Infectious Disease

Targeted echocardiographic screening for latent RHD in Northern Uganda

What’s Known
Echocardiograms use the echoes of sound waves to create “movies” of the beating heart, its valves, and other structures. While rheumatic heart disease (RHD) was prevalent in the United States as late as the 1900s, improved housing conditions and the availability of powerful medicines like antibiotics and penicillin have lowered its incidence to 0.04 to 0.06 cases per 1,000 U.S. children. In regions where streptococcal infections flourish, RHD remains a scourge. Using echocardiographic screening to identify latent RHD— which is apparent on echocardiography before the child has symptoms that can be spotted by clinicians—has the potential to reduce the disease’s global burden.

What’s New
Optimal implementation must account for whom to target, when, in which settings, and how often to screen. The team led by Children’s National Health System researchers and clinicians conducted the first family screening study in Northern Uganda to assess the utility of echocardiographic screening of first-degree relatives of children with latent RHD. They used existing school-based screening data to identify potential participants and invited all first-degree relatives older than 5 years for echocardiography screening. The study recruited 60 RHD-positive schoolchildren and matched them with 67 RHD-negative kids of similar age and gender. Some 1,122 family members were then screened. Children with any RHD were 4.5 times as likely to have a sibling with definite RHD, a risk that increased to 5.6 times if researchers looked solely at index cases with definite RHD. The team, led by Andrea Beaton, MD, a cardiologist at Children’s National, also found that mothers had a 9.3 percent rate of latent RHD—a high rate that was independent of whether their child was RHD-positive.

Questions for Future Research
Q: Many children living in RHD-endemic areas, exposed to the same environmental conditions as RHD-positive kids, are able to fend off disease. Are protective genes to credit for their resilience?
Q: What are the best approaches to train nurses and community workers in how to use lower-cost, handheld echocardiograms to facilitate large-scale screening in countries where healthcare resources are constrained?

Source:  Targeted Echocardiographic Screening for Latent Rheumatic Heart Disease in Northern Uganda: Evaluating Familial Risk Following Identification of an Index Case.” T. Aliku, C. Sable, A. Scheel, A. Tompsett, P. Lwabi, E. Okello, R. McCarter, M. Summar, and A. Beaton. Published online by PLoS June 13, 2016.

Congenital Zika Viral Infection Linked to Significant Fetal Brain Abnormalities

mosquito

What’s Known
According to the Centers for Disease Control and Prevention, Zika viral transmission is occurring extensively throughout Central and South America. Like other mosquito-borne viruses, Zika virus can be passed by pregnant women to developing fetuses. Unlike these other viruses, Zika has been implicated in a growing number of cases of Brazilian infants born with microcephaly, a condition characterized by undersized heads and severe brain damage. The precise strategy that the Zika virus uses to elude the immune system and the reason why fetal brain cells are particularly vulnerable remain unknown.

What’s New
A 33-year-old Finnish woman was 11 weeks pregnant when she and her husband traveled on vacation to Mexico, Guatemala, and Belize in late November 2015. The pair was bitten by mosquitoes during their trip, particularly in Guatemala. One day after returning to their Washington, DC home, the woman got sick, experiencing eye pain, muscle pain, a mild fever, and a rash. A series of early ultrasounds showed no sign of microcephaly or brain calcifications. A fetal ultrasound at the 19th week and a fetal MRI at the 20th week, however, revealed severe brain damage.

The brain of the 21-week-old aborted fetus weighed only 30 grams. Zika RNA, viral particles, and infectious virus were detected, and Zika virus isolated from the fetal brain remained infectious when tested. The concentration of virus was highest in the fetal brain, umbilical cord, and placenta. The mother remained infected with Zika virus at 21 weeks, some 10 weeks after her initial infection.

Questions for Future Research

  • Could serial measurements and blood tests more accurately detect and, ultimately, predict fetal abnormalities following Zika virus infection?
  • Why does the Zika virus replicate with ease within the womb?
  • At which stage of pregnancy are fetuses most vulnerable?
  • Which specific brain cells does Zika target?

Source:Zika Virus Infection with Prolonged Maternal Viremia and Fetal Brain Abnormalities.” R.W. Driggers, C.Y. Ho, E.M. Korhonen, S. Kuivanen, A.J. Jääskeläinen, T. Smura, D.A. Hill, R. DeBiasi, G. Vezina, J. Timofeev, F.J. Rodriguez, L. Levanov, J. Razak, P. Iyengar, A. Hennenfent, R. Kennedy, R. Lanciotti, A. du Plessis, and O. Vapalahti. The New England Journal of Medicine. June 2, 2016.

Drs. DeBiasi and du Plessis

Suspected domestic zika virus infection in Florida underscores the importance of ongoing vigilance

Drs. DeBiasi and du Plessis

Federal health officials continue to investigate the first possible cases of domestic Zika virus transmission in Florida. In light of the growing number of Zika infections, the vast majority of which have been associated with foreign travel, vigilance for additional cases is warranted – particularly as summer heat intensifies and mosquito populations grow. The Centers for Disease Control and Prevention (CDC) now advises that all pregnant women in the continental United States and U.S. territories be evaluated for Zika infection at each prenatal care visit. The CDC also recognizes that Zika-exposed infants will require long-term, multidisciplinary care.

In mid-May, Children’s National Health System Fetal Medicine Institute and Division of Pediatric Infectious Disease announced the formation of a Congenital Zika Virus Program to serve as a dedicated resource for referring clinicians and for pregnant women to receive counseling and science-driven answers about the impact of the Zika virus on pregnancies and newborns. Children’s clinicians have consulted on 30 pregnancies or births with potential Zika virus exposure and/or infection. As of Aug. 31, eight were Zika-positive or probable. One of the pregnancies was the subject of an article published by The New England Journal of Medicine.

”While we’re hopeful there are few local cases, the Congenital Zika Virus Program has been developing emergency response plans in collaboration with local departments of health to prepare for any eventuality,” says Roberta DeBiasi, MD, MS, Chief of the Division of Infectious Disease and Congenital Zika Virus Program co-leader.

Over the years, Children’s National has invested in equipment and highly trained personnel, building world-class expertise in infectious diseases, pediatric neurology, pediatric cardiology, genetics, neurodevelopment, and other specialties. Children’s clinicians are recognized leaders in next-generation imaging techniques, such as fetal MRI, which detects more subtle and earlier indications of impaired brain growth. A variety of divisions work together to offer multidisciplinary support and coordinated care to infants born with special needs. As the nation braces for the possible expansion of Zika virus infection to other states, Children’s National is facilitating the multi-step process of testing blood, urine, and tissue with state health departments, helping to ensure timely and precise information. Children’s National specialists guide Zika-affected pregnancies through the fetal period and are able to oversee and coordinate the care of Zika-affected infants after delivery. Care and clinical support is provided by a multidisciplinary team of pediatric neurologists, ophthalmologists, audiologists, physical and occupational therapists, infectious disease experts, and neurodevelopmental physicians.

The Children’s National multidisciplinary team includes:

  • Adre du Plessis, M.B.Ch.B., Director of the Fetal Medicine Institute, Chief of the Fetal and Transitional Medicine Division, and Congenital Zika Virus Program co-leader;
  • Roberta DeBiasi, M.D., M.S., Chief of the Division of Infectious Disease and Congenital Zika Virus Program co-leader;
  • Cara Biddle, M.D., M.P.H., Medical Director, Children’s Health Center, and a bilingual expert on complex care;
  • Dorothy Bulas, M.D., Radiologist in the Division of Diagnostic Imaging and Radiology;
  • Taeun Chang, M.D., Director, Neonatal Neurology Program in the Division of Neurophysiology, Epilepsy and Critical Care Neurology;
  • Sarah Mulkey, M.D., Ph.D., Fetal-Neonatal Neurologist, Fetal Medicine Institute;
  • Lindsay Pesacreta, M.S., F.N.P.-B.C., Board-Certified Family Nurse Practitioner; and
  • Gilbert Vezina, M.D., attending Radiologist in the Division of Diagnostic Imaging and Radiology and Director of the Neuroradiology Program.

Related Resources: Research at a Glance | Guidelines for Referring Clinicians
[Updated Sept. 13, 2016]

New program provides science-driven answers about zika virus’s impact on pregnancies

Drs. DeBiasi and du Plessis

Each week, as temperatures rise, the likelihood increases that the United States will experience domestic Zika virus transmission. Indeed, such domestic Zika transmission already is occurring in Puerto Rico and the U.S. Virgin Islands. The Children’s National Health System Fetal Medicine Institute and Division of Pediatric Infectious Disease announced the formation of a Congenital Zika Virus Program to serve as a dedicated resource for referring clinicians and for pregnant women to receive counseling and science-driven answers about the impact of the Zika virus on their pregnancies.

Over years, Children’s National has invested in equipment and highly trained personnel, building expertise in infectious diseases, pediatric neurology, pediatric cardiology, genetics, neurodevelopment, and other specialties. Children’s clinicians are recognized as national leaders in next-generation imaging techniques, such as fetal MRI, and a variety of divisions work together to offer multidisciplinary support and coordinated care to infants born with special needs. As the nation prepares for the Zika virus, Children’s National is facilitating the multi-step process of blood testing, helping to ensure timely and precise information. Children’s National specialists are able to guide Zika-affected pregnancies through the fetal period and can oversee the care of Zika-affected infants after delivery. Care and clinical support is provided by a multidisciplinary team of pediatric neurologists, physical therapists, infectious disease experts, and neurodevelopmental physicians.