study set for microbiology final

Tuberculosis, in detail

Tuberculosis Caused by Mycobacterium tuberculosis Obligate aerobe, very slow growing bacterium Easily identified by microscopy with proper staining Has mycolic acids (long-chain lipids) in cell wall that make it resistant to killing by macrophages Remember, some bacteria have specific structures or toxins that allow them to cause disease. Mycobacteria have other factors used in causing disease but the main component is mycolic acid Transmission Caused by inhalation of bacteria Coughing sneezing by infected patients release droplets with live bacteria Very small droplets can get past mucous barrier and pass deep into lungs Usually this disease is transmitted by close contact when an infected person coughs, sneezes, talks or sings (!) Bacteria in very small droplets can be inhaled and go deep in the lungs to the alveoli Alveolar macrophages usually engulf and kill the bacteria but in some cases an infection can become established https://www.cdc.gov/tb/ Plus video in TB basic facts https://www.cdc.gov/tb/topic/basics/howtbspreads.htm Some people develop TB disease soon (within weeks) after becoming infected, before their immune system can fight the TB bacteria. Other people may get sick years later, when their immune system becomes weak for another reason. Many people with TB infection never develop TB disease. Pathogenesis After infection, macrophages can become activated by contact with the bacterial cell wall and can kill bacteria. Mycobacteria can be killed and the infection cured in most healthy people (about 90% avoid infection) In unhealthy or HIV-infected people macrophages can engulf bacteria but they can then begin living inside the cells Bacteria then multiply inside cells attracting more macrophages, causing infection to be walled off in the lung Cells then form calcified lump in lung, disease is stopped at this point but not destroyed If immune defenses weaken then the bacteria are released into the lung or into the circulation Patients lungs are infected and symptoms include coughing possibly with bloody sputum. Infection my become disseminated (spread thru the body) Immune system overwhelmed, patient has weight loss and general weakness. Previously called consumption Symptoms Bad cough lasting 3 weeks or longer Chest pain, coughing up blood or bloody sputum, Weakness, fatigue, weight loss, loss of appetite Chills, fever, night sweats Epidemiology https://www.cdc.gov/mmwr/volumes/68/wr/mm6811a2.htm?s_cid=mm6811a2_w Tuberculosis (TB) is one of the world's deadliest diseases: One fourth of the world's population, is infected with TB. In 2017, 10.0 million people around the world became sick with TB disease. There were 1.3 million TB-related deaths worldwide. TB is a leading killer of people who are HIV infected Tuberculosis Stages of disease Latent tuberculosis infection Bacteria have established an infection in the lung but the body has fought them and stopped them from growing Person in this state is not infectious and can go through life without developing disease Changes in immune status, weakness, old age can activate the bacteria and cause TB disease TB disease Bacteria become active and start multiplying in lung and possibly in the body Person can now spread the bacteria to others Risk factors for TB disease include HIV infection, alcohol or drug use, health problems like diabetes, improper treatment for past TB infection Diagnosis Examine sputum by microscopy and staining Tuberculin test - injection of antigen into skin, cell-mediated response indicates bacterial exposure previously in the patient that caused a cellular immune response. This cellular response developed cytotoxic T cells that can attack the antigen in the tuberculin test. X-ray can show calcified lumps in lungs Treatment Multidrug antibiotic treatment for minimum of 6 months Failure to follow treatment develops antibiotic resistance These cases now include multi-drug resistant (MDR) strains and extensively drug-resistant (XDR) strains https://www.cdc.gov/tb/default.htm Worldwide incidence 9 million new cases per year, 2 million deaths/year Estimates are that 1/3 of world's population are infected HIV infection increases virulence of both diseases

Respiratory structures, upper and lower.

Upper respiratory system Nose and throat Also includes middle ear and auditory (Eustachian) tubes Tear ducts empty into the nasal cavity Don't forget the tonsils Lower respiratory system Starts at the larynx and goes down Windpipe (trachea) and bronchial tubes that bring air to the: Alveoli - the very small sacs in the lung where gas exchange takes place Alveolar macrophages that ingest microbes deep in the lungs Don't forget the cilia in the bronchi and trachea that move particles out of the lungs The cilia begin at the exit of the alveoli

Central nervous system structure

the CNS consists of the brain and spinal cord. blood circulation to this area is controlled by the structure of the blood vessels that supply nutrients to the brain. specialized capillaries in the CNS have tight junctions btwn epithelial cells that form "leaky" blood vessels, which allows many substances to pass into the tissues beyond the vessel (glucose, peptides, drugs, toxins, etc). this barrier with tight junctions prevents the passage of some substances through the blood vessels around the CNS-- lipid soluble drugs can pass through the barrier but not other substances like glucose or peptides. glucose and other nutrients are passed to the brain by special transporters in these capillaries with tight junctions.

circulatory system structures

heart, blood vessels, blood

Blood-brain barrier

A mechanism that prevents certain molecule from entering the brain but allows others to cross

Neisseria meningitides

Also called meningococcal meningitis Caused by Neisseria meningitidis Gram-negative, aerobic cocci with a capsule! 10% of people are healthy nasopharyngeal carriers Can be spread by coughing, sneezing, kissing, sharing chew toys Begins as a throat infection and a rash Bacteria invade the bloodstream and eventually get to the CNS Pathogenesis is similar to Hib Vaccination recommended for college students Due to crowding in dorms or large lecture halls this bacterium can pass quickly in this environment

COVID-19

COVID-19, which emerged in December 2019 from China. The virus that causes COVID-19 is named SARS-COV-2 Coronaviruses evolve quickly and have a long history of shifting between animal species. While many other coronaviruses in nature are not known to infect people, SARS-CoV-2, MERS-CoV and the original SARS-CoV are notable for their ability to infect a variety of different species. Research evidence suggests that all three coronaviruses originated in bats. SARS-CoV, the original serious human coronavirus then spread from infected civets to people. MERS-CoV spreads through infected dromedary camels to people. Scientists are trying to determine all the details about SARS-CoV-2 spread to people. What is the most common way that the virus spreads to people? How infectious is it? When do infected people start shedding the virus and become contagious to others? What is the pathogenesis of this disease? What pathology does it cause? Are there underlying health problems that make you more susceptible to serious or deadly consequences of infection? If you were infected and survived the infection could you get infected again or would you be immune to future infections? And more questions........ SARS-CoV-2, the cause of COVID-19 is a human-infecting Coronavirus Believed to have begun human transmission in China possibly in the Fall of 2019 (much controversy about this) Believed to have adapted from bats to another animal vector to humans. Still not absolutely confirmed but getting close. First known outbreak in Wuhan, China. Beginning of 2020 Due to global travel the virus spread rapidly worldwide in the first months of 2020 And then - the Pandemic WHO timeline Jan. 4th 2020 WHO reports cluster of pneumonia cases in Wuhan WHO and China identify a new coronavirus, COVID-19 Jan. 22, 2020 WHO determines that human-to-human transmission of COVID-19 is happening Due to many issues, a global pandemic is not declared until March The Virus +ssRNA virus. Enveloped virus. Spike protein, the viral ligand, binds to the peptidase angiotensin-converting enzyme 2 (ACE2) receptor. This determines the viral cell tropism ACE2 expression is highest in nasal epithelial cells followed by bronchial ciliated epithelial cells and type 2 pneumocytes Type 2 pneumocytes produce surfactants in the alveoli ACE2 is also found in capillary-rich areas like lungs, kidneys, gut, and brain The virus is transmitted mainly by respiratory droplets and aerosols in crowded or poorly ventilated areas. (Stay tuned for future updates) Once a person is infected, the peak of infectivity occurs before the onset of symptoms Viral Life Cycle Following exposure to the virus COVID-19 binds to the ACE2 receptor and various other cellular proteases which prepare the spike protein for fusion and release to the cytosol The virus is taken in within an endosome where fusion takes place The viral RNA is expressed and all the viral components necessary to form new virions are made The new virions are released coated in a host cell-derived envelope that contains the spike proteins Released viruses go on to infect more cells Pathogenesis/Pathology As far as we know now many people report few if any symptoms and recover completely 90% of those that are symptomatic will have evidence of pneumonitis 3-5 days post onset due to infection in lower respiratory tract Pneumonitis is likely due to infection of type 2 pneumocytes and the inflammation that occurs 80% of those that develop pneumonitis recover without specific treatment 7-10 days post onset the other 20% will deteriorate rapidly Usually admitted to the hospital with worsening fever, hypoxia, increased inflammatory response, and cardiovascular involvement As we have seen in many other diseases the inflammatory immune response can cause extensive damage. In this case it is likely in the lungs Signs and Symptoms Common signs and symptoms of COVID-19 include Fever or chills, Cough, Fatigue Shortness of breath or difficulty breathing Muscle or body aches, Headache New loss of taste or smell, Sore throat Congestion or runny nose, Nausea or vomiting Diarrhea Signs and symptoms of severe disease Indicators of severe illness Trouble breathing Persistent chest pain or pressure Inability to stay awake New confusion Pale, gray or blue-colored skin, lips or nail beds — depending on skin tone Complications Pneumonia and trouble breathing Organ failure in several organs Heart problems A severe lung condition that causes a low amount of oxygen to go through your bloodstream to your organs (acute respiratory distress syndrome) Blood clots Acute kidney injury Additional viral and bacterial infections Treatment This is a very new disease. We do not have many drug treatments available for viral diseases There are a number of possible treatment candidates and many that are unproven (See: The Internet) This is a rapidly changing field. Many are trying to develop the first really effective drug treatment Many are trying to muddy the waters (the nicest way I can say it) or just make money There are several that have been shown to have some efficacy Remdesivir Monoclonal antibodies (possibly, but still some issues) Corticosteroids (anti-inflammatory) Vaccines There are several vaccines available that have been shown protective against COVID-19 In the US we have Pfizer-BioNTech and Moderna which are mRNA viruses. Their contents include mRNA, lipids, buffers like potassium phosphate, acetic acid, and sucrose. The lipids form a nanoparticle that can enter our cells. The buffers and sucrose stabilize the mRNA. Johnson and Johnson's Janssen vaccine which is a viral vector vaccine. A segment of DNA coding for the spike protein is in an inactivated adenovirus. The virus enters our cells and the DNA can be expressed and the spike protein will be displayed on our cells near the injection site The mRNA vaccines can express the viral spike protein that will be displayed on the surface of our cells near the injection site. Our immune system cells will recognize the spike proteins as foreign and mount an antibody and cellular response Data indicates (so far) that the antibody response is not very long lived, approx. 6 months. The cellular response is still strong during the times tested. COVID-19 variants Good news - We have a vaccine!!! Bad news - as more and more people get infected with COVID-19 our immune system fights back and the virus mutates The mutants are so far more infectious. The may or may not be more pathogenic. So the longer it takes to vaccinate everyone in the entire world......the more variants there will be. So far the vaccines appear to be effective against the variants. You may be able to get infected but you will not get serious disease That is why it is good for the US to have herd immunity from vaccination but it is better, maybe critical, that the rest of the world gets vaccinated too. If we don't get this under control it may become like Influenza. Or maybe year round transmission. Endemic or epidemic. And a need for a new vaccine every year. Epidemiology - January 2020 to May 1, 2022 Global tally - about 500 million confirmed cases. 6 million deaths. US data 81 million confirmed cases, about 1 million deaths US seroprevalence data (Morbidity and Mortality Weekly Report -MMWR) Serological data based on viral nucleocapsid antibodies not spike protein from vaccination 75% of children and adolescents have serological evidence of previous COVID infection 18-49 = 64% 50-64 = 60% >65 = 33%

Influenza in detail

Common virus worldwide, usually causes seasonal epidemics, can cause worldwide pandemics 30-50,000 deaths/year in US Mostly in very young or elderly Infects upper and lower respiratory system Virus has surface proteins that bind to specific epithelial cells Vaccine produces antibody that blocks viral binding Symptoms Chills, fever, headache, body aches Sudden onset, high fever, and extreme fatigue usually distinguishes flu from common cold Influenza is an enveloped virus Spread by direct transmission (coughing or sneezing on someone), airborne droplets, or contact with contaminated surfaces Virus survival depends on where it lands and if it is protected by mucus Ethanol hand sanitizer is effective against this virus Vaccine formulation is new every year Virus mutates in host to evade immune response Vaccine takes a long time to produce sufficient doses for the new flu season Vaccine strain identified early in current season for next years vaccine Hopefully it will be effective Diagnosis by fast ELISA test using nasal swab or wash Treatment Antivirals are useful if given early in infection Relenza and Tamiflu (neuraminidase inhibitors) can shorten course of the disease if taken within 30 hours of onset Cell pathogenesis Initial symptoms of flu due to cytokine production causing inflammatory response, aches and pains Unlike common cold, flu causes much tissue damage Respiratory ciliated cells are destroyed Now you cannot remove fluid in lungs without coughing Loss of clearing from the lungs can lead to secondary bacterial infection, pneumonia especially in susceptible populations With some strains (1918 pandemic flu) massive immune response can lead to death Inflammation in lungs caused a fatal pneumonia in young adults. Likely due to their strong immune response to specific viral antigens Currently most influenza deaths are in the very young or very old since the circulating type has been around for a while. However, a new type is currently circulating in China. Direct transmission from birds to humans https://www.cdc.gov/flu/pandemic-resources/monitoring/irat-virus-summaries.htm The Influenza Virus Life Cycle The virus has a spike on its surface (Hemagglutinin) that binds to specific cells in a humans respiratory tract and another (Neuraminidase) used in virus release from the infected cell The virus contacts ciliated epithelial cells, penetrates them, and makes viral copies until the cell dies. This continues until the immune system produces enough effective antibodies to stop viral spread Hemagglutinin (H) spikes attach to host ciliated cells in the respiratory tract. Attachment bring virus into the cell Virus multiplies in cell and is released through host membrane where it picks up a membrane coat Neuraminidase (N) spikes are used to release virus from cell. The virus envelope has H on its surface and it can stick to host membrane in the currently infected cell. N breaks the bond and the virus is released with intact H to infect other cells Influenza Genetic Changes Antigenic drift - as your immune system fights the virus the virus fight back. This allows slightly different virus particles to evade the antibodies produced against the initial virus. Point mutations in genes encoding H or N spikes develop during course of disease due to crappy replication Changes may involve only one amino acid Allows virus to avoid mucosal IgA antibodies Now the virus is slightly different from the type used in the vaccine Antigenic shift - new strains of flu virus develop in birds and are transmitted to pigs. This causes big changes in H and N spikes to types that many people may have never been exposed to and have no immunity against. Probably due to genetic changes in different strains as they infect birds and pigs. Humans usually cannot get bird flu but birds can carry both human and bird strains. Pigs act as a mixing vessel where bird and human virus can shift into a new type Eg. Right now the vaccine is made from influenza A strains H1N1 and H3N2. If the circulating strain were to change rapidly then many people would be at risk There are 3 general types of human influenza virus. Type A is the major cause of the typical flu. The Flu Vaccine Vaccine strains grown in chicken eggs Virus harvested and inactivated before packaging Injection of virus will cause antibody response including some IgA which will travel to mucosal surface There is a nasal flu vaccine available for some populations. This produces a more robust IgA production in area of virus contact Depending on how well the circulating virus matches the vaccine strains the average level of immunity is between 25-60%. For 2015-2016 season through February the estimate is vaccine effectiveness at 59% so far this season. https://www.cdc.gov/flu/professionals/vaccination/effectiveness-studies.htm https://www.cdc.gov/flu/index.htm

Helicobacter pylori

H. pylori associated with stomach ulcers Mucus-producing and acid-producing epithelial cells line stomach. Mucus layer protects tissues from acid Bacterial infection from H. pylori for example in tissue disrupts protection, allows stomach acid to form a lesion (ulcer) H. pylori has an enzyme that produces ammonia, an alkaline substance that protects bacteria from acid near lesion Antibiotic treatment can kill bacteria, cure ulcer H. pylori infection is associated with contaminated water supply, not as common in developed countries Chronic infections can lead to stomach cancer

Inflammatory "itis's" (pharyngitis for example)

Inflammation of an organ is an "-itis" Pharyngitis - inflamed throat Laryngitis - inflamed voice box Tonsillitis - inflamed tonsils

definition of meningitis

meningitis is the inflammation of the meninges and the common symptoms are fever, head ache, light sensitivity, confusion, and neck pain

Scarlet fever

S. pyogenes in throat or even in skin infections can release toxins that cause reddening of the skin A Strep infection that releases an erythrogenic (reddening) toxin causes Scarlet fever S. pyogenes in throat or even in skin infections can release toxins that cause reddening of the skin A Strep infection that releases an erythrogenic (reddening) toxin causes Scarlet fever

Strep throat

Streptococcal pharyngitis (strep throat) Caused by Group A strep bacteria (GAS) S. pyogenes Infection can begin by exposure from new source penetrating tissues or weakened immune system allowing commensal bacteria to cause an infection. Possibly beginning as a minor viral infection. Inflammation is caused by the infection itself and exotoxins released by bacteria. Exotoxins can include streptokinases and streptolysins Viral infections and other bacterial infections often mistaken for strep throat. But presence of S. pyogenes is not conclusive evidence that a patient has a strep throat Strep throat can be identified by a rapid assay test and treated with antibiotics. Remember, treating viral infection with antibiotics is useless and can lead to antibiotic resistance

structure and location of the meninges

The brain and spinal cord are surrounded by several layers of specialized tissue and the cerebrospinal fluid (CSF) that acts like a cushion Inflammation of the meninges is called meningitis Caused by reaction to a microbial infection that gets past the blood-brain barrier A systemic inflammation can also cause the blood-brain barrier to get leaky and let microbes pass Inflammation of the brain is called encephalitis This is often caused by viruses like rabies, measles, chicken pox and any virus with encephalitis in the name

rheumatic fever (Streptococcus pyogenes)

This is an autoimmune complication usually from a S. pyogenes infection Most common in 4-18 years old. Usually following a strep throat Can present as arthritis and fever. Some cases may have autoimmune nodules at joints, Heart damage may be severe. In some cases repeated strep throat infection may cause new episodes of rheumatic fever. High risk patients may receive monthly prophylactic Penicillin G injections. https://www.cdc.gov/groupastrep/diseases-hcp/acute-rheumatic-fever.html Acute Rheumatic fever in US and worldwide

Streptococcus pneumoniae

Also called pneumococcal meningitis S. pneumoniae is also a common cause of pneumonia Caused by S. pneumoniae a gram-positive diplococcus) Currently this is the most common cause of bacterial meningitis due to Hib vaccine 70% of people are or have been healthy nasopharyngeal carriers Most common in children (1 month to 4 years) Mortality: 30% in children, 80% in elderly Vaccination recommended for children under 2 years of age Normal inhabitant of upper respiratory tract of 5-40% of humans Can cause pneumonia, sinusitis, otitis media, meningitis Antigenic based on capsular polysaccharide Certain types responsible for most pneumonia cases Pathogenesis based on capsule preventing or delaying phagocytosis Opsonizing antibody against specific capsular type prevents infection Loss of natural resistance 40-70% of humans are carriers of S. pneumoniae at some time in life Viral or other infections, allergy, age-related syndromes can predispose host to infection Pathogenesis Infection in alveoli causes inflammation and fluid buildup with RBC's and WBC's Bacteria may enter lymphatic system, cause sepsis Usually sudden onset with fever, chills, pain during breathing Invasion of bloodstream can lead to meningitis Treatment/Control Pneumococci susceptible to many antimicrobials Penicillin G has been drug of choice but some resistance is developing This drug treatment may not be effective against meningitis, only pneumonia Vaccines available and recommended. PCV13, 15, (conjugate) recommended for children and adults at low risk. PPSV23 (polysaccharide) recommended for over 65

Epstein Barr virus, cause of mononucleosis

Asymptomatic in children Causes infectious mononucleosis in adolescents, young adults EBV common worldwide (90% seropositive adults) In undeveloped areas it is an early childhood, asymptomatic disease. Development of permanent immunity In developed areas >50% of infections delayed until late adolescence, adulthood Spread by intimate contact (saliva) infects throat epithelia, then is latent in B-cells Incubation period 4-6 weeks Infectious for several weeks after incubation but......latency occurs The latency continues for life and you can reactivate and spread the virus at a later time Disease symptoms Fever, sore throat, swollen lymph glands, enlarged spleen Lasts from 1-4 weeks, resolves in 1-2 months, seldom >4 months

Bronchitis and pneumonia

Bacteria, viruses, and fungi can cause Bronchitis - inflammation of the upper region of the bronchi Bronchiolitis - inflammation of the middle region of the bronchi Pneumonia - infection and inflammation of alveoli in the lower lung region Pneumonia Infection of the lower respiratory system Can be caused by bacteria, virus, fungus Often named for bacteria that causes the disease. Eg. Pneumococcal pneumonia from S. pneumoniae Symptoms include a productive cough (you cough up fluids) fever, shortness of breath (dyspnea), chest pain during breathing Pneumonia Risk factors for pneumonia include smoking, HIV, some chronic diseases Can occur during influenza infection (bronchial cilia damaged, cannot clear bacteria from lungs by action of the muco-cilliary escalator) Treatment with antibiotics. May not work for elderly, chronically ill.

Blood/Lymphatic System

Blood A mixture of cells (red and white blood cells) and plasma (the liquid component) circulates in arteries and veins Arteries narrow to form capillaries that provide oxygen and nutrients to tissues Lymph Is plasma that has passed out of the capillaries , no red blood cells. Circulates in the tissues Carries nutrients to the tissues and picks up waste Lymphatic system - lymph nodes Lymph in the tissues is collected by the lymph vessels and recirculated back to the bloodstream Lymph vessels can easily pick up microorganisms or their products Lymph nodes containing macrophages, B cells and T cells. Antigen contact activates immune response

Sepsis and septic shock

Blood and lymph normally sterile, Infection or invasive medical procedures can cause contamination Blood may contain actively growing microbes or toxic products from the microbes Sepsis is a systemic inflammatory response to an infection Septic shock occurs when inflammation is so severe that fluid leaking from your blood vessels drops blood pressure to dangerous levels Condition can be fatal even with the addition of fluids to the circulation Can be caused by endotoxin released by death of Gram negative bacteria Sepsis and septic shock can occur from focal infection even if bacteria are not in the blood. Gram negative bacteria are the most common microorganism that causes septic shock Have endotoxin as part of LPS in cell wall, very potent for immune response Endotoxin can cause immune cells to release too much cytokine. Blood vessels become leaky, tissues swell, blood pressure drops dangerously low. However, Gram positive bacteria also cause sepsis Staphylococci and streptococci both have powerful exotoxins that can cause septic shock Invasive procedures can allow bacteria into bloodstream Puerperal sepsis (childbirth fever) also possible but uncommon due to modern hygienic practices Caused by S. pyogenes (beta hemolytic streptococcus) in uterus or abdominal cavity during birth or abortion procedure

Mycoplasmal Pneumonia (Walking Pneumonia)

Caused by Mycoplasma pneumoniae, a small bacterium without a cell wall. Causes what is commonly called atypical pneumonia or walking pneumonia. Disease is common in children and young adults May cause up to 20% of pneumonia cases (estimated 2 million cases/year) Person to person airborne droplet spread. Usually spread between people living together Incubation period 1-4 weeks Fever, headache, sore throat cough that lasts for weeks or months Estimates are that about 1 in 10 with Mycoplasma infection develop pneumonia Treat severe cases with antibiotics. Several types available for use. Severe symptoms can include serious pneumonia, asthma, encephalitis Can be diagnosed by serology or PCR ( bacterium is difficult to isolate and grow from sputum sample)

Rhinovirus (common cold)

Caused by Rhinoviruses (mostly) and several other types of viruses More that 200 known types that cause colds Infectious dose may be one rhinovirus Transmission most likely from contaminated fingers touching eyes or nose or contacting airborne droplets Virus may be viable for several hours on surfaces Symptoms include congestion, sneezing, runny nose. Usually no fever In majority of cases symptoms start 2 days after infection (can be as short as 20 hours or up to 4 days) For the first 3 days high numbers of virus in nasal mucus Why more colds in winter in temperate regions? Close contact? Low humidity makes for smaller, longer-lived droplets? Most cold viruses thrive at temperature slightly below normal body temperature This is why virus usually grows in nasal cells and stays isolated in upper respiratory system Virus can infect throat, lower respiratory system, middle ear May cause laryngitis, otitis media

Cholera

Caused by Vibrio cholerae, Gram negative rod, no endospore This bacterium is found in fresh or brackish water Can be endemic in some areas Sensitive to stomach acid so it requires a large dose to cause disease Disease caused by infection with this bacterium is Cholera Bacteria infect small intestine, grow and produce an exotoxin called "cholera toxin" The bacteria are not invasive This toxin causes abundant watery diarrhea (up to 3-5 gallons per day) Loss of fluids and electrolytes (salts, especially potassium) can cause shock, collapse and if untreated, death Treatment Rehydration therapy including intravenous replacement of fluids and salts Antibiotics can be effective Short term vaccine available for use in outbreaks

Rabies virus

Caused by the rabies virus Transmitted by animal bite Virus is in the saliva of infected animals and enters the muscle tissue thru a puncture wound Other exposures to saliva or infected tissues or aerosols are possibly infective but extremely rare Signs and symptoms Initially similar to flu. Fever, headache, weakness, discomfort. Can last for days Later includes itching at bite site followed by cerebral dysfunction. Anxiety, confusion, agitation, delirium, abnormal behavior. Excessive saliva. Disease characteristics Enters muscle by bite from infected animals saliva Moves through nerves to brain Multiplies in brain, causes inflammation (encephalitis) After 3-5 days signs of rabies appear (brain dysfunction). At this point it is fatal. Virus moves from brain to salivary glands. Excessive saliva now produced. Death follows this stage. Diagnosed in animal by 2 brain samples from different areas of the brain (post mortem) Results usually within 24-72 hrs (Rabies is an urgency, not an emergency) Humans diagnosed by samples of saliva, serum, spinal fluid, and sin biopsies of neck area https://www.cdc.gov/rabies/medical_care/index.html Rabies treatment CDC Treatment Immediately wash area with soap and water. Irrigate with iodine-based antiseptic if available Vaccine available, 4 shots in a 14 day period plus human rabies immune globulin (HRIG) If previously vaccinated then no HRIG is necessary Epidemiology Transmission almost exclusively by wild animals Raccoons transmit the most, then bats, skunks, and foxes

Rotavirus and Norovirus

Causes acute gastroenteritis Very common human diseases. Gastrointestinal diseases mush more lethal in developing countries Estimated that 90% of acute gastroenteritis cases caused by these 2 viruses Rotavirus - 3 million cases/yr in US. Estimated 90% of all children infected by 3 yrs of age Mostly in children and some of their unlucky parents Easily spread since high numbers of virus shed in feces Slight fever, diarrhea and some vomiting for about a week Peak transmission in winter. 1st vaccine withdrawn, live attenuated vaccine now available Norovirus - 20 million cases/yr in US. 50% of adults have evidence of exposure based on serology Fecal-oral transmission and even thru aerosols from vomiting. ID may be as low as 10 viruses Outbreaks often occur on cruise ships 2-3 days of vomiting/diarrhea. Virus still shed several days after patient is asymptomatic. Treat with oral rehydration or IV fluids in severe cases Naked virus (no envelope) so ethanol sanitizers not very effective. Mechanical removal probably most effective (also soap and water) Long survival on surfaces. Strong bleach solution effective. Many strains, immunity unlikely

Clostridium tetani

Common soil bacterium Obligate anaerobe, forms endospores Acquired by injury that gets contaminated by soil Bacteria do not spread from site of infection Usually in deep wounds with poor circulation, low oxygen Produces very potent neurotoxin (tetanospasmin) that spreads from wound site Toxin blocks neurotransmitter in muscle relaxation pathway Victim suffers non-stop muscle spasms Vaccine for tetanus is part of DTaP vaccine (diptheria, tetanus, and acellular pertussis) Booster required every 10 years Immunity good in young people, not so good in elderly DTaP vs Tdap vs Td. Check it out online Due to vaccination this disease is extremely rare (but..... https://www.livescience.com/64948-tetanus-unvaccinated-boy.html ) Clinical observations Incubation can be for days to weeks post injury Starts with localized muscular spasms (lockjaw), may become generalized (tetanic spasm) Any exterior stimulus can induce spasm Diagnose by history of injury, clinical symptoms Treatment Usually ineffective! Must take active measures. Treat by immunization, wound care, prophylactic antitoxin administration, penicillin Control by immunization

Rocky Mountain Spotted Fever (RMSF) (the disease and the tick life cycle)

First recognized in Snake river valley of Idaho in 1896 Called black measles due to rash In 1922 research into RMSF started in Hamilton after Montana's governor's daughter and son-in-law died from RMSF Rocky Mountain Labs (National Institutes of Health) started from a rough beginning in an abandoned schoolhouse Caused by intracellular bacterium Rickettsia rickettsii Transmitted by Rocky Mountain Wood Tick (Dermacentor andersoni) to animals (mice, deer in MT) D. andersoni very common in Western MT, especially in Bitterroot mountains Humans again accidental host as with Lyme disease About a week after tick bite a body rash develops includes palms of hands and soles of feet Rash accompanied by fever and headache Bacteria are intracellular so antibody response not very effective Serological tests not positive until late in illness so diagnosis usually requires observation of rash Antibiotic treatment is very effective R. rickettsii infection maintained in Dermacentor ticks by transovarial transmission - bacteria is passed from mother to larvae Transmission into mammalian host is similar to Lyme disease tick First symptoms 2-14 days after tick bite. About 1 week post infection rash similar to measles rash develops (except also on palms of hands and soles of feet also), fever and headache Bacteria infects endothelial cells lining blood vessels. Very few bacteria in the blood. Treatment with doxycycline should begin immediately, can be based on suspicion of disease. Use of other antibiotics is associated with higher risk of fatal outcome!

Gastroenteritis, diarrhea/dysentery

Gastroenteritis is the general term used for inflammation of stomach or intestines Gastroenteritis with diarrhea often requires oral rehydration therapy to replace fluids and electrolytes

Salmonella gastroenteritis

Gram negative bacterium. Facultative anaerobe. Can cause gastroenteritis - inflammation of stomach and intestine These bacteria commonly inhabit human and animal intestines Many different types (>2500 different serotypes) all considered pathogenic. Only around 50 serotypes commonly cause in disease in the US Gram negative rods, do not form endospores Infectious dose may be as low as 1000 bacteria Usually people are infected by contaminated foods or (occasionally) pets like turtles Normal cooking temperatures kill the bacteria Disease symptoms depend on bacterial dosage 12-72 hour incubation time before onset of symptoms Then fever, gut pain/cramping, diarrhea Bacteria penetrate into gut cells and multiply. They can pass out of these cells and enter lymphatics or blood circulation Recovery in several days but bacteria may be shed in feces for up to 6 months Mortality rate is very low (<1%) but highest in infants and elderly Thorough cooking kills bacteria but surfaces used to prepare foods can transfer bacteria to other items Treat with rehydration therapy Positive diagnosis by stool sample or contaminated food sample

Haemophilus influenza type b Hib

Gram-negative aerobic bacteria, part of normal throat microbiota Has capsule that makes it pathogenic. Especially those strains with the capsule subtype b (Hib) Causes meningitis, pneumonia, and ear infection (otitis media) Most cases occur in children under 4 years old Especially around 6 months of age as passive antibody protection from the mother starts to weaken This type of meningitis is prevented by the Hib vaccine Still accounts for about 45% of bacterial meningitis cases. Mortality rate of those infected is about 6% Gram negative coccobacilli. H. influenzae type b Antigens Based on capsular polysaccharides Transmission Direct contact with respiratory droplets from nasopharyngeal carrier or person with active infection Pathogenesis No exotoxins involved Non-capsulated form is part of normal respiratory microbiota Capsule is antiphagocytic. Capsule type b is the major virulence factor for this bacterium Type b carrier rate is <1% now due to vaccine coverage. Non-typeable strain rate is 50-80% Type b can cause meningitis, pneumonia, septic arthritis. Non-typeable can cause bronchitis, otitis media, sinusitis Meningitis due to Hib Colonized individuals develop invasive infection May be due to a viral infection in the area weakening the barrier, immune weakness or allergies Sinus region or choroid plexus are weak areas for blood brain barrier that may allow entry of bacteria Host factors involved can include loss of maternal antibodies or weak immune system in infants Clinical findings Often starts as middle ear or sinus infection Encapsulated bacteria can occasionally reach the bloodstream, travel to the meninges Immunity Before development of the vaccine Hib was the most common cause of bacterial meningitis in children 5 mos. to 5 years of age Antibodies can promote complement-based killing and phagocytosis of encapsulated Haemophilus so we can fight back Treatment Untreated infection can have up to 90% mortality Antibiotics are still effective........for now Prompt treatment can minimize neurological and intellectual impairment caused by meningitis Epidemiology In the United States, Hib disease is not common. In 2015, the incidence of invasive Hib disease was 0.08 cases per 100,000 in children younger than 5 years of age. It occurs primarily in under-immunized children and in infants. Prevented with use of a conjugated vaccine Conjugate can be tetanus toxoid or outer membrane proteins from Neisseria meningitidis This conjugated vaccine allows the immune system to recognize the capsular sugars and attack the encapsulated bacteria Contact with infected patient carries a low risk for adults but a high risk for nonimmune or unvaccinated siblings/young children

Hepatitis B, and C

Hepatitis B Same as HAV, add joint pain 5-10% chronic infections, can cause cirrhosis, cancer Hepatitis C Same symptoms as HBV but more asymptomatic hosts 55-85% chronic infections More chronic infection in hosts mean more cirrhosis, cancer Hepatitis B virus Enveloped virus. Spread by contact with blood or body fluids Sexually transmitted, injected drug users, and many others Virus infects hepatocytes. Cell-mediated immune response causes inflammation and cell lysis in the liver Acute infection - 95% of those infected as adults will recover completely Chronic infection - varies by age of infection Virus becomes chronic in 90% of infants and 25-50% of children 1-5 years old when infected Chronic infection can lead to cirrhosis of the liver or liver cancer many years after infection Treatment Vaccine available. Effective antibody level maintained for 20 years Drugs treatment for chronic cases but none reliably cure the disease. Patient may eventually require liver transplant Hepatitis C virus Enveloped virus Replicates in hepatocytes, small amount of virus released daily Transmitted through infected blood, transfusion, drug use, tattooing, dialysis Acute disease usually asymptomatic or very mild Antibody response to virus is not effective. Cell-mediated response kills infected cells but damages liver and does not completely clear the virus Most cases become chronic. Can lead to cirrhosis of liver or liver cancer. Can require liver transplant in many chronic cases Treatment Drug treatment with nucleotide analog Sovaldi (Gilead Sciences) $1000.00/pill, $84,000.00/course of drug for uncomplicated cases Estimated 3.2 million chronic cases in US. Most likely infected in 1970's and 1980's. About 25% will require liver transplant if untreated. You do the math! Chronic Hepatitis C In most cases 15-25% clear the virus so 75-85% have chronic infection Over time the chronic inflammation and cell damage either permanently damages large areas of the liver or causes changes that lead to cancer So in 100 infected people 75-85 are chronically infected 60-70 will develop chronic liver disease 5-20 will get cirrhosis of the liver over 20-30 years 1-5 will die from liver failure or liver cancer

encephalitis

Inflammation of the brain is called encephalitis This is often caused by viruses like rabies, measles, chicken pox and any virus with encephalitis in the name

Legionella

Legionella pneumophilia Gram-negative rod, resistant to low levels of chlorine sometimes found in water systems Can grow and form biofilms in low nutrient water, even in hot water systems Colonize air conditioning systems, showers, hot tubs, humidifiers Transmitted by inhaling aerosols; not transmitted from human to human Outbreak in NYC caused by contaminated air conditioning units on top of several buildings The bacteria was shown to have spread as much as 2 Km from the source and infected people Causes flu-like symptoms, lung congestion Disease more common and serious in smokers, heavy drinkers, those with chronic illnesses Mostly in men over 50 Legionella pneumophilia Aerobic, Gram negative, facultative intracellular bacterium Usually found intracellularly in amoeba in environment Found in moist, oxygenated conditions 8,000-18,000 hospitalizations per year Transmission Aerosolized bacteria can be inhaled. Many methods for transmission. Any infected water source that produces an aerosol can be route of transmission Signs and symptoms Cough, shortness of breath, muscle aches, fever, headaches Pontiac fever usually has milder symptoms Pathogenesis Inhalation of bacteria especially by weak or immunocompromised people causes most cases of this disease Bacteria easily grow in and multiply in alveolar macrophages and other phagocytes Bacteria multiply, burst cell, spreads infection Causes typical symptoms of pneumonia. Infection observable by radiography Bacteria cause either Legionnaire's disease (sometimes fatal) or Pontiac fever (usually self-limiting) 1 out of 10 cases of Legionnaires' are fatal. 1 out of 4 who get Legionnaires' in health care facility will die Immunity Antibodies produced but protection not well understood Cell-mediated response is critical since it is an intracellular pathogen Treatment Antibiotic treatment is recommended. Antibiotics used must be able to enter into the phagocyte in active form Epidemiology, Control Bacteria inhabit bodies of water that may be drinking water sources. Also inhabit cooling towers on air conditioning systems Can spread at least 6km from source Smoking, bronchitis, emphysema, diabetes, immunosuppression are all risk factors Control requires cleaning and sterilization of cooling towers, water sources

Clostridium botulinum

Most disease caused by intoxication, the ingestion of a previously formed toxin Infant botulism (most frequently from raw honey) is a gut infection with expression of toxin Wound botulism where bacteria or endospores enter skin in area with low oxygen perfusion (injected drug use) can also be a cause Botulinum toxin During intoxication toxin absorbed from gut Binds to presynaptic membranes of motor neurons in peripheral and cranial nerves Inhibition of neurotransmitter release at synapse prevents muscle contraction. Causes flaccid paralysis Lethal dose in humans approx. 1-2 ug/kg Toxin destroyed by heating - 20 min at 100oC BoTox also used for cosmetic purposes (wrinkles), relief of muscle spasm from cerebral palsy or other CNS disorders Normal neurotransmitter release requires protein (SNARE) complex to bind vesicles to membrane for release Botulinum toxin is proteolytic and cuts SNARE proteins preventing vesicle binding. No muscle activation Pathogenesis - Clinical findings 18-24 hrs after ingestion of toxin - visual disturbance (double vision), difficulty swallowing, can lead to respiratory paralysis, cardiac arrest. Patient conscious throughout. No fever, no antitoxin produced (no anti-botox antibodies, convenient!) In infants, poor feeding, weakness, paralysis (floppy baby syndrome) Treatment is by IV administration of trivalent antitoxin that neutralizes the toxin

Respiratory syncytial virus (RSV)

Pneumonia can occur as a complication of some viral infections, especially influenza. Influenza can kill your ciliated cells making it more difficult to clear bacteria from your lungs. Respiratory Syncytial Virus (RSV) Common in infants; 4500 deaths annually in infants 2-6 months of age Spread by coughing, sneezing, contact with respiratory secretions Often acquired outside of home (Eg. childcare) Epidemics usually in winter and early spring Symptoms: bronchitis, croup, or pneumonia in infants Coughing and wheezing, struggle to breath 25-40% of infected infants and young children show signs of pneumonia Diagnosis: serological test for both the viruses and antibodies to it Treatment with antiviral drug or in high risk cases with a monoclonal antibody that recognizes and binds to RSV

Poliovirus

Polio ssRNA genome, naked virus. Human host only, no other reservoir Likely ancient disease of mankind (Egyptian paintings) Recognized as a distinct disease in 1840, virus identified in 1908 Endemic disease worldwide until the 1880's In Europe, U.S., Australia, epidemics of paralytic disease increased until 1950's when a vaccine was developed Improved sanitation increased disease virulence starting in the early 20th century in the US and other developed countries. How is this possible? Transmission Poliovirus Only infects humans Eradication of this disease worldwide is very close. Once it is gone from humans it is permanently gone (cross your fingers) Fecal-oral or oral droplet transmission Person to person, contact with infected mucus or feces Can be food or water borne Virus is resistant to many treatments but killed by heat, chlorine Seasonal spread in temperate areas, mostly year-round in tropics Virus enters mouth, nose Infects throat, tonsils, intestinal tract Absorbed thru tissues, spreads systemically Systemic spread starts in lymphatic system, causes secondary fever, virus passes into bloodstream. Infectious virus released 7-10 days before and 7-10 days after symptoms appear. Initially oral and fecal release of virus but oral release quickly ends, fecal continues for several weeks Circulating virus in some cases may enter peripheral nerves, spread through axons. Neuronal intracellular multiplication can damage these cells, can cause paralysis Likelihood of paralysis increases with age you are when infected with the virus for the first time. With CNS involvement 1:1000 children have paralysis, 1:75 adults. Poliomyelitis (Polio) Transmitted by ingestion Initial symptoms: sore throat and nausea Viremia (large number of virus in general circulation) may occur; if persistent, virus can enter the CNS Destruction of motor cells and paralysis occurs in <1% of cases Paralysis more common if you get the disease as adolescent or adult, not as a child Prevention: vaccination Live attenuated oral vaccine provides immunity at site of infection in intestines. Protects against reinfection which could spread virus Inactivated (killed) polio vaccine is injected. Provides immunity to systemic polio infection so no paralysis but you can still get intestinal infection and spread the disease

Toxoplasma gondii - toxoplasmosis

Protozoan parasite with two host life cycle A definitive host where parasite sex occurs and An intermediate host where parasite invades tissues (meat) Cats (usually) are definitive host Cat eats an infected mouse and parasite multiplies in cat intestine Cysts form in cat colon and are released in feces Cysts mature to form spores with multiple parasites in each one Mice or ruminants ingest spores and parasites invade tissues Cats eat mice (or rarely, cows) Ingestion by humans From undercooked meat or accidental ingestion of spores from cat litter box Infection of human gut causes protozoans to penetrate gut wall and spread through body, invading tissues Eventually the parasite forms tissue cysts filled with infective parasites (this can continue the cycle if you are eaten by your cat - watch it closely!) Most human disease is asymptomatic but if pregnant woman gets toxoplasmosis then fetus can be infected Parasites can cause damage in various organs. Can cause brain damage or eye damage. Infection during certain stage of pregnancy can cause profound mental or optical defects to child or possible stillbirth

Clostridium difficile

Resident in gut in 2-5% of adults Antibiotic treatments cause increase in drug-resistant bacteria including C. difficile Less competition from normal gut bacteria allows increased growth of C. difficile and increase in its toxins Up to 25% of antibiotic-associated diarrhea caused by C. diff Use of certain antibiotics associated with this infection since they kill other bacteria, leave Clostridia. When antibiotic treatments stopped usually the diarrhea stops or get much better Colonized patients can have no symptoms but can shed endospores Shed in feces, bacterium easily transmitted by spores. Spores long-lived on surfaces Common syndrome in assisted living facilities, hospitals 2015 data - 500,00 cases, 29,000 deaths within 30 days of diagnosis. 15,000 directly attributed to C. diff. 80% of cases in 65 years or older

endocarditis

The endocardium is the inner layer of the heart, lining the heart muscle and covering the valves Endocarditis - inflammation of the endocardium Caused by subacute (slowly developing) or acute bacterial infection Subacute can come from tooth infection or extraction or tonsillectomies Bacteria can attack and infect defective heart valves or damaged heart muscle from past disease or damage Acute (rapidly progressing) can come from S. aureus or Streptococcal infection

Coronaviruses

These viruses have ribonucleic acid (RNA) as their genetic material and have many projections that look like a halo or "corona." This family of viruses causes many forms of the common cold. Coronaviruses are a large family of viruses that usually cause mild to moderate upper-respiratory tract illnesses, with symptoms like the common cold. There are hundreds of coronaviruses, most of which circulate among animals including pigs, camels, bats and cats. Sometimes those viruses jump to humans—called a spillover event—and can cause disease. Seven coronaviruses are known to cause human disease, four of which are mild: viruses 229E, OC43, NL63 and HKU1.

Lyme disease (all details including chronic)

Tick-borne bacterial disease Caused by spirochete Borrelia burgdorferi Carried by ticks in Central, East and West coast areas of US Very small tick, hard to tell you are being bitten Life cycle includes mice and deer Humans just accidental hosts Infection often diagnosed by bulls-eye rash on skin Flu-like symptoms as bacteria multiply in blood Antibiotic treatment usually effective Chronic infection can cause long-term symptoms including neurological and arthritis-like symptoms Larval tick (earliest stage) picks up bacteria from mouse reservoir. Bacteria have no effect on mice Ticks have 3 life stages, larva, nymph, adult Usually feed on mice and deer If infected tick gets on human host it takes at least 24 hrs to penetrate skin, usually 2-3 days before it starts taking blood meal Tick takes in blood and reinjects tick saliva and plasma back into host Bacteria start reproducing at bite site, usually produces erythema migrans, then spreads systemically Untreated infection can cause serious to severe symptoms Severe headache, neck stiffness Arthritis (autoimmune response to bacterial antigens) Facial palsy, joint pain Irregular heartbeat, dizziness, shortness of breath Short term memory loss Untreated infection can cause serious to severe symptoms Severe headache, neck stiffness Arthritis (autoimmune response to bacterial antigens) Facial palsy, joint pain Irregular heartbeat, dizziness, shortness of breath Short term memory loss Initial phase - flu-like symptoms 2nd phase - nerve damage (facial paralysis) , fatigue, or memory loss may occur Months later a 3rd stage may occur with arthritis lasting for years Arthritis likely due to immune response to bacteria or bacterial antigens Diagnosis difficult without evidence of tick bite Dependent on serology which is apparently difficult to interpret

Cytomegalovirus, all details

Widespread in entire population Transmitted by contact with body fluids (kissing, day care, sexual transmission) Virus probably latent in white blood cells Virus avoids antibodies by slow replication and spread between cells in contact with each other In healthy people infection causes either no symptoms or minor symptoms https://www.cdc.gov/cmv/ CMV Transmission Can be intrauterine if mother contracts virus just before or during pregnancy Virus in body fluids; saliva, urine, breast milk, sexual contact and transfusions Children can shed virus for months after initial infection Pathogenesis Asymptomatic or few (nonspecific) symptoms except in newborns Similar to mild case of infectious mononucleosis Treatment Nucleoside analog drugs similar to Acyclovir Complications Congenital infection can lead to long-term disabilities. Developmental defects, etc

otitis media (OM)

inflammation of the middle ear (also called tympanitis) Earache, can have many causes but the bacteria usually involved are: Strep. pneumoniae (35%) vaccine available H. influenzae (20-30%) vaccine available Strep. pyogenes (8-10%) Staph. aureus (1-2%) An infection of the middle ear either by bacteria or viruses can produce pus. Pressure against eardrum causes pain. Usually treated with broad-spectrum antibiotics which are effective against bacterial infections S. pneumoniae can also cause otitis media but vaccine for this bacterium has lowered incidence of earache by 6-7% (or about 1/2 million cases per year in US)

mechanisms that can cause meningitis

meningitis is caused by reaction to a microbial infection that gets past the blood-brain barrier, and systemic inflammation can also cause the blood-brain barrier to get leaky and let microbes pass. Can be caused by bacteria and viruses. Viruses are the most common cause of meningitis but usually cause milder disease Viral meningitis is more common in summer and fall Can be caused by enteroviruses that grow in your throat and intestinal tract Can also occur as a complication of mumps, chicken pox, or influenza Bacterial meningitis diagnosed by observation of bacteria in cerebrospinal fluid Often Gram stain is all you need to identify general bacterium type and this may indicate type of treatment you should start Only 3 types of bacteria cause most cases of meningitis All 3 have a capsule! Severe disease can develop rapidly Inflammation and shock are caused by the release of bacterial components during infection. Endotoxins from Gram negatives and peptidoglycan and teichoic acid from Gram positives will cause this reaction.