ACOG updates its recommendations on Influenza Vaccination During Pregnancy

The American College of Obstetricians and Gynecologists (ACOG) updated it committee opinion on influenza vaccination in pregnancy and post-exposure prophylaxis. This was published April 2018 and replaces Committee Opinion Number 608, September 2014.

This updated committee opinion is based on data that showed that only 54% of pregnant women in the USA were vaccinated during the 2016-2017 influenza season. This number needs to be worked on as the U.S. Health and Human Services’ Healthy People 2020 goal is vaccinating 80% of pregnant women against influenza.

Pregnant women are particularly susceptible to influenza infection and its resulting morbidities; therefore, influenza vaccination is an integral element of pre-pregnancy, prenatal, and postpartum care.

ACOG makes the following recommendations:

1) The Centers for Disease Control and Prevention’s (CDC) Advisory Committee on Immunization Practices and ACOG recommend that all adults receive an annual influenza vaccine. In addition, women who are pregnant or will be pregnant during the influenza season receive an inactivated influenza vaccine as soon as it is available.

2) Any of the licensed, recommended, inactivated influenza vaccine is safe during any trimester. Obstetrician-gynecologists and other health care providers should play an active part in counseling all pregnant women about the safety of influenza vaccine in pregnancy and its importance in protecting the newborn against the flu because of passive immunity.

3) It is recommended that every Obstetrician-gynecologist must get a flu vaccine every year and keep a stock of the vaccines in her office. If she is unable to provide the vaccination services, she should refer the patient to other provider, pharmacies or hospitals.

4) Patients who are allergic to egg and have had only hives can receive any licensed and recommended influenza vaccine that is otherwise appropriate for their age and health status.

5) In case the allergy symptoms are more serious than hives, the vaccine should be administered in an inpatient or outpatient medical setting including hospitals, clinics and physician offices.

6) Patients with flu-like illness should be started on antiviral medications, presuming it to be influenza. The provider should start the antiviral treatment based on clinical evaluation and not solely rely on the lab results.

7) All the office and hospital staff should also be encouraged to receive an influenza vaccine every year.

8) All pregnant women and women who are up to 2 weeks postpartum exposed to influenza virus because of close contact with an influenza patient should be started on post-exposure antiviral chemoprophylaxis (75 mg of oseltamivir once daily for 10 days). If oseltamivir is unavailable, zanamivir can be substituted, two inhalations once daily for 10 days.

Committee opinion

 Media courtesy: March of Dimes

Novel flu drug that kills the virus in 1 day get clearance in Japan

Japanese pharmaceutical company Shionogi claims that treatment with baloxavir marboxil, effectively kills influenza A and B virus in just 24 hours as opposed to the current user oseltamivir (sold under the brand name Tamiflu), which takes 72 hours to kill the virus.

Japan’s health ministry recently approved the drug and will be sold under the brand name Xofluza.

This is a welcome announcement in healthcare and pharma industry, in the midst of worst Flu season that the USA has experienced. Probably it could make the next flu season safer.  

Baloxavir marboxil prevents the replication of the virus by cap-dependent endonuclease activity of the viral polymerase unlike the existing drug oseltamivir (Tamiflu, Genentech), which acts by inhibiting the neuraminidase enzyme.

It’s prescription as single dose treatment irrespective of age greatly improves patients’ compliance as opposed to the twice-daily dose of oseltamivir for 5 days.

Baloxavir marboxil was tested in a randomized, double-blind, parallel-group, multicenter, placebo- and active-controlled study (CAPSTONE-1), which enrolled 1,436 otherwise healthy patients diagnosed with influenza. 

These patients with age between 20-64 years were randomized in a ratio of 2:1:2 to receive a single 1-time oral dose of 40 or 80 mg of baloxavir marboxil based on body weight or a placebo, or 75 mg BID of oseltamivir for 5 days.

Patients between 12-19 years of age were given baloxavir marboxil based on body weight. Those who weighed less than 80 kg received 40 mg of the drug while patients weighing more than 80 kg were given 80 mg.

The trial results showed that:

•   Patients who received Baloxavir marboxil had significantly lower viral titer at 1, 2 and 4 days
• Viral shedding in Baloxavir marboxil group was significantly less at 24 hours as compared to 72 hours in patients on oseltamivir and 96 hours in patients on placebo.
• The patients in the study group were afebrile in 24 hours vs 42 hours in the placebo group.
• The time to alleviation of symptoms (TTAS) was significantly shortened in the study group (53.7 hours) vs (80.2 hours) in the placebo group (p<0.0001). 
• The new drug was also well tolerated with significantly fewer side effects (20.7%) as compared to placebo (24.6%) or oseltamivir (24.8%).  

Shionogi is currently conducting another phase 3 trials with the drug in patients who are at high risk for Influenza.

Following the approval by Japanese health ministry in February, the drug could be on sale in Japan as early as May.

The head of co-developer Roche's pharma unit, Daniel O'Day, told Bloomberg, "The advantage is that it's one pill once, versus a course of therapy, so particularly for pandemic planning, this could be an advantage, you don't have the potential resistance that comes with not completing your course of therapy."

Shionogi and the Tamiflu maker Roche share the rights to sell Baloxavir marboxil in international market, but it will be almost a year before the drug enters US market.

Shionogi News Release

Novel emerging infectious diseases in pregnancy

Last two decades have seen epidemics of several infectious diseases which were previously not so prevalent worldwide. Pregnant mothers are especially prone to many infections because of anatomical and physiological changes that accompany pregnancy. The immune tolerance to semiallogenic fetus is because of down regulation of immunity, which puts the pregnant women at high risk of other infectious diseases reports a paper published in May 2017 issue of Journal Obstetrics and Gynecology.

The world has seen epidemics of four major and other minor emerging infectious diseases in the last two decades such as severe acute respiratory syndrome, the 2009 H1N1 pandemic influenza, Ebola virus, and, most recently, the Zika virus. Each of this infection has unique implications in pregnant women that are distinctly different from general population.

Each of this infectious disease has different clinical course, complications and future implications when occurring in pregnant women and requires special technique and skills and coordination at national and international levels to contain the outbreak, some basic principles are common to all for diagnosing and limiting the spread of these diseases.

A number of epidemiological factors have contributed towards emergence and widespread occurrence of these infection in pregnant women like global travel, development of microbial resistance and barriers towards vaccinations in pregnant women in-spite of increasing evidence of distinct benefits to mother and fetus.

Although the general principles of disease containment are common to all, some disease specific measures for treatment and prevention of individual infections in pregnancy are:

SARS: During the severe acute respiratory syndrome (SARS) outbreak by coronavirus in 2003, standard non-pharmaceutical measures were applied, and global containment was achieved in 5 months.

Influenza: All pregnant women should get influenza vaccine every year as soon as it is available and should not wait for the unpredictable influenza season to start. It is safe in all the trimester. The rapid influenza tests currently available has low sensitivity resulting in many false negative results. Hence, to err on the side of safety it is always recommended to prescribe oseltamivir as precaution and is recommended both by Centers for Disease Control and Prevention (CDC) and the American College of Obstetricians and Gynecologists.

Ebola virus: Women are always at high risk for contracting Ebola during an epidemic as they are the primary caregivers to other infectious family members. Women who are pregnant with the virus during acute Ebola epidemic usually transmit virus to the fetus, leading to intrauterine fetal death, stillbirth, or neonatal death. Ebola virus is also excreted in breast milk.

They also transmit the virus to healthcare providers and caregivers during labor or abortion. Standard precaution including the use of personal protective equipment (PPE) during labor and delivery for protection against blood and body fluids should be used along with rigorous hand hygiene, appropriate waste, sharps and laundry management and cleaning and decontamination.

WHO states that women who get pregnant after having being recovered from Ebola infection are not infectious but standard precautions and use of PPE should be implemented all the time during handling such patients. 

Zika virus: Zika virus is a flavivirus that has potential for sexual and vector born transmission by Aedes (Stegomyia) species of mosquitoes. It was declared as a public health emergency by the World Health Organization from 2016. A pregnant woman is susceptible to Zika virus in all three trimesters. Maternal Zika infection is associated with a range of adverse neonatal complications, most important of which is microcephaly. Peripartum transmission is also known to occur.

In absence of antiviral vaccine, CDC recommends that all pregnant women should postpone their travel to Zika infected areas and those who are in such areas should avoid mosquito bite especially during the day.

Pregnant women with laboratory-confirmed Zika virus infection can be offered amniocentesis to test for Zika virus RNA by RT-PCR after 15 weeks of gestation.

Deliveries of mothers with positive Zika infection should take place at specialized center.   

No specific antiviral treatment is available.

Abstract

Expert Discussion

WHO guide to Ebola disease in pregnancy

Media courtesy: InfectiousDiseaseAdvisor and Coherent news.