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The agents of human infectious diseases belong to five major groups of organisms:

Size of Microorganisms

Cell Wall

The cell wall is the outermost component common to all bacteria.

Some bacteria have surface features external to the cell wall, such as a capsule, flagella, and pili, which are less common components.

The cell wall is located external to the cytoplasmic membrane provides structural support and maintains the characteristic shape of the cell.

Cytoplasmic Membrane

Just inside the cell wall lies the cytoplasmic membrane, which is composed of a phospholipid bilayer

The membrane has four important functions:

(1) active transport of molecules into the cell,

(2) energy generation by oxidative phosphorylation 氧化磷酸化

(3) synthesis of precursors of the cell wall

(4) secretion of enzymes and toxins.

Cytoplasm

The cytoplasm has two distinct areas when seen in the electron microscope:

(1) An amorphous matrix that contains ribosomes 核糖体, nutrient granules营养颗粒, metabolites代谢产物, and plasmids质粒.

(2) An inner, nucleoid类核 region composed of DNA.

Structures Outside the Cell Wall

Capsule：

The capsule is a gelatinous胶状 layer covering the entire bacterium.

The capsule is important for four reasons:

(1) It is a determinant of virulence毒力 of many bacteria since it limits the ability of phagocytes吞噬细胞 to engulf吞没 the bacteria.

(2) Specific identification of an organism can be made by using antiserum抗血清 against the capsule.

(3) Capsule are used as the antigens in certain vaccines.

(4) The capsule may play a role in the adherence of bacteria to human tissues, which is an important initial step in causing infection.

Flagella

Flagella are long, whiplike appendages that move the bacteria toward nutrients and other attractants, a process called chemo taxis 趋化作用.

Flagella are medically important for two reasons:

(1) Some species of motile bacteria are common causes of urinary tract infections. Flagella may play a role in pathogenesis by propelling the bacteria up the urethra into the bladder.

(2) Some species of bacteria are identified in the clinical laboratory by the use of specific antibodies against flagellar proteins.

Pili (Fimbriae)

Pili are hair like filaments that extend from the cell surface. They are shorter and straighter than flagella.

Pili have two important roles:

(1) They mediate the attachment of bacteria to specific receptors on the human cell surface, which is a necessary step in the initiation of infection for some organisms.

(2) A specialized kind of pilus, the sex pilus, forms the attachment between the male (donor) and the female (recipient) bacteria during conjugation 共轭.

Bacterial Spores

These highly resistant structures are formed in response to adverse不利的 conditions.

Spore formation (sporulation) occurs when nutrients, such as sources of carbon and nitrogen, are depleted. The spore forms inside the cell and contains bacterial DNA, a small amount of cytoplasm, cell membrane, very little water, and most importantly, a thick, keratin 角质 like coat that is responsible for the remarkable resistance of the spore to heat, dehydration, radiation, and chemicals.

1 bacterium will produce 16 bacteria after 4 generations.

CONCEPT OF NORMAL FLORA

Normal flora is the term used to describe the various bacteria and fungi that are permanent residents of certain body sites, especially the skin, oropharynx, colon, and vagina.

Viruses and parasites (protozoa and helminths), which are the other major groups of microorganisms, are usually not considered members of the normal flora, although they can be present in asymptomatic individuals.

Pathogen

A microorganism is a pathogen if it is capable of causing disease; however, some organisms are highly pathogenic (i.e., they often cause disease), whereas others cause disease rarely.

Sterilization & Disinfection

Classification of Bacteria

Gram-Positive Cocci

There are two medically important genera of gram-positive cocci: Staphylococcus葡萄球菌  and Streptococcus链球菌.

Both staphylococci and streptococci are gram-positive cocci, but they are distinguished by two main criteria:

(1) Microscopically, staphylococci appear in grapelike clusters, whereas streptococci are in chains.

(2) Biochemically, staphylococci produce catalase 过氧化酶, whereas streptococci do not.

Staphylococcus aureus 金黄色葡萄球菌causes abscesses, various pyogenic 化脓的infections (e.g., endocarditis, septic arthritis, and osteomyelitis), food poisoning

Streptococci cause a wide variety of infections. S. pyogenes (group A streptococcus) is the leading bacterial cause of pharyngitis 咽炎

Gram-Positive    bacilli (Rods)

INTRODUCTION

There are four medically important genera of gram-positive rods:

Bacillus杆菌

Clostridium梭菌

Corynebacterium 棒状杆菌

Listeria 李斯特菌

Bacillus and Clostridium form spores, whereas  orynebacterium and Listeria do not.

Members of the genus Bacillus are     aerobic需氧的, whereas those of the genus Clostridium are anaerobic厌氧的.

SPORE-FORMING GRAM-POSITIVE RODS BACILLUS芽孢杆菌

There are two medically important Bacillus species:  

1. Bacillus anthracis causes anthrax炭疽

2. Bacillus cereus 蜡样芽孢杆菌causes food poisoning

NON–SPORE-FORMING GRAM-POSITIVE RODS

There are two important pathogens in this group:

Corynebacterium diphtheriae 白喉棒状杆菌 causes diphtheria.

Listeria monocytogenes单核细胞增多性李司忒氏菌: causes meningitis and sepsis败血症 in newborns, pregnant women, and immunosuppressed adults.It also causes outbreaks of febrile gastroenteritis胃肠炎. It is a major cause of concern for the food industry.

Gram-Positive Mycobacteria (分枝杆菌)

Mycobacteria are aerobic需氧的, acid-fast抗酸的 bacilli (rods).

They are gram-positive (but, they are stained poorly by the dyes used in Gram stain). They are virtually the only bacteria that are acid-fast耐酸.

Gram-Positive Actinomycetes (放线菌)

Actinomycetes are a family of bacteria that form long, branching filaments that resemble the hyphae菌丝 of fungi.

They are gram-positive, but some are also weakly acid-fast rods.

Gram-Negative Cocci

NEISSERIA 奈瑟氏菌属，淋球菌

The genus Neisseria contains two important human pathogens:

Neisseria meningitidis脑膜炎奈瑟菌 and    Neisseria gonorrhoeae淋球菌.

N. meningitidis mainly causes meningitis and meningococcemia 脑膜炎球菌血症, it is the leading cause of death from infection in children.

N. gonorrhoeae causes      gonorrhea淋病, the second most common bacterial disease in. It also causes     neonatal conjunctivitis新生儿结膜炎

Gram-Negative Rods Related to the Enteric Tract

ESCHERICHIA 埃希氏菌属 Diseases

E. coli大肠杆菌 is the most common cause of urinary tract infection and gram-negative rod sepsis. It is one of the two important causes of neonatal初生儿 meningitis and the agent most frequently associated with “traveler’s diarrhea,” a watery diarrhea. Some strains of E. coli are enterohemorrhagic肠出血性 and cause bloody diarrhea.

Gram-Negative Rods Related to the Respiratory Tract

There are three medically important gram-negative rods typically associated with the respiratory tract, namely, Haemophilus influenzae流感嗜血杆菌, Bordetella pertussis百日咳博德特氏菌, and    Legionella pneumophila嗜肺军团菌.

H. influenzae and B. pertussis are found only in humans, whereas L. pneumophila is found primarily in environmental water sources.

H. influenzae used to be the leading cause of meningitis in young children, but the use of the highly effective vaccine has greatly reduced the incidence of meningitis caused by this organism.

It is still an important cause of upper respiratory

tract infections (otitis media中耳炎, sinusitis, conjunctivitis, and      epiglottitis会厌炎) and sepsis脓毒病 in children. It also causes pneumonia in adults, particularly in those with chronic obstructive lung disease.

B. pertussis causes whooping cough (pertussis).

Initial symptoms are usually similar to those of the common cold with a runny nose, fever, and mild cough, but these are followed by weeks of severe coughing fits. Following a fit of coughing, a high-pitched whoop sound or gasp may occur as the person breathes in.

The coughing may last for 10 or more weeks, hence the phrase "100-day cough". A person may cough so hard that they vomit, break ribs, or become very tired from the effort.

Gram-Negative Rods Related to Animal Sources (Zoonotic Organisms)

Zoonoses动物传染病 are human diseases caused by organisms that are acquired from animals.

There are bacterial, viral, fungal, and parasitic zoonoses 人畜共患病.

Some zoonotic organisms are acquired directly from the animal reservoir, whereas others are transmitted by vectors带菌者, such as mosquitoes, fleas.

Gram-Negative Mycoplasmas (支原体)

Mycoplasmas are a group of very small, wall-less organisms, of which Mycoplasma pneumoniae is the major pathogen.

Gram-Negative Spirochetes (螺旋体) 

Three genera of spirochetes cause human infection:

(1)       Treponema米螺旋菌属, which causes syphilis梅毒;

(2)       Borrelia包柔氏螺旋体属, which causes Lyme disease莱姆病. An infectious disease caused by tick bites with symptoms such as measles and fever. （由扁虱叮咬而出现麻疹、发烧等症状的一种传染性疾病） and relapsing fever回归热; Patient will be periodic high fever is accompanied by general pain, hepatosplenomegaly and bleeding tendency. In severe cases, jaundice may occur.

(3)     Leptospira钩端螺旋体, which causes leptospirosis. Patients may be asymptomatic or present with headache, pain, fever, to severe pulmonary hemorrhage or meningitis. If this results in jaundice, kidney infection, or blood clotting, the disease is also known as Weil's disease.

Gram-Negative Chlamydiae (衣原体)

Chlamydiae are  intracellular bacteria (i.e., they can grow only within cells).

They are the agents of common sexually transmitted diseases, such as urethritis尿道炎 and cervicitis子宫颈炎, as well as other infections, such as pneumonia, trachomasha沙眼.

Gram-Negative Rickettsiae (立克次体)

Rickettsiae are obligate intracellular bacteria; that is, they can grow only within cells.

They are the agents of typhus斑疹伤寒, spotted fevers斑疹热, and Q fever.

Rickettsiae are very short rods that are barely visible in the light microscope.

Structurally, their cell wall resembles that of gram-negative rods, but they stain poorly with the standard Gram stain.

Viruses character

(1) Viruses are particles composed of an internal core containing either DNA or RNA (but not both) covered by a protective protein coat. Some viruses have an outer lipoprotein membrane, called an envelope, external to the coat. Viruses do not have a nucleus, cytoplasm, mitochondria, or ribosomes.

(2) Viruses must reproduce within cells, because they cannot generate energy or synthesize proteins.

(3) Viruses replicate in a manner different from that of cells (i.e., viruses do not undergo binary fission二分裂 ). One virus can replicate to produce hundreds of progeny viruses, whereas one cell divides to produce only two daughter cells.

Structure

Viruses range from 20 to 300 nm in diameter; Their shapes are frequently referred to in colloquial terms (e.g., spheres, rods, bullets, or bricks), but in reality they are complex structures.

The shape of virus particles is determined by the arrangement of the protein coat (capsid) of the virus.

Types of Virus

Replication(reproduce)

VIRAL GROWTH CURVE

when one virion (one virus particle) infects a cell, it can replicate in approximately 10 hours to produce hundreds of virions within that cell.

This remarkable amplification explains how viruses spread rapidly from cell to cell. Note that the time required for the growth cycle varies.

Pathogenesis

The ability of viruses to cause disease can be viewed on two distinct levels:

(1) the changes that occur within individual cells

(2) the process that takes place in the infected patient.

THE INFECTED CELL

There are four main effects of virus infection on the cell:

(1) death

(2) fusion of cells to form multinucleated多核的cells

(3) malignant transformation致命的核转换

(4) no apparent morphologic or functional change.

THE INFECTED PATIENT

Pathogenesis in the infected patient involves

(1) transmission of the virus and its entry into the host

(2) replication of the virus and damage to cells

(3) spread of the virus to other cells and organs

(4) the immune response, both as a host defense and as a contributing cause of certain diseases

(5) persistence of the virus in some instances.

Host Defenses

Host defenses against viruses fall into two major categories:

(1) nonspecific, of which the most important are interferons and natural killer cells;

(2) specific, including both humoral 体液的 and cell-mediated immunity.

NONSPECIFIC DEFENSES

1. Alpha & Beta Interferons干扰素

2. Natural Killer Cells

3. Phagocytosis吞噬作用

4. α-Defensins α-防御素

5. Mucociliary Clearance 粘液纤毛清除

6. Fever

SPECIFIC DEFENSES

1. Active Immunity

2. Passive Immunity

Active immunity can be elicited by vaccines containing killed viruses, purified protein subunits, or live, attenuated (weakened) viruses. In general, live viral vaccines are preferable to killed vaccines for three reasons:

(1) they induce a higher titer浓度 of antibody and hence longer-lasting protection;

(2) they induce a broader range of antibody (e.g., both IgA and IgG, not just IgG)

(3) they activate cytotoxic T cells, which kill virus-infected cells.

Passive immunity is provided by the administration of preformed antibody in preparations called immune globulins.

The immune globulins useful in the prevention of viral diseases.

Laboratory Diagnosis

There are five approaches to the diagnosis of viral diseases by the use of clinical specimens:

(1) identification of the virus in cell culture

(2) microscopic identification directly in the specimen

(3) serologic血清学的procedures to detect a rise in antibody titer浓度测定or the presence of IgM antibody

(4) detection of viral antigens in blood or body fluids

(5) detection of viral nucleic acids in blood or the patient’s cells.

1. IDENTIFICATION IN CELL CULTURE

The growth of viruses requires cell cultures because viruses replicate only in living cells, not on cell-free media the way most bacteria can.

Because many viruses are inactivated at room temperature, it is important to inoculate标本接种the specimen into the cell culture as soon as possible; brief transport or storage at 4°C is acceptable.

2. MICROSCOPIC IDENTIFICATION

Viruses can be detected and identified by direct microscopic examination of clinical specimens Three different procedures can be used.

(1) Light microscopy can reveal characteristic inclusion bodies or multinucleated giant cells.

(2) UV microscopy is used for fluorescent荧光antibody staining of the virus in infected cells.

(3) Electron microscopy detects virus particles, which can be characterized by their size and morphology.

3. SEROLOGIC PROCEDURES

A rise in the titer浓度测定 of antibody to the virus can be used to diagnose current infection.

Seroconversion血清转化 is the term used to describe the finding of antibody to a virus (or any microbe) in a patient’s serum when the patient previously had no antibody.

A serum sample is obtained as soon as a viral etiology is suspected , and a second sample is obtained 10 to 14 days later (convalescent-phase).

If the antibody titer in the convalescent-phase serum sample is at least fourfold higher than the titer in the acute-phase serum sample, the patient is considered to be infected.

4. DETECTION OF VIRAL ANTIGENS

Viral antigens can be detected in the patient’s blood or body fluids by various tests, but most often by an ELISA (Enzyme-Linked Immuno Sorbent Assay)酶联免疫吸附测定.

Tests for the antigen of human immunodeficiency virus (HIV) and the surface antigen of hepatitis B virus are common examples of this approach.

5. DETECTION OF VIRAL NUCLEIC ACIDS

Viral nucleic acids (i.e., either the viral genome基因组or viral mRNA) can be detected in the patient’s blood or tissues with complementary DNA or RNA (cDNA or cRNA) as a probe. 

Assays for the RNA of HIV and hepatitis C virus and the DNA of hepatitis B virus in the patient’s blood (viral load) are commonly used to monitor the course of the disease and to evaluate the patient’s prognosis.

Antiviral Drugs

PRINCIPLES OF ANTIVIRAL THERAPY

Compared with the number of drugs available to treat bacterial infections, the number of antiviral drugs is very small.

The major reason is virus replication is intimately 紧密地 involved with the normal synthetic processes of the cell.

Another is many cycles of viral replication occur during the incubation period when the patient is well.

Some viruses (e.g., herpes viruses) become latent within cells, and no current antiviral drug can eradicate根除 them.

Another limiting factor is the emergence of drug-resistant viral mutants 突变体.

Selective toxicity is the ability of a drug to inhibit viral replication

without significantly damaging the host cell. It is difficult to achieve a high degree of selective toxicity with antiviral drugs because the virus can only replicate within cells and uses many cellular functions during replication.

Viral Vaccines

Because few drugs are useful against viral infections, prevention of infection by the use of vaccines is very important.

Prevention of viral diseases can be achieved by the use of vaccines that induce active immunity or by the administration of preformed antibody that provides passive immunity.

Covid 19 (SARS- CoV-2)

covid-19 virus belongs to Coronavirus group,

it is a kind of zoonotic人畜共患的 single stranded RNA virus spreads between animals and humans.

It is the  seven of coronaviruses could cause humans illness.The viruses were generally spherical, The diameter is between 60-140nm. Virus particles have obvious spinous processes, about 9-12nm, causing the virus to exhibit a coronal shape. 

Transmission

COVID-19 is usually excreted through tiny particles formed by the patient's cough, sneeze, or breathing. The droplets usually fall to the ground or onto surfaces rather than travelling through air over long distances, Transmission may also occur through smaller droplets (called aerosol) that are able to stay suspended in the air for longer periods of time.

Aerosol transmission can happen during some medical procedures and potentially in crowded indoor spaces that are inadequately ventilated.

Less commonly, people may become infected by touching a contaminated surface and then touching their face.

Common symptoms

Fever

Cough

fatigue

shortness of breath,

loss of sense of smell.

Pneumonia

acute respiratory distress syndrome(ARDS).

Diagnosis

The standard test for current infection with SARS-CoV-2, uses RNA testing of respiratory secretions collected using a nasopharyngeal swab,

Chest X-ray examination

Since the disease manifests itself as pneumonia.

Chest computed tomography(CT)

Given the high sensitivity of the method, in particular

high-resolution CT (HRCT), is the method of choice in the study of COVID-19 pneumonia, even in the initial stages.

treatment

preventive measures

Primary treatment is symptomatic and supportive therapy.

hand washing,

wearing a face mask in public settings,

maintaining distance from other people,

covering one's mouth when coughing,

disinfecting surfaces,

increasing ventilation and air filtration indoors,

monitoring and self-isolation for people who suspect they are infected.

HERPES VIRUSES

HERPES VIRUSES ARE DNA ENVELOPED VIRUSES.

Three of the herpes viruses, HSV types 1 and 2 and varicella-zoster virus (VZV).

VARICELLA-ZOSTER VIRUS (VZV)

Disease

Varicella (chickenpox) is the primary disease;

Zoster (shingles) is the recurrent form.

Transmission & Epidemiology

The virus is transmitted by respiratory droplets and by direct contact with the lesions.

Varicella (chickenpox) is a highly contagious disease of childhood; Varicella occurs worldwide. use of the vaccine has significantly reduced the number of cases.

There is infectious VZV in zoster vesicles小囊泡. This virus can be transmitted, usually by direct contact, to children and can cause varicella.

Pathogenesis

VZV infects the mucosa of the upper respiratory tract, and then spreads via the blood to the skin, where the typical vesicular rash occurs. The virus infects sensory neurons and then flow into the cells of the dorsal root ganglia, where the virus becomes latent.

Later in life, frequently at times of reduced cell-mediated immunity or local trauma, the virus is activated and causes the vesicular skin lesions and nerve pain of zoster.

Clinical Findings

Varicella (chickenpox)

After an incubation period of 14 to 21 days, brief prodromal symptoms of fever and malaise 不适 occur. A papulovesicular丘疹性rash then appears in crops on the trunk and spreads to the head and extremities.

The rash evolves from papules to vesicles液胞, pustules, and, finally, crusts生痂. Itching (pruritus) is a prominent symptom, especially when vesicles are present.

Varicella is mild in children but more severe in adults.

Varicella pneumonia and encephalitis脑炎are the major rare complications, occurring more often in adults.

Immunity

Immunity following varicella is lifelong:

A person gets varicella only once, but zoster can occur despite this immunity to varicella.

Zoster usually occurs only once. The frequency of zoster increases with advancing age, perhaps as a consequence结果of waning immunity.

Prevention

There are two vaccines against VZV: one designed to prevent varicella, called Varivax, and the other designed to prevent zoster, called Zostavax.

Both contain live, attenuated减弱 VZV, but the zoster vaccine contains 14 times more virus than the varicella vaccine.

The zoster vaccine is effective in preventing the symptoms of zoster, but does not eradicate the latent state of VZV.

The varicella vaccine is recommended for children between the ages of 1 and 12 years, whereas the zoster vaccine is recommended for people older than 60 years and who have had varicella.

Because these vaccines contain live virus, they should not be given to immunocompromised people or pregnant women.

Hepatitis Viruses

Many viruses cause hepatitis. Of these, five medically important viruses are commonly described as “hepatitis viruses” because their main site of infection is the liver.

Hepatitis A virus (HAV)

Hepatitis B virus (HBV)

Hepatitis C virus (HCV)

Hepatitis D virus (HDV)

Hepatitis E virus (HEV)

HEPATITIS A VIRUS (HAV)

Disease

HAV causes hepatitis A.

Transmission & Epidemiology

HAV is transmitted by the fecal–oral route.

Virus appears in the feces roughly 2 weeks before the appearance of symptoms.

Children are the most frequently infected group, and outbreaks occur in special living situations such as summer camps and boarding schools.

Common-source outbreaks arise from fecally contaminated water or food such as oysters grown in polluted water and eaten raw.

HAV is rarely transmitted via the blood, because the level of viremia 病毒血症 is low and chronic infection does not occur.

Clinical Findings

The clinical manifestations of hepatitis are virtually the same, regardless of which hepatitis virus is the cause

Fever, anorexia, nausea, vomiting, and jaundice are typical. Dark urine, pale feces, and elevated transaminase 转氨酶 levels are seen.

Most cases resolve spontaneously自然地in 2 to 4 weeks. Hepatitis A has a short incubation period (3–4 weeks).

No chronic hepatitis or chronic carrier state occurs, and there is no predisposition倾向 to hepatocellular carcinoma 肝细胞癌.

Laboratory Diagnosis

The detection of IgM antibody is the most important test.

Treatment & Prevention

No antiviral therapy is available.

Active immunization with a vaccine containing

inactivated HAV is available. The virus is grown in human cell culture and inactivated with formalin. Two doses, an initial dose followed by a booster 6 to 12 months later, should be given. No subsequent booster dose is recommended. The vaccine is recommended for travelers to developing countries, for children ages 2 to 18 years. If an unimmunized person must travel to an endemic area within 4 weeks, then passive immunization should be given to provide immediate protection and the vaccine given to provide long-term protection.

This is an example of passive–active immunization.

HEPATITIS B VIRUS (HBV)

Disease

HBV causes hepatitis B.

Transmission & Epidemiology

The three main modes of transmission are via blood, during sexual intercourse, and from mother to newborn.

The observation that needle-stick injuries can transmit the virus indicates that only very small amounts of blood are necessary.

Clinical Findings

Many HBV infections are asymptomatic and are detected only by the presence of antibody to HBsAg. The mean incubation period for hepatitis B is 10 to 12 weeks.

The clinical appearance of acute hepatitis B is similar to that of hepatitis A. However, with hepatitis B, symptoms tend to be more severe, and life-threatening hepatitis can occur. Most chronic carriers are asymptomatic, but some have chronic active hepatitis, which can lead to cirrhosis and death.

Laboratory Diagnosis

The two most important serologic tests for the diagnosis of early hepatitis B are the tests for HBsAg and for IgM antibody to the core antigen.

Treatment

No antiviral therapy is typically used in acute hepatitis B. For chronic hepatitis B, entecavir 抗病毒药 (Baraclude) or tenofovir抗病毒药(Viread) are the drugs of choice.

Prevention

Prevention involves the use of either the vaccine or hyperimmune globulin or both.

(1) The vaccine contains HBsAg produced. The vaccine is highly effective in preventing hepatitis B and has few side effects.

(2) Hepatitis B immune globulin (HBIG) contains a high titer of HBsAb. It is used to provide immediate, passive protection to individuals known to be exposed to HBsAg-positive blood (e.g., after an accidental needle-stick injury).

Human Immunodeficiency Virus

Human immunodeficiency virus (HIV) is the cause of acquired immunodeficiency syndrome (AIDS).

Both HIV-1 and HIV-2 cause AIDS, but HIV-1 is found worldwide, whereas HIV-2 is found primarily in West Africa.

Transmission & Epidemiology

Transmission of HIV occurs primarily by sexual contact and by transfer of infected blood. 

Perinatal transmission from infected mother to neonate also occurs, either across the placenta, at birth, or via breast milk.

Clinical Findings

The clinical picture of HIV infection can be divided into three stages:

an early, acute stage;

a middle, latent stage;

and a late, immunodeficiency stage.

Clinical Findings

In the acute stage, which usually begins 2 to 4 weeks after infection, fever, lethargy, sore throat, and generalized lymphadenopathy 淋巴结病 occurs. Rash on the trunk, arms, and legs. Leukopenia白细胞减少症occurs.

In the middle stage of HIV infection, a long latent period, In untreated patients, the latent period typically lasts for 7 to 11 years.

The patient is asymptomatic during this period. Although the patient is asymptomatic and viremia 病毒血症 is low or absent, a large amount of HIV is being produced by lymph node cells but remains sequestered 使隔离 within the lymph nodes.

The late stage of HIV infection is AIDS, an increase in the frequency and severity of opportunistic infections.

The two most characteristic manifestations of AIDS are pneumonia and Kaposi’s sarcoma卡波济肉瘤.

Laboratory Diagnosis 

The presumptive diagnosis of HIV infection is made by the detection of antibodies in the patient’s serum.

During the first month after infection, antibody tests may be negative. These false negative tests are due to insufficient antibody being made early in infection to be detected.

The average time for seroconversion血清转化is 10 to 14 days, and most of those infected, but not all, will have seroconverted by 4 weeks.

Treatment

The two specific goals of treatment are

(1) to restore immunologic function which reduces opportunistic infections and certain malignancies, and

(2) to reduce viral load, which reduces the chance of transmission to others.

Unfortunately, no drug regimen results in a “cure” (i.e., eradicates the virus from the body), but long-term suppression can be achieved获得. However, if drugs are stopped, the virus resumes active replication, and large amounts of infectious virus reappear.

Prevention

No vaccine is available. Prevention consists of taking measures to avoid exposure to the virus (e.g., using condoms, not sharing needles, and discarding donated blood that is contaminated with HIV).

Basic Mycology

•There are two types of fungi: yeasts and molds.

• Yeasts grow as single cells that reproduce by asexual budding.

•Molds grow as long filaments (hyphae菌丝) and form a mat (mycelium菌丝体).

FUNGAL TOXINS & ALLERGIES

•In addition to mycotic霉菌性infections, there are two other kinds of fungal disease:

•(1) mycotoxicoses真菌[毒素]中毒症, caused by ingested toxins. The best-known mycotoxicosis occurs after eating Amanita mushrooms. These fungi produce five toxins.

•(2) allergies to fungal spores. Allergies to fungal spores are manifested primarily by an asthmatic reaction.

LABORATORY DIAGNOSIS

•There are four approaches to the laboratory diagnosis of fungal diseases:

•(1) direct microscopic examination

•(2) culture of the organism

•(3) DNA probe tests

•(4)serologic tests

ANTIFUNGAL THERAPY

•The drugs used to treat bacterial diseases have no effect on fungal diseases.

•The most effective antifungal drugs, amphotericin B两性霉素B and the various azoles氮唑类, exploit the presence of ergosterol in fungal cell membranes that is not found in bacterial or human cell membranes.

CANDIDA

•Dermatophytoses皮肤癣菌病are caused by fungi (dermatophytes) that infect only superficial keratinized角质细胞 structures (skin, hair, and nails), not deeper tissues.

•Dermatophytoses (tinea, ringworm) are chronic infections often located in the warm, humid areas of the body (e.g., athlete’s foot).

Typical ringworm lesions have an inflamed circular border containing papules and vesicles surrounding a clear area of relatively normal skin. The lesions are typically pruritic 痒的. Broken hairs and thickened broken nails are often seen. The disease is typically named for the affected body part (i.e., tinea capitis [head], tinea corporis [body], tinea cruris [groin], and tinea pedis [foot])

Cryptococcus neoformans

•Disease

•Cryptococcus neoformans新型隐球菌causes cryptococcosis 隐球菌病, especially cryptococcal meningitis.

•Cryptococcosis is the most common, life-threatening invasive fungal disease worldwide.

•It is especially important in AIDS patients.

•Properties

•C. neoformans is an oval, budding yeast surrounded by a wide polysaccharide capsule.

•Transmission

•C. neoformans occurs widely in nature and grows abundantly in soil containing bird (especially pigeon) droppings.

•The birds are not infected. Human infection results from inhalation吸入 of the organism.

•There is no human-to-human transmission.

•Pathogenesis & Clinical Findings

•Lung infection is often asymptomatic or may produce pneumonia. Disease caused by C. neoformans occurs mainly in patients with reduced cell-mediated immunity, especially AIDS patients, in whom the organism disseminates to the central nervous system (meningitis) and other organs.

•Subcutaneous nodules are often seen in disseminated disease. However, that roughly half the patients with cryptococcal meningitis fail to show evidence of immunosuppression.

•Laboratory Diagnosis

•In spinal fluid mixed with India ink, the yeast cell is seen microscopically surrounded by a wide, unstained capsule. Appearance of the organism in Gram stain is unreliable.

•Treatment

•Combined treatment with amphotericin B and flucytosine is used in meningitis and other disseminated disease.

Intestinal protozoa

•Entamoeba histolytica 阿米巴痢疾

Diseases

•Entamoeba. histolytica causes amebic dysentery and liver abscess.

•Entamoeba histolytica 阿米巴痢疾(溶组织阿米巴) 

•The life cycle of E. histolytica has two stages: the motile ameba (trophozoite) and the nonmotile cyst. The trophozoite is found within the intestinal and extraintestinal lesions and in diarrheal stools. The cyst predominates in non-diarrheal stools. These cysts are not highly resistant and are readily killed by boiling but not by chlorination of water supplies. They are removed by filtration of water.

Clinical Findings

•Acute intestinal amebiasis presents as dysentery (i.e., bloody, mucus-containing diarrhea) accompanied by lower abdominal discomfort, flatulence, and tenesmus.

•Chronic amebiasis with low-grade symptoms such as occasional diarrhea, weight loss, and fatigue also occurs. Roughly 90% of those infected have asymptomatic infections, but they may be carriers, whose feces contain cysts包囊 that can be transmitted to others.

•In some patients, a lesion called an ameboma 阿米巴肿 may form in the colon.

•Amebic abscess of the liver is characterized by right-upper-quadrant pain, weight loss, fever, and a tender, enlarged liver. Right-lobe abscesses can penetrate the diaphragm and cause lung disease.

•Most cases of amebic liver abscess occur in patients who have not had overt intestinal amebiasis.

Laboratory Diagnosis

•Diagnosis of intestinal amebiasis rests on finding either ameba(trophozoites) in diarrheal stools or cysts in formed stools

Treatment

•The treatment of choice for symptomatic intestinal amebiasis or hepatic abscesses is metronidazole (Flagyl)甲硝唑or tinidazole替硝唑片.  

•Prevention involves avoiding fecal contamination of food and water and observing good personal hygiene such as hand washing.

Blood & Tissue Protozoa 原虫

•PLASMODIUM 疟原虫

•Disease

•Malaria is caused by four plasmodia: Plasmodium vivax, Plasmodium ovale, Plasmodium malariae, and Plasmodium falciparum.

•P. vivax and P. falciparum are more common causes of malaria than are P. ovale and P. malariae. Worldwide, malaria is one of the most common infectious diseases and a leading cause of death.

•Pathogenesis

•Malaria is transmitted primarily by mosquito bites, but transmission across the placenta, in blood transfusions, and by intravenous drug use also occurs.

•Most of the pathologic findings of malaria result from the destruction of red blood cells. The enlarged spleen is characteristic of malaria.

•Epidemiology

•More than 200 million people worldwide have malaria, and more than 1 million die of it each year, making it the most common lethal infectious disease. It occurs primarily in tropical and subtropical areas, especially in Asia, Africa, and Central and South America.

•People who have lived or traveled in areas where malaria occurs should seek medical attention for febrile illnesses up to 3 years after leaving the malarious area.

•Clinical Findings

•Malaria presents with abrupt onset of fever and chills, accompanied by headache, myalgias肌痛, and arthralgias关节痛, about 2 weeks after the mosquito bite. Fever may be continuous early in the disease; the typical periodic cycle does not develop for several days after onset. The fever spike, which can reach 41°C, is frequently accompanied by shaking chills, nausea, vomiting, and abdominal pain. The fever is followed by sweats. Patients usually feel well between the febrile episodes. Splenomegaly 脾肿大is seen in most patients, and hepatomegaly 肝肿大occurs in roughly one-third. Anemia is prominent.

Laboratory Diagnosis

•Diagnosis tests on microscopic examination of blood.

Treatment

•The treatment of malaria is complicated. Chloroquine 氯喹is the drug of choice for treatment of uncomplicated malaria.

Prevention

•Chemoprophylaxis of malaria for travelers to areas. Other preventive measures include the use of mosquito netting, window screens, protective clothing, and insect repellents. The mosquitoes feed from dusk to dawn, so protection is particularly important during the night. Communal preventive measures are directed against reducing the mosquito population. There is no vaccine.

Nematodes  线虫类

•Taenia solium  猪肉绦虫

•Disease

•The adult form of T. solium causes taeniasis 绦虫病.

•T. solium larvae cause cysticercosis 猪囊虫病.

Taenia solium  猪肉绦虫

•Pathogenesis

•The adult tapeworm attached to the intestinal wall causes little damage.

•The cysticerci can become very large, especially in the brain, where they manifest as a space-occupying lesion.

•Living cysticerci幼虫do not cause inflammation, but when they die, they can release substances that provoke an inflammatory response. Eventually, the cysticerci calcify 钙化.

•Epidemiology

•The epidemiology of taeniasis and cysticercosis is related to the access of pigs to human feces and to consumption of raw or undercooked pork.

•The disease occurs worldwide but is endemic in areas of Asia, South America, and Eastern Europe. Most cases in the United States are imported.

•Clinical Findings

•Most patients with adult tapeworms are asymptomatic, but anorexia and diarrhea can occur. Some may notice proglottids节片 in the stools.

•Cysticercosis in the brain causes headache, vomiting, and seizures.

•Cysticercosis in the eyes can appear as retinitis, or the larvae can be visualized floating in the vitreous.

•Subcutaneous nodules containing cysticerci commonly occur.

•Cysts also are commonly found in skeletal muscle.

•Laboratory Diagnosis

•Identification of T. solium consists of finding gravid proglottids in the stools.

•Treatment

•The treatment of choice for the intestinal worms is praziquantel吡喹酮. The treatment for cysticercosis is either praziquantel or albendazole, but surgical excision切除 may be necessary.

•Prevention

•Prevention of taeniasis involves cooking pork adequately and disposing waste properly so that pigs cannot ingest human feces. Prevention of cysticercosis consists of treatment of patients to prevent autoinfection plus observation of proper hygiene, including handwashing, to prevent contamination of food with the eggs.

•Enterobius vermicularis 蛲虫 causes pinworm infection (enterobiasis).

Pathogenesis & Clinical Findings

•Perianal pruritus肛周瘙痒 is the most prominent symptom. Pruritus is thought to be an allergic reaction to the presence of either the adult female or the eggs. Scratching predisposes to secondary bacterial infection.

•Epidemiology

•Enterobius is found worldwide. Children younger than 12 years of age are the most commonly affected group.

•Laboratory Diagnosis

•The eggs are recovered from perianal skin by using the Scotch tape technique and can be observed microscopically.

•Unlike those of other intestinal nematodes, these eggs are not found in the stools. The small, whitish adult worms can be found in the stools or near the anus of diapered children. No serologic tests are available.

•Treatment

•Either mebendazole or pyrantel pamoate is effective. They kill the adult worms in the colon but not the eggs, so retreatment in 2 weeks is suggested. Reinfection is very common.

•Prevention

•Prevent reinfection.

Nonspecific (natural or innate) immunity

DRUGS ACTING ON THE CENTRAL NERVOUS SYSTEM

The main CNS neurotransmitters

Noradrenaline.

Dopamine多巴胺.

5-HT. 5-羟色胺

Acetylcholine(Ach).

Noradrenaline. Noradrenergic transmission is important in control of mood (functional deficiency resulting depression) controlling wakefulness, and alertness.

Dopamine多巴胺. Dopamine is important in motor control (Parkinsonism is due to dopamine deficiency), has behavioural effects (excessive dopamine activity is implicated in schizophrenia精神分裂症), important in hormone release (prolactin催乳素, GH) and dopamine in chemoreceptor trigor zone causes nausea and vomiting.

5-HT. Feeding behaviour, behavioural response (hallucinatory幻觉的behaviour), control of mood and emotion, control of body temperature and vomiting.

Acetylcholine(Ach). Ach has effects on arousal觉醒, on learning, and on short-term memory. Dementia痴呆and parkinsonism are associated with abnormalities in   cholinergic类胆碱pathways.

GENERAL ANESTHETICS  麻醉剂

General anesthesia involves the physiological changes:

Reversible loss of response to painful stimuli, loss of consciousness and loss of motor and autonomic reflexes.

General anesthetics are administered by inhalation or by intravenous静脉注射 routes.

They are classified into two on the basis of their route of administration as inhalation and intravenous anesthetics.

Inhalation anesthetics

The main agents are: Halothane, nitrous oxide, enflurane and ether.

1. Halothane三氟乙烷: Is the most widely used agent, highly lipid soluble, potent. It causes arrhythmia, and the risk of liver damage is high if used repeatedly.

2. Nitrous oxide: Oderless and colourless gas. It is rapid in action and also an effective analgesic agent. Its potency 效能is low, hence must be combined with other agents. It is a relatively free of serious unwanted effects.

3. Enflurane氟醚麻醉剂: Poorly metabolized in the liver, thus less toxic than halothane. It is faster in its action, less liable to accumulate in the body fat compared to halothane.

4. Ether醚: Has analgesic and muscle relaxant properties. It is highly explosive, causes respiratory tract irritation, postoperative nausea and vomiting. It is not widely used currently.

INTRAVENOUS ANESTHETICS

Intravenous anesthetics act much more rapidly, producing unconsciousness in about 20 seconds, as soon as the drug reaches the brain from the site of its injection.

These agents used for induction of anaesthesia followed by inhalation agent.

The main induction agent in current use is: thiopentone, etomidate, propofol, ketamine and short acting benzodiazepine (midazolam).

SEDATIVE AND HYPNOTIC催眠DRUGS

1. Benzodiazepines苯二氮. Benzodiazepines are the most important group, used as sedative and hypnotic agents.

2. Barbiturates巴比妥(phenobarbitone). They are nowadays less commonly used as sedative  and hypnotics.

3. β -adrenoceptor antagonists (e.g. propranolol心得安). They are used to treat some forms of anxiety, where physical symptoms (sweating, tremor, and tachycardia心动过速), are troublesome. They are not used as hypnotics.

Clinical Uses

• Treatment insomnia

• Anxiety

• Preoperative术前 mediations

• Acute alcohol withdrawal

• As anticonvulsants

• Chronic muscle spasm and spasticity痉挛

Unwanted effects

• Toxic effects due to acute over dosage causes prolonged sleep.

• Unwanted effects occurring during normal therapeutic use includes: drowsiness, confusion, amnesia遗忘, and impaired motor coordination.

• Tolerance and dependance: Pharmacokinetic and tissue tolerance and also cause physical dependance. i.e. stopping treatment after weeks or months causes an increase in symptoms of anxiety.

MANAGEMENT OF PARKINSONISM

Parkinsonism: Parkinsonism is characterized by a combination of rigidity僵硬, bradykinesia运动迟缓, tremor, and postural instability. It is due to the imbalance between the cholinergic胆碱能的 and dopaminergic多巴胺能的 influences on the basal ganglia 基底核.

Thus, the aim of the treatment is either to increase dopaminergic activity (by dopamine agonist兴奋剂) or to decrease cholinegic (antimuscarinic drugs) influence on the basal ganglia.

ANTIPSYCHOTIC AGENTS

Psychotic精神病 illness is characterized by delusion 幻想, hallucinations幻觉, thought disorder, social withdrawal and flattering of emotional response.

Antipsychotics are a group of drugs used mainly for treating schizophrenia 精神分裂症.

Antipsychotic agents are classified into typical neuroleptics神经松弛剂(chlorpromazine氯丙嗪, thioridazine安定, haloperidol氟哌啶, flupenthixol三氟噻醇) and atypical neurolopitics 非典型的神经药(clozapine氯氮平, sulpiride止呕灵).

Most antipsychotic drugs are readily but incompletely absorbed.

Many of these drugs undergo significant first-pass metabolism. Very little of any of these drugs is excreted unchanged.

Clinical uses

• Schizophrenia精神分裂症

• Mania躁狂

Adverse Reactions

• Extrapyramidal reactions as PARKINSONISM

• Seizures

• Autonomic nervous system effects (antimuscarinic 抗胆碱effects(increase heart rate, muscle relax), orthostatic hypotension直立性低血压)

• Metabolic and Endocrine Effects (weight gain, infertility, loss of libido and impotence)

ANTIDEPRESSANT AGENTS:

Depression is one of the most common psychic disorders. Antidepressants are the drugs which are mainly used in the management of depression.

Types of antidepressant drugs

1. Tricyclic三环类 antidepressants (TCAs)

2. Monoamine oxidase inhibitors单胺氧化酶抑制剂(MAOI)

3. 5-HT uptake摄入 inhibitors

4. Atypical非典型的 antidepressants

Pharmacokinetics

Most tricyclics are incompletely absorbed and undergo significant first-pass metabolism.

Clinical Indications:

TCAs are endogenous depression, panic attacks, Phobic恐惧  and bed-wetting in children.

MAOIs are used in severe depression refractory难治性 to other treatment and phobias恐惧.

Adverse Effects:

Postural hypotension, dry mouth, blurred vision, constipation, urine retention, sedation, are the most important side effects of TCAs.

MAOI cause postural hypotension, weight gain, and CNS stimulation causing restlessness, tremor, and insomnia.

Drug dependence and drug abuse

There are many drugs that human beings consume because they choose to, and not because they are advised to by physicians.