Cytomegaly – Mega-risky for Fetuses

30. November 2010

Whether herpes simplex on your lip or chicken pox: Herpes viruses are omnipresent. In nearly 90 percent of the cases, cytomegaloviruses cause almost no troubles. But they are dangerous for expectant mothers and patients with an immunodeficiency.

About 70 percent of all adults got in touch with the cytomegalovirus (HCMV) in the course of their life and create antibodies. Occasionally they complaint about a headache or pains in the joint after the first infection, or about maybe swollen lymph nodes or increased body temperature – all symptoms that remind of a flue-like infection.

“As long as our immune system is working, those viruses are harmless” – the virologist Prof. Dr. Bodo Plachter at the Mainz University knows that. And after the symptoms have passed, the virus remains in your body for the rest of your life. “It really gets dangerous for people with immunodeficiency, for example after organ transplantation when the rejection reactions have to be suppressed”. Crohn’s disease- or colitis ulcerosa-patients undergoing immunosuppressive therapy are also in this risk group, just as well as HIV patients mainly if the number of relevant helper cells of the immune system is considerably reduced. In these cases it might lead to life-threatening inflammation of inner organs. But preparations like Foscarnet, Ganciclovir or Valganciclovir hold the HCMV at bay.
Here are some news in prophylaxis: The original gold standard was to administer antiviral drugs for 100 days. Recent studies show that patients profit from an expansion of the treatment period in order to avoid getting a delayed virus infection after all. The administration with oral Valganciclovir in double the preventive therapy period prevented occurrence of a HCMV infection after kidney transplantation within twelve months by 56 percent. “The result substantiates that an expanded treatment with Valcyte can achieve an improvement”, says Dr. Atul Humar at the Alberta University in Canada. But not all virustatics can be used for pregnant women.

An immunoglobulin saves lives

But especially during pregnancy, HCMV is a serious threat: With one to two percent, cytomegalia is considered the most frequent infection of the unborn child – even before rubella and toxoplasmosis. And in about 40 percent of the infection cases, the virus is passed on to the unborn. At risk are especially those expectant mothers never in touch with cytomegalia before – which is half of all pregnant women after all. The preventive recommendations are to stay away from larger groups of children, let it be kindergartens, nurseries or newborn nurseries, because you will find the virus there in all probability. If you still get an infection the consequences – especially during the early pregnancy – are significant: Organ defects, later developmental disorders and mental handicaps. According to Adj. Professor Dr. Andreas Clad in Freiburg, in Germany alone about 600 to 800 children are born with irreversible damages caused by a HCMV infection.

Highly dosed antibodies against the HCMV – the so-called immunoglobulins – provide effective protection for the unborn and the expectant mother. Those are approved since 1982 for treatment of infections in transplantation patients. Specialized companies get these preparations from the blood of patients successfully fighting the HCMV. During therapy, the immunoglobulins as an antibody bind to the cytomegalia virus and inactivate it.
Figures confirm the effectiveness very impressively: In a study with 181 pregnant, HCMV infected women only three percent of the therapy group showed medically relevant anomalies, in the control group it were – believe it or not – 50 percent. Since immunoglobulins wander through the placenta, the unborn child can be treated. In addition to the original use for transplantation patients, new fields of application are opening here for immunoglobulins.

Breastfeeding innovative

No secret: Babies should be breastfed during the first months of their lives in order to develop a functioning immune system. This was problematic for mothers with HCMV infection since the infection can be passed on through the mother’s milk as well. They were recommended to forego breastfeeding. The company Virex GmbH, together with other partners, has developed an innovative solution. It is possible to treat mother’s milk by brief heating and rapid cooling for important proteins to keep their activity but the HCMV is inactivated thermally.

Organ transplantation on the save side

Transplantation patients profit as well, namely not only for HCMV prophylaxis: If they are treated with an according immunoglobulin prior to the surgery, the development of lymph gland cancer can be prevented effectively. Scientists at the University Hospital Heidelberg came to this conclusion. They assessed more than 40,000 data of the Collaborative Transplant Study. Although this malign disease is caused by the Epstein-Barr virus, a close relative of the cytomegalia virus, but “we found also antibodies against the Epstein-Barr virus in the antibody preparations against the HCMV”, explains Prof. Dr. Gerhard Opelz, Medical Director of transplantation immunology at the Heidelberg University Hospital. Those probably are responsible for prevention of lymphoma development. After surgery though, the immunoglobulin has to be administered in larger intervals, otherwise the protection will ‘expire’ after about one year.

Waiting for the vaccine

Despite all therapeutic options, vaccination is and remains to be the gold standard. Here the Children’s Hospital in Birmingham, Great Britain has some good news: Together with other researchers, the working group of Robert F. Pass introduced promising results of a phase II study. They succeeded to initiate the production of antibodies against HCMV with a genetically produced surface protein.

Thus women in child-bearing age could be protected reliably against a new infection, accordingly the number of innate cytomegalia infections decreased. In order to confirm these results, there is a large study going on in coordination with EMEA, the European Medicines Agency. And a few months ago, Novartis Vaccines and Diagnostics reported that they have secured an exclusive license for a vaccine against HCMV still in the phase of development. Their CEO Dr. Andrin Oswald: “We consider this vaccine candidate for prevention of cytomegalia virus infection extraordinary and promising.”

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