Articles on Medical Diseases and Conditions

Category: Viral Infections

Viral Infections

  • Hantavirus Pulmonary Syndrome

    This disease first appeared in a small epidemic among New Mexico Navaho Indians in mid1993 as a fatal respiratory infection with resemblance to influenza or mycoplasma disease. It subsequently affected some Europeans and Hispanics. Symptoms began as an upper respiratory infection with fever and myalgias, after which acute respiratory failure developed. Thrombocytopenia was present in about 70% of cases, and leukocytosis with mild neutrophil immaturity was frequent. The reservoir of infection was identified as the deer mouse.

    Diagnosis is possible using serologic tests for hantavirus antibody. Nucleic acid probe with PCR amplification can be attempted on peripheral blood leukocytes, although lung biopsy tissue yields twice as many positive results.

  • Rabies

    Human disease from rabies virus infection is very uncommon in the United States. The number of human cases in the United States is usually less than five per year, and only nine were reported from 1980 to 1987. However, there are always questions about the disease, and several thousand cases of animal rabies are confirmed each year (6975 in 1991). Until 1990, wildlife rabies was most common in skunks; beginning in 1990, raccoon cases have been most frequent, followed by skunks, bats, and foxes in order of decreasing numbers. Actually most animal bites are from caged rodent pets such as rabbits, gerbils, or mice. This is not a problem since rodents (including squirrels) very rarely are infected by the rabies virus even when wild. Interestingly, of the nine human rabies cases mentioned above, six did not give a history of bat or other animal contact when they were hospitalized. Non-bite transmission of rabies from human to human (e.g., contact with saliva or CSF) has not been proven in the United States to date.

    The standard procedure for suspected rabies in domestic dogs or cats is to quarantine the animal under observation of a veterinarian for 10 days. The incubation period in humans is 1-3 months (although inoculation through facial bites may have an incubation as short as 10 days), which provides enough time for diagnosis of the animal before beginning treatment in the person who was bitten. Animal rabies will produce symptoms in the animal within 10 days in nearly all cases.

    For wild animals, if the animal was defending itself normally, it might be captured and quarantined. If it was thought to be exhibiting abnormal behavior, the animal is usually killed and the head is sent for rabies examination of the brain. The head (or brain) should be kept at refrigerator temperature (not frozen) and sent to a reference laboratory (usually a public health laboratory) as soon as possible. If the specimen will be received within 1 day, it should be sent refrigerated with ordinary ice; it if is to be stored longer than 1 day, dry ice should be used.

    Diagnosis. Laboratory diagnosis consists of stained impression smears of the brain, mouse inoculation, and serologic tests. Impression smears from Ammon’s horn of the hippocampal area in the temporal lobe stained with Seller’s stain is the traditional method for diagnosis. The smears are examined microscopically for Negri body inclusions in neurons. Use of Seller’s stain has approximately 65% sensitivity, with sensitivity reported to be somewhat greater than this in dogs (75%-80%) and somewhat less in skunks and bats. Fluorescent antibody stains on the smears have more than 95% sensitivity and currently are the standard method for diagnosis. Mouse inoculation with fresh brain extracts also has more than 95% sensitivity but may eventually be replaced by tissue culture. Saliva from animals or humans can be used for mouse inoculation, but the sensitivity is not as great as brain testing. All specimens should be taken with sterile instruments, which should be immediately decontaminated by autoclaving after use. Serologic tests (ELISA method) for rabies antibody in serum or CSF can be done if the patient has not been immunized against rabies. For serum, this requires two specimens drawn at least 1 week apart. For CSF, a single specimen positive result is diagnostic.

  • Human Papillomavirus (HPV)

    More than 50 human papillomavirus strains (types) have been reported. The most common clinical manifestations are warts (on skin) and condylomata (papilloma lesions) in the genital area. HPV-1 is usually associated with warts on the sole of the foot and HPV-2 in nonplantar skin warts. In the female cervix, HPV-6 and 11 are found most often in flat benign condylomatous lesions and low-grade cervix dysplasia (CIN I and II), while types 16 and 18 are found in 80%-95% of patients with high-grade cervical dysplasia or carcinoma in situ (CIN III) and are also associated with some cases of carcinoma of the penis. There is also an association (although less strong) of type 16 with squamous carcinoma in situ of anogenital skin (Bowen’s disease) and invasive anal carcinoma. Diagnosis is most often made with immunohistologic stains or nucleic acid (DNA) probe methods on cervix biopsy specimens. Cervix biopsy produces considerably more positive results than cervical scrape specimens (four times more in one study). In one study, about one third of women with HPV infection had visually evident cervical lesions, about one third had no visible lesions but had HPV infection demonstrated by cytology, and the infection was demonstrated in about one third only by nucleic acid probe. All commercially available DNA probe kits are not equally sensitive.

  • Influenza Virus

    Influenza produces upper and lower respiratory tract infection. There are 3 major types or subgroups: A, B, and C. Antigenic mutations occur frequently in type A, permitting reinfection; but are much less common in types B and C. The best laboratory test is culture of nasopharyngeal secretions, especially by the newer and much more rapid (2-4 days) shell-vial culture technique. Antibody detection is available by CF, IFA, and ELISA. IgM and IgG can be assayed. Acute and convalescent specimens are needed unless the initial CF or IgM antibody response is positive in high titer (both CF and IgM antibody disappear in a few weeks). A rapid membrane-filtration cartridge EIA method is commercially available for influenza A virus, which was found to have 90% sensitivity (compared to culture) using nasopharyngeal washings and 39% sensitivity using pharyngeal gargle samples.

  • Respiratory Syncytial Virus

    Respiratory syncytial virus (RSV) is the most common cause of severe lower respiratory illness of infants and young children, causing 5%-40% of pneumonias and 60%-90% of bronchiolitis episodes. Peak incidence is at 2-3 months of age. About 30%-50% of children have been infected by 12 months of age and about 95% by age 5 years. However, no significant clinical immunity is produced; repeat infections may occur, and persons of any age may develop acute infection. The most common clinical illness is upper respiratory tract infection similar to the common cold. The virus is spread through airborne droplets. The incubation period is 2-8 days. Diagnosis can be made by culture, by tests for antigen, and by tests for antibody. The best specimen for culture is nasal washings; the next best is nasopharyngeal swab. In either case, the specimen should include cells from the posterior nose and pharyngeal epithelium, since they contain the virus. Swab specimens should be placed immediately into a transport medium, and any specimen should be placed into wet ice. However, culture is expensive, and usually must be sent to a reference laboratory with wet ice. Standard culture methods take 4-14 days; and shell-vial methods, 2-3 days. The virus survives only about 4 days at 4°C and dies quickly at ordinary freezer temperatures or at high temperatures. Culture (under optimal conditions) is still considered the gold standard for diagnosis. However, some investigators report less than optimum results (69%-83% sensitivity), especially with mailed-in specimens. Antibody detection methods include immunofluorescence and ELISA. Antibody detection methods have several drawbacks: the fact that sensitivity is often less than 50% in infants less than 3 months old; the need for acute and convalescent specimens unless sufficiently elevated IgM titers are present; and the necessity in most cases to send the serum specimens to a reference laboratory. Methods for antigen detection in patient specimens are also available,including fluorescent antibody and ELISA, with same-day results. Nasopharyngeal aspirates are reported to provide the best specimens. Compared to culture, sensitivity of these methods are about 80%-90% (range, 41%-99%). Antigen detection methods may be positive on some specimens that are negative by culture, especially with mailed-in specimens. Antigen detection is rapidly replacing culture and antibody detection for diagnosis of RSV infection. However, the sensitivity of different manufacturers’ kits may differ considerably.

  • Mumps

    Mumps is a disseminated virus infection, although the main clinical feature is salivary gland enlargement. Evidence of nonsalivary gland involvement is most commonly seen in adults. In men, orchitis (usually unilateral) is reported in about 20% of cases. Adult women occasionally develop oophoritis. Persons of any age may be affected by meningoencephalitis, the most serious complication of mumps. This is reported in 0.5%-10% of patients. Many persons with CSF changes are asymptomatic. Females are affected five times more frequently than males. Complications of mumps may appear before, during, or after parotitis, sometimes even without clinical parotitis. Diagnosis is made by culture or serologic tests. Saliva is probably best for culture; mouth swabs or CSF can be used. Serologic tests require acute and convalescent serum specimens.

  • Measles

    Measles (rubeola) is still important, even though widespread vaccination has begun. Measles is spread by droplet inhalation. Incubation lasts about 9-11 days, followed by 3-4 days of fever, cough, and sometimes conjuctivitis. Koplik’s spots appear on the oral mucosa in 50%-90% of patients about 2-3 days after symptoms begin. These last about 6-7 days. The typical measles skin rash begins about 4-5 days after onset of upper respiratory tract symptoms. The two main complications are encephalitis and pneumonia. Fortunately, encephalitis is rare, the incidence being 0.01%-0.2%. Due to the great frequency of the disease, however, the total number of cases is appreciable. About one third of those with encephalitis die, one third recover completely, and the remainder survive but show moderate to severe residua. Measles encephalitis is considered postinfectious because it develops 4-21 days after the onset of rash. Measles involves lymphoid tissue and respiratory epithelium early in the illness. Therefore, bronchitis, bronchiolitis, and pneumonia are fairly frequent. Most cases of pneumonia are due to superimposed bacterial infection (staphylococci, pneumococci, streptococci), but some are caused directly by the rubeola virus. Secondary bacterial otitis media is also fairly frequent. For diagnosis, culture and serologic tests are available. Standard culture takes 7-10 days. Culture depends on the stage of disease. For a period of 1 week ending with the first appearance of the rash, blood, nasopharyngeal swabs, or urine provide adequate specimens. After appearance of the rash, urine culture is possible up to 4 days. Beyond this, culture is not useful, and serologic tests must be employed using acute and convalescent serum specimens. Measles HI-detectable antibodies appear about the end of the first week after appearance of the rash and peak about 2 weeks later. Measles IgM antibody appears about 2 days following rash onset, peaks about 10-14 days after rash onset, and becomes undetectable at about 30 days. Interpretation is similar to that of rubella tests. However, one report indicates about 30% false negative IgM results even 3 weeks after disease onset. IgG acute and convalescent serum specimens can also provide a diagnosis.

  • Parvovirus B19

    Parvovirus B19 belongs to a genus that infects both animals and humans. These are small DNA viruses without an outer envelope. Replication appears to take place in erythroid precursors of the bone marrow. The two most common diseases produced are erythema infectiosum (“fifth disease”), a condition somewhat resembling rubella, but with a rash that has a somewhat different body distribution; and transient aplastic crises. Both are more frequent in children. In both conditions, the incubation period is about 5-15 days, but may be as long as 20 days. In both conditions there may be a viral-type prodrome with fever, malaise, and other symptoms. Most patients with aplastic crises due to B19 already have some type of hemolytic anemia (such as sickle cell disease), either congenital or acquired. Immunocompromised patients (such as those with HIV-1 infection) can also have aplastic crises. It is thought that B19 infection is responsible for 90% of aplastic crises in patients with these conditions.

    IgM antibody becomes detectable in the second week after infection and IgG antibody during the third week. IgM antibody decreases to nondetectable levels at roughly 6 months but can persist longer. The most commonly used tests are EIA for IgM antibody and nucleic acid (DNA) probe methods for viral antigen in serum or body fluids during acute illness. These tests would usually have to be obtained at large reference laboratories or university centers.

  • Varicella-Zoster Virus (VZV)

    Varicella-zoster virus (VZV) is a member of the herpesvirus group. Infection is spread through direct contact with skin lesions or through droplet inhalation. The incubation period is about 14 days (range, 9-21 days). Primary infection is usually varicella (chickenpox). The period of skin rash lasts about 4-6 days. This may be preceded by a short prodromal period. The period of contagion is said to be from 2 days before the rash until no new skin lesions appear and all old ones become crusted. Usually there is lifelong immunity to new infection (although not always). Complications are not common but are not rare. They include pneumonia, encephalitis, and Reye’s syndrome (20%-30% of Reye’s syndrome follows varicella infection). Incidence and severity of complications are increased in immunocompromised persons. Twenty-three percent to 40% of bone marrow transplant patients develop primary VZV infection or reinfection. Varicella infection in pregnancy may affect the fetus in 5%-10% of cases.

    After the varicella syndrome is over, the virus begins a latent period in sensory nerve ganglion cells. Later on, it may reactivate in the form of zoster. Reactivation is more common in persons with malignancy or in those who are immunocompromised. It becomes more frequent with increasing age. About 10%-20% of the population is affected. Neuralgia is the most frequent symptom. A rash is also relatively frequent, often in the distribution of a dermatome. Encephalitis, sensory and motor neurologic abnormality, and ocular abnormality may occur.

    Laboratory tests include Tzanck test smears of varicella-zoster lesions. Sensitivity is said to be 50% or less in varicella and 80% or less in zoster. This procedure is described in the section on simplex and the microscopic appearance is the same. Culture of lesions can be done, but results in varicella are reported to be 34%-78% positive and in zoster to be 26%-64%. Serologic tests can be done using fluorescent antibody (FA), ELISA, and slide LA. EIA is said to be 50% sensitive (range, 36%-94%); FA, about 75% (range, 69%-93%); and LA, about 60% (52%-76%). It appears that antibody production (and, therefore, sensitivity) is greater in otherwise healthy children than in adults. IgM antibody rises in varicella about 5-6 days after the rash begins and peaks at about 14 days; it rises in zoster about 8-10 days after onset of the rash and peaks at about 18-19 days. Some patients with VZV infection who later are infected by herpesvirus type 1 experience an anamnestic rise in VZV antibody. Nucleic acid (DNA) probe methods have also been reported for skin lesions and for CSF specimens.

  • Human Herpesvirus 6 (HHV-6) and 7 (HHV-7)

    Human herpesvirus 6 (HHV-6) was first isolated and characterized in 1986. It infects predominately T-lymphocytes of the CD4 (helper) type, but also B-lymphocytes, megakaryocytes, and probably other cells. It is the sixth described member of the Herpesvirus family (the others being HSV-1, HSV-2, EBV, CMV, and varicella-zoster). Infection takes place mainly in the first 2-3 years of life, with antibodies detected in 52% to “almost all” (over 90%) of young children and up to 80% of adults. Similar to the other herpesviruses, a lifelong low-grade or latent infection is produced and reactivation may occur. HHV-6 is now well accepted as the cause of exanthema subitum (roseola infantum). Evidence has been presented for possible involvement in other conditions, such as heterophil-negative mononucleosis, transient febrile illnesses in children, and a type of chronic fatigue syndrome with CNS involvement centered in Nevada and California. One report suggests a role in idiopathic bone marrow transplant failure, seen in about 20% of bone marrow transplants. There is some reported serologic evidence of HHV-6 reactivation associated with CMV infection.

    Tests have been described to detect HHV-6 IgG antibody, mostly fluorescent immunoassay and ELISA. Tests for antigen in patient peripheral blood monocytes have also been described, both fluorescent immunoassay and nucleic acid probe with PCR amplification. These tests are currently available only in research laboratories or large reference laboratories.

    HHV-7 was identified in 1990. It is frequently found in saliva and apparently causes frequent subclinical infection similar to HHV-6. Also similar to HHV-6, HHV-7 has been reported to cause some cases of exanthema subitum in young children. Serologic testing for IgG antibody has been reported using indirect immunofluorescent methodology.