Cytomegaly
| Classification according to ICD-10 | |
|---|---|
| B25 | Cytomegaly |
| P35.1 | Congenital cytomegaly |
| ICD-10 online (WHO version 2019) | |
Cytomegaly or cytomegaly (previously: inclusion body disease ) is a disease in humans that is caused by the human cytomegalovirus (HCMV), also known as human herpes virus 5 (HHV 5). The virus belongs to the Herpesviridae family . After infection, it remains in human cells for life. Even after the disease has ended, it can still be excreted in saliva and urine for weeks.
Course of the disease and symptoms
The initial infection with the human cytomegalovirus proceeds in 99% with no or only minor symptoms, so that those affected often do not notice the cytomegalovirus infection.
It can take two to six weeks from infection to the possible appearance of the first signs of illness. Since many infections go unnoticed, the incubation time can not yet be specified more precisely. This usually results in a fever and swelling of the lymph nodes , but headaches and body aches can also occur.
Up to 60% of healthy people are carriers of HCMV and it remains in lymphatic tissue for life.
In immunocompromised (e.g. after bone marrow transplants or organ transplants) patients, CMV is an important cause of increased morbidity and lethality. The disease is often based on a reactivation of a latent virus infection. The lungs, gastrointestinal tract, CNS, and eyes can all be involved. For such patients z. A prophylaxis option is currently being tested.
HCMV infections during pregnancy
If the human cytomegaly virus is usually harmless for healthy adults, the virus is particularly dangerous during pregnancy and it can even be life-threatening for unborn children.
Human cytomegaly virus (HCMV) infection is the most common infection that is transmitted from mother to fetus during pregnancy . About 0.3-1% of all pregnant women become infected with the virus, and in 40% the infection is transmitted to the unborn child. If during the first or second third of pregnancy to an infection, it can cause birth defects in the child. These occur particularly frequently in the cardiovascular system , gastrointestinal tract , skeleton and muscles . Besides were hepatosplenomegaly ( enlargement of the liver and spleen ), petechiae , a microcephaly , intracerebral calcifications and chorioretinitis observed (retinitis). As a result, around 60 children die each year in Germany alone, and more than 1,000 are born with CMV-related disabilities. The spectrum of disabilities ranges from hearing impairments to severe mental retardation with an intelligence quotient (IQ) below 70. The mortality rate is 12 to 30%. Nine out of ten surviving children have long-term effects.
The HCMV infection is usually harmless to the mother. It runs like a mild flu and is therefore often not recognized. Only the massive consequences of the infection that are visible in the fetus on ultrasound are noticeable . A decision on a potential abortion of medical indications can be taken after a positive ultrasound finding ( microcephaly , intracerebral calcification. Ä u.) And a positive virus detection by PCR are present. Until now, termination of pregnancy was the only “therapy”, although this decision often had to be made at a comparatively late point in time, after the 20th week of pregnancy.
The risk of developing HCMV infection during pregnancy affects women who are "HCMV-seronegative"; H. who have not yet had HCMV infection. In order to recognize the HCMV infection in them in good time, a test for HCMV antibodies (HCMV-IgG) would have to be done regularly during pregnancy . This test is not yet part of maternity care, among other things because no therapy has been available so far. Seronegative pregnant women should therefore avoid exposure to the virus (especially nannies ). Illnesses during pregnancy ( embryopathy ) must be reported.
In 2005 a study was published in which the successful prevention and treatment of congenital HCMV infection with an HCMV hyperimmunoglobulin (HIG) was reported. In prevention, the HCMV-infected mothers were treated with the active ingredient Cytotect in order to prevent the infection from spreading to the unborn child. Even if the child was already infected, the mother was treated in this study. A more recent study with higher scientific standards, however, indicates that hyperimmunoglobulin has no significant effect in protecting the newborn. Rather, there is evidence here that the administration of hyperimmunoglobulin can lead to premature births and reduced growth. In this respect, according to the current state of knowledge, therapy with hyperimmunoglobulin should only be considered in rare cases in the case of an infection of the mother at an early stage of pregnancy.
After birth
Symptoms of a cytomegaly infection often only appear in newborns weeks or months after birth, and in small children sometimes only years later as what is known as the cytomegaly virus syndrome . This can lead to neurological deficits such as early childhood brain damage, developmental delays and inner ear hearing loss , jaundice , bleeding into the skin due to damage to the vessel walls, disorders of blood clotting and enlargement of the spleen and liver.
The infection occurs through the breast milk of seropositive mothers. In premature births and positive HCMV antibody -Proof should in any case to the breastfeeding be omitted. Infection is fatal in around three in ten children affected.
For premature babies, however, breast milk is very important because of its components for the body's defense and growth. It is therefore possible to treat the breast milk before feeding it. However, studies show that freezing breast milk is not 100% safe and that infections can still occur. A second variant is to warm the milk for a longer period of time (30 min., 63 ° C). However, the important components of the milk are also destroyed and significantly reduced. The latest procedure is a short-term treatment in which the breast milk is heated to 62 ° C in approx. 90 seconds and after 5 seconds on this max. Temperature is immediately cooled back to 30 ° C. With this process developed by the University of Tübingen and Virex GmbH, the essential components of breast milk are preserved and thus the value for the child. Study results confirm the reliable inactivation of HCMV in breast milk.
Behavior changes
According to a study by Jaroslav Flegr at the University of Prague, the virus causes behavioral changes similar to those that he has already observed in latent toxoplasmosis , such as less motivation to discover new things. He attributes the similar symptoms to a common mechanism of action, presumably a chronic inflammatory reaction in the brain. The strength of the symptoms is statistically significantly increased in people who are infected by both pathogens. Infected people are also less likely to be affected by minor infections; the authors attribute this to a "stimulation" of the immune system, which has to keep the latent infection under control.
Complications
In rare cases, this infection can lead to serious illnesses such as hepatitis , pneumonia or polyneuritis in otherwise healthy people .
With a weakened immune system
For people with a weakened immune system , cytomegaly can become a serious condition. People are particularly at risk
- after kidney transplants
- in leukemia after stem cell transplants , frequent occurrence of CMV pneumonia.
- during therapy with cytostatics
- In AIDS with a low CD4 + cell count, there is a risk of CMV retinitis with an acute risk of blindness. In addition, brain inflammation , nerve inflammation and nerve root inflammation can also occur as opportunistic complications.
Lymphocytic - plasmacellular interstitial inflammation with giant cell formation in the nucleus and cytoplasm can then occur in almost all organs . Severe pneumonia is very common. Additional bacterial infections and ulcers in the gastrointestinal tract are particularly feared . Such complications can even be fatal.
Diagnosis
As a matter of routine, evidence of an infection with the human cytomegalovirus (HCMV) can be provided in the laboratory in a few minutes from human serum and plasma using immunological in vitro tests for the quantitative determination of IgG and IgM antibodies against the cytomegalovirus. The results of this test will serve as evidence of a past or recently acquired HCMV infection. An indication for use is given in pregnant women and blood donors. Viruses can also be cultivated on human connective tissue cells , whereby the cell changes that can be observed after several weeks (detachment of infected cells from the cell structure, giant cell formation with plasmatic inclusion bodies, so-called " owl eye cells ", see Tzanck test ) are typical of an HCMV infection ( cytopathic effect ). Much faster diagnostic detection is carried out using real-time PCR . In addition, the HCMV can be detected during the acute infection via the pp65 antigen . However, if the infection is in a latent phase, i.e. in a phase without symptoms, only the pp67 antigen can be detected. This can therefore also be used to monitor the success of the therapy.
Serious HCMV diseases are usually associated with a CD3 number <200 µl. The CD3 number is an indicator of the course of treatment. The CD3 receptor or simply CD3 is a recognition molecule that z. B. occurs on the surface of T lymphocytes .
therapy
If cytomegaly occurs in otherwise healthy people, special treatment is not required in most cases. Treatment of the symptoms is usually sufficient. Special antivirals or immunoglobulins are only used in immunocompromised people. Then treatment with ganciclovir or foscarnet is usually more successful than with acyclovir . It is important to watch out for a bacterial infection. She should be treated with antibiotics immediately . The effectiveness of the active ingredient CMX001 was shown in a study with 230 patients .
prevention
So far there is no effective vaccination for prophylaxis . With the attenuated ( attenuated ) HCMV strain Towne as a vaccine approach , only limited protection could be achieved. However, various vaccines are under development.
Web links
- Self-help group by and for parents of premature children with CMV infection
- Initiative for the prevention of congenital cytomegaly infections
- detailed presentation at netdoktor.at
Individual evidence
- ↑ Chemaly et.al .: Letermovir for Cytomegalievirus Prophylaxis in Hematopoetic Cell Transplantation . In: New England Journal of Medicine . tape 370 , no. 19 , 2014, pp. 1781 .
- ^ Giovanni Nigro, Stuart P. Adler, Renato La Torre, Al M. Best: Passive Immunization during Pregnancy for Congenital Cytomegalovirus Infection. In: New England Journal of Medicine . Volume 353, September 29, 2005, pp. 1350-1362, doi: 10.1056 / NEJMoa043337 .
- ↑ Maria Grazia Revello, Tiziana Lazzarotto, Brunella Guerra, et al .: A Randomized Trial of Hyperimmune Globulin to Prevent Congenital Cytomegalovirus. In: New England Journal of Medicine . Volume 370, April 3, 2014, pp. 1316-1326, doi: 10.1056 / NEJMoa1310214
- ↑ Horst Buxmann, Klaus Hamprecht, Matthias Meyer-Wittkopf, Klaus Friese: Cytomegalovirus primary infection in pregnancy In: Deutsches Ärzteblatt . Volume 114, pp. 45–52, doi: 10.3238 / arztebl.2017.0045
- ↑ Martina Novotná, Jitka Hanusova, Jiří Klose et al .: Probable neuroimmunological link between Toxoplasma and cytomegalovirus infections and personality changes in the human host. In: BMC Infectious Diseases. 2005, No. 5, p. 54, doi: 10.1186 / 1471-2334-5-54 ( full text as PDF file ).
- ↑ Heinz-Walter Delank: Neurology. 5th, revised and supplemented edition. Enke, Stuttgart 1988, ISBN 3-432-89915-7 , p. 156.
- ↑ Francisco M. Marty, Drew J. Winston, et al. a .: CMX001 to Prevent Cytomegalovirus Disease in Hematopoietic Cell Transplantation. In: New England Journal of Medicine . Volume 369, 2013, pp. 1227-1236, doi: 10.1056 / NEJMoa1303688 .
- ↑ Birgit Schrage: Development of a DNA vaccine against the human cytomegalovirus. Dissertation, Institute for Cell Biology and Immunology at the University of Stuttgart, July 2002 ( online as a PDF file ).
