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Chapter 27

Terms in this set (65)

Circulation of Blood and Lymph
Supplies nutrients and O2 to cells, removes waste
• Also heats, cools to maintain optimum temperature
• Infections can be serious, since infectious agents can become systemic, or carried throughout body
• Conditions named after infectious agent
• Bacteremia, viremia, and fungemia
- Does not imply a disease state and may not involve symptoms—e.g., person can become transiently bacteremic after brushing teeth
Sepsis
(blood poisoning) is illness from circulating agent or toxins
- Can cause blood pressure to plummet,
leading to septic shock
Cardiovascular System
Heart, blood vessels, blood
Lymphatic System
Lymph, lymph vessels, lymph nodes, and lymphoid organs including tonsils, appendix, spleen
• Phagocytic cells remove infectious agents, foreign material
Both Cardiovascular and Lymphatic System normally sterile (T or F)
True
The heart
• Muscular pump enclosed in fibrous sac, or pericardium
• Septum divides into right and left sides; each divided into two chambers: atria (receive blood), ventricles (discharge)
- Valves at entrance and exit of each ventricle prevent blood flow from reversing
- Infections of heart valves uncommon; can be serious
Blood Vessels
• Arteries, veins, capillaries
• Arteries have thick muscular walls; blood is bright red due to oxygenated hemoglobin
- Infections rare, but aorta can be
weakened by syphilis
- Arteriosclerosis increases risk of heart attacks, stroke; bacteria, viruses may play a role
• Veins contain dark red blood depleted
of O2; valves prevent backflow, since pressure is low
Lymphatics (Lymphatic Vessels)
Vessels resemble blood capillaries, but larger • Carry almost colorless lymph; comes from plasma
• Seeps through capillaries to become interstitial fluid surrounding tissue cells, which it bathes, feeds
• Easily permeable, takes up foreign material • One-way valves, contraction of vessel walls,
compression by body's muscles maintain flow to multiple lymph nodes
• Contain phagocytic cells and lymphocytes to trap, destroy foreign material such as microbial cells
• Lymph flows out of nodes through vessels that combine into one large tube, the thoracic duct
• Discharges into large subclavian vein behind left collarbone, back into main blood circulation
• Infection of limb may result in visible red streak spreading from infection site called lymphangitis
• Blood, lymph both carry leukocytes, antimicrobial proteins (antibodies, complement, lysozyme, interferon); inflammatory response may cause vessels to clot
Spleen
• Fist-sized organ behind stomach; has two tissue types
• Red pulp (multiple blood-filled passageways)
- Cleans blood by filtration
- Can produce new blood cells
- Has reserve of monocytes
• White pulp (lymphoid tissue)
- Contains B and T lymphocytes
Bacterial diseases of the blood vascular system
Not common; can kill quickly or proceed slowly
• Usually bacteria carried into bloodstream by flow of lymph from area of infection in tissues
Endocarditis
infection of heart valves or surfaces
Acute bacterial endocarditis
starts suddenly with fever
• Usually caused by virulent species such as Staphylococcus aureus or Streptococcus pneumoniae
- Quickly destroy heart valves, form abscesses in muscle that lead to heart failure
Subacute bacterial endocarditis
usually caused by organisms with little virulence, proceeds more slowly
• Less likely to be fatal
Sepsis is caused by:
both Gram-negatives and positives,
also other infectious agents
Signs and Symptoms of Subacute bacterial endocarditis (SBE)
• Noticeable fatigue, slight fever
• Typically become gradually ill and
lose energy over weeks or may suddenly develop
Causative agent of subacute bacterial endocarditis (SBE)
• Usually normal microbiota of mouth or skin such as viridans streptococci and Staphylococcus epidermidis
- Shed from heart valve into blood
- Identified by cultivating samples from arm vein
- Not always possible; may be cleared by lung phagocytes; others cannot be cultured in cell-free media (e.g., Coxiella burnetti)
- PCR, nucleic acid probes used to identify
Pathogenesis of Subacute Bacterial Endocarditis (SBE)
• Bacteria enter blood during dental procedures, tooth brushing, or trauma; can get trapped in thin blood clots that form around deformed heart valves
- Multiply, form protective biofilm
- Bacteria continually wash off into circulation; pieces of infected clot (septic emboli) can break off, block important blood vessels, lead to tissue death
- Can cause vessel to weak and balloon out: aneurysm
• High antibody levels often found; may lead to harmful immune complexes that may lodge in skin, eyes, other structures; trigger inflammatory response
- Glomerulonephritis in kidneys
• May penetrate heart tissue: abscesses, damaged valves
Epidemiology of Subacute Bacterial Endocarditis (SBE)
• Viridans streptococci less common recently, but increasingly antibiotic-resistant
- May be from prophylactic antibiotic treatment
• Also occurs in injected-drug abusers, patients with intravenous catheters, artificial heart valves
- Usually infected with S. epidermidis, S. aureus, S. enterococci, wide variety of species
Treatment and Prevention of Subacute Bacterial Endocarditis (SBE)
• Long term antibacterial medications
• Artificial implants often must be replaced
• No methods to prevent; antibacterial medications given before bacteremia- causing procedures in susceptible individuals
Signs and Symptoms of Sepsis and Septic Shock
• Severe sepsis results in violent shaking, chills, fever
- Often rapid breathing, anxiety
• If septic shock develops, urine output drops, respiration and pulse increase, arms and legs become cool, dusky
Causative agent of Sepsis and Septic Shock
• Systemic infection by any microorganism can cause
• Most fatal cases involve Gram-negatives due to endotoxin
• Normal members of microbiota of large intestine, especially facultative anaerobes E. coli, other enterobacteria, also
anaerobes such as Bacteroides
• Environmental bacteria such as Pseudomonas aeurginosa
Pathogenesis of Sepsis and Septic Shock
• Almost always from infection site other than bloodstream
• Normal body defenses compromised by medical treatments (surgery, catheters, certain medications)
• Progresses in stages
• Toll-like receptors (TLRs) on macrophages, neutrophils detect pathogen-associated molecular patterns (PAMPs) (endotoxin, other bacterial products); release cytokines
- Systemic release yields cytokine storm - Complement pathway also activated, further amplifies
- Additional phagocytes recruited, produce more TLRs; increased sensitivity to PAMPs further amplifies
• Response to PAMPs and damage-associated molecular patterns (DAMPs) yields devastating outcomes
- Inhibition of systems that normally control inflammation
- Suppression of adaptive immune response
- Activation of coagulation cascade causes small clots to form in capillaries; blockage leads to hypoxia, necrosis
- Widespread clotting called disseminated intravascular coagulation (DIC); may lead to multiorgan failure
- Phagocytes release tissue-damaging lysosomal enzymes; may seriously damage lungs
- Hypotension causes further damage, organ failure
- Patient may survive initial sepsis but not later effects
Epidemiology of Sepsis and Septic Shock
• Mainly a healthcare-associated disease; bloodstream infections in patients with impaired host defenses
• Rates increasing, likely due to longer life spans, antibiotic suppression of normal micro- biota, immunosuppressive medications
• Use of medical equipment where biofilms readily form (respirators, catheters) also increases risk
Treatment and Prevention of Sepsis and Septic Shock
• Antimicrobial medications to clear causative organisms
- Bacteriocidal antibiotics often lyse cells, increase risk of endotoxin from Gram-negative organisms
• Treatment for shock, tissue hypoxia
• Fluid replacement and support for organ dysfunction
• New treatments being evaluated
- Monoclonal antibodies against endotoxin or pro- inflammatory cytokines (e.g., tumor necrosis factor)
- Drotrecogin alfa (activated human protein C), which opposes effects of pro-inflammatory cytokines
• Sepsis prevented by quick identification, treatment
• Treatment of predisposing conditions
Signs and Symptoms of Tularemia (Rabbit Fever or Deer Fly Fever)
• If injury, ulceration typically develops at site after 2-5 days
- Regional lymph nodes enlarge
- Fever, chills, aches
- Usually clear in 1-4 weeks, sometimes last months
• If organism inhaled or infects lungs from bloodstream, pneumonia can occur
- Dry cough, pain beneath sternum due to enlarged lymph nodes
- Tularemic pneumonia rare; mortality rate ~30% if untreated
Causative agent of Tularemia (Rabbit Fever or Deer Fly Fever)
• Francisella tularensis: non-motile, aerobic, Gram-negative rod; requires medium enriched with cysteine
- Named after Edward Francis, who studied in early 1900s, and Tulare County, CA, where first studied
Pathogenesis of Tularemia (Rabbit Fever or Deer Fly Fever)
• Enters breaks in skin, mucous membranes • Carried to regional lymph nodes; become large, tender
- Nodes may fill with pus and drain spontaneously • Spreads via lymphatics and blood vessels • Grows within phagocytic cells that ingest
- May explain why disease persists in some despite high antibody titers
Epidemiology of Tularemia
• Widespread in Northern Hemisphere, including all states in U.S. except Hawaii; found in wild animals
- In eastern U.S., infection from tick bites in summertime
- Cases often from skinning rabbits, hence name
- Animals generally free of illness but are carriers
- In western U.S., infections from ticks and deer flies
- 150-250 cases reported annually
- Epidemics of inhalation tularemia have occurred from dust from mowing lawns, rodent-infested buildings
- Can be contracted by ingesting contaminated material
- F. tularensis listed as category A (highest-risk) bioterrorism agent
Treatment and Prevention of Tularemia
• Streptomycin usually effective; also ciprofloxacin or gentamicin
• Use of rubber gloves and goggles or face shields when skinning or handling wild animals
• Insect repellants, protective clothing help protect against insect and tick vectors
- Removal of ticks helps avoid
• Thorough cooking of meat from wild animals
Signs and Symptoms of Brucellosis (Undulant Fever or Bang's Disease)
• Symptoms start gradually, are vague
• Mild fever, sweating, weakness, aches and pains, enlarged lymph nodes, depression, weight loss
• Recurrence of fevers over weeks or months • Recovery within 2 months without treatment; only 15% symptomatic for more than 3 months
Causative agent of Brucellosis (Undulant Fever or Bang's Disease)
• Brucella are small, aerobic, nonmotile Gram-negative rods with complex nutritional requirements
- Only one species (Brucella melitensis), but named after host: B. abortus (cattle), B. canis (dogs), B. melitensis (goats), B. suis (pigs)
Pathogenesis of Brucellosis (Undulant Fever or Bang's Disease)
• Penetrate mucous membranes or breaks in skin, are disseminated to heart, kidneys, other parts of body
• Infection causes enlargement of spleen
• Can grow within phagocytes, avoid antibodies, antibiotics
• Low mortality rate; death generally from endocarditis
• Osteomyelitis (bone infection) is rare complication
Epidemiology of Brucellosis (Undulant Fever or Bang's Disease)
• Typically chronic infection of domestic animals
- Mammary glands, uterus
• Causes millions of dollars in agricultural losses globally
• Occupational exposure, consumption of unpasteurized milk products, hunting; category B bioterrorism agent
Treatment and Prevention of Brucellosis (Undulant Fever or Bang's Disease)
• Doxycycline with rifampin or streptomycin for 6 weeks
- Some chronic cases may require 6 months or more
• Pasteurization of dairy products, inspection of animals for evidence of disease
• Protective gear (goggles or face shield, gloves) for veterinarians, butchers, slaughterhouse workers
• Attenuated vaccine controls disease in domestic animals
Signs and Symptoms of the Plague (Black Death)
• Following flea bite, symptoms appear within 2-6 days
- Enlarged and tender lymph nodes called buboes
- High fever, shock, delirium, patchy bleeding under skin
• Following inhalation of respiratory droplets from infected patient or animal, pneumonic plague may develop
- Cough, bloody sputum arise within 1-3 days • If spread by bloodstream, septicemic plague may develop
- Endotoxin released causes shock, also disseminated intravascular coagulation, which causes bleeding into skin and organs, produces red or black patchy rash
Causative agent of the Plague
• Yersinia pestis: like other enterobacteria, facultatively anaerobic, Gram-negative rod
- Non-motile, grows best at 28°C
- With certain dyes, ends stain more intensely
Pathogenesis of the Plague (Black Death)
• Forms biofilms in digestive tract of infected fleas, blocks
- Fleas starve, increasing likelihood of feeding - Causes bacteria to be
regurgitated into bite
wound
- Can transmit via saliva even if unobstructed
• Multiple virulence factors allow it to avoid host defenses
• Some on bacterial chromosome, others on plasmids
• Protease (Pla) clears lymphatics and capillaries of clots, inactivates certain complement system components
- Allows organisms to spread
- Taken up by macrophages in regional lymph nodes
- Sense intracellular conditions, turn on genes to resist killing effects of macrophages, multiply
- Acute inflammatory reaction develops in lymph nodes
• Infected macrophages die, release bacteria • Now ready to withstand host defenses
- Yops proteins and capsule allow Y. pestis to avoid phagocytosis; iron acquisition proteins trap hemin
• Lymph nodes become necrotic; numerous bacteria spread into bloodstream
- Endotoxins cause septicemic plague
- Dark hemorrhages and dusky skin, mucous
membranes from DIC probably inspired "black death"
- 10-20% infect lungs, leading to pneumonic plague; respiratory droplets can transmit fully virulent pathogen
Epidemiology of the Plague (Black Death)
• From 1346-1350, killed ~25% of population of Europe
- Crowded conditions in cities, large rat population
• Plague listed as category A bioterrorism disease
• Endemic in rodent populations worldwide except Australia
• In U.S., mostly occurs in about 15 states in the West
- Prairie dogs, rock squirrels, their fleas main reservoir
- Rats, rabbits, dogs, cats can also be hosts
- Hundreds of species of fleas able to transmit; remain infectious for a year or more - Respiratory droplets produced by coughing can spread
- Cases increasing as humans expand into areas where main reservoirs live; African countries highest number
Treatment and Prevention of the Plague (Black Death)
• Antimicrobial medications especially if given within 24 hours of onset of symptoms
• Bubonic plague has ~50-80% mortality without treatment
• Pneumonic plague has ~100% mortality if untreated
• Rat control measures (garbage disposal, rat-proofing buildings, rat extermination programs) important
- Extermination must be combined with insecticide use to prevent escape of infected fleas from dead rats
• No current vaccine, but new genetically engineered vaccines being evaluated under joint agreement among U.S., Canada, and U.K.
• Tetracycline given preventatively to exposed individuals
Signs and Symptoms of Infectious Mononucleosis (Mono or Kissing Disease)
• Appear after long incubation period, usually 30-60 days
• Fever, soar throat covered with pus, marked fatigue, enlargement of spleen and lymph nodes
• Fever, sore throat gone in ~2 weeks; others in ~3 weeks
Causative agent of Infectious Mononucleosis (Mono or Kissing Disease)
• Epstein-Barr virus (EBV), a double-stranded DNA virus of herpesvirus family
• Identical in appearance, but not closely related to others
Pathogenesis of Infectious Mononucleosis
• Infects mouth, throat
• Replicates, is carried to lymph nodes
• Infects B lymphocytes
- Productive: virus replicates, kills B cell
- Non-productive: latent infection as plasmid or provirus; most common, causes proliferation of B cells, production of immunoglobulins
• B cell proliferation causes lymph node and spleen enlargement; spleen occasionally ruptures, is fatal
• T cells actively respond, destroy
B cells with productive infections since they display viral antigens
- Abnormal lymphocytes seen in smears are effector cytotoxic T cell responding to infected B cells
• EBV genome detectable in nearly all cases of Burkitt's lymphoma and nasopharyngeal carcinoma
- Other factors likely involved
• May be factor in some malignant tumors in immunocompromised
Epidemiology of Infectious Mononucleosis
• Worldwide distribution
• Infects individuals in crowded, poorer groups at early age without significant illness
• In more affluent populations, fewer are infected
- Lack immunity, may therefore get when exposed later in life (e.g., entering college)
- In 15-24 year olds, only ~1/2 of infections symptomatic
• EBV present in saliva for up to 18 months after infection
- Occurs intermittently for life
- Mouth-to-mouth kissing is important mode of transmission in young adults
• By middle age, most have antibody, indicating infection
Treatment and Prevention of Infectious Mononucleosis (Mono or Kissing Disease)
• Antivirals such as acyclovir, famciclovir inhibit productive infection; helpful in rare serious cases
- No activity against latent infection
• Cortison-like medication sometimes useful in relieving airway obstruction from swollen tissue
• Avoiding saliva of others, including contaminated items such as tooth- brushes, drinking glasses
• No vaccine
Signs and Symptoms of Yellow Fever
• Mild form most common, yields fever, slight headache
• Severe disease produces high fever, nausea, bleeding from nose and into the skin, "black vomit" from gastrointestinal bleeding, and jaundice
- Mortality rate can reach 50% or more
• Reasons for variation in severity unknown
- Probably due to infectious dose and host immunity
Causative agent of Yellow Fever
• Enveloped, single-stranded RNA arbovirus of flavivirus family
• Transmitted by bite of infected Aedes aegypti mosquitoes
Pathogenesis of Yellow Fever
• Transmitted by bite of infected mosquito, multiplies in local host cells, enters bloodstream, is disseminated
• Liver damage results in jaundice and decreased production of clotting proteins
• Injury to small blood vessels produces petechiae, tiny hemorrhages, throughout body
• Viral replication, immune system response damages circulatory system, causes bleeding, disseminated intravascular coagulation (DIC)
• Kidney failure commonly results from loss of blood flow
Epidemiology of Yellow Fever
• Infected mosquitoes, primates in tropical jungles in Central and South America and Africa
Treatment and Prevention of Yellow Fever
• No proven antiviral treatment
• Spraying insecticides, eliminating breeding sites of vector
• Control in jungle almost impossible; mosquitoes live in forest canopy, transmit to monkeys
• Highly effective attenuated vaccine available
Signs and Symptoms of Dengue Fever
• Many cases asymptomatic or subclinical
• If occur, begin with sudden onset of fever for 2-7 days
- May recur 12-24 hours later (biphasic fever) • Headache, joint and muscle pain, pain behind eyes, maculopapular rash that may later become hemorrhagic, with development of petechiae
- Rash does not appear in mild cases, often leading to misdiagnosis of influenza or other viral disease
• Mild mucosal bleeding may occur in nose or gums
• Sore throat, abdominal pain, vomiting, diarrhea may occur
• Usually self-limiting, rarely fatal
• Dengue hemorrhagic fever (DHF) can occur in second infection, may lead to dengue shock syndrome (DSS)
- Weak, rapid pulse, moist skin, restlessness, low blood pressure, bleeding in form of petechiae, easy bruising
- Massive gastrointestinal, vaginal bleeding may occur
- Widespread blood clotting, DIC may develop later
- DHF mostly found in children under 15; can be fatal
Causative agent of Dengue Fever
• Single-stranded RNA virus of flavivirus family
• Four closely related serotypes (DENV1, DENV2, DENV3, DENV4) transmitted Aedes mosquitoes
- A. aegypti most commonly, also A. albopictus
Pathogenesis of Dengue Fever
• Dengue viruses injected by mosquito, infect keratinocytes and epidermal dendritic cells
- Cells migrate to lymph nodes; monocytes and macrophages are recruited, also become infected
- Virus multiplies in macrophages, are disseminated
- Humoral and cell-mediated immune responses clear
- Pathogenesis not well understood; no animal model
• DHF and DSS better understood, occur in people with second dengue infection by a different strain than the first
• Antibody-dependant enhancement (ADE) suggested to explain severity of disease
- Preexisting dengue antibodies thought to bind to viruses, form immune complexes, but not neutralize
- Instead, facilitate viral entry into cells expressing Fc receptors, especially macrophages
- Infected macrophages produce cytokines, result in cytokine storm; along with activated complement and cytokines from memory T cells causes damage
Epidemiology of Dengue Fever
• Known as "break-bone fever" or bone-crusher disease"
- Causes severe joint and muscle pain
• Most common, fastest spreading viral disease in the world
• Predominantly in tropical or subtropical regions with high rainfall and plentiful fresh water
- Includes Southeast Asia, western Pacific, eastern Mediterranean, the Americas, rural areas in Africa and the Caribbean; endemic in more than 100 countries
• Increased geographical spread linked to international travel, breakdown of vector control measures, and global trade of goods that increase vector habitats
• WHO estimates 50 million new cases each year
- 2.5 billion at risk of contracting
Treatment and Prevention of Dengue Fever
• Analgesics can help; aspirin, non-steroidal anti-inflammatory (e.g., ibuprofen) avoided, can worsen bleeding
• Oral rehydration therapy, platelet or blood transfusions
• Mosquito control: insecticides, biological control
• Use of insecticide-treated mosquito nets, insect repellants
• Significant vaccine progress; tetravalent vaccine difficult
Chikungunya (CHIK)
• Named after African word, means "that which bends up"
• Caused by Chikungunya virus, an alphavirus of Togaviridae family
• Transmitted by Aedes mosquitoes, especially A. aegypti and A. albopictus
• Signs, symptoms similar to dengue fever
• Fever lasts 2-5 days, followed by severe joint pain especially in extremities that can persist weeks or months
- Chronic joint problems may develop
• Occurs mainly in Africa, Asia, and Southeast Asia
• Vector now present in Brazil, Central America, the U.S.,
and many European countries; has adapted to conditions
• No specific treatment; vector control important
Ebola Hemorrhagic Fever
• Ebola Hemorrhagic Fever (EHF)
• Caused by Ebola virus, named after Ebola River Valley in Democratic Republic of the Congo
• Five different species; four cause disease in humans
• Is one of two virus genera in Filoviridae family
• Causes severe, often fatal disease
• Rapid onset of fever, headache, abdominal pain, joint and muscle pain, sore throat, macular rash, and bleeding
• Virus causes capillary fragility and disrupts clotting; patients bleed from mucous membranes and body orifices; bloody vomit, diarrhea common
• Massive internal and external bleeding leads to fatality in 50-80% of cases; death is by multiorgan failure or shock
• Found in various African countries where social and economic conditions favor
• Patients kept hydrated; blood, O2 levels maintained
• Plasma containing coagulation factors given • Prevention is difficult; natural reservoir is unknown
- Suspected fruit bats carry
• Ebola virus transmitted by contact with bodily fluids
• Found in other animals including gorillas, chimpanzees; high mortality makes them unlikely reservoirs
• Quick diagnosis, rapid response essential to prevent spread; healthcare workers must be stringent in use of protective gear and infection-control measures
Marburg Hemorrhagic Fever
• Caused by Marburg virus, second genus in family Filoviridae
- Named for German town of Marburg; several died from MHF after handling infected African green monkeys
• Signs, symptoms similar to EHS; include fever, rash, abdominal pain, nausea; jaundice, liver failure may occur
- Bleeding from orifices is rare
• Patients may be misdiagnosed because symptoms resemble malaria or typhoid fever as well
• Fatality rate up to 25%
• Found in Africa; cases in Europe and U.S. imported
• Treatment, transmission, reservoir comparable to EHF
Protozoa infect cardiovascular, lymphatic systems
• Millions infected annually worldwide
• Malaria is leading cause of morbidity and mortality
• Trypanosoma brucei causes African sleeping sickness
• T. cruzi causes Chagas' disease
• Leishmania species cause visceral leishmaniasis
Malaria
• Ancient disease, found in early Chinese, Hindu writings
• During 4th century B.C., the Greeks noticed association with swamps, began drainage projects to control
• Italians named malaria, or "bad air" in 17th century
• In 1902, Ronald Ross received Nobel Prize for demonstrating life cycle of protozoan cause of malaria
• Most common serious infectious disease worldwide
• In 1955, WHO began program for global elimination
• Insecticides such as DDT to kill vector
• Diagnosing and treating infected patients
• Initially successful—52 nations participated
- By 1960, 10 had eradicated
• Unfortunately, mosquito vectors developed resistance
• In 1976, WHO acknowledged failure
• Today, over 300 million infected annually
- More than 1 million deaths per year
- More than when the eradication programs first began
Signs and Symptoms of Malaria
• Flulike, with fever, headache, and pain in joints, muscles
• Begin about 2 weeks after being bitten sometimes later
• After 2-3 weeks, symptoms fall into three phases
- Cold phase: shaking chills that last as much as an hour
- Hot phase: temperature rises sharply to 40°C or more
- Wet phase: temperature falls, drenching occurs
• Cycle of intense symptoms is called a paroxysm
• Except for fatigue, patient feels well until 24 or 48 hours later, when next paroxysm occurs
Paroxysm
Cycle of intense symptoms
Causative agent of Malaria
• Protozoa of genus Plasmodium, transmitted by infected female mosquito species of genus Anopheles
• P. vivax, P. falciparum, P. malariae, P. ovale, P. knowlesi
• Complex life cycle: liver stage (exoerythrocytic stage) and red blood cell stage (erythrocytic stage)
• Infectious form is called sporozoite; is carried by bloodstream to liver, infects hepatocytes
• Parasites enlarge, divide asexually, produce thousands of merozoites, which infect red blood cells (RBC)
- Some species can form hypnozoites that can live in hepatocytes for years before reproducing
• Merozoites develop into larger motile trophozoite (feeding stage) and then schizont (reproducing stage)
• Schizont divides asexually to yield merozoites when RBC ruptures; then enter new RBCs and multiply, repeat cycle
• Some that enter RBCs develop into gametocytes (specialized sexual forms), which are transmittable form
• Upon entering mosquito intestine, drop in temperature stimulates male and female gametocytes to become gametes, fertilize, form zygotes
- Zygotes form cysts that divide asexually into numerous offspring, rupture, release sporozoites, which find way to salivary glands and saliva
Pathogenesis of Malaria
• Recurrent paroxysms followed by feeling healthy result from cycle of growth and release of merozoites from RBCs
• Infections in all the millions of RBCs becomes synchronous
• Spleen enlarges to cope with high levels of foreign material and abnormal red blood cells, which it removes
- Malaria is most common cause of splenic rupture
• Parasites cause anemia
• Immune system strongly stimulated, may fail
• People generally develop some immunity from repeated infections; crosses placenta and partially protects newborn
- Greatest risk of death is to children over 6 months
• P. falciparum infections often very severe
- Probably because it can infect all RBCs
- Others only infect either young or old RBCs
• RBCs become rigid, stick to each other, capillary walls
- Vessels block, deprive tissues of O2
- Cerebral malaria can result, is particularly serious
• P. vivax and P. ovale often relapse because they form hypnozoites that live in liver in dormant state
- Months or years later, can begin growth, start new erythrocytic cycles of infection
Epidemiology of Malaria
• Once common in temperate and tropical areas of the world
- Eliminated from continental U.S. in late 1940s
- Mostly a disease of warm climates; half of world's population lives in endemic areas
• Reservoirs are infected mosquitoes and humans
- Only Anopheles females feed on blood and transmit
• Blood transfusions, sharing of needles among intravenous drug users can transmit
• Some people of black African heritage are genetically resistant, RBCs lack receptors for the parasite
• Individuals with certain genetically determined blood diseases (e.g., sickle cell anemia) partially protected
Treatment and Prevention of Malaria
• Complicated since different stages of life cycle respond to different medications
• Chloroquine and newer mefloquine effective against erythrocytic stages of sensitive strains
- Will not cure liver infection with P. vivax or kill gametocytes of P. falciparum
- Primaquine or newer tafenoquine generally effective
• Prevention has become a global focus
• In 1998, new initiative called Roll Back Malaria started
- Goal to reduce deaths by 75% by 2015
- But rate has continued to increase despite
- Resistance to medications has spread
• Drug resistance an increasing problem
• Artemisinin-based combination therapies (ACTs) now widely available, helping to reduce incidence of malaria
• Number of vaccines being tested
- Most promising gives only 30% protection in children
• Indoor spraying with DDT, use of insecticide-impregnated bed nets, elimination of mosquito breeding areas
• Adequate funding a continuing problem
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