhood. infects up to 90% of some US populations) - Treatment: medications that target HSV DNA polymerase can shorten the duration of the symptoms or prevent recurrences. - prevention: sunscreen can prevent recurrences due to ultraviolet exposure

Sporadic viral encephalitis

- few widely scattered cases occur all the time - usually due to herpes simplex virus but other viruses such as mumps, measles and infectious mononucleosis are occasionally involved - most cases are due to activation of latent virus - mostly patients recover from the disease but are left with permanent damage such as epilepsy, paralysis, deafness, or difficult thinking - no preventive measures for herpes simplex encephalitis - medication given promptly can shorten the illness and improve the outcome

Helicobacter pylori Gastritis

- gastritis means inflammation of the stomach - bacterial cause of gastritis was identified around 1980s and its link with ulcers and gastric malignancy was established - Barry Marshall, one of the scientists who discovered the bacterium, intentionally drank a culture of H. pylori and developed the disease - signs and symptoms: infections are often asymptomatic, peptic ulcers can cause abdominal pain, tenderness, and bleeding. Gastritis can result in belching, bloating and sometime vomiting - incubation period: usually undetermined - causative agent: Helicobacter pylori, a curved, gram negative, microaerophilic bacterium, with multiple polar flagella covered by sheaths - pathogenesis: H. pylori cells survive stomach acidity by producing urease and burrowing within the stomach's mucous coating. Bacterial products and inflammation damage the mucosal layer, which can lead to peptic ulcers. Cancer rarely develops, but most with stomach cancer are infected with H. pylori. urea is normally found in gastric juices because it is released as proteins are degraded. Breath test is used for its diagnosis. - epidemiology: probably fecal-oral transmission. incidence increases with age - treatment: a combination of antibiotics and a medication that inhibits stomach acid production. - prevention: no proven preventive

Kissing disease (infectious mononucleosis, mono)

- high incidence among people between the age of 15 and 24 years (students) - lymphocytes and monocytes are collectively called peripheral blood mononuclear cells - this disease is characterized by increased mononuclear cells in the peripheral blood causative agent: Epstein-Barr virus (EBV) named after its discoverers - it is a double stranded DNA virus of the herpesvirus family - EBV can immortalized immature B cells, and can result in Burkitt's Lymphoma Incubation period: 1 to 2 month symptoms: flu like symptoms, including fever, sore throat covered with pus, fatigue, enlargement of spleen and lymph nodes - in most cases, the fever and sore throat are gone in about 2 weeks, and enlarged lymph node in 3 weeks - persons may return to school or work after 4 weeks but fatigue may persist for several months - but in some cases, severe exhaustion and difficulty in concentrating which prohibit from normal activities for months pathogenesis: productive infection of epithelial cells of throat and salivary ducts; latent infection of B lymphocytes; hemorrhage from a ruptured spleen is rare but serious complication - the proliferating lymphocytes are responsible for the large number of mononuclear cells epidemiology: spread by saliva; lifelong recurrent shedding of virus into saliva of asymptomatic, latently infected individuals - no animal reservoir - mouth to mouth kissing is an important mode of transmission in young adults, so called kissing disease Prevention and treatment: antiviral acyclovir and famciclovir inhibit productive infection; however, they do not have any activity against the latent infection - analgesics (pain relievers) can be used to reduce localized symptoms - avoid saliva from other person and objects (tooth brushes or drinking glasses) contaminated with another's saliva - no vaccine is available

lower digestive system infection

- hundreds of thousands of children around the world die of diarrheal illnesses each year - most of the individuals die of diarrhea are infants, but no age group spared - fatal cases are less common in America compared to developing countries, but millions of diarrhea cases do occur annually in USA - some physicians refer diarrheal disease as gastroenteritis while others use the term stomach flu - diarrheal illness is a common result of bacterial infections; however, some viruses can also cause it - bacteria also use the intestine as portal of entry to rest of the body, thereby causing other types of infection - incubation time usually 1 to 2 days - how are these infections causes? toxins, epithelial cell damage, cell invasion - treatment: rehydration, antibiotics, vaccines

Enteropathogenic E. coli (EPEC) strains epidemiology

- important cause of chronic diarrhea in infants and outbreaks in hospital nurseries and bottle fed infants

treating CDI

- stop the use of antibiotics. If this is not an option and recurrent infections occur, the use a different antibiotic - vancomycin and metronidazole are common alternative - fidaxomicin, a narrow spectrum antibiotic with less effect on the normal intestinal microbiota, was approved in 2011 to treat CDI - human fecal transplantation/ fecal microbiota transplant (FMT) from healthy donor is a promising treatment

pathogenesis of Shigellosis

- invasion of and multiplication within intestinal epithelial cells; death of cells, intense inflammation and ulcerations of intestinal lining (causes signs of dysentery) - some strains of Shigella dysenteriae produce a potent Shiga toxin, a A-B toxin - shiga toxin enters the blood and then the B portion binds to endothelial cells that line the small blood vessels, particularly in the kidneys - this allows the A subunit to then enter the cells where it halts the protein synthesis which leads to cell death - Shiga toxin is important because it is responsible for hemolytic uremic syndrome (HUS) an often fatal condition that can follow S. dysenteriae dysentery - In HUS, RBCs break up in the tiny blood vessels, resulting in anemia and kidney failure - symptoms of HUS sometimes include paralysis or other signs of nervous systems injury - Shiga toxin is also produced by strains of Escherichia coli (E. coli O157:H7) that cause HUS

Salmonella Gastroenteritis

- is caused by numerous serotypes of Salmonella enterica and can be acquired from many animal sources - in USA about 1.2 million cases per year resulting in about 400 deaths - large outbreaks are usually due to commercially distributed foods contaminated by animal feces Signs and symptoms: - incubation time: 6 hours to 3 days - generally characterized by diarrhea (sometime bloody), abdominal cramps, nausea, vomiting, headaches and fever - the disease is usually short-lived and mild, but that varies depending on the virulence of the infecting strain and the number of cells infested

Hansen's disease (Leprosy)

- it is relatively a minor problem in Western world at present but used to be common in Europe and America - it is mainly a problem in tropical and underdeveloped countries with an estimated 600,000 active cases - about 200 cases per year in the US causative agent: Mycobacterium leprae, aerobic, acid fast, non culturable rod shaped bacteria - grows very slowly with a generation time of about 12 days - typically stained in beaded manner - cannot grow in the absence of living cells (footpad of mice) - can be grown in armadillos and monkeys incubation period: 3 moths to 20 years; usually 3 years symptoms: disease develops gradually, generally with the onset of increased or decreased sensation in certain areas of skin which typically have increased or decreased pigmentation - these areas enlarge and thicken. They lose hair sweating ability and all sensation - the nerves of the arms and legs become visually enlarged with accompanying pain, which later change to numbness, muscle wasting, ulceration and loss of fingers or toes - changes are most obvious in the face, with thickening of the nose and ears and deep wrinkling of the facial skin - collapse of the supporting structure of the nose occurs with accompanying congestion and bleeding pathogenesis: invasion of small nerves of skin, multiplication in macrophages; course of disease depends on immune response of host; in tuberculoid leprosy, activated macrophages limit the growth of the bacterium but the damage to infected nerve cells leads to disabling deformities; in lepromatous leprosy, cell mediated immunity fails, allowing unrestrained growth of M. leprae - only known pathogen which infects peripheral nerves - two types: tuberculoid leprosy and Lepromatous leprosy Epidemiology: direct contact with M. leprae from mucous membrane secretions (nasal secretion of lepromatous case) treatment: antimicrobial medication prevention: no vaccine

Lyme disease

- it was first reported from Lyme, Connecticut in mid 1970s and cause of the disease was established in ticks by Dr. Willy Burgdorfer at Rocky mountain lab, Montana in 1982 - about 30,000 new cases every year, making it the most common vector-borne disease in the US signs and symptoms: early localized infection: enlarged rash that resembles a bull's eye develops at the site of the bite; lymph node enlargement near bite, flu like symptoms. Early disseminated infection: heart and nervous system involvement. Late persistent infection: chronic arthritis and nervous system impairment - Erythema migrans: the characteristic rash is the hallmark of Lyme disease but is present in only two thirds of the cases Incubation period: several days to several weeks causative agent: Borrelia burgdorferi, a spirochete Pathogenesis: spirochetes injected into the skin by an infected tick multiply and spread radially; spirochetes enter the bloodstream and are carried throughout the body; immune reaction to bacterial antigens causes tissue damage - organisms generally do not cross placenta of pregnant women - affected joints have high concentrations of highly reactive immune cells and immune complexes epidemiology: spread by the bite of ticks, lxodes species, usually found in association with animals such as white-footed mice and white-tailed deer living in wooded areas -Ixodes sp: called black legged tick - because of their small size these ticks often feed and drop off their host without being detected - zoonotic disease and widespread in US - ticks are mostly active from May to September and so the is the Lyme disease Treatment: early treatment with appropriate antibiotic; prolonged antibiotic therapy in chronic cases Prevention: avoiding ticks, protective clothing, tick repellents. No vaccine

digestive system infections mouth

- large collections of bacteria can build up on teeth in a biofilm and these masses of bacteria are called dental plaque - overtime, mineral salts deposit in the plaque, creating a crusty substance called dental calculus or tartar - plaque organisms consume oxygen and create conditions that permit the growth of strict anaerobes - dental plaque, gingival crevices and fissures in the teeth provide such habitats - saliva, which contains sIgA, lysozyme and lactoferrin, plays an important role in protecting the oral cavity

Salmonella pathogenesis

- like V. cholerae, most Salmonella serotypes are killed by stomach acid, and thus large number of bacteria are needed to establish infection - in the distal small intestine, the bacteria attach to specific receptors on the surface of intestinal epithelial cells - contact with epithelial cells activates type III secretion system that transfer bacterial effector proteins into the epithelial cells and bacteria is taken in by endocytosis 0 the bacteria multiply within phagosome and discharged from the base of the cells by exocytosis; however, some escape the phagosome and multiply in the cytoplasm - macrophages and neutrophils take up any bacteria that are released, but macrophages are often destroyed as a result - the infection remains localized and inflammatory response increases epithelial cell fluid secretion, causing diarrhea

Salmonella epidemiology

- most cases of Salmonella gastroenteritis originate from a nonhuman animal source; the bacteria live in the intestinal tract of different types of domestic animals - spread by infestation of food contaminated by animal feces, especially poultry - poultry often carry S. enterica and eggs can be contaminated - children are infected by colonized but apparently healthy pets (lizards, snakes, and turtles) that shed bacteria in feces - the disease has been on the rise, largely due to mass production and distribution of food.

tooth decay (dental caries)

- most common chronic disease of human beings and is the main reason for tooth loss - signs and symptoms: none until advanced disease; then roughness, discoloration, broken tooth, throbbing pain - incubation period: months before cavity is detectable - causative agent: cariogenic bacteria in dental plaque, particularly Streotococcus mutans (thrive under acidic conditions below pH 5 - pathogenesis: bacteria in plaque produce acid from dietary sugars; slowly dissolves the tooth enamel; sucrose is critical for cariogenic plaque formation (causes tooth decay) - epidemiology: worldwide distribution, incidence depending on dietary sucrose, natural or supplemental fluoride. More prevalent in the young - treatment: mechanical removal of plaque. - Prevention: sealing pits and fissures in children's teeth, restriction of dietary sucrose, supplemental fluoride (fluoride makes enamel harder and more resistant to dissolving in acid)

Bacterial nervous system infections

- most common infections involve bacterial growth within the CNS and meninges causing meningitis and abscesses - peripheral nerves can be infected as in case of Hansen's disease/leprosy - meningitis usually induced an intense inflammatory response with a marked accumulation of white blood cells in the CSF and swelling of the brain tissue - the case fatality rate for untreated bacterial meningitis can approach 100% - three important causative organisms or meningitis are 1. streptococcus pneumoniae 2. Neisseria meningitidis 3. Haemophilus influenzae - these 3 bacteria species are uncommon causes of meningitis in newborns as most mothers have Abs against these microbes that cross placenta and protect baby - meningitis in infants during the first month is usually due to bacteria that colonize the mother's birth canal e.g. Streptococcus agalactiae, a group B streptococcus which colonizes the vagina in 15 to 40% of pregnant women - women are tested for the presence of S. agalactiae in the late pregnancy and treated with antimicrobials if positive - newborn babies are susceptible to gram negative robs e.g. E. coli from mothers intestinal tract because mother's Abs to the organisms are of IgM class, which do not cross the placenta and cannot confer immunity to the infant - there are 6 antigenic types of Haemophilus influenzae labeled a through f but type b causes the most cases of serious disease - H. influenzae b polysaccharide (t-independent Ag) is covalently linked to a bacterial protein e.g. diphtheria toxoid (conjugate vaccine) and is used for children vaccination - use of conjugate vaccine resulted in dramatic decrease in meningitis and other complications caused by H. influenzae type b. - streptococcus pneumoniae (pneumococci) is the leading cause of meningitis in adults - prominent cause of otitis media, sinusitis and pneumonia conditions that often precede pneumococcal meningitis - N. meningitidis (meningococcus) differs from other causes in that it is often responsible for epidemics of meningitis

preventing transmission via blood and blood products (HIV)

- most people with HIV do not know they are infected; thus it is advisable to consider all blood as HIV infected - screening of potentially blood donors for HIV infected - screening of potentially blood donors for HIV risk factors and their blood for antibody to HIV - screening tests have reduced the risk of HIV transmission from artificial insemination and organ transplantation - sterile needle and syringe exchange programs help prevent the spread of HIV among injected drug abusers - infectious HIV persists in blood or plasma samples taken from AIDS patients for at least 1 week - HIV on contaminated objects and surfaces is inactivated by disinfectants and heat (56 degrees Celsius or more for 30 minutes) - household sodium hypochlorite 5.25% bleach diluted 1:10 is a cheap and effective disinfectant for general use

Salmonella treatment and prevention

- most people with Salmonella gastroenteritis recover without antimicrobial treatment - antimicrobial medication usually is not advised except in systemic tissue or bloodstream infections - antimicrobial resistant strains can be a significant problem - prevention relies on adequate cooking and proper handling of food - surveillance and tracing contaminated sources using PulseNet are also important

STEC strains epidemiology

- mostly O157:H7 E. coli but other serotypes also involved - can be foodborne, and epidemics have involved ground beef, unpasteurized milk, apple juice, bean sprouts, and green leafy vegetable - inadequately cooked hamburgers had been blamed as source of many of STEC outbreaks - food and drink contaminated with cattle feces have been the source of many epidemics - cattle harbor O157:H7 without any ill effects and an important reservoir - infectious dose of STEC stains is very low so in addition to foodborne transmission, they are easily spread by direct contact

Mumps

- mumps in an acute viral illness that preferentially attacks parotid glands - was very common in US previously but now very rare because of routine childhood vaccination - signs and symptoms: fever, headache, loss of appetite, followed by painful swelling of parotid glands (spasm of the underlying tissue makes it difficult to chew or talk. Some cases do not show involvement of parotid glands and show other symptoms). Meningitis can occur. Painful enlargement of the testicles; pelvic pain in women - headaches and stiff neck indicates meningitis which is a common manifestation of mumps - pregnant women with mumps usually miscarry, but birth defects do not result - serious consequences are rare and are most likely happen in older people which include deafness and encephalitis - incubation period: generally 15 to 21 days - causative agent: mumps virus, a single-stranded RNA virus (member of paramyxoviridae family) - pathogenesis: the virus initially replicates in the upper respiratory tract, then spreads throughout the body in the bloodstream. In the salivary glands, the virus multiples in the cells that line the ducts and kills them. Inflammatory responses cause swelling and pain. (infection occurs when virus-laden droplets of saliva are inhaled by a person lacks immunity to mumps.) - epidemiology: humans are the only source of the virus. infections are often asymptomatic, so the disease can be spread unknowingly. - treatment: no antiviral therapy is available - prevention: an effective attenuated vaccine is available.

a successful HIV vaccine

- must induce both mucosal and bloodstream immunity, because HIV disease is primarily sexually transmitted - should get around the problem of HIV antigenic variability - should stimulate cellular and humoral responses against virulence determinants - should induce neutralizing antibodies

normal flora of the intestines

- the bacteria make up about one-third of the fecal weight - numbers of anaerobic bacteria, notably members of genus Bacteroides make up about 99% of the microbial population - the remaining microbes are facultatively anaerobic, primarily E. coli and other member of Enterobacteriaceae - fecal organisms are an important source of opportunistic pathogens, especially for the urinary tract - intestinal bacteria synthesize several useful vitamins and prevent colonization of the intestines by pathogens - antibiotic treatment (especially with broad-spectrum) results in dysbiosis and antibiotic-associated diarrhea - in some case this types of diarrhea is caused by toxin producing strains of Clostridium difficile, which colonizes intestine following antibiotic therapy

nervous system anatomy and physiology

- nervous system disease affect the people's ability to move, to feel, or to think, depending upon the neuronal branch affected and can be very severe in nature - brain and spinal cord make up the central nervous system (CNS) while peripheral nervous system (PNS) is made of nerves composed of bundles of axons that carry information to and from the CNS - peripheral nerves (motor and sensory) innervate almost every tissue and connect to the CNS - motor nerves carry messages from the CNS to various parts of the body and make them act - sensory nerves transmit sensations like heat, pain, light and sound from the periphery to the CNS - all nerves are made up of axons and transmit information along the nervous stem - the nerves sometime may regenerate if cut or damaged, but they can not e repair if killed as in poliomyelitis - some viruses and toxins can move from one place to another through nerve fibers - some herpes viruses remain latent in nerve cells for many years - encephalitis- generalized inflammation or infection of the brain - the brain has four cavities called ventricles, which are more filled with a clear fluid called cerebrospinal fluid (CSF) - CSF bath both the brain and the spinal cord and is normally acellular and sterile - three membranes called meninges cover the surface of brain and spinal cord - outer membrane: dura and two inner membranes: arachnoid and pia which are separated by a space through which CSF flows - inflammation or infection of meninges is called meningitis Meningoencephalitis: when both meninges and brain are infected - CNS infection diagnosis normally involves lumbar puncture to withdraw a sample of CSF - the identification of causative agent of CNS infection in CSF helps in prescribing a proper antimicrobial treatment

HIV vaccine prospects

- no approved vaccine against HIV is yet available - if available, HIV vaccine could be used in two ways: preventive vaccine, therapeutic vaccine - it is extremely difficult to produce an effective HIV vaccine - despite difficulties and number of challenges for developing HIV vaccine a great deal of research is still aimed at this effort and the hope for effective vaccine is still there

bacterial disease of the blood and lymphatic systems

- not very common but are always dangerous - usually the bacteria from an infected area in the tissue are carried into the bloodstream by lymph - infective endocarditis (IE)

Treatment and prevention

- oral rehydration therapy (ORT): giving appropriate fluids by mouth-can be used to counteract the loss of fluid and electrolytes (salt) from diarrhea - an oral rehydration salts (ORS) solution that consists of water, glucose and electrolytes can be highly effective life saver in severe diarrheas regardless of cause - WHO has also developed a list of recommended home fluids (RHF) that can be used to prevent dehydration - if oral rehydration can not be tolerated e.g. if patient is vomiting then intravenous hydration may be required - antibacterial medications are mostly not helpful. They often prolong the illness as they depress the normal flora - however, antibacterial medications can be life saving in cases where the bacterium invades beyond intestine - for children in developing countries, zinc supplements decreases the length and severity of diarrheal disease - sewage treatment, hand washing, and chlorinating drinking water are important measures to control diarrheal diseases - in the USA, surveillance using PulseNet, a DNA subtypes resource, helps track illness caused by specific intestinal pathogens - this helps track illness caused by specific intestinal pathogens - this helps public health agencies detect foodborne outbreaks so that intervention strategies can be applied - severe water diarrhea can be fatal unless the lost fluid is replaced promptly - only a few vaccines are available, and these are pathogen specific - most of vaccines are not very effective as they fail to elicit a sufficient sIgA response to limit pathogen colonization

normal flora of mouth

- over 600 types of bacteria in the mouth, but Streptococcal species (obligate fermenters) that produce lactic acid as a by-product of sugar metabolism, are the most numerous in the mouth - the microbes attach to specific receptors on the host cells lining different parts of the mouth - the difference in the distribution of various receptors in the mouth account for the distribution of various species of Streptococci in different parts of the mouth - the foul-smelling end products of anaerobic metabolism are associated with halitosis, also called as bad breath

Black Death/Plague

- plague was responsible for the death of about one fourth of the Europe population between 1346 and 1350 - crowded conditions and a large rat population played the major role - plque is a potential bioterrorism disease, listed as category A signs and symptoms: high fever, large lymph nodes called buboes, skin hemorrhages; sometimes bloody sputum (if lungs are involved) incubation period: usually 1 to 6 days causative agent: Yersinia pestis, a gram negative rod, a member of the Enterobacteriaceae with multiple virulence factors (intracellular, safety pin appearance) pathogenesis: enters the body with bit of infected flea or inhalation; bacteria taken up by macrophages. Intracellular environment causes the bacterial cells to produce multiple virulence factors that allow attachment to host cells, and provide defense against the immune system. Three forms of plaque: 1. bubonic 2. septicemic 3. pneumonic epidemiology: endemic in rodents and their fleas, particularly in the western US. Bubonic plague is transmitted by fleas; pneumonic plaque can be transmitted person to person in respiratory droplets. Pneumonic plague is the most dangerous because Y. pestis is fully virulent at the time of transmission treatment: prompt diagnosis and antibacterial treatment necessary to prevent high mortality. prevention: currently no vaccine available; new vaccines are under development. avoiding contact with wild rodents and their burrows. Insecticides and rat control

Enteroinvasive E. coli (EIEC) strains epidemiology

- primarily cause disease in young children in developing countries and usually do not spread by direct contact - humans appear to be the only source of infection

cholera toxin

- the bacterium produces a potent enterotoxin, cholera toxin (CT), which is responsible for the symptoms of cholera - CT is a heat-labile toxin and is a classic A-B toxin - B fragment has no toxic activity but binds to specific receptors on the microvilli of epithelial cells, allowing A portion to enter the cell which is responsible for toxicity - A fragment locks G protein in the active mode. This results in the activation of enzyme adenylate cyclase which converts ATP to cAMP which in turn causes secretion of water and electrolytes from epithelial cells - CT is encoded by a bacteriophage that infects V. cholerae, an example of lysogenic conversion - the same bacterial gene regulates the synthesis of cholera toxin and the pili so both these factors which are required for the disease production are synthesized simultaneously

TSE in humans

- rare in humans, occurring in only 0.5 to 1 cases per million - most cases occur sporadically as Creutzfeldt-Jacob disease - another form, kuru, is associated with cannibalism, as formerly practiced by some New Guinea natives symptoms: behavioral changes, anxiety, insomnia and fatigue, progressing over weeks or months to the hallmarks of the disease which include muscle jerks, lack of coordination and dementia. - effected people suffer deteriorating intellectual function, impaired judgment, memory loss and loss of normal muscle function, ending in death usually within a year time incubation period: usually many years causative agent: in 1997, Dr. Stanley Prusiner received a Nobel Prize for his work on the causative agents of these diseases known as proteineous infectious particles or prions - Prions: misfolded form of a normal cellular protein PrPc Main characteristics of prions: increase in quantity during incubation period of the disease. - resistant to UV and ionizing radiation - resistant to heat, formaldehyde and disinfectants - relatively resistant to proteases - lack nucleic acids and so resistant to nucleases - much smaller than the smallest virus - identical amino acid sequence to a normal cellular protein, but folded differently pathogenesis: prions replicate in dendritic cells in various parts of the body (spleen and lymphoid tissues) by converting normal proteins to more prions - transmission to the brain, aggregation into insoluble masses (plaques) outside the nerve cells causing cell malfunction and cell death epidemiology: human to human transmission by corneal transplantation and by contaminated surgical instruments, probable transmission to human by eating contaminated beef - Sporadic Creutzfeld- Jacob disease in those over age 45 years; median age of mad cow associated variant cases only 28 years prevention and treatment: prions are inactivated by autoclaving in concentrated (1N) sodium hydroxide, no treatment, invariably fatal

Rotaviral gastroenteritis

- rotaviruses cause most cases of viral gastroenteritis in infants and children - before the vaccine was available (2006), rotavirus infections in USA resulted in half a million emergency room and clinic visits and over 55,000 hospitalization each year - worldwide more than 200,000 children still die from rotavirus infection each year symptoms: incubation period of 24 to 48 hours - start abruptly with vomiting and slight fever, followed by profuse watery diarrhea - symptoms are usually gone in about a week - unless adequate replacement fluid is given, death can occur from dehydration causative agent: rotaviruses represent a major subgroup of the reoviridae family. Its name came from rota means wheel - rotaviruses are naked viruses and have a double-walled capsid pathogenesis: infect mainly the epithelial cell lining the upper part of the small intestine - this causes cell death and decreased production of digestive enzymes 0 the damaged epithelial lining fails to absorb fluids, leading to watery diarrhea - one of viral proteins functions as enterotoxin, causing fluid secretion epidemiology: spread by the fecal-oral route. They cause about 25% of traveler's diarrhea cases - childhood epidemics generally occur in winter in temperate climates - generally, most children are infected before 5 years of age - rotaviruses that infect a wide variety of young wild and domestic animals do not cause human disease treatment and prevention: no direct treatment of rotavirus infection - infants and children are given IV fluids to prevent dehydration - hand washing, disinfectant use and other sanitary measures help limit the spread of rotaviruses - attenuated vaccines approved since 2006, administered to infants, resulted in a substantial decline in this disease

Salmonella gastroenteritis causative agent

- salmonellas are motile gram negative rods and are member of enterobacteriaceae - more than 2,400 serotypes based on differences in somatic (O), flagellar (H), and capsular (K) antigens - two species: S. enterica and S. bongori (this species rarely isolated from humans) - the serotype of salmonella strain is significant both an epidemiological and a disease standpoint - certain serotypes cause enteric fever instead of gastroenteritis and thus the serotype is often included with the name e.g. Salmonella enterica serotype Dublin - for convenience, the name is often shortened, as in Salmonella Dublin - note that the serotype is not italicized, and the first latter is capitalized, which distinguishes it from species name - Salmonella serotype Typhimurium and Salmonella serotype Enteritidis are most commonly isolated in the US

gram negative septicemia epidemiology

- sepsis is mainly a healthcare associated disease - patients with impaired host defenses, cancer and other malignancies, diabetes and organ transplants are particularly vulnerable - increasing incidence of disease relates to: 1. increasing life span 2. antibiotic suppression of normal flora 3. immunosuppressive medications and 4. medical equipment such as catheter and respirators where biofilms readily develop

pathogenesis of gram negative septicemia

- septicemia almost always originates from an infection somewhere in the body other than the blood stream - changes in the body defenses as a result of medical manipulations such as dental work, surgery, placement of catheters etc allows microbes to infect the blood - septicemia/septic shock results from the presence of endotoxin in the bloodstream released from the outer cell walls of gram negative bacteria - the antibiotics used for treatment of these bacterial infections further enhance the release of endotoxin - symptoms result from excessive cytokine release (IL-1, TNF - a) from tissue macrophages and circulating leukocytes - the lung particularly has serious, irreversible damage because of its high number of macrophages and extensive lung damage often results in death

Viral disease of the blood and lymphatic systems

- several viral illnesses affect the lymphatic system and blood vessels - infectious mononucleosis - yellow fever - dengue fever - Ebola and Marburg viruses - chikungunya - zika virus - HIV disease, cause of AIDS, also affects the cells of the lymphatic system and causes lymph node enlargement

The pathogenesis of bacterial disease of the lower digestive system

- severe water diarrhea occurs as a result of rapid water loss and electrolytes from intestinal cells. This causes severe dehydration - because of the reduced blood volume, the blood flow may not be sufficient to keep vital organs working properly, a potentially fatal situation - invasion or cell damage elicits a strong inflammatory response - this primarily occurs in the large intestine and results in the pus and blood in the feces that characterize dysentery - proteins injected by type III secretion systems can also elicit an inflammatory response.

viral disease of upper digestive system

- some viral diseases involve the upper alimentary tract but produce more dramatic symptoms elsewhere in the body. - examples: * measles: Koplik's sports in the mouth, a dramatic skin rash and respiratory symptoms * chickenpox causes oral blisters and ulcers but s striking skin rash * infectious mononucleosis (mono, kissing disease) can cause multiple oral ulcers and bleeding gums but also cause enlarged lymph nodes and spleen - two vial diseases that have dramatic signs and symptoms involving the upper digestive system * oral herpes simplex (cold sores): characterized by painful oral ulcers * mumps: causes enlarged and painful parotid glands

bacterial diseases of lymph nodes and spleen

- the enlargement of the lymph node and spleen is a characteristic feature of diseases that involve the mononuclear phagocyte system - enlargement of lymph nodes and spleen (splenomegaly) normally occurs due to increased cell division and blood flow during an immune response - three examples of these diseases are: tularemia, brucellosis, and plague - these diseases are uncommon in the US, however, they are constant threat due to their widespread existence in animals - the best preventive method against these diseases is to understanding these disease their pathogenesis.

Microbial population of esophagus and stomach

- the esophagus has a relatively sparse microbial population - one reason for the relative lack of microbes is the sIgA containing mucus and saliva that bathe the lining of esophagus - the esophagus rarely becomes infected except in individuals with AIDS or other immunodeficiencies - the gastric juices are highly acidic and most bacterial cells cannot survive in the hostile environment of stomach. Thus, a normal empty stomach has few microorganisms

HIV and AIDS causative agent

- the human immunodeficiency virus (HIV) is a retrovirus, the common term for members of the Retroviridae family - HIV is an enveloped, single stranded virus which has duplicate copies of a single-stranded RNA genome - all retroviruses encode reverse transcriptase, an enzyme that uses RNA genome as template to make complementary DNA strand - there are two district types of HIV (HIV-1 and HIV-2) and they have only about 50% genetic similarity - most AIDS cases, in the US, and most other parts of the world are caused by HIV type 1 (HIV-1) and more is known about this virus - HIV-2 are prominent cause of AIDS in West Africa and causes a less severe form of the disease

microbial population of intestines

- the lower digestive system includes the small and large intestines as well as the pancreas and liver - many types of bacteria are killed by bile, but those adapted to live in intestinal tract resist its bactericidal effect - bile salts are used in selective media to isolate enteric bacteria - only small number of bacteria live in the upper small intestine because of the flushing action of rapidly passing digestive juices limits their ability to colonize surfaces - they are usually aerobic and facultative anaerobic Gram negative rods and some streptococci - the bacterial population increases as move toward the large intestine which contains about 10^11 bacteria per gram

how do enteric bacteria cause disease?

- the pathogenesis of bacterial intestinal disease involves different mechanisms - different strains of the same species can differ in way they cause disease and the same strain can employ more than one mechanism - many of the responsible genes are on plasmids, phages or other mobile genetic elements, which can be transferred from one species to another by horizontal gene transfer - attachment to the intestinal surface is often a prerequisite for infection, and this typically involves adhesins on pili

2. blood and blood products Epidemiology of HIV disease

- the second most important mode of transmission is through HIV infected blood and blood products - HIV can be spread among IV (intravenous) drug abusers who share hypodermic needles - it can also be transmitted to healthcare workers by needle stick but the risk is low (0.3%) - although HIV can be transmitted in whole blood and blood products such as plasma and clotting factors, these are not screened for antibodies suggests that the donor was infected, so product is not used

Preventing vertical transmission of HIV

- the spread of HIV from infected mother to newborn can safely be precented in two thirds of cases by treating mother during pregnancy with zidovudine (AZT) and newborn infants for 12 weeks - more potent and newer combinations of AZT and other antiretroviral (ARV) therapies are widely used and may be more effective - use of ARVs during breast feeding period, in the mother or the infant, or both, can reduce HIV transmission - elective caesarian section significantly reduces the risk of HIV transmission to newborn baby, probably by avoiding HUV containing fluids in the birth canal

HIV infection and AIDS

- the terms HIV and AIDS are not synonymous - a person can be infected with HIV but may not be ill - AIDS is only the end stage of a complex disease that has many signs and symptoms that precede immunodeficiency - Three important terms: HIV infection: when a person first contracts HIV, he or she has an HIV infection but may not be ill HIV disease: implies that HIV infection is causing signs and symptoms AIDS: the last stage of HIV disease, defined by decreased CD4+ lymphocyte (helper T cells) levels and the presence of specific opportunistic infections

Structure of HIV

- the virus envelope originates from the host cell membrane and encloses viral core - virion core is composed of capsid protein (p24), two copes of single stranded RNA genome and 3 viral enzymes 1. Reverse transcriptase (RT) 2. protease (PR) 3. integrase (IN) - these three enzymes are tightly associated with the RNA and are the targets for anti-HIV medications - different strains of HIV exist and can be divided in 4 groups. Group M (major) is the most common

Treatment and prevention of HIV

- to prevent resistance to medications, a combination of medications a cocktail called highly active antiretroviral therapy (HAART) or antiretroviral therapy (ART) is prescribed - current ART treatment consist of three drugs: 2 NRTIs and either a protease inhibitor or an NNRTI - in some cases, these medications are available in fixed-dose combinations - in many cases, this therapy can clear the patient's blood of detectable viral nucleic acid, stop progression of disease and even allow partial recovery of immune function - HAART/ART does not cure AIDS/HIV disease but delays the progression of HIV disease to AIDS - HAART/ART is used to improve the quality of the person's life, reduce the risk of other complicating diseases and lower the HIV set point (virus load) - HAART/ART treatment stop the production of virions but does not eliminate HIV provirus hidden in the host genome - when HAART/ART medication is stopped, viremia/viral set point rebounds to pretreatment levels - many HIV strains fail to respond to HAART/ART because they developed resistance to medication - toxic effects of the meidications are another limitation of anti-HIV therapy e.g. zidovudine (AZT) can cause anemia, low white blood cell count, vomiting fatigue, headache and muscle and liver damage - a big limitation of the use of anti- HIV HAART/ART medication is their very high cost which makes them unaffordable in many parts of the world - decreases in HIV drug prices and approval of three generic drugs by US FDA have made treatment available to more number of HIV patients worldwide - educating people including school children about HIV and how it is transmitted is a powerful weapon against the AIDS epidemic - people who are at increased risk for HIV disease are advised to get tested for HV and then they can ensure that they do not spread the virus to others - if HIV infection is detected earlier, prompt preventive treatment for infections and cancers that complicate the disease can be given - no approved vaccine against HIV infection prevention. Thus, prevention efforts must be aimed at avoiding transmission

infections of the teeth and gums

- tooth enamel beings to dissolve at about pH 5.5 - different types of bacteria in the plaque

Epidemiology lower digestive system

- transmission is by fecal-oral route which occurs by ingesting food/water contaminated with animal/human feces - sexual practices that lead to oral-anal contact can also transmit intestinal pathogens - intestinal pathogens sensitive to acid generally have a high infectious dose. In contrast, acid-resistant pathogens have a low infectious dose - disease cased by bacteria that have a low infectious dose are easily transmitted through direct contact as well as in contaminated foods or water - bacterial infections that have a high infectious dose are usually transmitted only in contaminated foods or water - people with low gastric acidity are more susceptible to intestinal infections

gram negative septicemia prevention and treatment

- treatment of sepsis is difficult, because it is a complex syndrome involving several host responses - antimicrobial medications directed against causative microbes are indicated for treatment - bactericidal antibiotics lyse bacteria, releasing endotoxin from gram negative bacteria and worsens the effects of sepsis - measures to correct shock and poor oxygenation - fluid replacement and support for organ dysfunction 0 prompt identification and effective treatment of localized infections in people with impaired immune responses - conditions like bedsores and pyelonephritis in patients with cancer and diabetes which commonly lead to septicemia can be prevented by taking proper care of the patient

Common infections of the lower digestive system

- vibrio cholerae - Escherichia coli (e. coli) - Shigella - salmonella - campylobacter - clostridium difficile

Viral diseases of the lower digestive system

- viral infections of the lower digestive tract affect all age groups, resulting in million of cases each year in USA alone - both alimentary tract ad accessory organ such as live are affected

it is extremely difficult to produce an effective HIV vaccine because:

- virus has multiple mechanisms to avoid the adaptive immune responses - critical HIV antigens change rapidly due to the high error rate of reverse transcriptase, meaning the antibodies produced against one antigenic variant do not protect against another - HIV causes syncytia formation, allowing the virus to pass directly from cell to cell without coming in contact with antibodies - lack of a good animal model for HIV and AIDS and it is difficult to test new vaccines for safety effectiveness

AIDS signs and symptoms

- when helper T cells drop to low levels, immunodeficiency develops, a stage that characterizes AIDS - with severe immunodeficiency, the individual contracts various opportunistic bacterial, viral and fungal infections or tumors that chacterize AIDS - these may include Kaposi's sarcoma, B-lymphocyte tumors, pneumocystis pneumonia, toxoplasmosis, cytomegalovirus disease and mycobacterial disease - as expected, at this stage of the disease symptoms vary widely according to the kind of infection - most people with AIDS also suffer with fever, weight loss, fatigue, and diarrhea a set of problems referred to as AIDS related complex (ARC) - person may suffer persistent enlargement of lymph nodes, a condition known as 'lymphadenopathy syndrome' (LAS) - without treatment, AIDS is fatal

Escherichia coli gastroenteritis pathogenesis steps

1- pathogenic strain of E. coli enters by the fecal-oral route, either directly from an infeccted person or with contaminated food or drink 2- most strains colonize the small intestine and produce watery diarrhea 3- others invade the large intestine and cause dysentery 4- some strains produce Shiga toxin, which is absorbed by the bloodstream and causes hemolytic uremic syndrome 5- the bacteria exit the body with feces

Six pathovars (pathogenic varieties) of E. coli

1. Shiga toxin producing E. coli (STEC) strains: - these strains also referred as enterohemorrhagic E. coli (EHEC) - STEC produce many potent toxins that cause death of intestinal epithelial by interfering with protein synthesis - toxins are closely related to shiga toxins of S. dysenteriae but unlike shigellas, STEC do not penetrate intestinal epithelium - the toxin production of EHEC depends on lysogenic conversion by a distinct bacteriophage - most of the strains identified in outbreaks belong to a single serotype O157:H7, but there are important exceptions - STEC typically colonize large intestine and cause A/E lesions - mostly bloody hemorrhagic diarrhea because of action of shiga toxins - about 5 to 10% infected people develop hemolytic uremic syndrome (HUS) 2. Enterotoxigenic E. coli (ETEC) - make pili that allow them to attach to and colonize the small intestine - ETEC produces one or more toxins. One such toxin heat labile toxin (LT) is nearly identical to cholera toxin in action and antigenicity 3. Enteroinvasive E. coli (EIEC): invade the intestinal epithelium, causing a disease similar to shigellosis 4. Enteropathogenic D. coli (EPEC): produce pili that allow them to colonize the small intestine, where they inject effector proteins that cause A/E lesions 5. Enteroaggregative E. coli (EAEC): grow in characteristic aggregations (bricklike) 6. Diffusely adhering E. coli (DAEC): grow as diffuse layer

typhoid mary

1900 to 1907 - worked as a cook in the New York City area for seven different families - first quarantine (1907-1910) - release and second quarantine (1915-1938)

Cholera

Cholera causes potentially fatal diarrhea. There have been seven cholera pandemics since 1800s - South America remianed cholera free for 100 years until 1991 when disease appeared in Peru. about 700,000 cases and 6,323 deaths were reported in South and Central America - introduction of cholera into Haiti in 2010 posed a new threat (over 300,000 cases and 5,000 deaths reported) - symptoms: the classic example of watery diarrheal disease - the diarrheal fluid can amount to 20L a day and because of its appearance has been described as rice water stool - vomit also occurs in most people at the onset of disease - many people suffer muscle cramps caused by loss of fluid and electrolytes. Several dehydration can lead to multiple organ failure and death

Escherichia coli gastroenteritis overview

Epidemiology: common in travelers; can be foodborne or waterborne; fecal-oral route transmission; some strains have an animal source Treatment: replacement of fluids and electrolytes (treatment of E. coli gastroenteritis varies according to symptoms and infecting strains) prevention: handwashing; pasteurization of drinks, thorough cooking of meats, Bismuth compounds help prevent traveler's diarrhea (Pepto-Bismol) - PulseNet helps track infections caused by E. coli O157:H7 - antibacterial medications are no longer routinely used as most cases are self-limiting. in promotes the development of resistant bacterial strains

Epidemiology of E. coli gastroenteritis

Just as the symptoms and pathogenesis of E. coli gastroenteritis depend on the infecting strain, so does the epidemiology

Toxoplasmosis

Signs and symptoms: usually asymptomatic in healthy individuals, but somtimes sore throat, fever, enlarged lymph nodes. Encephalitis may develop in immunodeficient individuals, resulting in confusion, poor coordination, weakness, paralysis, seizures, and coma. Fetal infections can result in stillbirth, birth defects, epilepsy, intellectual disability, retinitis - it rarely develops among healthy individuals but common in people with HIV disease incubation period: usually unknown causative agent: Toxoplasma gondii (Banana shaped protozoa), an apicomplexian protozoan infectious for most warm blooded animals. Sexual reproduction occurs in cats, the definitive hosts. infected cats discharge oocytes with their feces. When mature oocysts are ingested, a form of T. gondii is released that then penetrates host cells, develops into a rapidly multiplying form, and spreads throughout the body. As immunity develops, multiplication of the parasite slows, and tissue cysts are formed. Tissue cysts remain viable and infectious for the lifetime of the animal. pathogenesis: organisms penetrate host cells and multiply, causing cell destruction. With development of immunity the infection is brought under control. Tissue cysts persist, resulting in a latent infection. Organisms are released from tissue cysts if immunity is impaired. Epidemiology: worldwide distributions. Infection acquired by eating inadequately cooked meat or by ingesting mature oocysts. Treatment: not usually treated in healthy adults; antimicrobial medications if the patient is pregnant or immunocompromised prevention: avoid inadequately cooked meat and contact with foods or material that may contain oocysts from cat feces. Antimicrobial medications are given to immunodeficient individuals with a latent infection

Giardiasis (protozoan disease)

The most commonly identified waterborne illness in the US - occurs worldwide and is responsible for many cases of traveler's diarrhea signs and symptoms: mild- indigestion, intestinal gas, nausea. Severe- vomiting, diarrhea, abdominal cramps, weight loss (becomes chronic in some cases and long term carriers) incubation period: 6 to 20 days causative agent: Giardia lamblia, a flagellated pear-shaped protozoan with two nuclei G. Lamblia exist in two forms 1. growing feeding Trophozoite 2. a dormant cyst pathogenesis: ingested cysts survive stomach passage: trophozoites emerge from cysts in the small intestine, where some attach to epithelium; mucosal function is impaired by adherent protozoa and immune response epidemiology: ingestion of fecally contaminated water (both human and animal feces); low infectious dose; person to person spread (oral-anal contact can also transmit giardiasis) treatment: several antimicrobial medication options prevention: boiling, filtering, or disinfecting drinking water

Viral disease of the nervous system

a wide variety of viruses can infect the nervous system causing meningitis or encephalitis - many viruses that typically affect other body systems can occasionally infect the CNS. These include: Epstein Bar virus, rubeola, varicella-zoster, herpes simplex, mumps, enteroviruses - disease in which the CNS is the primary target include meningitis, encephalitis, polio and rabies

botulism

a classical severe form of food poisoning and is not a nervous system infection - A-b toxin - discussed here as paralysis is the main symptoms - it is one of the most feared of all disease as it strikes without warning and is often fatal - the majority of cases worldwide represent foodborne botulism caused by eating food contaminated with the organism and toxin - a small percentage of cases occur when the organism colonize the intestine or wound causing intestinal wound botulism respectively Causative agent: Clostridium botulinum - a stickily anaerobic, gram positive, endospore forming rod shaped bacterium - endospores are formed near the end of the cell - they resist boiling but killed by autoclaving symptoms: usually begins 12 to 36 hours after ingestion of contaminated, improperly canned non acidic or toxic food - in most cases symptoms start with dizziness, dry mouth and blurred or double vision - abdominal symptoms: abdominal pain, nausea, vomiting and diarrhea or constipation in 30 to 90% cases depending upon the strains of the causative organism - progressive paralysis involving all voluntary muscles - respiratory paralysis is the most common cause of death - presence of paralysis distinguishes botulism from other forms of food poisoning pathogenesis: Clostridium botulinum endospores germinate and the resulting vegetative cells multiply in favorable environments, releasing botulinum toxin. The toxin may be consumed in food (foodborne botulism), producing bells growing in the intestinal tract (intestinal botulism; in babies this is called infant botulism) or made by cells infecting a wound (wound botulism). Circulating toxin binds to motor nerves and stops the transmission of nerve signals to the muscles, producing flaccid paralysis Epidemiology: endospores widespread in soil, aquatic sediments, and dust. Foodborne botulism is often due to consuming an improperly processed home-canned, low acid food. Intestinal botulism typically occurs in infants (infant botulism) and sometimes involves endospore containing honey. Would botulism often involves injection drug abuse Treatment: depends on the type of botulism, but may involve intravenous administration of antitoxin and artificial respiration. Prevention: specific for the type of botulism. Foodborne botulism is prevented through proper food handling and home-canning methods; also, boiling home canned foods for 10 minutes just prior to serving. Intestinal botulism is difficult to prevent, but honey should not be fed to infants younger than one year of age. Wound botulism is prevented through prompt and appropriate wound care.

Cryptosporidiosis

a major hazard not only to those with immuno-deficiency, but to the public at large - a 1993 waterborne outbreak of the disease in Milwaukee involved more than 400,000 people signs and symptoms: fever, loss of appetite, nausea, abdominal cramps, watery diarrhea (last for months and life threatening in immunodeficient persons incubation period: usually about 6 days (rand 4 to 12 days) causative agent: Cryptosporidium parvum, an apicomplexan. Its life cycle takes place entirely within the epithelial cells of the small intestine. (acid-fast staining of oocysts) Pathogenesis: ingested oocysts release sporozoites in the intestine. The sporozoites invade epithelial cells, causing an inflammatory response. Secretion of water and electrolytes increases; absorption of nutrients decreases. (cell-mediated immunity is important in controlling the infection) (responsible for many cases of traveler's diarrhea) Epidemiology: oocysts of C. parvum are immediately infectious. The infectious dose is low, so person to person spread occurs easily. Infeccted individuals can discharge the oocysts for weeks after symptoms subside. The oocysts resist chlorination, and pass through many municipal water filtration systems. Wide host range. (C. parvum is particularly difficult to control as it has a wide host range, infecting domestic animals such as dogs, pigs, and cattle Treatment: antimicrobial medications prevention: pasteurization of beverages, boiling or filtering drinking water. Sanitary disposal of human and animal feces signs and symptoms: diarrhea, abdominal pain, blood in feces (amebic dysentery) incubation period: 2 days to several months causative agent: Entamoeba histolytica pathogenesis: ingested cysts excyst, releasing trophozoites; these feed on mucus and bacteria in the large intestine; cytotoxic enzyme kills intestinal cells. The trophozoites may penetrate the intestinal wall and are sometimes carried to the liver and other organs, resulting in abscesses - irritation on the intestine lining causes cramps and diarrhea - the diarrheal fluid is often blood, and the condition is referred to as amebic dysentery epidemiology: ingestion of fecally contaminated food or water; disease associated with poverty, migrant workers, and men who have sex with men - humans are the only important reservoir - infect up to 50 million people worldwide, mostly in developing countries treatment: antimicrobial medication (metronidazole and paromomycin) prevention: good sanitation and personal hygiene

disease caused by prions: Transmissible Spongiform Encephalopathies

a mysterious group of chronic degenerative brain disease of wild and domestic animals and humans - mink, elk, mule deer, sheep, goats and cattle are effected - sheep: scrapie - cattle: bovine spongiform encephalopathy (BSE; Mad cow disease) - deer and elk: Chronic wasting disease (CWD) - microscopically, brain tissue affected by these disease has a spongy appearance due to the loss of nerve cells and other changes - this is why these disease together referred to as TSEs - brain and other tissues from affected animals can transmit the disease to normal animals of the same and sometimes different species - these diseases become really important when, in 1996, a previously unrecognized spongiform encephalopathy in humans was described during a United Kingdom mad cow disease epidemic - the fact that mad cow disease may be transmitted to humans by eating contaminated beef made BSE is a disease of paramount public health importance - BSE cases were reported recently in both Canada and USA

Epidemic viral encephalitis

a number of cases appear in a limited period of time in a given area - bigger problem than sporadic viral encephalitis as the larger number of people can be effected - although symptoms are very similar to sporadic encephalitis, the causative agent, pathogenesis, epidemiology, prevention and treatment are different signs and symptoms: abrupt onset, fever, headache, vomiting, disorientation, paralysis, seizures, deafness, coma - only few of those infected develop encephalitis incubation period: first symptoms within a few days; encephalitic symptoms often within the first week - all the viruses are enveloped, single stranded RNA viruses - Arthropod borne viruses (Arboviruses) - West Nile virus infection was first introduced into New York in 1999 and it is a mosquito borne infection - migrating birds soon spread the virus 20 Eastern states from Maine to Florida and new is present in almost whole US (2011) Pathogenesis: replication of virus at the site of the mosquito bite, replication in lymph nodes, then viremia and invasion of brain tissue. Nerve cells in the brain destroyed. Process halted by neutralizing antibody - knowledge of pathogenesis is incomplete - very young and elderly suffer the most Epidemiology: viruses transmitted to humans from birds or rodents by mosquitoes treatment: no accepted treatment for arboviral encephalitis prevention: chicken sentinels to warn of arbovirus epidemics. insecticides and other anti mosquito measures - horses are infected before the first human cases appear

poliomyelitis

also known as infantile paralysis and polio - it is now targeted for global elimination - the characteristic feature is selective destruction of motor nerve cells usually of the spinal cord - this results in permanent paralysis of one particular group of muscles such as those of an arm or leg - atrophy of leg due to polio - plaques in the cell culture - two individuals who are most responsible for the control of this terrifying disease will not see its imminent elimination from the world - Albert Sabine died in 1992 and Jonas Salk in 1995 and none of them got the Nobel Prize Signs and symptoms: headaches, fever, stiff neck, nausea, pain, muscle spasm, followed by paralysis - muscle shrink and bone do not develop normally in affected areas - in severe cases, muscles of respiration are paralyzed incubation period: 7 to 14 days causative agent: polioviruses 1, 2, 3, members of the picornavirus family - enterovirus subgroup - small, non enveloped single stranded positive sense RNA viruses pathogenesis: virus infects the throat and intestine, cirulates via the bloodstream, and enters some motor nerve cells of the brain or spinal cord; infected nerve cells lyse upon release of mature virus - in most persons, the immune system control the infection and complete recovery takes place epidemiology: spreads by the fecal-oral route; asymptomatic and nonparalytic cases common treatment: artificial ventilation for respiratory paralysis; physical therapy and rehabilitation - there is no treatment for polio, but individuals receive supportive care such as rest, intravenous fluids and pain medications prevention: vaccination - control of polio using vaccines represents one of the greatest success stories - two vaccines: oral polio vaccine (OPV, called Sabin vaccine attenuated polio virus) and inactivated polio vaccine (IPV; Salk vaccine, given by injection) - the the years following 1988 when WHO resolved to eradicate polio, number of countries with epidemic disease has reduced from 125 to three only (Afghanistan, Nigeria and Pakistan)

pathways to the CNS

brain has no normal flora and is sterile. Well protected environment of brain prevents it from infectious agents - the following routes are used by pathogenic microbes and viruses to reach the brain and spinal cord 1. bloodstream: is the main source of CNS infections - blood brain barrier (BBB) normally resists the entry of cells and microbes into the brain except in rare cases - inflammation may increase permeability of the BBB - many medicines include penicillin cannot cross BBB normally unless their concentration is very high in the blood 2. Nerves: a number of disease affect CNS by infection of peripheral nerves (herpes, prions, rabies, tetanus toxin) 3. Bone: infections of the bones of sinuses, mastoids, or middle ear may penetrate the CNS. Skull fractures predisposes a person to recurring infections of the CNS

surface glycoprotein (SU or pg120) HIV component

cap-like portion of the spikes, with which virus attaches to host receptors

Cholera causative agent and pathogenesis

causative agent: Vibrio cholerae, a curved, gram negative rod - there are several different serotypes, grouped according to differences in their O antigen - the two major serotypes: O1 which is pandemic and O139 which is largely limited to Asia - it can tolerate strong alkaline conditions and high salt concentrations (halotolerant). These two characteristics are used to design appropriate selective media pathogenesis: As V. cholerae is killed by acid produced in the stomach, large number must be ingested to establish infection - Vibrio cholerae attaches to small intestine mucosa through pili or other surface proteins and multiplies on the epithelial cells but does no visible damage to them

Diffusely adhering E. coli (DAEC) strains epidemiology

cause diarrhea outbreak in children

Enteroaggregative E. coli (EAEC) strains epidemiology

cause epidemic diarrhea in children, diarrhea in AIDS patients and traveler's diarrhea

peridontal disease

chronic inflammatory disease involving gums and tissues around the roots of the teeth - signs and symptoms: gingivitis characterized by tender, bleeding gums. Chronic periodontitis characterized by bad breath; red, shiny gums that bleed easily; loose teeth; and exposed based of teeth - incubation period: gingivitis - days periodontitis - months or years - pathogenesis: plaque formed at the gum margins causes the inglammatory response associated with gingivitis. If plaque extends into the gingival crevices, the strong inflammatory response damages tissues that support the teeth, causing chronic periodontitis (calcium salts deposit in the plaque and cause dental calculus (tartar)) - epidemiology: gingivitis can begin in childhood; periodontitis primarily affects older people, particularly smokers and immunodeficient individuals - treatment: surgical treatment in severe cases of periodontitis to clean tooth roots. - prevention: avoid buildup of plaque (flossing and tooth brushing)

capsid protein (CA or p24) HIV component

coat protein - most abundant protein in the virus and serum levels can be measured to detect early HIV infection

Antiretroviral medications

entry inhibitors: interfere with viral entry into host cells NRTIs: chain terminators that stop DNA replication NNRTIs: inhibit reverse transcriptase integrase inhibitors: prevent integration of HIV cDNA into host genome Protease inhibitors: prevent virions from maturing

protease (PR) HIV component

enzyme involved in viral protein processing

integrase (IN) HIV component

enzyme that inserts viral cDNA into host genome

Reverse transcriptase (RT) HIV component

enzyme that makes copy of viral RNA into DNA

Cholera epidemiology and treatment and prevention

epidemiology: ingestion of fecally contaminated food or water; sometimes associated with marine crustaceans Treatment: replacement of fluid and electrolytes using intravenous or oral rehydration therapy prevention: purifying water and handwashing; vaccine available - use of boiled water and cooked food - both live attenuated oral vaccine and killed vaccine are available

Undulant fever (Brucellosis, Bang's disease)

few cases of human brucellosis each year in the US; however, many more cases go unreported annually -brucellosis is a zoonotic infection and a potentially bioterrorism threat - it is listed as a category B threat signs and symptoms: recurrent fever. body aches, weight loss, enlargement of lymph nodes; symptoms usually lessen even without treatment but may becomes chronic Incubation period: usually 5 to 21 days causative agent: Brucella melitensis, a small, aerobic, gram negative rod pathogenesis: organisms penetrate mucous membranes and are carried to heart kidneys, meninges, and other parts of the body via the blood and lymphatic system; they resist killing by macrophages and grow within these cells - enlargement of spleen - osteomyelitis is the most frequent serious complication epidemiology: main source of human infections: domestic animals. Disease also occurs in wild animals such as moose, caribou, bison; butchers, farmers, veterinarians, those who drink unpasteurized milk are at risk treatment: appropriate antibiotics prevention: vaccination of domestic animals; pasteurization of milk and milk products; gloves and face shields

fungal diseases of the nervous system

fungi very rarely invade the CNS of healthy people, but cancer, diabetes and AIDS patients and immunosuppressed people risk serious disease - common fungi from the soil and decaying vegetation sometimes infect the nose, sinuses and lungs - fungi then through blood can penetrate to the brain and cause inflammation of brain and meninges and causes patient's death - these infections are dangerous as they are difficult to treat with antimicrobial medication

hepatitis C

hepatitis C is the most common chronic, blood-borne infection in the USA and greater than 3 million American are infected - it was discovered when post-transfusion hepatitis continued to occur even after HBV was excluded. symptoms: - incubation period average about 6 weeks - same as that of hepatitis A and B except they are generally milder - about 65% of infected individuals have no symptoms relating to the acute infection, and only about 25% have jaundice - in most cases, the HCV infection become chronic - cirrhosis and the liver cancer developed in 10 to 20% of patients causative agent: hepatitis C virus (HCV) is an enveloped, single stranded, positive sense RNA virus - belongs to the family Flaviviridae - many types and subtypes - the virus was successfully cultivated in vitro in 2005 pathogenesis: infection usually occurs from exposure to contaminated blood - most people with acute infection lack symptoms, but more than 80% develop chronic infection - the virus infects the liver and incites inflammation and immune responses - after that disease process starts and stops and then, weeks or months later, shows marked inflammation epidemiology: transmitted by blood from an infected person - about 50% of tranmission in the US are due to sharing of syringes by illegal drug abusers - sharing tooth-brushes, razors and towels can be responsible - tattoos and body piercing can also transmit the disease - transmission by sexual intercourse (semen) is an uncommon means of transmission, although it can occur among those with multiple partners and sexually transmitted diseases - the risk of contracting the disease from blood transfusion is now extremely low because of effective screening of donating blood treatment and prevention: group of new anti-HCV medications referred to as direct acting antivirals (DAAs) - DAAs specifcally interfere with HCV-encoded proteins - HCV targets of DAAs include: 1. polymerase, 2. protease, and 3. NS5A a protein required for replication of viral genome - specific combinations of DAAs are taken orally. One formulation includes sofosbuvir (a nucleotide analog) along with velpatasvir (an NS5A inhibitor) - in early studies, the new treatment resulted in greater than 97% cure rate - no vaccine is available for preventing hepatitis C. Vaccination against hepatitis A and B is recommended to avoid dual infections that might severely damage the liver - avoidance of alcoholic beverages is recommended as alcohol has toxic effects on the already damaged liver.

Rabies

in the US, vaccination do dogs and cats against rabies has practically eliminated them as a source of human disease - the rabies virus present among wildlife is a constant threat to non-immunized domestic animals and humans - the most feared of all disease as its terrifying symptoms almost invariably lead to death symptoms: fever, headache, nausea, vomiting, sore throat, cough at onset - the characteristic and strong symptoms of rabies is a tingling or twitching sensation at the site of viral entry, usually an animal bite - other symptoms include encephalitis, agitation, confusion, hallucinations, seizers, hydrophobia, and increased sensitivity to light, sound, and touch - later, spasms of the muscles of mouth and throat, the body temperature rises steeply, increased salivation, difficult swallowing and frothing at the mouth, coma and death incubation period: usually 30 to 60 days; sometimes many months or years causative agent: rabies virus, single stranded RNA, rhabdovirus family, has an unusual bullet shape pathogenesis: during incubation period, virus multiplies at site of bit, then travels via nerves to the central nervous system; it multiplies and spreads outward via multiple nerves to infect heart and other organs - characteristic inclusion bodies called Negri bodies form at the site of rabies virus replication in brain, but cells are not lysed Epidemiology: bite of rabid animal, usually a bat. Inhalation is another possible mode - widespread in wild animals. In the US, skunks, racoons and bats constitute the chief reservoir hosts - in most cases, transmitted by the saliva of a rabid animal - transmitted by inhaling aerosols containing the virus, such as from bat feces Treatment: immediately wash wound with soap and water and apply antiseptic; inject rabies vaccine and human rabies antiserum as soon as possible. No effective treatment once symptoms being - an individual bitten by a rabid animal should receive a series of four injections of inactivated vaccine. Prevention: avoid suspect animals; immunize pets

Meningococcal meningitis

mostly occurs in 6 to 11 month old children, but also occurs frequently in older children and adults - considered a dangerous disease as sometime it can progress to death within few hours - however, most patients respond to treatment and recover without permanent damage to nervous system symptoms: the first symptoms in most of bacterial meningitis are similar - usually begin with mild cold which is followed by the sudden onset of a severe throbbing headache, fever, pain and stiffness of neck, nausea and vomiting - deafness and changes in consciousness progressing to coma may develop - purplish spot called petechiae, resulting from small hemorrhages may appear on the skin - infected person may develop chock and die within 24 hours - however, progression of the illness is usually slower, allowing time for treatment incubation period: 1 to 7 days Causative agent: Neisseria meningitidis, the meningococcus - a gram negative, encapsulated, diplococcus - 13 antigenic groups but most serious infections are due to A, B, C, Y and W135 - group B and C are most common in the US and Europe; type A most common in Africa and Asia Pathogenesis: meningococci adhere by pili, colonize upper respiratory tract, enter bloodstream; carried to meninges and spinal fluid, (decreased glucose concentration in CSF); inflammatory response obstructs normal outflow of fluid; increased pressure caused by obstructed flow impairs brain function; damage to motor nerves produces paralysis; endotoxin release leads to shock (decreased blood pressure) - inflammatory response may induce pus formation and clot which cause brain swelling and infarcts (death of tissue due to loss of blood supply) epidemiology: close contact with a case or carrier; inhalation of infectious droplets; crowding and fatigue predispose to the disease - common in military recruits and college dormitories - humans are the only source of infections treatment: antibiotics prevention: age specific vaccines; antibiotics given to people exposed - the case fatality rate is less than 10% in treated cases

Listeriosis

it is a food borne disease and healthy people usually have asymptomatic infections or trivial symptoms signs and symptoms: fever and muscle aches, with or without gastrointestinal symptoms; headache and stiff neck mark the onset of meningitis - pregnant women usually miscarry or deliver terminally ill premature or full term infants incubation period: a few days to 2 to 3 months; in newborn babies, 1 to 4 weeks causative agent: Listeria monocytogenes, a non-spore forming gram positive rod able to grow at 4 degrees Celsius pathogenesis: ingested L. monocytogenes cells penetrate the intestinal epithelium and enter the bloodstream; the resulting bacteremia spread to the meninges, causing meningitis - in pregnant women crosses placenta and produces abscesses in the fetus Epidemiology: epidemic from contaminated foods. Pregnant women develop bacteremia that may result in fetal infections of miscarriage. Infants contract infection at birth. Elderly and those with immunodeficiency, cancer, and diabetes also at high risk - organism widespread in natural waters and vegetation - carried in the intestine of asymptomatic animals and humans Treatment: antibacterial medications prevention: care in handling, cooking of raw meats; thorough washing of vegetables; reheating of cold cuts, hot dogs, and refrigerated leftovers - can grow at refrigeration temperatures

Norovirus gastroenteritis

noroviruses are the most common cause of viral gastroenteritis in the USA (21 million cases annually) - originally, they were called Norwalk viruses as first implicated in gastroenteritis epidemics from Norwalk, Ohio - it is classified under category B bioterrorism agent because they spread easily and can cause large outbreaks signs and symptoms: usually causes abrupt onset of nausea, vomiting and watery diarrhea - incubation period is 12 to 48 hours - vomiting is typically most severe in older children and adults, and generally resolved within the first day or two - dehydration may occur - noroviruses are naked, single stranded RNA virus and belongs to Caliciviridae family - noroviruses infect the epithelium of upper small intestine and produce changes similar to those with rotaviruses - immunity to noroviruses is only short term and thus people can have repeated infections - the virus has only recently been cultivated in the laboratory - transmission is primarily by oral-fecal route. Vomit contains infectious viral particles - the disease is highly contagious due to low infectious dose of the virus and a concern for health facilities - very common on cruise ships and college dormitories - more than 50% of foodborne disease outbreaks are due to norovirus, so CDC has started CaliciNet - handwashing, disinfectant use and other sanitary measures help limit the spread of noroviruses - no vaccine and no antiviral medication

virulence factors of Yersinia pestis

on slide 18 of lecture 34 Pla (protease) coded by pPCP1 plasmid Yops (proteins) coded by PCD1 plasmid V antigen coded by PCD1 plasmid F1 coded by pMT1 plasmid PsaA (adhesin) coded by chromosome Complement resistance coded by chromosome iron acquisition coded by chromosome

1. Sexual contact Epidemiology of HIV disease

primary cause of HIV spread - indiscriminate sexual intercourse with multple partners without condoms is a major factor in the transmission - virus is present in semen and cervical and vaginal secretions - HIV enter the vaginal, rectal, penile, or urethral mucosa through tiny lesions that occur during sexual intercourse - the disease can be transmitted by either male to male or male to female sexual contact with an infected person - the risk of spread by anal sex is greater than that of vaginal sex

sepsis or septicemia and septic shock

sepsis, an infection induced systemic inflammatory response, is a common health care associated illness - sepsis is mostly caused by release of bacterial products - particularly endotoxins from gram negative bacteria that cause excessive damage that can lead to life threatening illness symptoms: violent shaking chills and fever usually accompanied by anxiety and rapid breathing - in septic shock, there is low urine output but increased respiration and pulse rate - the arms and legs become cool and dusky color - bruising and bleeding can also occur causative agents: systemic infection by any microorganisms can cause sepsis - although more than half of cases are caused by gram positive bacteria, gram negative bacteria are more likely to cause fatal septicemias due to the presence of endotoxin e.g. E. coli, P. aeruginosa and Bacterioides sp. - shock is common in septicemia cases and despite treatment only about half of all effected people survive

shigellosis signs and symptoms and causative agent

shigellosis is distributed worldwide and average 20,000 cases per year have been reported in USA signs and symptoms: - incubation period: short, generally 1 to 3 days - the classic symptom is dysentery but some Shigella species causes watery diarrhea - other symptoms are headache, vomiting, fever, stiff neck, convulsions, and joint pain - commonly fatal for infants in developing countries causative agent: - gram negative, nonmotile enterobacteria, four species for Shigella: S. dysenteriae, S. flexneri, S. boydii, and S. sonnei the least virulent

Tularemia (Rabbit fever or deer fly fever)

signs and symptoms: Ulcer at site of entry, enlarged lymph nodes in area, fever, chills, aches; pneumonia if causative agent is inhaled incubation period: 1 to 10 days usually 2 to 5 days causative agent: Fracisella tularensis; an aerobic, gram negative rod pathogenesis: organisms are ingested by phagocytic cells, grow within these cells, and then spread throughout body epidemiology: present among wildlife in Northern Hemisphere; risk mainly to hunters and others who dandle wildlife; acquired when the organism penetrates a mucous membrane or enters broken skin, as may occur when skinny wild animals; bite of infected insect or tick Treatment: antibiotics prevention: avoiding bites of insects and ticks; wearing rubber gloves. goggles. when skinning animals

Campylobacteriosis

signs and symptoms: diarrhea, fever, abdominal cramps, vomiting, bloody stools (in about half of the cases) incubation period: usually 2 to 5 days causative agent: campylobacter jejuni, a curved gram negative microaerophilic rod pathogenesis: lo infectious dose. The bacteria multiply (in small and large intestines) within and beneath the epithelial cells, causing an inflammatory response, Bloodstream invasion is uncommon. Complicated by Guillian-Barre syndrome on rare occasions (tingling of feet followed by progressive paralysis of the legs, and arms and rest of the body) epidemiology: large foodborne and waterborne outbreaks originate from poultry and other animals; person to person spread rare - about 1.3 million cases and 100 deaths per year in USA - infectious dose of C. jejuni is as low as 500 organism - poultry is a common source of infection and up to 90% of raw poultry products harbor the organisms Treatment: antibiotics in severe cases - typically, self-limiting - antibiotic azithromycin or fluoroquinolones for severe cases prevention: relies on adequate cooking and proper handling of food, particularly poultry. Water chlorination and pasteurization of beverages are effective control measures

Typhoid and paratyphoid fevers

signs and symptoms: fever, severe headaches, constipation and abdominal pain; sometimes followed by intestinal rupture, internal bleeding, shock and death (examples of enteric fevers) incubation period: 1 to 3 weeks Causative agent: Salmonella serotype Typhi (typhoid fever) and Salmonella serotype paratyphi (paratyphoid fever) gram negative, members of the Enterobacteriaceae (S. typhi colonizes gall bladder and carriers shed bacteria for years) Pathogenesis: cross the intestinal epithelium via M cells; taken up by macrophages and then multiply within them; bacteria are carried in the bloodstream to locations throughout the body. The peyer's patches are sometimes destroyed, leading to rupture of the intestine and hemorrhage epidemiology: humans are the only source of infection. Person to person fecal-oral transmission Treatment: antimicrobial medications (surgical removal of the gall bladder is often necessary to rid Salmonella typhi carriers of their infection preventions: attenuated and inactivated vaccines for typhoid fever; no vaccine for paratyphoid fever

Protozoan disease of the nervous system: African Sleeping Sickness (African trypanosomiasis)

signs and symptoms: tender nodule at site of tsetse fly bite; fever, enlargement of lymph nodes; later, involvement of the central nervous system, uncontrollable sleepiness, headache, poor concentration unsteadiness, coma, death Incubation period: weeks to several years causative agent: Trypanosoma brucei, a flagellated protozoan (antigenic variation is a classical feature) pathogenesis: the protozoa multiply at site of tsetse fly bite, then enter blood and lymphatic circulation; as new cycles of parasites are released, their surface protein changes and the body is required to respond with new antibodies epidemiology: bites of infected tsetse flies transmit the trypanosomes through fly saliva; wild animal reservoir for T. brucei rhodesiense treatment: antimicrobial medications prevention: protective clothing, insecticides, clearing of brush where flies breed

clostridium difficile infection (CDI) summary

signs and symptoms: variable; mild diarrhea to pseudomembranous colitis, a potentially fata inflammation of the colon incubation period: usually less than a week causative agent: Clostridium difficile, a gram positive, rod-shaped, endospore-forming anaerobe pathogenesis: toxins disrupt host cell actin and cell signaling causing lethal effects to the intestinal epithelium epidemiology: primarily occurs in patient on antibiotic therapy treatment: when practical, stop antimicrobial medications; otherwise, an antimicrobial medication that targets C. difficile. Fecal transplant to restore normal intestinal microbiota Prevention: includes handwashing and disinfection of surfaces

Matrix protein (MA or p17) HIV component

stabilizes virion

transmembrane protein (TM or gp41) HIV component

stalk-like portion of the spikes; it anchors the spikes to the viral envelope

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Viral meningitis

viral meningitis is more common than bacterial meningitis - mostly a much milder than bacterial meningitis disease and does not require specific treatment. Patients usually recover in 7 to 10 days - in most cases of 'aseptic meningitis' (negative for bacterial pathogens), viruses are responsible for the disease signs and symptoms: abrupt onset, fever, severe headaches, stiff neck, often vomiting; sometimes sore throat, rash or chest pain incubation period: usually 1 to 4 weeks causative agent: most cases: small non enveloped RNA enteroviruses of the picornavirus family, usually coxsackie or echoviruses pathogenesis: viremia from primary infection spreads to the meninges. Fewer leukocytes enter cerebrospinal fluid than with bacterial infections, and many are monocytes rather than neutrophils Epidemiology: enteroviruses are transmitted by the fecal-oral route, mainly in summer and early falls Treatment: no specific treatment Prevention: handwashing, avoiding crowded swimming pools during enterovirus outbreaks

Viral encephalitis

viral meningitis is usually a mild illness. - but viral encephalitis is more severe and causes permanent disability or death. It can be sporadic or epidemic