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TEMPLATE DESIGN © Just another TORCH infection? Natan Cramer MD, Sarah Williamson MD, Ashley Bartholomew MD, Wasl Al-Adsani DO University of Arizona Department of Pediatrics, Tucson, AZ Case Presentation Discussion The genus Listeria is a group of motile facultative anaerobic gram positive bacilli, which on culture often resemble diphtheria. The organism is able to grow in low temperatures and therefore can contaminate processed meats and refrigerated dairy products. Human transmission is by the maternal-fetal route in the vast majority of cases. The pathogen becomes internalized by host cells by phagocytosis and then spreads to neighboring cells. Due to the intracellular nature of the organism, immunity is conferred mainly by T-cell activation of monocytes. The mononuclear response often induces a pyogenic meningitis and granulomatous response in multiple seeded organs including the placenta (figure 4). The risk of listeriosis is about 20 fold higher in pregnant women than in nonpregnant healthy adults with about 1/3 of cases diagnosed in pregnant females. Infection typically occurs in the third trimester with the transient bacteremia causing flu-like symptoms as the hallmark of a symptomatic infected pregnant woman. The incidence of perinatal and neonatal listeriosis is about 2-13 per 100,000 live births. Perinatal and neonatal infection represents 30 to 40% of the human caseload. Newborns are at greatest risk for developing severe infection and may present with either early onset or late onset infection. Early onset listeriosis is transmitted transplacentally and diagnosed as sepsis in the first week of life, while late onset usually presents after 6 days of life with meningitis. Early onset disease carries a 25% risk of mortality with 65% of infants born prematurely, whereas late onset disease carries a 15% mortality risk. It may also be associated with granulomatosis infantiseptica, which is a slightly elevated pale rash with a bright erythematous base (figure 4). As in the infant in our case, 50% of early onset infections are preceded by a maternal flu-like illness about 2 to 14 days prior to delivery and the cutaneous lesions often occur on the back and lumbosacral region. Common complications include hydrocephalus and subsequently intellectual disability. Patient Course The patient was able to be extubated on day of life 5 and was stable on room air by the time of discharge from the NICU. She had serial head ultrasounds and only developed mild hydrocephalus with stable head bleeds. She had a brain MRI on day of life 79 that showed a hypoplastic cerebellum, which may be related to her prior bleeds. She passed her ABR hearing screen and was discharged home with family on day of life 94. Congenital Infections With clinical features soon after birth of septicemia, intracranial findings and skin lesions, the presentation of neonatal listeriosis may appear similar to congenital (TORCH) infections such as toxoplasmosis, syphilis, viruses including HIV and CMV, and rubella. Toxoplasmosis: Spread via fecal-oral route. Clinical manifestations include triad of chorioretinitis, hydrocephalus, and intracranial calcifications. Syphilis: Neonates asymptomatic at birth but present about 1-2 months of age with diffuse maculopapular rash and snuffles. HIV: Presents with various opportunistic infections similar to those seen in immunocompromised adults. CMV: The most common congenital infection in the United States. Presents with IUGR, periventricular calcifications, hepatosplenomegaly, prematurity, and skin manifestations such as a diffuse maculopapular rash. Rubella: Characteristic “blueberry muffin” rash, lymphadenopathy, IUGR, and hepatosplenomegaly. Many of these infections in the neonate may present with a septic-like picture in addition to signs of lethargy, poor feeding, and hypotonia. CMV and rubella were initially placed higher on the differential with our patient because they are common intrauterine infections, they have a similar petechial rash, and our patient’s maternal rubella immunity status was equivocal. Summary References Acknowledgements It is important to keep listeriosis on the differential when evaluating newborns for infection because a high index of suspicion is necessary to avoid missing this diagnosis. Listeria infection in neonates is serious although rare and can have devastating consequences if not treated appropriately. It is initially indistinguishable from other causes of sepsis and meningitis, so empiric antibiotics in the first month of life should include a penicillin. Also, consider treating pregnant women who present with fever and flu-like symptoms empirically with a penicillin. We encourage pediatricians to counsel families to avoid unpasteurized dairy and uncooked meats during pregnancy as a primary means of prevention. The main food items to consider for proper storage and consumption include dairy products, meat products, and vegetables. Vegetables should be thoroughly washed, and dairy products should be consumed only if pasteurized. Care should be taken to avoid meat products that are pre-cooked and stored in the refrigerator. Bortolussi R & Mailman TL. “Listeriosis.” In: Remington JS, Klein JO, Wilson CB, eds. Infectious Diseases of the Fetus and Newborn Infants. 7th ed. Philadelphia, PA: Sanders; 2011: Del Pizzo J (2011). “Focus on diagnosis: congenital infections (TORCH).” Pediatr Rev, 32(12): Federman DD & Nabel EG, eds. Infectious Diseases: The clinician’s guide to diagnosis, treatment and prevention. United States: Decker Intellectual Group; Long S, Pickering L, Prober C, eds. Principles and Practice of Pediatric Infectious Disease. Philadelphia, PA: Churchill Livingstone/Elsevier; 2012: Marcdante K & Kliegman RM, eds. Nelson Essential of Pediatrics. 7th ed. Philadelphia, PA: Elsevier Saunders; Okike IO, Lamont RF & Heath PT (2013). “Do we really need to worry about listeria in newborn infants?” Pediatr Infect Dis J. 32(4): Stegmann B & Carey J (2002). “TORCH infections. Toxoplasmosis, other (syphilis, varicella-zoster, parvovirus B19), rubella, cytomegalovirus (CMV), and herpes infections.” Curr Womens Health Rep. 2(4): Baby Girl NJ was born at 28 weeks via breech spontaneous vaginal delivery following preterm labor to a 27 year old G4P2 now 3 mother. Pregnancy was complicated by only one prenatal visit (no labs) as well as a day of fever and a flu-like illness a week prior to delivery. Maternal GBS status was unknown at the time of delivery, and mom received one dose of ampicillin less than 4 hours prior to delivery. Spontaneous rupture of membranes with meconium stained fluid was followed by precipitous delivery. Baby initially demonstrated no respiratory effort and no detectable heart rate. She required positive pressure ventilation after which her heart rate increased to over 100. She was intubated by 10 minutes of life and was transferred to the NICU. Growth parameters were th percentile for gestational age. The baby was noted to have mild pancytopenia, extensive petechiae and bruising (figure 1), and preterm delivery concerning for congenital infection. Maternal prenatal labs were not available at birth, so she was started on ampicillin and gentamicin empirically and received a hepatitis B vaccine and HBIG within 6 hours of life. A blood culture was drawn and urine was sent for CMV (later found to be negative). Head ultrasound ordered within the first few days of life to look for bleeds and/or calcifications as part of TORCH workup had evidence of intraventricular hemorrhage (figure 2). Placental pathology showed evidence of inflammation and fibrosis. Mom's RPR was found to be reactive, although baby's RPR was non-reactive. Mom's confirmatory testing for syphilis was negative, and she was found to be rubella equivocal and HIV negative. Baby’s blood culture grew Listeria monocytogenes after 48 hours (figure 3). Further questioning revealed that mom ate unpasteurized cheeses during pregnancy. Ampicillin was continued as was gentamicin but at synergistic dosing. A repeat blood culture was drawn and negative and a CSF culture did not grow listeria. The baby improved clinically, her pancytopenia and petechiae resolved as well, and she completed a 14 day course of antibiotic therapy. Figure 1 – Petechiae and ecchymoses on lower back of premature neonate. Figure 2 – Head ultrasound showing left grade 4 and right grade 3 intraventricular hemorrhage. Figure 3 – Plate growing Listeria monocytogenes (left) and microscopic evaluation showing gram positive rods (right). We would like to thank Dr. Kareem Shehab for his advice and guidance on this project. Figure 4 – Granulomatosis infantiseptica rash (left) and placenta with multiple abscesses (right) not seen in our patient. Photo credit: Patrick Berche, P é diatrie (1999)
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