Ординатура / Офтальмология / Английские материалы / Basic Sciences in Ophthalmology_Velayutham_2009
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Eosinophilia and elevated serum IgE levels are common but, because they occur in many parasitic infections, are not diagnostic in themselves. Assays to detect specific antibodies to Onchocerca and PCR to detect onchocercal DNA in skin snips are now in use in specialized laboratories and are highly sensitive and specific.
The Mazzotti test is a provocative technique that can be used in cases where the diagnosis of onchocerciasis is still in doubt (i.e., when skin snips and ocular examination reveal no microfilariae). A small dose of DEC (0.5 to 1.0 mg/kg) is given orally; the development or exacerbation of pruritus or rash within hours is highly suggestive of onchocerciasis.
Treatment
Ivermectin
LOIASIS
Etiology
Loiasis is caused by L. loa (the African eye worm), which is present in the rain forests of West and Central Africa. Adult parasites (females, 50 to 70 mm long and 0.5 mm wide; males, 25 to 35 mm long and 0.25 mm wide) live in subcutaneous tissues; microfilariae circulate in the blood with a diurnal periodicity that peaks between 12:00 noon and 2:00 P.M.
Clinical Features
Manifestations of loiasis in natives of endemic areas may differ from those in temporary residents or visitors. Among the indigenous population, loiasis is often an asymptomatic infection with microfilaremia. Infection may be recognized only after subconjunctival migration of an adult worm or may be manifested by episodic. Calabar swellings, evanescent localized areas of angioedema and erythema developing on the extremities and less frequently at other sites. Nephropathy, encephalopathy, and cardiomyopathy are rare. In patients who are not residents of endemic areas, allergic symptoms predominate, episodes of Calabar swelling tend to be more frequent and debilitating, microfilaremia is rare, and eosinophilia and increased levels of antifilarial antibodies are characteristic.
Pathology
The pathogenesis of the manifestations of loiasis is poorly understood. Calabar swellings are thought to result from a hypersensitivity reaction to the adult worm.
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Diagnosis
Definitive diagnosis of loiasis requires the detection of microfilariae in the peripheral blood or the isolation of the adult worm from the eye or from a subcutaneous biopsy specimen from a site of swelling developing after treatment (Fig. 33.25). PCR-based assays for the detection of L. loa DNA in blood are now available in specialized laboratories and are highly sensitive and specific. In practice, the diagnosis must often be based on a characteristic history and clinical presentation, blood eosinophilia, and elevated levels of antifilarial antibodies, particularly in travelers to an endemic region, who are usually amicrofilaremic. Other clinical findings in the latter individuals include hypergammaglobulinemia, elevated levels of serum IgE, and elevated leukocyte and eosinophil counts.
Fig. 33.25: Peripheral blood smear showing L. loa
Treatment
Diethyl Carbamazine, Albendazole, Ivermectin.
ACANTHAMOEBA
There are seven species of Acanthamoeba known to infect humans. Acanthamoeba culbertsoni is common.
Characteristic Features
Acanthamoeba spp. exists in two forms, trophozoite and cyst. Both the forms occur in infected tissue. Trophozoites are 15 microns to 45 microns in size. The nuclear characters are similar to Naegleria fowleri. They produce fine, tapering, hyaline pseudopodia called acanthopodia. Motility is sluggish. Aflagellate stage is absent in Acathamoeba spp. as against Naegleria fowleri. The cysts have double wall. The inner wall is smooth and the outer wall is wrinkled and ragged. They are round and measure 8-25 microns. The cyst survives in dust for many years.
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Pathogenesis
Acathamoeba occur in soil and water. Trophozoites as well as cysts are infective to human beings (Fig. 33.26). The infection is through the contamination of traumatized skin or eyes and by inhalation. In primary infections the skin and lungs are involved.
Acanthamoeba can produce keratitis. Contact lens users are at an increased risk. Infection can occur in swimmers. Deeper corneal invasion with perforation and loss of vision may follow Acanthamoeba keratitis. Most of the non-ocular infections are due to and corneal lesions are usually due to A. polyphagia.
Fig. 33.26: Acanthamoeba
Lab Diagnosis
The cysts of Acanthamoeba are present in corneal scrapping
Treatment: Acanthamoeba keratitis respond to a combination of neomycin drops, dibromopropamid ointment and propamide isethionate.
VIROLOGY
Viruses consist of a nucleic acid surrounded by one or more proteins. Some viruses also have an outer-membrane envelope. Viruses differ from other replicating organisms in that they do not have ribosomes or enzymes for highenergy phosphate generation or for protein, carbohydrate, or lipid metabolism. Viruses are obligate intracellular parasites—that is, they require cells in order to replicate. Typically, viral nucleic acids encode proteins necessary for replicating and packaging the nucleic acids into new viral particles.
Viral Structure
Viruses have from a few to 200 genes. These genes may be embodied in a single-strand or double-strand DNA genome or in a single-strand sense, a single-
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strand or segmented antisense, or a double-strand segmented RNA genome. Sense-strand RNA genomes can be translated directly into protein. Sense and antisense genomes are also referred to as positive-strand and negative-strand genomes, respectively. The viral nucleic acid is usually associated with one or more virus-encoded nucleoproteins in the core of the viral particle. The viral nucleic acid is almost always enclosed in a protein shell called a capsid. Because of the limited genetic complexity of viruses, their capsids are usually composed of multimers of identical capsomers. Capsomers are in turn composed of one or a few proteins. Capsids have icosahedral or helical symmetry. Icosahedral structures approximate spheres but have two-, three-, and fivefold axes of symmetry, while helical structures have only a twofold axis of symmetry. The entire structural unit of nucleic acid, nucleoprotein(s), and capsid is called a nucleocapsid. Many human viruses have a simple nucleocapsid structure. For these viruses, the outer surface of the capsid mediates contact with uninfected cells. Other viruses are more complex and have an outer envelope that is derived from membranes of the infected cell.
Stages of Infection
At the cellular level, viral infection proceeds in stages.
Viral Interactions at the Cell Surface First, virus adsorbs to a receptor on the cell surface. Adsorption is the consequence of a molecular interaction of a viral surface protein with a molecule on the cell's plasma membrane.
After adsorption, viruses penetrate through or fuse with the cell membrane, lose their sensitivity to neutralizing antibody, and become uncoated as they enter the cytoplasm. For all viruses, penetration and uncoating result in viral nucleocapsid or nucleoprotein entry into the cytoplasm. Penetration and uncoating as well as subsequent steps in viral replication depend on the cell's energy metabolism and on biochemical changes in the cell's plasma membrane and cytoskeleton.
Viral Gene Expression and Replication After uncoating and release of viral nucleoprotein into the cytoplasm, the viral genome is transported to a site for expression and replication. In order to produce infectious progeny, viruses must (1) replicate their nucleic acid, (2) produce structural proteins, and
(3) assemble the nucleic acid and proteins into progeny virions.
Fig. 33.27: Cytopathic effect in cell culture showing giant cell formation
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HERPES VIRUSES
Definition
Herpes simplex viruses (HSV-1, HSV-2; Herpesvirus hominis) produce a variety of infections involving mucocutaneous surfaces, the central nervous system (CNS), and—on occasion—visceral organs. The advent of effective chemotherapy for HSV infections has made prompt recognition of these syndromes even more clinically important than in the past.
Etiologic Agent
The genome of HSV is a linear, double-stranded DNA molecule (molecular weight, ~100 × 106) that encodes more than 75 gene products. The genomic structures of the two HSV subtypes are similar.
Pathogenesis
Exposure to HSV at mucosal surfaces or abraded skin sites permits entry of the virus and initiation of its replication in cells of the epidermis and dermis. Investigators have identified several cell receptors that are ligands for HSV attachment proteins. Studies to define how these receptors influence viral replication and pathogenesis are under way. Initial HSV infection is often subclinical—i.e., without clinically apparent lesions. Both clinical acquisition and subclinical acquisition are associated with sufficient viral replication to permit infection of either sensory or autonomic nerve endings.
Clinical Presentation
HSV has been isolated from nearly all visceral or mucocutaneous sites. The clinical manifestations and course of HSV infection depend on the anatomic site involved, the age and immune status of the host, and the antigenic type of the virus. Primary HSV infections (i.e., first infections with either HSV-1 or HSV-2 in which the host lacks HSV antibodies in acute-phase serum) are frequently accompanied by systemic signs and symptoms, involve both mucosal and extramucosal sites, and have a longer duration of symptoms, a longer duration of virus isolation from lesions, and a higher rate of complications than recurrent episodes of disease. Both viral subtypes can cause genital and oral-facial infections, and the infections caused by the two subtypes are clinically indistinguishable. However, the frequency of reactivation of infection is influenced by anatomic site and virus type. Genital HSV-2 infection is twice as likely to reactivate and recurs 8 to 10 times more frequently than genital HSV-1 infection. Conversely, oral-labial HSV-1 infection recurs more frequently than oral-labial HSV-2 infection. Asymptomatic shedding rates follow the same pattern.
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Oral-Facial Infections Gingivostomatitis and pharyngitis are the most frequent clinical manifestations of first-episode HSV-1 infection, while recurrent herpes labialis is the most frequent clinical manifestation of reactivation HSV infection. HSV pharyngitis and gingivostomatitis usually result from primary infection and are most commonly seen in children and young adults. Clinical symptoms and signs, which include fever, malaise, myalgias, inability to eat, irritability, and cervical adenopathy, may last from 3 to 14 days. Lesions may involve the hard and soft palate, gingiva, tongue, lip, and facial area. HSV-1 or HSV-2 infection of the pharynx usually results in exudative or ulcerative lesions of the posterior pharynx and/or tonsillar pillars. Lesions of the tongue, buccal mucosa, or gingiva may occur later in the course in one-third of cases. Fever lasting from 2 to 7 days and cervical adenopathy are common. It can be difficult to differentiate HSV pharyngitis clinically from bacterial pharyngitis, Mycoplasma pneumoniae infections, and pharyngeal ulcerations of noninfectious etiologies (e.g., Stevens-Johnson syndrome). No substantial evidence suggests that reactivation oral-labial HSV infection is associated with symptomatic recurrent pharyngitis.
Eye Infections HSV infection of the eye is the most frequent cause of corneal blindness in the United States. HSV keratitis presents with an acute onset of pain, blurring of vision, chemosis, conjunctivitis, and characteristic dendritic lesions of the cornea. Use of topical glucocorticoids may exacerbate symptoms and lead to involvement of deep structures of the eye. Debridement, topical antiviral treatment, and/or interferon therapy hastens healing. However, recurrences are common, and the deeper structures of the eye may sustain immunopathologic injury. Stromal keratitis due to HSV appears to be related to T cell-dependent destruction of deep corneal tissue. An HSV-1 epitope that is autoreactive with T cell-targeting corneal antigens has been postulated to be a factor in this infection. Chorioretinitis, usually a manifestation of disseminated HSV infection, may occur in neonates or in patients with HIV infection. HSV and varicella-zoster virus can cause acute necrotizing retinitis as an uncommon but severe manifestation.
Diagnosis
Staining of scrapings from the base of the lesions with Wright's, Giemsa's (Tzanck preparation, or Papanicolaou's stain demonstrates characteristic giant cells or intranuclear inclusions of herpesvirus infection. These cytologic techniques are often useful as quick office procedures to confirm the diagnosis. Limitations of the cytologic method are that it does not differentiate between HSV and varicella-zoster virus infections, that it is relatively insensitive, and that the correct identification of giant cells requires experience.
HSV infection is best confirmed in the laboratory by isolation of virus in tissue culture or by demonstration of HSV antigens or DNA in scrapings from
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lesions. HSV causes a discernible cytopathic effect in a variety of cell culture systems
PCR is found to be more sensitive.
Treatment
Acylovir, Famciclovir are effective
VARICELLA ZOSTER
Varicella-zoster virus (VZV) causes two distinct clinical entities: varicella (chickenpox) and herpes zoster (shingles). Chickenpox, a ubiquitous and extremely contagious infection, is usually a benign illness of childhood characterized by an exanthematous vesicular rash. With reactivation of latent VZV (which is most common after the sixth decade of life), herpes zoster presents as a dermatomal vesicular rash, usually associated with severe pain.
VZV is a member of the family Herpesviridae, sharing with other members such structural characteristics as a lipid envelope surrounding a nucleocapsid with icosahedral symmetry, a total diameter of approximately 180 to 200 nm, and centrally located double-stranded DNA that is about 125,000 bp in length.
Pathogenesis
Primary Infection: Transmission is most likely to take place by the respiratory route; the subsequent localized replication of the virus at an undefined site (presumably the nasopharynx) leads to seeding of the reticuloendothelial system and ultimately to the development of viremia. Viremia in patients with chickenpox is reflected in the diffuse and scattered nature of the skin lesions and can be verified in selected cases by the recovery of VZV from the blood. Vesicles involve the corium and dermis, with degenerative changes characterized by ballooning, the presence of multinucleated giant cells, and eosinophilic intranuclear inclusions. Infection may involve localized blood vessels of the skin, resulting in necrosis and epidermal hemorrhage. With the evolution of disease, the vesicular fluid becomes cloudy because of the recruitment of polymorphonuclear leukocytes and the presence of degenerated cells and fibrin. Ultimately, the vesicles either rupture and release their fluid (which includes infectious virus) or are gradually reabsorbed.
Recurrent Infection: The mechanism of reactivation of VZV that results in herpes zoster is unknown. Presumably, the virus infects the dorsal root ganglia during chickenpox, where it remains latent until reactivated. Histopathologic examination of representative dorsal root ganglia during active herpes zoster demonstrates hemorrhage, edema, and lymphocytic infiltration.
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Clinical Manifestations
Chickenpox: Humans are the only known reservoir for VZV. Chickenpox is highly contagious, with an attack rate of at least 90% among susceptible (seronegative) individuals. Persons of both sexes and all races are infected equally often. The virus is endemic in the population at large; however, it becomes epidemic among susceptible individuals during seasonal peaks— namely, late winter and early spring in the temperate zone. Children between the ages of 5 and 9 are most commonly affected.
The incubation period of chickenpox ranges between 10 and 21 days but is usually between 14 and 17 days. Secondary attack rates in susceptible siblings within a household are between 70 and 90%. Patients are infectious approximately 48 h prior to the onset of the vesicular rash, during the period of vesicle formation (which generally lasts 4 to 5 days), and until all vesicles are crusted.
Clinically, chickenpox presents as a rash, low-grade fever, and malaise, although a few patients develop a prodrome 1 to 2 days before onset of the exanthem.
The most common infectious complication of varicella is secondary bacterial superinfection of the skin, which is usually caused by Streptococcus pyogenes or Staphylococcus aureus. This complication may result from excoriation of skin lesions after scratching. Gram's staining of skin lesions should help clarify the etiology of unusually erythematous and pustulated lesions.
The most common extracutaneous site of involvement in children is the CNS.
Other complications of chickenpox include myocarditis, corneal lesions, nephritis, arthritis, bleeding diatheses, acute glomerulonephritis, and hepatitis. Hepatic involvement, distinct from Reye's syndrome and usually asymptomatic, is common in chickenpox and is usually characterized by elevated levels of liver enzymes, particularly aspartate and alanine aminotransferases.
Herpes Zoster: Herpes zoster, a sporadic disease, is the consequence of reactivation of latent VZV from the dorsal root ganglia. Most patients have no history of recent exposure to other individuals with VZV infection. Herpes zoster occurs at all ages, but its incidence is highest (5 to 10 cases per 1000 persons) among individuals in the sixth through the eighth decades of life. Recurrent herpes zoster is exceedingly rare except in immunocompromised hosts, especially those with AIDS.
Herpes zoster, also called shingles, is characterized by a unilateral vesicular eruption within a dermatome, often associated with severe pain. The dermatomes from T3 to L3 are most frequently involved. If the ophthalmic branch of the trigeminal nerve is involved, zoster ophthalmicus results.
CNS involvement may follow localized herpes zoster.
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Laboratory Findings
1.Isolation virus in the tissue culture
2.PCR
3.ELISA for antibodies
Prophylaxis
A live attenuated varicella vaccine has been licensed and is recommended for administration to all immunocompetent children and adults at risk of infection.
Treatment
Acyclovir and Famciclovir is effective.
ADENOVIRUS
Adenoviruses are complex DNA viruses that measure 70 to 80 nm in diameter. Human adenoviruses belong to the genus Mastadenovirus, which includes at least 47 serotypes. Adenoviruses have a characteristic morphology consisting of an icosahedral shell composed of 20 equilateral triangular faces and 12 vertices. The protein coat (capsid) consists of hexon subunits with groupspecific and type-specific antigenic determinants and penton subunits at each vertex primarily containing group-specific antigens.
Clinical Manifestations
In children, adenoviruses cause a variety of clinical syndromes. The most common is an acute upper respiratory tract infection, with prominent rhinitis. On occasion, lower respiratory tract disease, including bronchiolitis and pneumonia, also develops. Adenoviruses, particularly types 3 and 7, cause pharyngoconjunctival fever, a characteristic acute febrile illness of children that occurs in outbreaks, most often in summer camps. The syndrome is marked by bilateral conjunctivitis in which the bulbar and palpebral conjunctivae have a granular appearance. Low-grade fever is frequently present for the first 3 to 5 days, and rhinitis, sore throat, and cervical adenopathy develop. The illness generally lasts for 1 to 2 weeks and resolves spontaneously. Febrile pharyngitis without conjunctivitis also has been associated with adenovirus infection. Adenoviruses have been isolated from cases of whooping cough with or without Bordetella pertussis; the significance of adenovirus in that disease is unknown.
In adults, the most frequently reported illness has been acute respiratory disease caused by adenovirus types 4 and 7 in military recruits. This illness is marked by a prominent sore throat and the gradual onset of fever, which often reaches 39°C (102.2°F) on the second or third day of illness. Cough is almost always present, and coryza and regional lymphadenopathy are frequently seen.
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Physical examination may show pharyngeal edema, injection, and tonsillar enlargement with little or no exudate. If pneumonia has developed, auscultation and X-ray of the chest may indicate areas of patchy infiltration.
Adenoviruses have been associated with a number of non-respiratory tract diseases, including acute diarrheal illness caused by types 40 and 41 in young children and hemorrhagic cystitis caused by types 11 and 21. Epidemic keratoconjunctivitis, caused most frequently by types 8, 19, and 37, has been associated with contaminated common sources such as ophthalmic solutions and roller towels. Adenoviruses also have been implicated in disseminated disease and pneumonia in immunosuppressed patients, including recipients of solid-organ or bone-marrow transplants and patients with AIDS. In the latter group, high-numbered and intermediate serotypes have been isolated, usually in the setting of low CD4+ counts, but their isolation frequently has not been clearly linked to disease manifestations. Adenovirus nucleic acids have been detected in myocardial cells from patients with "idiopathic" myocardiopathies, and adenoviruses have been suggested as causative agents in some cases.
Laboratory Diagnosis
1.Isolation of virus in tissue culture
2.Detection of antibodies by ELISA
3.PCR
Treatment
Only symptom-based treatment and supportive therapy are available for adenovirus infections, and no clinically useful antiviral compounds have been identified. Live vaccines have been developed against adenovirus types 4 and 7 and have been used to control illness in military recruits. These vaccines consist of live, unattenuated virus administered in enteric-coated capsules. Infection of the gastrointestinal tract with types 4 and 7 does not cause disease but stimulates local and systemic antibodies that are protective against subsequent acute respiratory disease due to those serotypes. Vaccines prepared from purified subunits of adenovirus are being investigated. Adenoviruses are also being studied as live-virus vectors for the delivery of vaccine antigens and for genes.
AIDS AND HIV
AIDS was first recognized in the United States in the summer of 1981, when the U.S. Centers for Disease Control and Prevention (CDC) reported the unexplained occurrence of Pneumocystis carinii pneumonia in five previously healthy homosexual men in Los Angeles and of Kaposi's sarcoma (KS) in 26 previously healthy homosexual men in New York and Los Angeles. Within months, the disease became recognized in male and female injection drug