zika virus

Malaria drug may prevent Zika virus from infecting fetus

Studying pregnant mice, researchers at Washington University School of Medicine in St. Louis found that Zika virus manipulates the body's normal barrier to infection, and that hydroxychloroquine, a malaria drug related to chloroquine, interferes with this process, protecting the fetus from viral infection.Zika virus infects the fetus by manipulating the body’s normal barrier to infection, according to a new study of pregnant mice. Moreover, the study showed that a drug that interferes with this process protects the fetus from viral infection. That drug is already approved for use in pregnant women for other medical purposes.
Devastating consequences of Zika virus infection are suffered in the womb, where the virus can cause brain damage and sometimes death.

Studying pregnant mice, researchers at Washington University School of Medicine in St. Louis have learned that the Zika virus infects the fetus by manipulating the body’s normal barrier to infection. Moreover, they showed that a malaria drug that interferes with this process protects the fetus from viral infection. That drug already is approved for use in pregnant women for other medical purposes.

“We found that the malaria drug hydroxychloroquine effectively blocks viral transmission to the fetus,” said senior author Indira Mysorekar, PhD, an associate professor of obstetrics and gynecology, and of pathology and immunology. “This drug already is used in pregnant women to treat malaria, and we suggest that it warrants evaluation in primates and women to diminish the risks of Zika infection and disease in developing fetuses.”

The findings are published July 10 in The Journal of Experimental Medicine.

In late 2015, doctors in Brazil began to notice a surge in the number of babies born with microcephaly, or unusually small heads, an indicator of neurological damage. The epidemic soon was linked to the mosquito-borne Zika virus, which was spreading through the tropical parts of the Americas. Doctors advised pregnant women to avoid mosquito bites by wearing bug spray and long-sleeved clothing, but had little other advice to offer. There were, and still are, no drugs or vaccines approved for use in pregnant women to protect them or their fetuses from Zika infection.

The developing fetus is uniquely vulnerable to damage from infection, so the body mobilizes robust defenses to keep microbes from ever reaching the fetus in the first place. The placenta is the last line of defense. Mysorekar and others have shown that a process known as autophagy — the cellular waste-disposal pathway by which cells grind up debris, unwanted organelles and invading microbes — is an important part of the formidable placental barrier to infection. However, previous studies by Mysorekar and others have shown that Zika not only can invade the placenta, but multiply there.

To learn more about how Zika breaches the placenta, Mysorekar, postdoctoral fellow Bin Cao, PhD, and colleagues infected human placental cells with Zika virus. They found that exposure to the virus activated genes related to autophagy.

However, when the researchers treated the cells with drugs to ramp up the autophagy pathway, the number of cells infected with Zika virus increased. Drugs that suppressed autophagy resulted in fewer placental cells infected with Zika virus. In other words, the virus multiplied and spread more effectively when the researchers dialed up the barrier response, and performed more sluggishly when they dialed it down. The virus seemed to be doing a form of microbial martial arts, turning the body’s weapons to its own advantage.

Mysorekar and colleagues verified these findings using mice whose autophagy response was hobbled by low levels of a key autophagy protein. They infected two groups of pregnant mice with Zika: one in which the autophagy process was disrupted and the other in which it worked normally.

Five days after infection, the mothers with a weak autophagy response had about the same amount of virus in their bloodstreams as the mice with a normal response. However, in mice with a weak autophagy response, the researchers found 10 times fewer viruses in the placenta and the heads of the fetuses and less damage to the placentas.

“It appears that Zika virus takes advantage of the autophagy process in the placenta to promote its survival and infection of placental cells,” Cao said.

Since hydroxychloroquine suppresses the autophagy response, the researchers questioned whether it also could protect fetuses against Zika.

To find out, they repeated the mouse experiment using only mice with a normal autophagy response. Female mice at day nine of pregnancy were infected with Zika and then dosed with hydroxychloroquine or placebo every day for the next five days.

Following treatment, the researchers found significantly less virus in the fetuses and placentas from the mice that had received hydroxychloroquine. In addition, these placentas showed less damage and the fetuses regained normal growth. Both the untreated and the treated mothers had about the same amount of Zika virus in their bloodstreams, indicating that hydroxychloroquine was able to protect fetuses even when the virus was circulating through the mother.

Although hydroxychloroquine has been used safely in pregnant women for short periods of time, the researchers caution that further studies are needed before it can be used in pregnant women to fend off Zika. Pregnant women living in areas where Zika circulates may need to take the drug for the duration of their pregnancies, and the safety of hydroxychloroquine for long-term use is unknown.

“We would urge caution but nevertheless feel our study provides new avenues for feasible therapeutic interventions,” said Mysorekar, who is also co-director of the university’s Center for Reproductive Health Sciences. “Our study suggests that an autophagy-based therapeutic intervention against Zika may be warranted in pregnant women infected with Zika virus.”

The Women’s OB/GYN Medical Group strives to better the lives of all women with a holistic approach to women’s health. Call for an appointment today: (707) 579-1102. Visit our website: www.womensobgynmed.com


Story Source:

Materials provided by Washington University School of Medicine. Original written by Tamara Bhandari. Note: Content may be edited for style and length.


Journal Reference:

  1. Indira Mysorekar et al. Inhibition of autophagy limits vertical transmission of Zika virus in pregnant mice. The Journal of Experimental Medicine, July 2017 DOI: 10.1084/jem.20170957

Read this article on ScienceDaily: Washington University School of Medicine. “Malaria drug protects fetuses from Zika infection: Treatment prevents virus from crossing placenta to infect fetus, mouse study shows.” ScienceDaily. ScienceDaily, 10 July 2017. www.sciencedaily.com/releases/2017/07/170710091702.htm.

The Women’s OB/GYN Medical Group of Santa Rosa shares the latest facts about Zika Virus

The OB/GYN Medical Group gives an overview of the Zika virus, what women should consider before becoming pregnant and what pregnant women who may have been exposed to the virus should do.

get the facts about zika virus, pregnancy in the U.S.Under normal circumstances, an expectant mother intent on delivering a healthy baby might be warned by her OB/GYN to adopt a heathier diet, stay fit and avoid alcohol. Today every woman either thinking of conceiving or currently pregnant is no doubt tuned into a brand new danger associated with childbearing, namely – the Zika virus.
Nothing induces fear in the heart of a pregnant woman quite like a threat to their unborn baby. By all reports Zika virus is at once invisible, nearly indictable and insidious. But, is there really anything about this virus to concern women in the U.S.? Is it all hype or are there precautions that can be taken? The Women’s OB/GYN Medical Group offers some answers.

What is Zika Virus?

According to the latest information from the Centers for Disease Control & Prevention (CDC) Zika virus disease is caused by a virus that is spread to people primarily through the bite of an infected Aedes species mosquito. Prevailing symptoms of infection include fever, rash, joint pain and conjunctivitis. In healthy people the symptoms are generally mild and last for about a week. People infected with Zika normally recover quickly and rarely get so sick that they require medical care or hospitalization. Symptoms are so mild in most people, in fact that they might not realize they have been infected or suspect that their symptoms stem from a mosquito bite. Following infection, immunity to the disease results.

Zika Virus and Pregnancy

The real concern with Zika happens when a pregnant woman is infected. So far, the primary way for a pregnant women become infected has been through an encounter with an infected mosquito. It is now also known that Zika virus can be spread by a man to his sex partners and when a pregnant woman has become infected she can then pass Zika virus to her child either during pregnancy or at delivery. Health officials have recently begun to suspect that infection in pregnancy can also lead to an increased rate of miscarriages.

The results can be devastating for both the mother and the child, as there is increasing evidence that Zika infections leads to microcephaly, a birth defect that causes the baby’s head to be severely underdeveloped. Microcephaly also causes the baby’s brain to be smaller and therefore the child is unlikely to developed normally.

So far, experts contend that no local mosquito-borne Zika virus disease cases have occurred in U.S. although there have been a number of travel-related cases. With 80 percent of all cases going undiagnosed (due to the mild nature of the infection) the number of travelers returning to the U.S. who have encountered the virus will only continue to rise. The CDC says that the most disturbing outbreaks may have recently begun in Brazil, but now they are occurring in countries all over the world, particularly those with wetter, warmer climates. At this point, there’s no telling where the virus will spread to, but the list of countries for pregnant women to avoid currently include; Barbados, Bolivia, Ecuador, Guadeloupe, Saint Martin, Guyana, Cape Verde, and Samoa.
What is the risk of becoming infected in the U.S.?

The National Science Foundation has just released a map of the States more likely to encounter Zika virus. Although still a projection of what may become a possibility, the research team ran two computer models to determine the potential risk in the mainland United States. According to that map the lower southern and eastern portion of the U.S. where temperatures are mildest are the most at risk. And the risk will continue to rise as temperature go up and the hot summer months get closer.

Protecting Against Zika

The CDC advises pregnant women to delay or avoid travel to any known area where Zika virus is spreading. And if avoiding travel is not an option, they recommend discussing with a healthcare provider prior to departure, and to strictly follow steps to prevent mosquito bites while traveling. At this point, pregnant women with male partners living in or traveled to a known Zika virus area should take precautions by using condoms or avoid having sex during pregnancy.

Women are also advised to talk to a healthcare provider if they have recently returned from an area known to have a problem with Zika, regardless of whether or not they have been sick. If Zika virus infection is suspected, the patient can be tested by a healthcare provider for the virus. If tests confirm infection, ultrasounds can be employed to monitor the fetus’ development, and an OB/GYN practitioner should closely follow the case. CDC also recommends that an infectious disease specialist with expertise in pregnancy management become involved.

About Women’s OBGYN Medical Group

The provider team of expert OB/GYN physicians, certified nurse midwives, family nurse practitioners, and medical assistants provides unmatched care to patients in our region. As women proudly serving women, we understand the needs and expectations of our patients. For more information, visit our website or call (707) 579-1102. We urge you to contact our office to schedule an appointment with one of our physicians if you have any concerns about your pregnancy and/or the Zika virus.
More info: Miscarriages … of American women with Zika Virus http://www.statnews.com/2016/02/10/zika-american-women-miscarriages/