Friday, August 5, 2016

First Zika virus vaccine enters phase 1 trials in US.

A healthy volunteer receives the NIAID Zika virus investigational DNA vaccine as part of an early-stage trial to test the vaccine’s safety and immunogenicity. This is the first administration of this vaccine in a human.
Credit: NIAID

The National Institute of Allergy and Infectious Diseases (NIAID) made a press announcement on August 3,2016 about its recent launch of phase I clinical trials for its newly developed DNA Zika vaccine.

Zika is rife in Puerto Rico, American Samoa, the US Virgin Islands, and Florida and United States department of defense(DoD) recently confirmed about 30 cases of Zika virus infection among troops. As per Florida Department of Health recent update there are 15 total number of non-travel related infections and 55 pregnant patients have been infected due to either local transmission, sex with an infected partner or travel.[1] A total of more than 6,400 Zika cases have been reported in the US and its territories.[2]  

The NIAID Zika virus vaccine is investigational and was developed in the beginning of this year. The vaccine contains bio-engineered, non-infective Zika virus plasmid that contains genetic code for protein of the Zika virus. When injected into our body by intramuscular route, the DNA quickly assemble into a virus like particle, that has lost its infecting capabilities. It incites an immune response in the host by making antibodies and T cells.

The DNA vaccine, is delivered on the site on skin via a short electrical pulse that propels the DNA, which seeks  human cells through a process called electroporation.

It is also known from the animal experiment that despite being genetically different, all strains of the Zika virus have identical surface antigen, thereby vaccine developed against one will be effective against others too. [3]

According to John Mascola, MD, director of NIAID’s Vaccine Research Center (VRC), “DNA or gene-based vaccines include antibodies, but they also can activate the cell-mediated immune response, which ultimately could yield strong and durable protection against disease.”

DNA vaccines are new in the vaccine armament and no other DNA vaccine has been approved by US.[4] But since they do not need to grow live virus, DNA vaccines have short development time.[5]
The vaccine will be tested in 80 healthy volunteer in Maryland and Atlanta. The volunteers will receive the first shot at the same time and then they are divided into 4 groups of 20 each receiving the subsequent shots at varying intervals to study which dosing schedule works best. All the participants will be closely monitored for 44 weeks of initial vaccine administration.[6]They will be tested to measure the immune response to the vaccine at 18 and 24 months after the initial dose.

Researchers have already tested the vaccines in animal studies and found them to be effective and safe. When monkeys were exposed to Zika virus 4 weeks after the second dose, they showed no clinical signs of infection nor the virus was found in the blood.[7]

Meanwhile, a similar vaccine developed by The Infectious Disease Research Centre (IDRC) and the Centre de recherche du CHU (Centre hospitalier de l’UniversitĂ©) at Laval University in Canada has also begin its phase 1 clinical trials.

The vaccine is temporarily named GLS-5700, and is manufactured by Inovio, based in Plymouth Meeting, Pennsylvania, and GeneOne Life Science, of Seoul, South Korea.

At this point of time around 18 countries around the world are competing each other to develop Zika virus vaccines including French pharmaceutical giant Sanofi SA and GlaxoSmithKline.

According to CDC Zika virus infection is a public health emergency because of its causation of congenital birth defects. Currently 61 countries and territories are infected with Zika virus and 12 countries have reported birth defects due to Zika.

If the phase 1 trial is successful, the vaccine will enter phase 2 trial in early part of 2017. But, even at this pace it will be another 2 years before it is commercially available.


Thursday, August 4, 2016

Douching doubles the risk of developing ovarian cancer.

Clinical pearls:

  • Douching and not talc was associated with increased risk of ovarian cancer in the sister study. 
  • ACOG and NHS both does not support douching and other vaginal washing practices that do more harm than good by eliminating the healthy vaginal flora. 

A National Health study in US linked the age old ritual of douching to subsequent development of ovarian cancer. Women who douche have nearly twice the risk as compared to women who do not practice it.

According to Department of Health and Human services(HHS) one quarter of women between the ages of 15 and 44 practice douching. [1] Studies have linked douching to Bacterial Vaginosis, Pelvic Inflammatory Disease(PID), STIs, including HIV, preterm birth, ectopic pregnancy and vaginal irritation or dryness. [2] A meta-analysis of more than 10,000 HIV-negative women in sub-Saharan Africa found that intravaginal use of drying agents was associated with an increased risk of BV and HIV.[3] 

American College of Obstetricians and Gynecologists (ACOG) and most practitioners strongly advice against douching and ACOG list it as one of the cause of vaginitis, women continue to practice it because of they see it as a cleaning ritual leading to positive health benefits.[4] The NHS also advise against douching and use of scented wipes and vaginal deodorants.

The new National Institute of Environmental Health Sciences study published online on 20 June,2016 in the Epidemiology Journal recruited 50,884 participants of the “Sister study” and followed them to see the link between douching and ovarian cancer. [5]The sister study is conducted by the National Institute of Environmental Health Sciences of the US Department of Health and Human Services. The study enrolled 50,884 women between ages 35–74 whose sister have breast cancer and followed them from 2003 to 2009, across all 50 US states and Puerto Rico.  Due to the shared environment and genetics, this landmark study provides a great chance of identifying risk factors for breast cancer.

All the women were free of breast or ovarian cancer at baseline. The women were asked about douching and use of talc during the previous 12 months before enrolment.

At the end of the follow up period (median 6.6 years) 154 women were diagnosed with ovarian cancer. Women practicing douching has nearly twice the odds of developing malignancy as compared to women who did not douche. The association looked even stronger when only women without the breast cancer gene in the family were analyzed.

Contrary to previous studies, this particular study did not find any association between talc use and ovarian cancer. (HR=0.73) although talc users were twice as likely to practice douching. (OR=2.1)
This is the first study to trying to find a link between douching and ovarian cancer.

Senior author Clarice Weinberg commented: “There are a number of health reasons not to douche, and I can’t think of any reason to do it.”

Vagina cleans itself naturally and douching cause more harm by cleaning away the healthy bacterial flora. The Office on Women's Health at the U.S. Department of Health and Human Services (HHS) says that due to squirting of the douching solution the bacteria are pushed inside uterus, fallopian tube causing PID.

A study conducted by Brown, J et al in 2016 shows women practice intravaginal washing due to personal hygiene and sexuality. It is common to get cleaned up after or before sex. Majority of these women learn the practices from their mothers or electronic or print media. Many women believe that since departmental stores aisles are packed with these products of personal hygiene, they must be safe to use.

But douching products do not fall under FDA regulation, as they are considered cosmetics. Hence, these products do not have to undergo safety tests like drugs.

The pilot study does not prove causation and larger studies are needed in the area. Perhaps women who douche frequently might have other pathologies going on which may be the cause for the behavior. We need to see more studies in the future. 

[1]Centers for Disease Control and Prevention. (2013). Key Statistics from the National Survey of Family Growth, 2006–2010.
[3] Low N, Chersich MF, Schmidlin K, Egger M, Francis SC, van de Wijgert JH, et al. Intravaginal practices, bacterial vaginosis, and HIV infection in women: individual participant data meta-analysis. PLoS medicine. 2011;8(2):e1000416. 

Wednesday, August 3, 2016

A New York Federal Judge rules in favor of Bayer’s Mirena IUD, dismissing 1,300 Lawsuits.

A federal judge has ruled in favor of Bayer against all the 1300 lawsuits filed by women who claimed to have suffered from internal injuries after Mirena was inserted.

It all started in 2011 when a woman filed the first complaint. Since then other have joined in claiming to have uterine perforation, inflammation, organ damage, and a host of other medical complications. Bayer has long marketed the IUD as a “hassle free” birth control for busy, on the go moms.

Bayer was warned by FDA in 2009 to scale down the positive effects of Mirena and also put forth the negative effects. The letter also stated that Mirena’s advertisements are misleading consumers by exaggeration of its abilities and do not display the side effects and risks of the IUD. Mirena was approved by the FDA in 2000, and since than Bayer has spent tens of millions of dollars advertising the IUD directly to the consumers.[1]

By the year 2009, it was so popular among women that nearly 7.5% American women had it implanted by then and have generated billions of dollars in revenue for the manufactures.

The lawsuits against Mirena comes in many forms, and in multiple states across the US. Women have claimed to have uterine perforation, increased risk of neurological damage and painful surgical removal, ovarian cysts, headache, migraines, acne, depression, and mood swings. The most common complaint is device migration , damaging and perforating the internal organs.   A website  TheTruth About Mirena  contains many other side effects and makes a grim reading.  

In the year 2015, Bayer had settled 8,250 cases for $1.7 billion but there are still lawsuits pending in national and state courts across the country. All are individually filed complaints but still a class action lawsuit is not filed yet.

In March 2016, US District Judge Cathy Seibel granted Bayer’s motion to bar the plaintiff’s expert witnesses from testifying in the court about perforation caused by the device. She found that the testimony was not backed by scientific literature and was made up just for the purpose of litigation.

Bayer’s lawyer claimed that perforations might have occurred during insertion, but were only detected later and there is no evidence that Mirena causes uterine perforations.[2]

Without expert witness testimony, no jury could rule in favor or against the IUD. So, on August 1, 2016 she ordered that the verdict should go in favor of Bayer in all 13000 cases.[3]


Tuesday, August 2, 2016

Late Menarche, Late Menopause and Longer Reproductive lifespan linked to increased longevity.

Clinical Pearls:

  • Women who had menarche at age 12 or more and experienced menopause at age 50 or beyond have increased odds of living up to age 90 as compared to women who have early menarche and early menopause.
  • Those women whose reproductive life span lasted 40 years, were 13% more likely to celebrate 90 birthdays than women who were in reproductive period for 33 years. (odds ratio [OR]= 1.13).

A new study by researchers at University of California, San Diego found an interesting correlation between the age at menarche and menopause and longevity. Women who enter the reproductive period late and also have a late menopause are more likely to live till age 90.

The research implicated that women who had menarche at age 12 or more and experienced menopause at age 50 or beyond have increased odds of living up to age 90. 

According to Dr Aladdin Shadyab, of the University of California, San Diego School of Medicine "People have always wondered whether the timing of reproductive events affect longevity, but no study to date has evaluated that relationship."

The study was published in recent issue of Menopause, the journal of North American Menopause Society. [1]

The research team used data for Women’s Health Initiative study (WHI). The Women's Health Initiative (WHI) is a long-term national health study that recruited women from 1993 to 1998 and followed them until 2014 focusing on strategies for preventing chronic health diseases in postmenopausal women. This multi-million dollar, ground-breaking study has far reaching implications and have provided the health care providers with practical information to prevent and treat some of the major diseases impacting postmenopausal women. [2]

The study participants included 16,251 women from diverse racial and ethnic background all born before August, 1924. Multivariable logistic regression models were used to determine the association, adjustments were made of demographics, reproductive history and lifestyle of the women.

The average age of the study participants was 74. 7 years and 8,892 (55%) of the women lived through age 90.

As compared to those women who had an early menarche before age 12, those women who were at-least 12 or older at menarche have a 9% increased chances of living upto age 90. (odds ratio [OR]= 1.09).

Similarly, women who were at least 50 at the time of last period are 20% more likely to live till 90, as compared to women who stopped menstruating before age 50. The same was true for women who underwent surgical menopause. (odds ratio [OR]= 1.19).

Longevity was also tied to a longer reproductive life span. Those women whose reproductive life span lasted 40 years, were 13% more likely to celebrate 90 birthdays than women who were in reproductive period for 33 years. (odds ratio [OR]= 1.13).

The authors of the study cannot pinpoint a single reason behind this association, but multiple factors come into play.

Early menarche is often associated with obesity, Diabetes and CVD while early menopause is also linked to increased risk of CVD. These associated co-morbidities in women experiencing early menopause may be responsible for shorter life span.

Genome-wide association study of age at natural menopause identified genetic variants involved in DNA replication and repair pathways which is crucial in aging. Thus genetics is also an important factor.

The study has limitations of not knowing the longevity of the parents and other family members of the participants along with the work history and stress, which plays an important role in deciding longevity.

One other study published this week in Proceedings of the National Academy of Sciences and Biological Psychiatry, has shown that women with early menopause suffer from insomnia which accelerates aging and shortening the life span.[3]

The last decade has seen rapid improvement in life expectancy of older women adding average of 7 years to their life expectancy as compared to men[4] with a current total population of 1.3million women over the age of 90+.  Women surviving into their 90s outnumber men by a ratio of almost three to one.[5]

The authors conclude "With secular trends showing decreasing age at menarche, increasing age at menopause, and a concurrent rise in longevity, additional studies in younger birth cohorts will be needed in the future to precisely define the relationship between the timing of reproductive events and a woman's length of life."