HIV can also be spread via blood or blood products, most commonly with shared contaminated needles used by persons engaging in intravenous drug use.
Mothers who are HIV infected can pass the virus on to their fetuses in utero or to infants via breast milk.
The source of HIV is a sick person or a virus carrier. The patients are infective during all the life.
When HIV infects a cell, it must use its reverse transcriptase enzyme to transcribe its RNA to host cell proviral DNA. It is this proviral DNA that directs the cell to produce additional HIV virions, which are released.
When the CD-4 lymphocyte count drops below 200/microliter, then the stage of clinical AIDS has been reached. This is the point at which the characteristic opportunistic infections and neoplasms of AIDS appear.
Clinical picture
Incubative period of HIV-1 at sexual way of infection lasts from 2-3 weeks to 2-3 months, sometimes I year.
The early signs of the disease are increase of temperature, cough, nausea, vomiting, diarrhea, presence of antibodies to HIV infection with simultaneous loss of body mass (20 kg during the last 2-3 years).
After those lymphatic nodes of different localization as well as the liver and spleen enlarge, lymphopenia and hypergammaglobulinemia develop. The signs of the disease also depend on the lesion in the definite system, i.e. meningoencephalitis, pneumonia, gastritis, duodenitis, nephritis.
Next stage is appearance of oncological diseases or generalized infection.
The clinical spectrum of HIV infection is now recognized to comprise
1. Acute viral infection sometimes associated with immune complex disease.
2. Persistent generalized lymphadenopathy.
3. Chronic active viral infection with constitutional symptoms or AIDS related complex.
4. Immunodeficiency leading to opportunistic infections or tumors (AIDS).
5. Chronic encephalopathy caused by HIV
6.Chronic active viral infection with immunocomplex disease (such as thrombocytopenic purpura).
The signs of suspected AIDS (according to WHO)
Prolonged fever of unclear origin.
Chronic diarrhea (not less than 2 months).
Unexplainable body weight loss (by 10% or more).
Pneumonia of unclear origin resistant to standard therapy.
Lymphopenia.
There are AIDS-ihdicating diseases (according to WHO)
Candidosis of the esophagus, trachea, bronchi, lungs.
Extrauterine cryptococcosis.
Cryptosporiosis with diarrhea for more than 1 month.
Pneumocyst pneumonia.
Cytomegalovirus lesion of some organs (except for the liver, spleen, lymphatic nodes in the patients over 1 month).
Infection caused by herpes simplex, persisting more than I month in the patients aged over 1 month.
Toxoplasmosis of the CNS in the patients aged over 1 month.
Malignant lymphomas seen with AIDS are typically of a high grade and extranodal, often in the brain. They are very aggressive and respond poorly to therapy.
Kaposi’s sarcoma (KS) produces reddish purple patches, plaques, or nodules over the skin and can be diagnosed with skin biopsy. Visceral organ involvement eventually occurs in 3/4 of patients with KS.
Morphology
At autopsy the gross pathology of AIDS can be split into three general categories as follows:
1. The morphologic manifestations of profound lymphoid depletion.
2. Infections caused by opportunistic pathogens.
3. Unusual neoplasms such as Kaposi’s sarcoma and high-grade lymphoma.
The early stage of HIV is characterized by enlarged lymph nodes and the follicular hyperplasia.
With disease progression, the frenzy of B-cell proliferation subsides and gives way to a pattern of severe follicular involution. The follicles are depleted of cells; and the organized network of follicular dendritic cells is disrupted. The germinal centres may even become hyalinised. These “burnt-out” lymph nodes are atrophic and small and may harbor numerous opportunistic pathogens. In the empty-looking lymph nodes and in other organs, the presence of infectious agents may not be readily apparent without the application of special stains.
In later stages of AIDS, spleen and thymus also appear to be “wastelands”.
Non-Hodgkin’s lymphomas, involving the nodes as well as extranodular sites, such as the liver, gastrointestinal tract, and bone marrow, are primarily high-grade diffuse B-cell neoplasms.
Neurologic complications, especially the AIDS-dementia is an important cause of morbidity in patients in advanced stages of infection. The pathologic abnormalities in patients with AIDS-dementia complex are variable. Multinucleated cells in the brain are found in a subgroup of patients with severe disease. These cells are derived from macrophages and support viral replication. These are thus markers of productive infection. All histopathlogic abnormalities are most prominent in the subcortical structures, and besides multinucleated cells they include diffuse pallor of the white matter and vacuolar myelopathy.
Lymphocytic meningitis is seen in patients around the time of seroconversion and is defined as occurring in the absence of any demonstrable opportunistic pathogens.
HIV encephalitis is a multifocal process characterized by inflammatory foci including multinucleated giant cells, mainly seen in white matter, basal ganglia and brain stem.
Diffuse poliodystrophy is the term applied to neuronal loss, microglial activation and gliosis in CNS grey matter.
Cerebral vasculitis is seen most prominently in childhood HIV disease of the brain.
BACTERIAL INFECTIONS OF CHILDHOOD
Diphtheria (D)
Diphtheria is an acute infectious disease characterized by fibrinous inflammation in the focus of primary fixation of the causative agent and general intoxication due to exotoxin absorption.
Etiology and pathogenesis
Diphtheria is caused by a slender, gram-positive rod Corynebacterium diphtheria, which is passed from person to person via aerosols or traumatic skin.
Diphtheria is amenable to virtually complete eradication by routine immunization with diphtheria toxoid. Even in medically advanced countries, however, diphtheria may occur when immunization procedures break down because of war, complacency, or cultism.
Transmission to nonimmune individuals usually occurs by the respiratory route.
Diphtheria is a composite of a local inflammation and a systemic intoxication. Toxic produced locally by toxigenic strains of C. diphtheriae is responsible for an inflammatory reaction on body surfaces at the site of infection (usually the oral pharynx, from which the process often extends to the nose or larynx).
Occasionally the tracheal, esophageal, or gastric mucosa is involved as well.
Less commonly, but particularly in the tropics, cutaneous trauma or burns may be the site of diphtheria.
The umbilical cord (in diphtheria neonatorum), the genital tract, and the conjunctivae are rare sites.
Incubation period is 2-10 days.
The diphtheria bacillus multiplies at the site of attachment on the mucosa and excretes exotoxin. The exotoxin causes local necrosis of the epithelium, paretic dilatation of the vessels with disturbance of their permeability, edema of the tissues and release of fibrinogen from the vascular bed. Fibrinous films are formed on the surface of the damaged mucous membrane.
Exotoxin affects cardiovascular, nervous systems and adrenal glands. This simultaneous damage causes hemodynamic disturbances in the organism; excretion of the exotoxin from the organism is accompanied by the damage of tubular epithelium of the kidneys.
The disease is more common in children; at present the disease is more frequent in children over 7 years.
Morphology
Clinical-morphological classification
1. Diphtheria in the pharynx.
2. Diphtheria in the respiratory tract.
3. Rarely forms of diphtheria.
Diphtheria in the pharynx
Local changes:
Cervical adenopathy seems out of proportion to the pharyngeal lesion.
Soon small gray or white patches of exudate appear on the pharyngeal mucosa, usually over the tonsils. These enlarge and coalesce and, with the accumulation of blood, become gray or black. This exudate constitutes the characteristic diphtheritic inflammation, which consists of leukocytes and numerous bacteria enmeshed in a dense network of fibrin.
The lymphoid tissues both in regional lymph nodes and systemically (as in the spleen) undergo hyperplasia with the development of prominent germinal centers that are often centrally necrotic.
The soft tissue of the neck is swollen. In severe toxic forms, the edema is considerable and can involve the anterior surface of the chest.
General changes are accompanied with toxinemia and appear:
1. Diphtheria toxin is particularly toxic to myocardium.
Toxic myocarditis develops in the heart. Alterative and interstitial forms of myocarditis are distinguished. The cavities of the heart are dilated; the muscle is dull, flabby, variegated. Parietal thrombi can be observed.
In the early stages, interstitial edema, cloudy swelling of myocardial fibers, and the accumulation of fine cytoplasmic granules of lipid are seen microscopically. The changes of cardiomyocytes are characterized by fat degeneration and small foci of myolysis.
If myocarditis develops at the beginning of the 2nd week of the disease and the death is caused by acute cardiac failure and an arrhythmia, the condition is called early cardioplegia. Due to diphtheritic myocarditis the cardiosclerosis and congestive heart failure develop.
2. Diphtherial toxin has a special affinity for peripheral nerves (often in glossopharyngeal nerve, diaphragmatic nerve, vagus, sympatic nerves).
Toxic effects are manifested in degeneration or even destruction of myelin membrane. Axis cylinders undergo swelling and rarely necrosis.
Parenchymatous neuritis with dvelopment of the late paralysis of the palate, diaphragm, and heart develops. The paralytic effects of diphtheritic neuropathy are often sharply localized.
Paralysis of the voluntary muscles of the palate may produce a peculiar nasal quality of the voice and a tendency to regurgitate fluids through the nose.
Paralysis of the diaphragm may lead to aspiration pneumonia.
Late paralysis of the heart may lead to acute cardiac failure.
Involvement of extraocular muscles may produce diplopia, and involvement of the ciliary body may result in defective visual accommodation.
Clinically apparent weakness or paralysis of limbs is rare. Neuropathic manifestations of diphtheria are usually temporary and disappear within 2 or 3 months if the patient survives.
3. Hemorrhages, degeneration and necrosis of the cells are observed in the medullary layer of the adrenal glands, foci of necrosis and disappearance of lipids are seen in the cortical layer. Acute adrenal insufficiency may develop.
4. A nonspecific, nonsuppurative interstitial nephritis is frequent in diphtheria and is believed to be responsible for the proteinuria often observed. Necrotic nephrosis and massive necroses of the cortical layer in the severe cases of toxic diphtheria are observed in the kidneys. The renal lesion usually resolves completely in patients who recover.
5. The liver is characteristically enlarged; hepatocytes exhibit cloudy swelling and less commonly focal necrosis.
Diphtheria in the respiratory tract
Diphtheria of the respiratory tract is characterised by croupous inflammation of the larynx, trachea, and bronchi with formation of fibrinous films, which can be discharged at cough.
The epithelial surface becomes necrotic and easily adherent to the overlying membrane; this adherence explains why raw bleeding, points are exposed when the membrane is forcibly removed. If particularly extensive, the local process may produce mechanical respiratory obstruction, stridor, and even asphyxia.
Croupous inflammation of the larynx in diphtheria is called true croup, propagation of the process in the small branches of the bronchial tree is called descending croup, which may be accompanied by development of focal pneumonia.
Complications in diphtheria of the respiratory tract are caused by
- Asphyxia due to obstruction of fibrinous films.
- Intubation or tracheotomy, which can result in decubitus.
- Secondary infection in decubitus causes purulent perichondritis of the cartilages of the larynx, phlegmon, and purulent mediastinitis.
Death is caused by
- Asphyxia (spasm of the larynx in true croup or occlusion of the respiratory tract with fibrinous films) or by accompanying pneumonia and purulent complications.
- Early cardioplegia in myocarditis and late cardioplegia or paralysis of the diaphragm due to parenchymatous neuritis when antitoxic serum is not administered in time.
Scarlet fever (SF)
Scarlet fever is one of the forms of streptococcal infection, it is an acute infectious disease accompanied by local inflammatory changes mainly in the pharynx and typical generalized rash. The disease is common in children (3-12 years old), but it can also be observed in the adults.
Etiology and pathogenesis
The causative agent is beta-hemolytic streptococcal group A of different serological types.
The patients are infected by inhalation (air-droplets rout), but the disease can also be transmitted through personal belongings and foodstuffs (mainly milk).
Incubation period is 3-7 days.
Pathogenesis of scarlet fever is complicated and explained by third factors: erythrogenic toxin, microbial invasion and allergic reactions.
The duration of the disease is divided into two periods, toxic (first) and infectious allergic (second) ones.
In the early stages there is rather severe pharyngitis and tonsillitis. These, combined with fever, vomiting, and headache, make up the cardinal prodromal symptoms of scarlet fever. Because there is no specific strain of beta-hemolytic streptococci responsible for scarlet fever, bacteriologic studies do not provide a means for early diagnosis; in other words, a diagnosis of throat infection caused by S. pyogenes is not a diagnosis of scarlet fever. The diagnosis cannot be positively made until the second stage of the disease, which is reached 1 to 5 days after the onset.
Morphology
1. Toxic period (1-2 weeks).
Local changesappear the inflammatory process in the site of the primary fixation (tonsils, skin, lungs, seldom-genital tract), which is accompanied by regional lymphangitis and lymphadenitis. This is called “primary scarlatinic affect”and “primary scarlatinic complex”. “Primary scarlatinic affect” is characterized by catarrhal or necrotic tonsillitis.
Catarrhal tonsillitis (during the first few days) is manifested by hyperemia of pharynx (“flaring pharynx” or “burning faucet”) with involvement to oral cavity and tongue. It presents a “strawberry” appearance because of the erythematous papillae that project from a gray-coated background. When peeling occurs, the tongue becomes beefy red and glistening.
Necrotic tonsillitis is characterized by coagulative necrosis and ulceration. Microscopically, there is a characteristic acute, edematous, neutrophilic inflammatory reaction within the affected tissues. Necrosis may involve the soft palate, pharynx, auditory tube (Eustaphian tube), middle ear; it can pass from the lymphatic nodes to the subcutaneous fat of the neck. Rejection of the necrotic masses results in ulcers. Cervical lymphatic nodes are plethoric, juicy, enlarged, with foci of necrosis and marked myeloid infiltration.
General changes.
The general changes depending on toxemia are first of all rash.
A punctate erythematous rash that is most abundant over the trunk and inner aspects of the arms and legs manifests exanthema. The face is also involved, but usually a small area about the mouth (nasolabial triangle) remains relatively unaffected, to produce a circumoral pallor.
Microscopically, there is a characteristic acute, edematous, neutrophilic inflammatory reaction surrounding the affected tissues (skin and lymph nodes).
The inflammatory involvement of the epidermis is usually followed by hyperkeratosis of the skin, which accounts for the scaling during defervescence. The hyperemia and resultant red coloration of skin are manifestations of toxic injury (atony and dilatation) of vascular endothelium. This hyperemia blanches on pressure and disappears on death; thus little of the characteristic skin reaction is evident at autopsy.
The second period (allergic).
The second period may develop on the 3rd - 5th week of the disease rarely.
The second period begins with moderate catarrhal tonsillitis.
The most significant is development of acute or chronic glomerulonephritis with possible nephrosclerosis development.
Skin rash, vasculitis, serous arthritis, verrucous endocarditis can be observed.
Complications are divisible into three major categories:
1 The results of bacterial disseminations locally – otitis media, sinusitis, cervical adenitis, phlegmon of the neck, acute suppurative mastoiditis, and retropharyngeal abscess.
2 The result of bacterial dissemination generally – metastatic foci of infection throughout the body, or trunk septicemia.
3. The manifestation of extraordinary reactions to toxins (this may be brought about by hypersensitivity) – interstitial nephritis or myocarditis, pericarditis, nonsuppurative arthritis, and glomerulonephritis.
The death is caused by toxemia or septic complications.
Meningitis (M)
Meningitis (leptomeningitis) is an acute or chronic inflammatory process chiefly affecting the pia and arachnoid mater, cerebrospinal fluid (CSF) and may be caused by bacteria, fungi, or parasites.
It is usually caused by an infection, but chemical meningitis may also occur in response to a nonbacterial irritant introduced into the subarachnoid space.
Infectious M. can be broadly classified as acute pyogenic (usually bacterial), aseptic (usually viral), and chronic (bacterial or fungal).
Meningococcal infection is an acute infectious process which has three main forms: nasopharyngitis, purulent meningitis and meningococcemia.
This is characterized by periodic epidemics, the disease is more common in children under 5 years, but the disease may occur in persons of any age.
The typical patient with acute pyogenic meningitis has general signs of infection with the added symptoms and signs of meningeal irritation: headache, photophobia, irritability, clouding of consciousness, and neck stiffness.
Etiology. The causative agent is meningococcus (Neisseria meningitidis), which discharges the endotoxin.
Morphology
Meningococcal nasopharyngitis
It is characterized by catarrhal inflammation of the mucosa with marked hyperemia, edema of the posterior wall of the pharynx and hyperplasia of lymphatic follicles.
This form is of great epidemiological importance as clinical diagnosis is often difficult. Bacteriologic investigation is necessary for diagnose.
Meningococcal meningitis
It is characterized by the hyperemia of the pia mater, saturated with dull serous exudate during the first days of the disease.
By the end of the 2nd - 3rd day the exudate becomes thicker, green-yellow, purulent. By the 5th -6th day it becomes denser due to fibrinous effusion.
The process begins with basal surface and passes through, the perivenous spaces to the convex surface mainly of anterior portion of the brain, locating there in the form of a yellow-green “cap”.
The purulent process involves the meninges of the spine.
The meningeal vessels are enlarged and stand prominently.
The infection may extend into the ventricular system through the foramina of Magende and Luschka causing ventriculitis.
Other complications of meningitis include hydrocephalus resulting from ventricular obstruction or meningeal fibrosis, subdural effusion caused by fluid leading into the subdural space through defects in the arachnoid and occuring most commonly in children, and cranial nerve palsies probably related to inflammatory involvement of nerve roots crossing the subarachnoid space.
The death may occur from the brain swelling with wedging of the cerebellum tonsils to the great foramen and strangulation of the oblong brain during the acute period.
Later the cause of death is meningoencephalitis, purulent ependymitis or general cerebral cachexia due to hydrocephalia and atrophy of the brain hemispheres during the following periods.
Meningococcemia
Duration is 24-48 hours.
Bacteriemia and endotoxinemia lead to endotoxic shock with the development of syndrome of disseminated intravascular coagulation.
Changes on the organs are characterized by generalized damage of microcirculation, skin rash, changes in the joints, vascular membrane of the eyes, adrenal glands and kidneys. Changes in the serous layers of the pericardium are observed.
The changes of the microcirculation are characterized by vasculitis and necrosis.
The rash is hemorrhagic, star-like, located mainly on the buttocks, lower extremities, eyelids and scleras. There may be vesicles or dull dryish foci of necrosis in the centre of the skin elements. Purulent arthritis is observed in the small joints of the extremities.
Focal necroses and hemorrhages or bilateral massive hemorrhages with the development of acute adrenal insufficiency (Waterhouse-Friderichsen syndrome) are noted in the adrenals.
Necrosis of nephrothelium of the tubules (necrotic nephrosis) is observed in the kidneys.
Serous meningitis and hemorrhage may occur.
The death of the patients is caused by bacterial shock, its severity is aggravated by hemorrhages to the adrenals; acute renal insufficiency is not so common (in the adults). When the duration of the disease is prolonged, the death occurs from septicemia or purulent meningitis.
GASTROINTESTINAL INFECTIONS
Shigella bacillary dysentery (D)
Dysentery refers to diarrhea with abdominal cramping and tenesmus in which loose stools contain blood, pus, and mucus.
Bacillary D. is caused by Shigella dysenteriae, S. flexneri, S. boydii, and S. sonnei as well as certain O-type enterotoxic E.coli.
Transmission occurs by the fecal-oral route.
Symptoms appear 2 to 5 days after the ingestion of bacteria. The dose of organisms and the status of host defenses influence the incubation period and severity.
The key to the pathogenicity of Shigella is its ability to invade and multiply in the epithelium and lamina propria of the terminal ileum and colon, and destroy host cells.
Endotoxin probably adds to necrosis, but the role of enterotoxin produced by some species of Shigella in the pathogenesis of dysentery is uncertain.
While clearly secondary to invasion, Shiga toxin probably contributes to the profuse diarrhea that precedes dysentery in some patients.
This enterotoxin, which is related antigenically to the enterotoxin of enteropathogenic E. coli, activates membrane-associated adenyl cyclase. Thus, shiga toxin, like cholera toxin and E. coli enterotoxin, induces hypersecretion of fluid and electrolytes from the mucosa of the terminal ileum. Water and electrolyte balance must be maintained to prevent dehydration, prostration, and impaired mental status.
Morphology
Colitis has 4 stages:
1. Catarrhal colitis. The mucosa becomes edematous and hyperemic, and is covered by pus and mucus.
2. Fibrinous colitis. Within the course of 24 hours, a fibrinosuppurative exudate first patchily, then diffusely covers the mucosa and produces a dirty gray-to-yellow pseudomembrane, consisting of necrotic mucosa, neutrophils, fibrin, and erythrocytes. Sloughed pseudomembrane, together with blood-tinged mucus, comprises the characteristic dysenteric stool of shigellosis.
3. Ulcer formation (ulcerative colitis).
4. Healing of the wound. The epithelium persists only in the depths of the crypts, and goblet cells contain no mucus in the acute stage. Epithelial regeneration is rapid and healing is complete in 2 weeks.
Histologically, there is predominantly mononuclear leukocytic infiltrate within the lamina propria, but the surfaces of the ulcers are covered with an acute, suppurative, neutrophilic reaction accompanied by congestion, marked edema, fibrin deposition, and thromboses of small vessels. As the disease progresses, the ulcer margins are transformed into active granulation tissue. When the disease remits, this granulation tissue fills the defect, and the ulcers heal by regeneration of the mucosal epithelium.
In case of solitary follicle cell hyperplasia, they enlarge and protrude over the surface of the mucous membrane (follicular colitis and follicular-ulcerative colitis).
Lymphadenitis develops in the regional lymphatic nodes. Common changes are spleen hyperplasia, fatty degeneration in the heart and liver, small-focal necroses in the liver, necrosis of renal tubular epithelium.
Complications of dysentery are
- Perforation (microperforation) of the ulcer with development of. paraproctitis or peritonitis, intestinal phlegmon.
- Intraintestinal hemorrhage
- Scar stenosis of the intestine is less common.
- Extraintestinal complications are bronchopneumonia, pyelonephritis, serous (toxic) arthritis, and pylephlebilic abscesses of the liver, amyloidosis, intoxication, and cachexia.
The death may cause by intestinal or extraintestinal complications.
Amebiasis
The protozoan parasite Entamoeba histolytica infects approximately 500 million persons in developing countries. The disease is common in India, Mexico, and Colombia. Amebae cause dysentery – bloody diarrhea, intestinal pain, fever – when they attach to the colonic epithelium, lyses colonic epithelial cells, and invade the bowel well.
Morphology
Amebiasis most frequently involves the cecum and ascending colon, followed in order by sigmoid, rectum, and appendix. In severe, full-blown cases, however, the entire colon is involved.
Amebae invade the crypts of the colonic glands, burrow through the tunica propria, and are halted by the muscularis mucosae. As the lesion progresses, the overlying surface mucosa is deprived of its blood supply and sloughs. The earliest amebic lesions show neutrophilic infiltrates in the mucosa, which later develop into ulcers that contain few host inflammatory cells and areas of extensive liquefactive necrosis.
The mucosa between ulcers is often normal or midly inflamed.
In about 40% of patients with amebic dysentery, parasites penetrate portal vessels and embolize to the liver to produce solitary, or less often multiple, discrete abscesses, some exceeding 10 cm in diameter. Amebic liver abscesses have a scant inflammatory reaction at their margins and a shaggy fibrin lining. Because of hemorrhage into the cavities, the abscesses are sometimes filled with a chocolate-colored, odorless, pasty material likened to anchovy paste. Secondary bacterial infection may make these abscesses purulent. As the amebic abscesses enlarge, they produce pain by pressing on the liver capsule and can be visualized with ultrasound. Amebic liver abscesses are treated with drainage and drugs or with drugs alone
Rarely, amebic abscesses reach the lung and the heart by direct extension or appeared through the blood into the kidneys and brain.
Salmonellosis and typhoid fever
Salmonellae are flagellated, gram-negative bacteria that cause a self-limited and water-borne gastroenteritis or a little-threatening systemic illness marked by fever.
Salmonellas invade nonphagocytotic interstitial epithelial cells as well as tissue macrophages.
Typhoid fever
Typhoid fever (enteric fever) is an acute intestinal infectious disease caused by Salmonella typhy abdominalis. Epidemics are possible but at present the disease is rare, its course is not severe. The infection is parenteral.
The source of infection is a sick person or a human carrier whose excretions (faeces, urine, sweat) contain the microbes.
Pathogenesis
The bacteria multiply in the lower portion of the small intestine and produce endotoxins.
On penetrating the intestinal mucosa, the organisms enter Peyer’s patches and solitary follicles, quickly enter lymphatic vessels and mesenteric nodes, whence they reach the liver and then, by the thoracic duct, the bloodstream. All this occurs in the incubation period, usually 10 to 14 days. This is the first stage of the disease; in which generalization of the infection occurs before localizing lesions draw attention to the intestine.
Bacteremia develops (1st week of the disease); the bacillus can be isolated from the blood (homoculture). Bacteremia is associated with generalization of the infection.
Beginning with the 2nd week antibodies to the causative agent are determined in the blood with agglutination reaction (Widal’s reaction).
Bacteremia is also associated with elimination the causative agent that is excreted with the sweat, milk, urine, faeces, and bile. The patient is especially infective during this period.
The most favourable conditions for the life of the bacteria are in the bile where they intensively multiply (bacteriocholia).
They are excreted with the bile to the small intestine and cause hyperergic reaction in the previously sensibilized lymphatic follicles. The condition results in necrosis of the intestine lymphatic system.
Morphology
The changes in typhoid fever can be local and generalized.
Local changes occur in the mucous membrane and lymphatic system (group and solitary follicles of the intestine). The most prominent changes develop in the Peyer's patches of the ileum (ileotyphus).
These changes develop in 5 stages. Each stage takes approximately one week.
1. Medullar swelling is acute proliferative granulematous inflammation in lymphoid apparatus of intestine with development macrophagal granulomas (“typhoid granuloma”). They consist of large macrophages with pail-pink cytoplasm, containing bacteria. In mucosa the catarrhal inflammation is found out. Proliferation of phagocytes with enlargement of reticuloendothelial and lymphoid tissues throughout the body develop. Peyer’s patches in the terminal ileum become sharply delineated, plateau-like elevations up to 1 cm in diameter, with enlargement of draining mesenteric lymph nodes. Follicles are protruded in intestine lumen. Their surface is striated and like brain.
2. Necrosis. After 7 to 10 days, the picture in the intestine is complicated by necrosis and ulceration of areas that formerly exhibited lymphoid hyperplasia.
3. Ulcer formation (“unclear ulcers”).In the second week, the mucosa over the swollen lymphoid tissue is shed, resulting in oval ulcers with their long axes in the direction of bowel flow. In the colon, ulcers are smaller and punctate, corresponding to the smaller lymphoid follicles there. Edges of ulcer are irregular with necrotic tissue. Macrophages, lymphocytes and plasma cells, whereas neutrophils are present near the ulcerated surface.
4. “Clean ulcer” has regular shape without necrotic tissue. In this stage the perphoration can develop.
5. Healing (recovery).Granulomas are sclerosed, necroses undergo to petrification.
General changes. The changes in typhoid fever may be typical only for this disease as well as characteristic for any infection.
Roseolar-papular rash and typhoid granuloma in different organs occurs.
The latter are the processes in the organs of the lymphatic system and degenerative changes in the parenchymal organs.
The spleen is enlarged, soft, and bulging, with uniformly pale red pulp, obliterated follicular markings, and prominent sinus histiocytosis and reticuloendothelial proliferation.
The liver shows small, randomly scattered foci of parenchymal necrosis in which the hepatocytes are replaced by a phagocytic mononuclear cell aggregates, called “typhoid nodule”.
These distinctive nodules also occur in the bone marrow and lymph nodes.
Gallbladder colonization, which may be associated with gallstones, causes a chronic carrier that may require cholecystectomy to eliminate bacterial shedding.
Atypical forms are pneumotyphus, cholangiotyphus.
Complications
Intestinal (intraintestinal hemorrhages, ulcer perforation, peritonitis).
Extraintestinal (pneumonia, purulent perichondritis of the larynx, Zenker’ s necrosis of the abdominal muscles, osteomyelitis, intramuscular abscesses).
The death is caused by the complications.
Salmonellosis
Salmonellosis is an intestinal infection caused by salmonellas. It is anthropozoonosis and occurs both in human beings and animals.
The most often pathogenic organism is Salmonella typhi murium, salmonella enteritidis, salmonella cholera suis.
Incubation’s period is 12-36 hours.
Clinical symptoms are accompanied with endotoxin and endotoxinemia: fever, diarrhea and hypotony and endotoxic shock.
Pathology. Salmonellas cause three types of human disease (salmonellosis): interstitial (toxic), septic, typhoid.
1. Interstitial salmonellosis (gastroenteritis) develops in food poisoning. It is characterized by acute gastroenteritis causing severe-dehydration of the organism. The disease resembles cholera that is why it is called “home cholera”.
2. Septic salmonellosis (septicemic diseases without specific organ-system localization) differs from interstitial one in hematogenic generalization of the causative agent with formation of metastatic abscesses in different organs while the changes in the small intestine are not significantly pronounced.
3. Typhoid salmonellosis (specific enteric fevers) resembles typhoid fever.
Complications. Toxicoinfectious shock, purulent complications, dysbacteriosis when the treatment is inadequate.
Cholera
Cholera is an acute gastrointestinal infectious quarantinic disease and is characterized by diarrhea and exicosis.
The vibrios never invade the enteric epithelium but instead remain within the lumen and secrete their endotoxin.
Secretory diarrhea is caused by released of an endotoxin, called cholera toxin, which is nearly identical to E.coli endotoxin.
This is due to the exotoxin of the Vibrio cholera, which evokes an intense outpouring of watery fluid and electrolytes into the gut lumen, resulting in severe diarrhea and hypovolemic shok.
Vibrio cholera is comma-shaped, gram-negative bacteria that have been caused of seven great long-lasting epidemics (pandemics) of diarrheal disease. Vibrio cholera locates in water often.
The only significant natural reservoir of cholera appears to be humans, and the only clinically significant portal of entry is the alimentary tract by the fecal-oral route. V. cholera are appreciably sensitive to normal gastric acidity.
The incubation period is usually 1 to 5 days, after which a profuse watery diarrhea occurs usually without tenesmus or abdominal distress.
Fluid loss can exceed 10 liters per day. Prostration is therefore rapid and profound.
The disease is ordinarily self-limited, with death or recovery occurring within a few days. An asymptomatic convalescent carrier state is uncommon but can occur.
Drinking water contaminated with V. cholera and food prepared with contaminated water is infectious. Those with a normal gastric acidity are much less susceptible than those with low levels of stomach acid as a result of a gastrectomy or other cause. Vibrios traverse the stomach, enter the small intestine and propagate.
Clinical-morphological stages of cholera
1. Choleric enteritis is characterized by the hard diarrhea. Morphologically: swelling of enterocytes, serous edema of the intestine mucosa.
2. Choleric gastroenteritis is characterized by the hard diarrhea and vomit, increase of dehydration. The loss of sodium and water causes severe diarrhea, called “rice-water stool”. Fluid loss may exceed 1 liter per hour.
3. Choleric exicosis (algid):
Acute dehydration, hypovolemic shock, and metabolic acidosis follow quickly.
The patient exhibits dry skin, sunken eyes, lethargy, cyanosis, a weak pulse, faint heart sounds, hemoconcentration, and elevation of serum proteins. The hematocrit may rise to 55-65 and the plasma specific gravity to 1.035-1.050. Patients are usually a febrile; body temperature may be subnormal.
Rigor mortis develops quickly and persists for several days. The outlines of the muscles are well pronounced (“gladiator posture”).
The skin is dry, creasy (especially on the fingers, “beef-steak hands”). Due to rapid development of rigor mortis, resembles “goose’s skin”.
The mucous membranes, subcutaneous fat and muscles are dry; the muscles become dark red. The blood in the veins is thick, dark. The serous membranes are also dry, covered with sticky transparent mucus, which is stretched out in the form of threads.
Changes in different organs due to dehydration (spleen, liver, gallbladder, kidneys, myocardium, brain) can be.
The spleen diminishes, its capsule becomes creasy, the follicles are atrophic, and pulp hemosiderosis is observed.
Degeneration and focal necroses in the liver develop. Bile formation is disturbed. The gallbladder is not distended, filled with clear light bile (“white bile”).
Necrotic nephrosis of the main portions of nephron (the changes observed in oliguria and acute renal failure) is noted in the kidneys.
There are degenerative and necrobiotic changes in the brain and myocardium.
Treatment is prompt rehydration, and under such circumstances most patients survive. After the onset of diarrhea, urine production ceases, but renal function improves when fluid and electrolytes are replaced. Inadequate replacement, however, leads to prolonged renal failure, with acute damage of tubules and the vacuolar lesions of hypokalemia.
Complications
There are nonspecific and unspecific complications of cholera. Cholera typhoid and post-cholera uremia are specific complications. Nonspecific complications are pneumonia, abscesses, phlegmon, erysipelas, and sepsis.
The death occurs in algid period and is caused by dehydration, coma, uremia, and intoxication. At present owing to early adequate treatment (administration of water and salts, antibiotics) the death rate has been considerably decreased.
Escherichia coli Infection
Escherichia coli,a gram-negative bacillus that is part of the intestinal flora, is also an important opportunistic pathogen, causing diarrhea and dysentery, urinary tract infections, pneumonia, and neonatal meningitis. E. colicauses at least three patterns of human enteric diseases: enterotoxigenic, enteroinvasive, and enteroadherent.
1. Enterotoxigenic E. colicauses a diarrheal disease by elaborating two plasmid-mediated enterotoxins. The heat-labile toxin is antigenically, structurally, and functionally related to the cholera toxin, although the toxin of E. coliis less potent than that of cholera. As in cholera, the resulting activation of adenylcyclase produces a hypersecretory diarrhea. The heat-stable toxin of E. coliis different from cholera toxin and apparently acts to impair sodium and chloride absorption and to reduce the motility of the small intestine. Dehydration and electrolyte imbalance is a significant cause of morbidity and mortality when appropriate rehydration is lacking - a common combination among infants in less developed countries. Enterotoxigenic E. coliis also responsible for 50% of traveller's diarrhea.
2. Enteroinvasive E. coliproduces a dysentery-like disease resembling shigellosis, although it is less severe and requires a much larger infecting dose of organisms. Enteroinvasive E. coliinvades the intestinal mucosa and causes local tissue destruction and sloughing of necrotic mucosa. Bloody mucoid stools contain neutrophils.
3. Enteroadhesive E. colihas only recently been associated with diarrheal diseases. Enteroadhesiveness is plasmid-dependent and is apparently mediated by pili, which bind tightly to receptors on the intestinal epithelial cells. The mechanism of diarrhea is unknown.
About 80% of all infections of the urinary tract in humans, ranging from mild cystitis to fatal pyelonephritis, are caused by E. coli.In addition, E. coliis the etiologic agent in many cases of nosocomial pneumonia, most often in elderly patients with underlying chronic disease. Aspirates of endogenous oral flora containing E. coliappear to be the cause of this bronchopneumonia, although in bacteremic patients pneumonia may result from seeding by septic emboli. Empyema is a common complication, especially in patients with disease lasting more than a week.
Only rarely does E. coli cause meningitis in adults, but it is a major cause of neonatal meningitis. Between 40% and 80% of infants with E. colimeningitis die, and the survivors frequently suffer from neurologic or developmental anomalies.
TUBERCULOSIS
Tuberculosis is a chronic communicable disease with specific granulomatous inflammation caused by a variety of tubercle bacilli, especially Micobacterium tuberculosis hominis and M. t. bovis.
The organism is a strict aerobe and thrives best in tissues with high oxygen tension like in the apex of the lung.
The lungs are the prime target, but any organ may be infected. The characteristic lesion is a specifical granuloma with central caseous necrosis.
Tuberculosis still continues to be worldwide in distribution, more common in poorer countries of Africa, Latin America and Asia. Other factors contributing to higher incidence of tuberculosis are malnutrition, inadequate medical care, poverty, crowding, chronic debilitating conditions like uncontrolled diabetes, alcoholism and immunocompromised states like AIDS.
Mode of transmission
Human beings acquire infection with tubercle bacilli by one of the following routes:
By inhalation into the respiratory tract.
Ingestion. Through ingestion into GI tract leads to development to tonsillar or intestinal tuberculosis.
Inoculation. Through mucous membranes of mouth and throat, skin.
Transplacental route results in development of congenital tuberculosis in fetus from infected mother and is a rare mode of transmission.
Spread of tuberculosis
1. Local spread. This takes place by macrophages carrying the bacilli into the surrounding tissues.
2. Lymphatic spread. Tuberculosis is primarily an infection of lymphoid tissues. Primary complex is primary focus with lymphangitis and lymphadenitis.
3. Hematogenous spread. This occurs either as a result of tuberculous bacillemia because of the drainage of lymphatics into the venous system or due to caseous material escaping through ulcerated wall of a vein. This produces millet seed-sized lesions in different organs of the body like lungs, liver, kidneys, bones and other tissues and is known as miliary tuberculosis.
4. By the natural passages.
Infection may spread from:
Lung lesions into pleura (tuberculous pleurisy).
Transbronchial spread into the adjacent lung segments.
Tuberculous salpingitis into peritoneal cavity (tuberculous peritonitis).
Infected sputum into larynx (tuberculous laryngitis).
Swallowing of infected sputum (ileocecal tuberculosis).
Renal lesions into ureter and down to trigone of bladder.
Hypersensitivity and immunity in tuberculosis
Hypersensitivity or allergy, and immunity or resistance, plays a major role in the development of lesions in tuberculosis.
Tissue changes seen in tuberculosis are not the result of any exotoxin or endotoxin but are instead the result of host response to the organism, which is in the form of development of cell-mediated hypersensitivity (or type IV hypersensitivity) and immunity.
Tissue reaction to tubercle bacilli is different in healthy organism not previously infected (primary infection) from an organism who is previously infected (secondary infection).
1. In the primary infection, intradermal injection of tubercle bacilli into the skin evokes no visible reaction for 10-14 days. After this period, a nodule develops at the inoculation site, which subsequently ulcerates and heals poorly. This process is a manifestation of delayed type of hypersensitivity and is comparable to primary tuberculosis in children.
2. In the secondary infection, the tubercle bacilli are injected into the skin who has been infected with tuberculosis 4-6 weeks earlier. In 1 -2 days, the site of inoculation is indurated and dark, attaining a diameter of about 1 cm. The skin lesion ulcerates which heals quickly and the regional lymph nodes are not affected. This is called Koch’s phenomenonand is indicative of hypersensitivity and immunity in the host.
Hypersensitivity and immunity are closely related and are initiated through T lymphocytes sensitised against specific antigens in tuberculin.
Tuberculin (Mantoux) skin test. This test is done by intradermal injection of 0.1 ml of tuberculoprotein, purified protein derivative (PPD). Delayed type of hypersensitivity develops in individuals who are having or have been previously infected with tuberculous infection which is identified as an indurated area of more than 15 mm in 72 hours. However, patients having disseminated tuberculosis may show negative test due to release of large amount of tuberculoproteins. A positive test is indicative of cell-mediated hypersensitivity to tubercular antigens but does not distinguish between infection and disease. The test may be false positive in atypical mycobacterial infection and false negative in sarcoidosis, some viral infections, Hodgkin’s disease and fulminant tuberculosis.
Immunisation against tuberculosis. Protective immunisation against tuberculosis is induced by injection of attenuated strains of bovine type of tubercle bacilli, Bacilli Calmette Guerin (BCG). Cell-mediated immunity with consequent delayed hypersensitivity reaction develops with healing of the lesion, but the cell-mediated immunity persists, rendering the host tuberculin-positive and hence immune.
Evolution of tubercule
The sequences of events, which take place when tubercle bacilli are introduced into the tissue, are as under:
The inhaled organism enters the alveolus and is ingested by the alveolar macrophage. The M. tuberculosis can either be killed by the macrophage; its growth inhibited or multiplies inside the macrophage.
It behaves more like a parasite and lives in symbiosis with the cell.
The macrophages start phagocytosing the tubercle bacilli. In 2-3 days, the macrophages undergo structural changes as a result of immune mechanisms - these modified macrophages resemble epithelial cells and are called epithelioid cells.
The macrophages continue to enter the tissue either from circulating monocytes or from local proliferation. Release of cytokines in response to sensitised CD 4 + T cells and some constituents of mycobacterial cell wall play a role in formation of granuloma.
Some of the macrophages form multinucleated giant cells by fusion of adjacent cells. The giant cells may be Langhans’ type or they may be foreign body type. The giant cells may have 20 or more nuclei. These nuclei may be arranged at the periphery like horse-shoe or ring or clustered at the two poles, or they may be present centrally (foreign body giant cells).
Around the mass of epithelioid cells and giant cells is a zone of lymphocytes, plasma cells and fibroblasts. The lesion at this stage is called hard tubercle due to absence of central necrosis.
Within 10-14 days, the centre of the cellular mass begins to undergo caseation necrosis. This stage is called soft tubercle, which is the hallmark of tuberculous lesions.
Acid-fast bacilli are difficult to find in these lesions and may be demonstrated at the margins of recent necrotic foci and in the walls of the cavities.
In granuloma enclosed by fibrous tissue, calcium salts may get deposited in the caseous material (dystrophic calcification) and sometimes the lesion may even get ossified over the years.
Types of tuberculosis
I. Primary tuberculosis
II. Post primary tuberculosis
a) Secondary tuberculosis
b) Hematogenous tuberculosis
Primary Tuberculosis
The infection of an individual who has pot been previously infected or immunised is called primary tuberculosis or Ghon’s complex or childhood tuberculosis.
Primary complex or Ghon’s complex is the lesion produced at the portal of entry with foci in the draining lymphatic vessels and lymph nodes. Commonly involved tissues for primary complex are lungs and hilar lymph nodes.
The incidence of disseminated form of progressive primary tuberculosis is particularly high in immunocompromised host (in patients of AIDS).
The primary complex in lungs is located in the lower part of the right upper lobes or the upper part of the lower lobes in 3, 8,9,10 segments usually. The initial infection produces only slight abnormalities and may cause only slight malaise and mild fever.
Primary complex or Ghon’s complex in lungs consists of 3 components:
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