82 FR 51839 - Agency Forms Undergoing Paperwork Reduction Act Review

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Centers for Disease Control and Prevention

Federal Register Volume 82, Issue 215 (November 8, 2017)

[Federal Register Volume 82, Number 215 (Wednesday, November 8, 2017)]
[Notices]
[Pages 51839-51841]
From the Federal Register Online  [www.thefederalregister.org]
[FR Doc No: 2017-24314]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Centers for Disease Control and Prevention

[30Day-18-17AZX]


Agency Forms Undergoing Paperwork Reduction Act Review

    In accordance with the Paperwork Reduction Act of 1995, the Centers 
for Disease Control and Prevention (CDC) has submitted the information 
collection request titled Zika Puerto Rico Study: Zika Virus RNA 
Persistence in Pregnant Women and Congenitally Exposed Infants in 
Puerto Rico to the Office of Management and Budget (OMB) for review and 
approval. CDC previously published a ``Proposed Data Collection 
Submitted for Public Comment and Recommendations'' notice on April 19, 
2017 to obtain comments from the public and affected agencies. CDC did 
not receive comments related to the previous notice. This notice serves 
to allow an additional 30 days for public and affected agency comments.
    CDC will accept all comments for this proposed information 
collection project. The Office of Management and Budget is particularly 
interested in comments that:
    (a) Evaluate whether the proposed collection of information is 
necessary for the proper performance of the

[[Page 51840]]

functions of the agency, including whether the information will have 
practical utility;
    (b) Evaluate the accuracy of the agencies estimate of the burden of 
the proposed collection of information, including the validity of the 
methodology and assumptions used;
    (c) Enhance the quality, utility, and clarity of the information to 
be collected;
    (d) Minimize the burden of the collection of information on those 
who are to respond, including, through the use of appropriate 
automated, electronic, mechanical, or other technological collection 
techniques or other forms of information technology, e.g., permitting 
electronic submission of responses; and
    (e) Assess information collection costs.
    To request additional information on the proposed project or to 
obtain a copy of the information collection plan and instruments, call 
(404) 639-7570 or send an email to [email protected]. Direct written comments 
and/or suggestions regarding the items contained in this notice to the 
Attention: CDC Desk Officer, Office of Management and Budget, 725 17th 
Street NW., Washington, DC 20503 or by fax to (202) 395-5806. Provide 
written comments within 30 days of notice publication.

Proposed Project

    Zika Puerto Rico Study: Zika Virus RNA Persistence in Pregnant 
Women and Congenitally Exposed Infants in Puerto Rico--New--National 
Center of Birth Defects and Developmental Disabilities, Centers for 
Disease Control and Prevention (CDC).

Background and Brief Description

    The Puerto Rico Department of Health (PRDH) reported the first case 
of autochthonous transmission of Zika virus (ZIKV) in December 2015. As 
of December 16, 2016, Puerto Rico reported 35,648 ZIKV cases, more than 
any other location in the U.S., and health officials expect the number 
of cases to continue to rise. Among the cases, 2,864 have been among 
pregnant women, and the PRDH announced the first case of microcephaly 
in a fetus with confirmed ZIKV infection on May 13, 2016. Currently, 
testing for ZIKV infection can be done by either using rRT-PCR to 
detect the presence of ZIKV RNA or by serologic testing to detect IgM 
and neutralizing antibodies. rRT-PCR testing is the preferred and 
suggested method for diagnosing ZIKV infection because it provides a 
definitive diagnosis and is not subject to the limitations (e.g., 
cross-reactivity) associated with serology testing. However because 
level of viremia is generally low and RNA concentrations decline over 
time, ZIKV rRT-PCR has generally only been considered for a short 
testing window (2 weeks).
    Currently, the CDC and the PRDH recommend ZIKV testing of all 
pregnant women living in areas with active ZIKV transmission, such as 
Puerto Rico. Symptomatic pregnant women should have serum and urine 
tested for the presence of ZIKV RNA by rRT-PCR within two weeks of 
symptom onset. Symptomatic pregnant women tested more than two weeks 
after symptom onset and symptomatic women with negative rRT-PCR test 
results should have serologic testing. CDC recommends serologic testing 
of asymptomatic pregnant women at the initiation of prenatal care and 
again during their second and third trimesters as a part of routine 
care; CDC recommends serum and urine rRT-PCR testing after a positive 
or equivocal serological test result to identify persistent RNA and to 
provide a definitive diagnosis. For infants, CDC currently recommends 
ZIKV testing within two days of life for infants born to women with 
laboratory evidence of possible ZIKV and for infants who have abnormal 
clinical or neuroimaging findings suggestive of congenital ZIKV 
syndrome, regardless of maternal ZIKV test results.
    Limited data suggest that ZIKV RNA might be detectable for a much 
longer period in whole blood than in serum or urine; however, 
researchers have primarily seen these results in non-pregnant adults. 
While ZIKV RNA typically only persists in serum for 3-7 days and is 
thought to clear by 10 days, animal data suggest that pregnancy may be 
associated with prolonged detection of ZIKV RNA. An ongoing study of 
pregnant Rhesus macaques found ZIKV RNA in plasma up to 36 and 71 days 
post first trimester infection, and up to 9 and 36 days after third 
trimester infection. Preliminary results from a first trimester-
infected macaque with detectable virus for 71 days indicate that the 
fetus had no clinical signs of microcephaly but fetal necropsy showed 
ZIKV RNA in the axillary lymph nodes, bone marrow, and optic nerve 
(although not in brain tissue). By comparison, two non-pregnant female 
animals no longer had detectable RNA at 17 days post-infection.
    Limited data from human studies also suggest that pregnant women 
have persistent detection of ZIKV RNA in serum. Symptomatic women had 
detectable virus at 17, 23, 44, and 46 days post symptom onset and one 
asymptomatic woman was still rRT-PCR positive 53 days after returning 
from travel. In one symptomatic pregnant woman with prolonged detection 
of ZIKV RNA, the pregnancy ended as a fetal loss and researchers found 
ZIKV RNA in the fetus. Findings from these case reports and series led 
to the hypothesis that persistent detection of RNA in pregnant women 
may be a marker of fetal infection and thus, potentially a marker of 
adverse fetal outcomes including microcephaly and brain abnormalities. 
However, researchers need more data including whether the detection of 
IgM influences the risk of adverse infant outcomes.
    Researchers know even less about persistent detection of ZIKV RNA 
and IgM in infants. One case study reported persistent ZIKV RNA 
detection in a male child born in Brazil at 40 weeks gestation with 
brain abnormalities. Fifty-four days after birth, the infant's serum, 
saliva, and urine all tested positive for ZIKV RNA; the detection of 
ZIKV RNA continued in the infant's serum on day 67 and had cleared by 
day 216. The infant exhibited no obvious illness or evidence of being 
immunocompromised when examined on day 54. However, he demonstrated 
neuropsychomotor developmental delay, with global hypertonia and 
spastic hemiplegia, by 6 months of age. The duration of IgM detection 
in infants is also important to determine the window of diagnostic 
utility of this test for infants not tested at birth.
    Due to the short window of time during which ZIKV RNA is typically 
detectable in serum, expanding rRT-PCR testing to asymptomatic women 
and women outside of the two-week window may provide more information 
than serologic testing alone. This is because positive serology does 
not allow for definitive diagnosis of infection as false positives and 
cross-reactivity with other flaviviruses complicates diagnosis. The 
rRT-PCR, per standard, requires a blood sample obtained by venipuncture 
for ZIKV RNA detection. However, recent unpublished data from the 
Institute Pasteur have demonstrated that in 57% of patients there was a 
significantly longer ZIKV RNA detection in capillary blood samples 
collected from Zika positive pregnant women tested with rRT-PCR than in 
venous samples. Similar findings from a study conducted during the 
Ebola outbreak showed that capillary blood samples can be used as an 
alternative to venous blood samples, and may be a more accurate method 
for monitoring viral load.
    If prolonged ZIKV RNA persistence is, in fact, a marker of fetal 
infection and

[[Page 51841]]

adverse outcomes, determining the prevalence of prolonged detection of 
ZIKV RNA is essential for clinical management of pregnant women with 
ZIKV infection and public health planning for the outbreak. Further, 
understanding persistent ZIKV RNA in congenitally-exposed infants is 
also important for clinical management of infants and identifying 
adverse outcomes that may present several months after birth. Finally, 
understanding the relationship between persistence and viral load may 
inform clinical guidance and management of pregnant women and their 
families.
    In this study, we will estimate the prevalence and duration of 
persistent ZIKV RNA in pregnant women and congenitally exposed infants. 
We will also evaluate the diagnostic utility of PCR testing for ZIKV 
RNA on capillary blood and determine if persistent ZIKV RNA in pregnant 
women is associated with adverse outcomes or infection in infants. 
Finally, we will examine the association of different factors that are 
associated with persistent detection of ZIKV RNA in pregnant women and 
congenitally exposed infants.
    This study will provide critical data in establishing guidance for 
testing in pregnant women and congenitally exposed infants. There are 
no costs to the respondents other than their time. The total estimated 
annual burden hours are 785.

                                        Estimated Annualized Burden Hours
----------------------------------------------------------------------------------------------------------------
                                                                                                      Average
                                                                     Number of       Number of      burden per
          Type of respondents                   Form name           respondents    responses per   response  (in
                                                                                    respondent        hours)
----------------------------------------------------------------------------------------------------------------
ZIKV positive Pregnant women..........  Pregnant women screening             150               1            2/60
                                         form.
ZIKV positive Pregnant women..........  Pregnant women                       150               1            8/60
                                         enrollment
                                         questionnaire.
ZIKV positive Pregnant women..........  Pregnant women symptom               150               1            8/60
                                         questionnaire.
ZIKV positive Pregnant women..........  Pregnant women follow-up             150              30            8/60
                                         questionnaire.
ZIKV positive Pregnant women..........  Infant enrollment and                150               1            8/60
                                         delivery questionnaire.
ZIKV positive Pregnant women..........  Infant follow-up                     150               6            8/60
                                         questionnaire.
----------------------------------------------------------------------------------------------------------------


Leroy A. Richardson,
Chief, Information Collection Review Office, Office of Scientific 
Integrity, Office of the Associate Director for Science, Office of the 
Director, Centers for Disease Control and Prevention.
[FR Doc. 2017-24314 Filed 11-7-17; 8:45 am]
 BILLING CODE 4163-18-P