The characteristic process associated with viral infections is cellular replication, which may or may not lead to cell death. Interferon plays a major role in body defenses against viral infections. Antibodies are valuable in preventing the entry and bloodborne spread of some viruses, but the ability of other viruses to spread from cell to cell places the burden of adaptive immunity on the T cell system, which specializes in recognizing altered self histocompatibility antigens (histocompatibility leukocyte antigen [HLA]). Macrophages may also play a role in immunity. Some of the most virulent viruses for human beings are zoonoses (e.g., rabies). Other viruses, however, can persist for years without symptoms and can then be reactivated to cause serious disease, possibly including tumors.

New viruses can cause old diseases, and old viruses can cause new diseases (see Chapters 21 to 25 for representative examples of immunologically important viral diseases). The mutation rates of viruses, especially ribonucleic acid (RNA) viruses such as human immunodeficiency virus (HIV), are extraordinarily high. Consequently, RNA viruses evolve much more rapidly under selective conditions than their hosts and contemporary RNA viruses may have descended from a common ancestor only relatively recently. The survival of influenza A and B viruses as new viruses depends on a continual evolution of mutants. These mutant forms are not recognized by the body as being variations of past viral expo sures. The most frequent cause of new viral infections is old viruses that are not natural infections of human beings, but rather are accidentally transmitted from other species as zoonoses.

Organisms intermediate between viruses and bacteria are obligatory intracellular organisms with cell walls (e.g., rickettsiae) and without cell walls but capable of extracellular replication (e.g., Mycoplasma). Immunologically, the former are closer to viruses and the latter are closer to bacteria.

Dengue Fever

The rapidly expanding global footprint of Dengue fever is a public health challenge. An estimated 50 million infections occur every year in about 100 countries with the potential to spread to further. According to the World Health Organization and the Centers for Disease Control and Prevention, Florida and the coastal areas of Texas are included in the geographic areas that have high suitability for Dengue transmission. The major areas of disease are endemic tropical and subtropical latitudes (e.g. India, South east Asia). The primary vector is the urban-adapted Aedes aegypti mosquito. Global trade, with the unintentional transport of mosquitoes, and increased travel by viremic people, urban crowding, and ineffective mosquito control are all factors in this modern pandemic.

Dengue can be caused by one of four single-stranded, positive-sense RNA viruses (serotypes dengue virus type 1 to dengue virus type 4) of the Flavivirus genus. After an incubation period of 3 to 7 days, signs and symptoms start suddenly and follow three phases—initial febrile phase, a critical phase at about the time that the fever subsides (defervescence), and the final spontaneous recovery phase.

Most dengue virus infections are asymptomatic, with a wide variety of clinical manifestations. Signs and symptoms range from mild febrile illness to severe and fatal disease.

Laboratory diagnostic testing is by detection of viral com ponents in serum or directly by serologic testing. Diagnostics tests are as follows:

• Viral component testing

      • Detection of viral nucleic acid in serum by reverse transcriptase polymerase- chain reaction (RT-PCR)

      or

      • Detection of soluble nonstructural protein 1 (NS1) by enzyme-linked immunosorbent assay (ELISA) or lateral-flow rapid testing

 • Serologic testing

      • Detection of IgM seroconversion by ELISA

     Or

 • Lateral flow methods

     Or

 • Detection of IgG in secondary infections by ELISA or lateral flow methods

Currently, no effective antiviral agents are available to treat dengue infection. Treatment is supportive. If patients have severe bleeding, a blood transfusion can be lifesaving. Clinical research with potential drugs or vaccines is ongoing.

Herpesviruses

Two members of the human herpesviruses, cytomegalovirus (CMV) and Epstein-Barr virus (EBV), are described in detail in Chapters 21 and 22. The following sections briefly describe other members of the human herpesvirus family, including herpes simplex, varicella-zoster, and human herpesvirus-6.

All the human herpesviruses are large, enveloped DNA viruses that replicate within the cell’s nucleus. The virus gains an envelope when the virus buds through the nuclear membrane, which has been altered to contain specific viral proteins.

The herpesviruses cause a number of clinical diseases, although they share the basic characteristic of being cell associated, which may partly account for their ability to produce subclinical infections that can be reactivated under appropriate stimuli.

Herpes Simplex Virus

Herpes simplex virus (HSV) can be cultured from the oropharynx in about 1% of healthy adults and from the genital tract of slightly less than 1% of asymptomatic adult women who are not pregnant. HSV is widespread. Human beings are the only natural hosts or known reservoir of infection. The incubation period is 2 to 12 days. The incidence of seropositivity rises to almost 100% in some populations by the age of 45 years. Antibody prevalence in adults varies greatly with socio economic class; 30% to 50% of upper socioeconomic class adults have detectable antibody to HSV compared with 80% to 100% of adults in lower socioeconomic groups.

The most frequent manifestation of HSV infection is the common cold sore or fever blister. HSV has been shown to be related to a wide variety of clinical syndromes and to subclinical infection, occurring with primary or recurrent disease. Recurrent HSV disease usually results from the reactivation of latent virus resting in paraspinal or cranial nerve ganglia that innervate the site of primary infection. Distant sites may be involved. Activated virus presumably travels down the axon to the skin (or other site) and induces disease. In some cases, exogenous reinfection can occur. Recurrence with cell-to-cell spread of virus occurs in the presence of serum-neutralizing antibodies.

Two cross-reacting antigen types of HSV have been identified, type 1 (HSV-1) and type 2 (HSV-2). HSV-1 is generally found in and around the oral cavity and in skin lesions that occur above the waist. HSV-2 is isolated primarily to the genital tract and skin lesions below the waist.

Congenital and Neonatal Infection

 Malnutrition, severe illness, many acute childhood illnesses, and prematurity predispose infants and young children to disseminated primary infection. Neonatal HSV infections may be acquired in the antenatal or perinatal period. Active lesions in the mother’s genital tract at birth present the greatest risk of infection to the newborn. The spectrum of disease in an infected newborn varies from subclinical to severe. In cases of overwhelming generalized infection, the infant may develop encephalitis and respiratory failure; hepatic failure, with increasing jaundice and adrenal insufficiency, may occur. Infants who survive severe infection are frequently left with some neurologic damage and may have recurrent vesicular skin lesions for many years.

Laboratory Diagnosis

Methods for the laboratory diagnosis of HSV include isolation of the virus and direct detection of antigen in tissues or cytologic preparation through the use of immunofluorescence or immunoenzyme methods. In addition, detection of the virus in body fluids (using monoclonal antibodies) can be performed with immunoassays or immunoblot techniques. Serologic diagnosis of primary infections can be demonstrated when a fourfold or higher positive-sense RNA viruses rise in titer occurs. Titers may rise significantly in early recurrent infection but usually become stable at moderately hig

h levels after multiple recurrences.

Varicella-Zoster Virus

Varicella-zoster virus (VZV) is the cause of two different types of clinical diseases resulting from the same virus infection. Primary infection with the virus results in the clinical manifestations of chickenpox. After a primary infection, the virus enters a latent phase, presumably within nuclei in the dorsal root ganglia. Reactivation of the virus results in the characteristic clinical manifestation of (zoster), known as shingles.

Epidemiology and Etiology

Human beings are the only natural hosts of VZV. Varicella primarily affects children age 2 to 5 years. The virus is endemic and highly contagious. Periodic epidemics do occur. The presumed route of transmission is through the respiratory tract.

Zoster is less communicable than varicella. This sporadic disease occurs most frequently in older individuals. Antibodies to varicella do not protect against reactivation or clinical zoster. The reactivation of VZV is associated with a depressed immune response. Patients with AIDS, older adults, and immunocompromised persons are at high risk of developing disease. In addition, manipulation of the spinal cord, local radiation therapy, and therapy that suppresses cellular immunity have been associated with triggering the onset of zoster.

Varicella has an incubation period of 14 to 17 days. There may be a 1- to 3-day prodromal period of fever, headache, and malaise. This precedes the eruption of the characteristic red macular rash, which progresses to papules, vesicles, and pus tules that crust over and shed without scarring. Successive crops of lesions continue to appear for 2 to 6 days; therefore, multiple lesions in various stages of development are present at any one time.

The name of the virus reflects two associated diseases— varicella (chickenpox) and zoster (shingles). Primary infection with the virus results in the clinical manifestation of chicken pox. After this, the virus enters a latent phase, presumably within nuclei of neurons in dorsal root ganglia or cranial nerve sensory ganglia. The reactivity of the virus results in the clinical manifestations characteristic of zoster.

Signs and Symptoms

Complications of VZV include pneumonitis, encephalitic conditions, nephritis, hepatitis, myocarditis, arthritis, and Reye’s syndrome. Susceptible individuals who are immunosuppressed have a greater risk of complications after VZV exposure. Another complication can include febrile purpura, which can occur a few days after the onset of the rash and is seen in children and adults. This complication is characterized by thrombocytopenia and hemorrhage into the vesicles. Postinfection purpura, which begins 1 to 2 weeks after the appearance of the rash, is characterized by thrombocytopenia with gastrointestinal, genitourinary, cutaneous, and mucous membrane hemorrhage. More severe hemorrhagic complications include malignant varicella with purpura and purpura fulminans.

Zoster Infection. Zoster infection is characterized by vesicular eruptions, typically confined to one or two adjacent derma tomes. The viral replication follows the nerve fiber. Neuralgia accompanies the skin eruptions and can last for months after the skin heals. Persistent neuralgia can be severe and can last months or longer.

Neonatal Varicella Infection. Neonatal varicella may be acquired in utero or in the perinatal period and can result in congenital abnormalities. The infant is at greatest risk if the mother’s illness occurs 4 days or less before delivery.

Laboratory Diagnosis

 The laboratory diagnosis of VZV is similar to HSV methods. Serologic methods include indirect immunofluorescence, which detects antibodies to specific membrane antigens, and EIA.

Rapid preliminary diagnosis can also be made by direct immunofluorescence to detect viral antigens in vesicular lesions. A smear of cells taken from lesions enables direct examination. A presumptive diagnosis can be made by examining scrapings from the base of a vesicular lesion and histologically observing multinucleated giant cells containing intranuclear inclusion bodies, or by observing virus particles on electron microscopy. The best way to confirm VZV infection is to recover the virus in human diploid fibroblast cell cultures.

Antibodies to varicella are detectable within several days of the onset of rash and peak at 2 to 3 weeks. Antibodies to zoster increase more rapidly and are detectable at the onset of clinical symptoms. Because of the rapid turnaround time and correlation with clinical symptoms, serologic methods are preferable to viral isolation methods. In addition, ELISA methods are valuable for assessing the immune status of adults.

Prevention

 A vaccine is available for those in high-risk groups. The vaccine can be administered prior to an infection or to prevent reinfection because of waning immunity.

Human Herpesvirus 6

 A new virus classified as a herpesvirus because of its shape, size, and in vitro behavior has been identified. Genomic analysis shows the virus to be molecularly unrelated to other human herpesviruses. Initially the virus was called B-lymphotropic virus, but subsequent studies indicated that T cells are the primary target of infection. This viral agent is classified as human herpesvirus 6 (HHV-6).

Patients with serologic evidence of acute HHV-6 infection are reported to experience mild nonspecific symptoms and cervical lymphadenopathy. The same agent has been implicated as the cause of roseola infantum (exanthema subitum). Up to 75% of infants develop antibody to HHV-6 by age 10 to 11 months, which suggests a high rate of seropositivity in the general population.

Laboratory methods include direct examination by immunofluorescence or immunoperoxidase staining of cells taken from lesions. In addition, PCR, DNA probes, and serologic methods (e.g., ELISA, radioimmunoassay, indirect immunofluorescence, latex agglutination) can be used.

Culture methods include the cocultivation of the patient’s peripheral blood cells with cord blood mononuclear cells and examination of these cultures after 5 to 10 days by electron microscopy. Anticomplement immunofluorescence of infected cell culture has also been used for antibody detection and titration.

اخر الاخبار

اخبار العتبة العباسية المقدسة

في موكب العتبتين المقدستين.. المجمع العلمي ينظم محفله القرآني الدولي الأول بالنجف الأشرف

معمل ثلج الكفيل يرفع طاقته الإنتاجية لنحو 3 آلاف قالب يوميّاً خلال زيارة الأربعين

المجمع العلمي ينشر محطاته القرآنية على مختلف الطرق الرئيسة المؤدية إلى كربلاء

مجمع أبي الفضل العباس (عليه السلام) يرفع إنتاج الصمون لأكثر من 25 ألف قطعة يوميًا

المزيد

الآخبار الصحية

قد يؤدي إلى فشل القلب.. تحذير من مسكن آلام يستعمله الملايين

هل الجري يساعد على فقدان الوزن؟.. إليك ما يقوله الخبراء

ماذا يحدث لجسمك عند شرب عصير البطيخ بانتظام؟

علماء يكتشفون أن نقص عنصر غذائي "شائع" قد يسبب الزهايمر

المزيد

الآخبار التكنلوجية

المعادن الحيوية قد تنضب خلال 10 سنوات.. دراسة صادمة ؟

"إنستغرام" يستنسخ خاصية شائعة من منافسه "سناب شات"

رواد فضاء يغادرون محطة الفضاء الدولية بعد مهمة استمرت 5 أشهر

"كريساليس".. سفينة فضائية ستسافر بالبشر إلى أعماق النجوم ؟!

المزيد

مواضيع ذات صلة

Immunologic Manifestations of Fungal Diseases

The Structure of Antibodies

Myelomas and Monoclonal Antibodies

Telling the Difference Between Foreign and Self

The Basic Adaptive Immune Response

The Immunoglobulin Domain and Variations

Deficiencies of the Immune Response

Hypersensitivity

Cytokines

Complement Deficiencies and Pathogen Evasion

Complement Pathways

T Cells