Adenovirus

Adenoviruses are double-stranded DNA viruses of about 60–90 nm, lacking an envelope. The capsid contains 252 capsomeres and shows icosahedral symmetry. The capsomeres consist of hexons, pentons, and fibres (so named after their configuration), which are responsible for the induction of group- and type-specific antibodies. Thirty-four immunologically distinct types (serotypes) are recognised in humans.

Adenoviruses were first isolated from adenoid tissue and have a certain affinity for lymph glands, where they may remain latent for years. They also invade the respiratory tract, the gastrointestinal tract, and the conjunctiva. Adenovirus infections are widely distributed and common, with most infections occurring in childhood. The contagious disease is normally acute and self-limiting, but infections may be prolonged and asymptomatic, possibly remaining latent for a very long time. The seasons with the highest rates of general adenovirus infections are winter and spring, independent of geographic locations and climatic conditions. Epidemics may occur in populations crowded together, for example, ARD in military groups, PCF in swimming pools, and EKC in medical facilities.

*Adenovirus Grade 2 antigen (strain Adenoid 6)

Cytomegalovirus (CMV)

Cytomegalovirus (CMV) is a member of the herpesvirus group (Betasubfamily, DNA virus of 150-200 nm). These viruses share a characteristic ability to remain dormant within the body for extended periods. Initial CMV infection, which may have few symptoms, is always followed by a prolonged, inapparent infection during which the virus resides in cells without causing detectable damage or clinical illness. Severe impairment of the body’s immune system due to medication or disease consistently reactivates the virus from the latent or dormant state. CMV is found universally throughout all geographic locations and socioeconomic groups, infecting between 50% and 85% of adults. CMV infection is more widespread in developing countries and in areas with lower socioeconomic conditions. For the vast majority of people, CMV infection is not a serious issue, but it poses a risk to certain high-risk groups: the unborn baby during pregnancy, people who work with children, and immunocompromised individuals, such as organ transplant recipients and those infected with HIV. The presence of the virus or infection may be identified by microscopy, PCR, serology: CBR, and the detection of antibodies by ELISA. IgM antibodies are the first to be produced by the body in response to a CMV infection. They are present in most individuals within a week or two after the initial exposure. IgM antibody production rises for a short period and then declines. After several months, the level of CMV IgM antibody usually falls below detectable levels. Additional IgM antibodies are produced when latent CMV is reactivated.

IgG antibodies are produced by the body several weeks after the initial CMV infection and provide protection against primary infections. Levels of IgG rise during the active infection, then stabilise as the CMV infection resolves and the virus becomes inactive. After a person has been exposed to CMV, they will have a measurable amount of CMV IgG antibody in their blood for the rest of their life. CMV IgG antibody testing can be used, along with IgM testing, to help confirm the presence of a recent or previous CMV infection.

An interesting new application for the CMV IgG Buccal Swab ELISA (RUO) is the screening of donors prior to transplantation. CMV infection or reactivation after transplantation has been associated with negative effects on overall survival. As many donor centres have switched to buccal swabs for sample collection, we offer a test to determine CMV status from dried cheek swab samples, eliminating the need for invasive blood collection.

Epstein-Barr Virus (EBV)

Infectious mononucleosis is an acute lymphoproliferative disease that is common in children and young adults and is caused by the Epstein-Barr Virus (EBV). The EBV is one of the herpesviruses (gamma). Characteristic clinical features include fever, sore throat, lymphadenopathy, an associated absolute lymphocytosis greater than 50%, containing at least 10% of atypical lymphocytes in the peripheral blood, the development of transient heterophil and persistent antibody responses against EBV, and abnormal liver function tests. Four per cent of infected young adults show an icteric manifestation, and 50% have splenomegaly.

In addition, EBV is implicated in Burkitt lymphoma, nasopharyngeal carcinoma, and Hodgkin’s disease. A syndrome similar to infectious mononucleosis can also be caused by cytomegalovirus, toxoplasmosis, and other viral infections. Therefore, the differential diagnosis is of major importance. Serological tests, such as EIA, are very useful for the detection of anti-EBV IgG and IgM antibodies, especially in cases where heterophil antibodies are absent.

In a fresh infection, IgM antibodies against VCA and EA are determined by immunofluorescence or ELISA. Later on, VCA IgG appears, followed by EBNA-1 IgG antibodies. Correspondingly, the simultaneous activation of VCA IgM and EBNA-1 IgG indicates a reactivation of an EBV infection.

Hantavirus

Hantaviruses are negative-sense RNA viruses in the Bunyaviridae family. Humans may be infected with hantaviruses through urine, saliva, or contact with rodent waste products. Some hantaviruses can lead to serious diseases in humans, such as haemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). Human infections of hantaviruses have almost entirely been linked to contact with rodent excrement, but recent human-to-human transmission has been reported with the Andes virus in South America. Hantavirus has an incubation period of two to four weeks in humans before symptoms of infection occur. Regions especially affected by HFRS include China, the Korean Peninsula, Russia (Hantaan, Puumala, and Seoul viruses), and northern and western Europe (Puumala and Dobrava virus).

Influenza

Influenza viruses are RNA viruses of the family Orthomyxoviridae. They are divided into three types: A, B, and C, which are differentiated by the specificity of a soluble antigen associated with the internal ribonucleoprotein component of the virion. The virions are spherical particles, measuring 80-120 nm in diameter, consisting of the ribonucleoprotein component and enveloped by matrix protein and a lipid bilayer. This bilayer contains two spike-like structures: viral haemagglutinin (H) and viral neuraminidase (N). Influenza viruses are respiratory tract pathogens transmitted via direct contact, large-droplet infection, or by contaminated surfaces.

Influenza types A and B are responsible for epidemics of respiratory illness that occur almost every winter, often leading to increased rates of hospitalisation and death. Type C infections typically cause either very mild respiratory illness or no symptoms at all. It does not cause epidemics and lacks the severe public health impact seen with influenza types A and B. Pandemics of influenza A virus infections have occurred at intervals of 10 to 20 years since 1890. This is thought to result from alterations in the composition of the H and N antigens (antigenic “drift” and antigenic “shift”). Currently, two subtypes of influenza A and B are circulating worldwide. Influenza is usually a self-limiting illness lasting for 3 to 7 days, although some people, particularly children, the elderly, and other vulnerable groups, may develop serious and potentially life-threatening complications, such as pneumonia.

Japanese Encephalitis

Japanese encephalitis, formerly known as Japanese B encephalitis to differentiate it from Encephalitis A (Economo’s A encephalitis), is a disease caused by the mosquito-borne Japanese encephalitis virus (JEV). The JEV belongs to the Flaviviridae family. Domestic pigs and wild birds, particularly herons, serve as reservoirs of the virus. Transmission to humans can result in severe symptoms. Among the most important vectors of this disease are the mosquitoes Culex tritaeniorhynchus and Culex vishnui. The disease is most prevalent in Southeast Asia and East Asia. Exposure to JEV can lead to a condition marked by several symptoms, including encephalitis. The JE IgG/IgM ELISA test uses a recombinant antigen called JERA, which serves as a rapid serological marker for JEV infection. The JERA protein is a recombinant antigen composed of peptide sequences from different regions of the Japanese encephalitis virus.

Mumps

Mumps viruses are RNA viruses of the family Paramyxoviridae. The virions are spherical particles measuring 150-250 nm in diameter, consisting of a ribonucleoprotein with helical symmetry and enveloped by matrix protein and a lipid bilayer, which contains two spike-like structures: viral haemagglutinin (H) and viral neuraminidase (N). Mumps virus primarily affects the parotid and related salivary glands; however, the infection can lead to central nervous system (CNS) disease and the accumulation of the virus in cerebrospinal fluid (CSF).

Mumps (epidemic parotitis) is an acute, contagious viral disease that mostly occurs in children. Nearly 50% of all infections are subclinical. The highest incidence of clinical manifestations is found in the age group of 4 to 15 years. Secondary infections are rare due to long-lasting immunity. Between 10% and 35% of mumps cases develop orchitis, which almost always occurs after puberty. The process is usually unilateral, and the prognosis is generally good. Mumps virus has been one of the most important causes of viral CNS disease (meningitis and encephalitis) in the USA, although the incidence has greatly decreased with widespread vaccination.

Parvovirus B19

Parvoviruses are cubic, single-stranded DNA viruses measuring about 18-32 nm in diameter and lacking an envelope. Parvovirus B19 infects only humans, and since there are no cross-reactivities between animal parvoviruses and B19, transmission between pets and humans is not possible.

Parvovirus B19 is the causative agent of erythema infectiosum, also known as “fifth disease,” which is a mild rash illness that most commonly affects children. Infected individuals are contagious during the early part of the illness before the rash appears, which means that in adults, the rate of epidemics can reach about 60%. Approximately 20% of adults and children infected with parvovirus B19 do not develop any symptoms. However, individuals infected with the virus will develop lasting immunity, which protects them from future infections.

Parvovirus B19 infection may cause serious illness in individuals with sickle-cell disease or other types of chronic anaemia, as well as in those with compromised immune systems (such as individuals with leukemia or cancer, those born with immune deficiencies, those who have received organ transplants, or those living with HIV infection). Occasionally, less than 5% of all pregnant women infected with parvovirus B19 may experience serious complications, such as the risk of haemolytic disease of the fetus (Morbus haemolyticus fetalis).

Respiratory Syncytial Virus (RSV)

Respiratory syncytial virus (RSV) is a negative-sense, enveloped RNA virus. The virion varies in shape and size, with an average diameter ranging between 120 and 300 nm. It is unstable in the environment, surviving only a few hours on surfaces, and is readily inactivated. RSV is the causative pathogen for the most common respiratory tract infection. RSV infections typically occur during annual community outbreaks in the late autumn, winter, or early spring months. The timing and severity of outbreaks can vary from year to year.

Most infants are infected with RSV during their first winter season; between 25% and 40% will exhibit signs or symptoms of bronchiolitis or pneumonia, with 0.5% to 2% requiring hospitalisation. Most children recover within 8 to 15 days, and the majority of those hospitalised for RSV infection are under 6 months of age. By the age of two, most children will have serological evidence of RSV infection. RSV also causes repeated infections throughout life, typically associated with moderate-to-severe cold-like symptoms. However, severe lower respiratory tract disease can occur at any age, particularly among the elderly or those with compromised cardiac, pulmonary, or immune systems.

Rubella Virus

Rubella is an enveloped RNA virus belonging to the togavirus. It has a spherical shape measuring about 50-70 nm in diameter. There appears to be only one antigenic type, and no cross-reactivity with alphavirus or other members of the togavirus group has been found. Rubella viruses are pathogens of the respiratory tract and transmitted mainly by droplet infection.

Rubella is a worldwide common contagious disease with mild constitutional symptoms and a generalized rash. In childhood, it is an inconsequential illness, but when it occurs during pregnancy, there is a significant risk of severe damage to the fetus. The risk of congenital rubella depends primarily on the month of pregnancy in which infection is acquired: overall, app. 16% of infants have major defects at birth following maternal rubella in the first 3 months of pregnancy. Congenital rubella infection may lead to a syndrome with single or multiple organ involvements, known as embryopathia rubeolosa. In some cases infection is inapparent but results in consequential damages as eye defects, deafness, growth retardation, and others. Naturally acquired immunity usually is long-lasting, but reinfection is possible due to decreasing levels of circulating antibodies. For immunization a vaccine containing live virus is used.

Rubella Infection may be identified by detection of virus by PCR (prenatal), Hemagglutination inhibition (HAI), Haemolysis-in-gel test (HiG), detection of antibodies by EIA, ELISA. Measurement of antibodies in the serum is important for the determination of the immune status. Even a previous infection though rather overt may not yield a long-lasting immunity, but may result in an antibody titer too low to prevent reinfection. Especially the screening of adolescents and young women should be a mandatory routine in prenatal care.

Varicella Zoster (VZV)

Varicella-Zoster Virus (human herpesvirus 3, HHV-3) belongs to the alpha-subfamily of Herpesviridae. The virus particles measure about 145 nm in diameter. They consist of double-stranded DNA and are surrounded by an icosahedral protein capsid and an envelope, which contains both host cell and viral components. The virus is typically transmitted via respiratory secretions, and a single serotype causes varicella (chickenpox), a highly infectious childhood disease, and zoster (shingles), a neurodermic disease. Both diseases are found worldwide.

Varicella is the acute disease that follows primary contact with the virus, whereas zoster is the response of a partially immune host to a reactivation of the varicella virus, which remains in the body in latent form. Varicella is endemic, and children between the ages of 2 and 6 are most commonly affected. The course of the disease is usually mild and only complicated in immunocompromised children. Rare fatal cases show multiple necrotic lesions in the brain, lungs (varicella pneumonia), kidneys (haemorrhagic nephritis), spleen, bone marrow, and occasionally the intestinal tract. The lethality of varicella is below 0.1%. In the less frequent adult infections, the disease is more severe, and complications are expected in around 5% of all cases.

Zoster has a low incidence but increases in frequency and severity with advancing age. Usually, the process remains localised, but generalisation is more likely in cases of immunosuppression. Fatal cases are extremely rare and are nearly always caused by an underlying disease.

Zika Virus

Zika Virus (ZIKV) is a single-stranded RNA virus of the Flaviviridae family (genus Flavivirus). It was first isolated in 1947 from a sentinel rhesus monkey during a yellow fever study in the Zika Forest of Uganda. Since its discovery, ZIKV circulation has been detected in Africa and Asia, where it has caused sporadic human infections. In 2007, its emergence on Yap Island, Micronesia was reported, marking the transmission of Zika virus outside Africa and Asia. Since 2013, ZIKV has been reported in French Polynesia, New Caledonia, Cook Islands, Easter Island (Chile), Samoa, and Vanuatu. In early 2015, it spread initially to Brazil and subsequently to additional countries in the Americas.

ZIKV is primarily transmitted through the bite of an infected Aedes species mosquito (A. aegypti and A. albopictus). However, there have been reports of less common transmission routes, such as blood transfusion, perinatal transmission, and sexual contact. The incubation period of Zika virus disease is not known precisely but is likely to be a few days. It is estimated that only one in five people infected with ZIKV will develop signs or symptoms.

Clinical manifestations of ZIKV infection are described as being very similar to those of Dengue virus (DENV) and Chikungunya virus (CHIKV) infections, but usually milder. The most common clinical signs and symptoms are a maculopapular rash, low-grade fever, arthralgia, myalgia, headache, and conjunctivitis. Less frequently reported symptoms include oedema, sore throat, cough, vomiting, and haematospermia.

Human infections with ZIKV are usually mild and self-limiting, with symptoms generally resolving spontaneously after 3–7 days. Arthralgia may persist for up to one month. In rare cases, after a Zika virus infection, Guillain-Barré syndrome (GBS), a disorder of the peripheral nerves, may occur. There is now considered to be a likely correlation between Zika virus infection during pregnancy and congenital brain malformations.