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Short version of b change
Transcript of Short version of b change
Thank you for your attention!
And one more thing...
Why should we pursue prevention through behavioral change?
What behaviors should we address?
Frequent hand washing, especially after exposure to a child's saliva or urine
Handling dirty laundry
Touching the child's toys
Avoid certain types of contact with young children
Kissing on the mouth
Sharing washcloths, utensils, food or drink
Clean toys, countertops, etc.
CMV does not remain viable for long after drying out
CMV does not remain viable for long on hands
CMV remains wet during oral transmission behaviors
Hands rarely get wet with urine
Among healthy children, CMV viral loads may be higher in saliva than in urine
Strong evidence for oral transmission--infants ingesting breast milk (Lanzieri, Pediatrics, 2013)
Oral transmission behaviors are common
Not washing hands following diaper changes is uncommon
How do we find out what works?
No major adverse effects among 2583 pregnant women in behavioral intervention (Vauloup-Fellous, JCV, 2009)
None of 130 seronegative pregnant women complained the behaviors were burdensome or anxiety provoking (Adler, IDOG, 2011)
In focus group research, some of the 35 women voiced concerns about prevention messages (feasibility, remembering, modifying cherished habits); however, all said that if they were pregnant they would want to know the messages and would try to follow them. (Levis, unpublished data)
Consider a "know your risk" approach
Behavioral interventions consist of individual-, community-, and/or structural-level measures designed to change individuals' behaviors
Design behavioral intervention in France
Picone, BJOG, 2009; Vauloup-Fellous, JCV 2009
What is a behavioral intervention?
Likely transmission routes
So, researchers tried a more comprehensive approach
CMV shedding is more frequent in children than in adults
Children in day care shed more frequently than children not in day care
Provide test results
Counseling on behavioral changes
Message content is one part of this step
Cannon, RMV, 2011
Significant burden of disease
Infant with microcephaly
Examples of impact of congenital CMV
Child with cerebral palsy, hearing loss, and intellectual disability
Child with spastic quadraplegic cerebral palsy, vision loss, microcephaly, intracranial calcifications, and epilepsy
Child with hearing loss
30,000-40,000 congenital CMV infections
3,500 symptomatic infections
>5500 children with permanent sequelae
Estimated annual disease burden in US
Dollard, Rev Med Virol, 2007
Burden relative to other important conditions
Adapted from Cannon & Davis, BMC Public Health, 2005
No licensed vaccine available
Vaccine unlikely in the near-term
(Griffiths, Vaccine, 2013; Krause, Vaccine, 2013)
(Fowler, JAMA, 2003)
69% protection against
gB subunit vaccine reduces maternal infection by 50% during 1st year
(Pass, NEJM, 2009)
gB subunit vaccine reduces duration of viremia in organ transplant recipients (Griffiths, Lancet, 2011)
First CMV vaccines developed
(Elek, Lancet, 1974; Plotkin, Infect Immun, 1975)
Treatment for fetal infection or disease
The good news
Randomized, controlled trial (RCT) in Italy found a modest but not statistically significant positive effect (Revello, NEJM, 2014)
Also, the frequency of adverse obstetrical events was higher in the treated group
A large, multi-center RCT is currently being conducted in the United States
Pregnant women with primary CMV infections were significantly less likely to transmit CMV to fetuses when treated with CMV hyperimmune globulin (HIG) (Nigro, NEJM, 2005)
Some other observational studies reported a positive effect of HIG treatment (e.g., Visentin, CID, 2012)
The good news
IV ganciclovir and oral valgancyclovir have significant toxicities, especially neutropenia
Infants with symptomatic congenital CMV with central nervous system (CNS) manifestations had better hearing and developmental outcomes if treated with 6 weeks IV ganciclovir (Kimberlin, J Peds, 2003)
Trial underway to treat infants with symptomatic congenital CMV with 6 months of oral valgancyclovir (Kimberlin, JID, 2008).
Congenital CMV is an invisible disease
Mothers do not know when they are infected
Many infected babies are asymptomatic at birth
When babies have symptoms, they are often non-specific
Congenital CMV usually cannot be diagnosed retrospectively
Few women have heard of congenital CMV
Ross, J Womens Health, 2008
Same study design
Similar study population
2005 vs. 2010
Cannon, Prev Med, 2012
CMV has lowest awareness of all conditions
No increase in awareness over time
"...from the practical standpoint, it appears that we must await the development of a successful vaccine before beginning to control this common congenital virus infection."
"It is likely that
careful attention to handwashing
, especially after handling oral secretions or diapers, will help reduce the chances of acquiring CMV." (Pass, Pediatrics, 1985)
"Individuals who have intimate contact with infants or young children...should
wash their hands
with warm soapy water after contact with the child." (Bale, AJDC, 1986)
"In general, isolation of known CMV excretors is unnecessary, but
by caretakers should be emphasized." (Nankervis, Adv Ped Infect Dis, 1986)
Cannon et al., unpublished data
Cannon et al., unpublished data
Unlikely transmission routes
If there is sufficient evidence about viral transmission and disease causation, what is the pattern for how should we proceed?
Surgeon General warned about the hazards caused by cigarette smoking in 1964
Since then there has been a continuous effort to find interventions that effectively encourage people to quit or never start
In 1986, the CDC made the following recommendation:
"...High-risk persons with a negative test result should be counseled to reduce their risk of becoming infected by: (1) Reducing the number of sex partners... (2) Protecting themselves during sexual activity with any possibly infected person by taking appropriate precautions to prevent contact with the person's blood, semen, urine, feces, saliva, cervical secretions, or vaginal secretions..." (MMWR, March 14, 1986)
Earliest effective interventions were reported in 1989
Stowell, JID, 2012
"...mechanical ventilation of infants with respiratory CMV infection does not generate an infectious aerosol. Virus could not be recovered from sites not in direct contact with infected secretions..."
Faix, PIDJ, 1989
Where in the world is CMV?
"Counseling should cover careful handling of potentially infected articles, such as diapers, and
when around young children..." (ACOG, 2000)
"When caring for children,
, particularly after changing diapers, is advised to decrease transmission of CMV. " (Pediatric Red Book, 2012)
Cannon & Davis, 2005
Initial behavioral approach?
Don't hand it over.
But are these too many behaviors?
Can a risk gradient approach help?
This is a lot of steps
This is fewer steps
Data about CMV on hands?
3/44 in day care center (Hutto, JID, 1986)
Data about CMV on surfaces?
2/70 in day care center (Hutto, JID, 1986)
But you are unlikely to hear that you should use hand washing to prevent the transmission of other herpesviruses, such as those that cause:
Likely risk gradient for CMV transmission
Are you around young children?
How many sex partners do you have?
One possible approach for behaviors to address
1. When you kiss a young child, try to avoid contact with saliva. For example, you might kiss on the forehead or cheek rather than the lips.
2. Try not to put things in your mouth that have just been in a child’s mouth. For example:
Forks or spoons
3. Wash your hands after touching a child’s saliva or urine, especially after:
Wiping a child’s nose or mouth
If you do not have soap and water, use an alcohol-based hand sanitizer.
Prevention messaging idea
What's been tried so far
Virginia (Finney 1993)
Virginia (Adler 1996)
Virginia (Adler 2004)
France (Picone, Vauloup-Fellous, 2009)
Rhode Island (Anderson)
11 non-pregnant mothers of children in day care
39+14 CMV-negative mothers with children shedding CMV
166 CMV-negative mothers of children in day care
5173 pregnant women
~200 pregnant women
~200 pregnant women
We'll find out in the 10am session!
Behavior & infection
Behavior & infection
Behavior & process
Behavior & process
Before & after
No & yes
Protective behaviors increased, risky behaviors decreased
Infection rates decreased with intensity of intervention
No difference in infection rates between intervention groups
Infection rates decreased 4-fold
Study in progress
Study in progress
Is CMV important enough?
What behaviors do I need to change?
What are the benefits? Costs?
How do I correctly do the behaviors?
How do I remember the behaviors?
CMV lessons learned
Preliminary research has identified some factors that may encourage a woman to practice CMV prevention behaviors, including:
• Hearing about behavioral prevention from healthcare provider
• Being aware that she is CMV-seronegative (and therefore at risk for a primary infection)
• Knowing that she is pregnant (rather than simply trying to become pregnant)
• Hearing a message that is framed in compelling and culturally appropriate ways based on audience research
General lessons from behavioral research
Many interventions do not work
Even effective interventions only work for a subset of participants
Recommendations are often based on intermediary outcomes
Use audience research
Ground interventions in health behavior theories
Future lessons to be learned
To bundle or not to bundle with other health messages?
To test or not to test for CMV?
Best settings for interventions?
Universal or targeted interventions?
100's of HIV interventions
24 cited in The Community Guide
in The Community Guide and Compendium of HIV Prevention Interventions
show effectiveness of behavioral change outcomes rather than HIV prevention
For example, Community Guide recommended behavioral interventions for the prevention of unprotected anal intercourse had a mean odds ratio of 0.57
Remember risk gradient
Know your audience
Involve behavioral scientists
Exposed to young children?
Multiple sex partners?
Save $100 million
Prevent disability in 500 children
Reach 1 in 3 pregnant women
Reduce risk by 1/3
Reactions to CMV messages and interventions
Pattern in other areas:
1. Identify and disseminate the recommended behaviors
2. Work to develop interventions that are effective in promoting the behaviors
"Empiric evidence for the effectiveness of exclusion and isolation strategies is limited; rather, strategies are based on infection-control principles."
Start with how CMV is transmitted
Example of trying to understand the risk gradient
A new paradigm
for CMV researchers
Meta-analysis of parent-child attachment indicates that disorganized attachment requires severe disruptions such as:
Frightening parental behavior (in the absence of abuse)
Severe and long-term parental depression
(van Ijzendoorn, Develop Psychopathol, 1999)
Stowell, unpublished data
Experiment with behavioral interventions
Ways to experiment:
CMV persists in the environment until it dries out
CMV is less contagious than viruses that spread through the air
Younger children have more CMV in their saliva than do older children
Children have more CMV in their saliva than in their urine
Children have more CMV in their saliva than do adults
Higher risk groups
"Know your risk" approach