II.1 lecture 17

• human cytomegalovirus HCMV


  Also known as human herpesvirus 5
• CMV remains a well recognized cause of disease in the newborn infant following intrauterine infection (congenital CMV) and in immunosuppressive patients
• CMV


  A double-stranded DNA virus and is a member of the herpesviruses
• Human cytomegalovirus


  A member of the viral family known as herpesviruses, Herpesviridae, or human herpesvirus-5 (HHV-5)
• Like other herpesviruses, after recovery of the initial infection, CMV remains dormant within the host
• Viral reactivation occurs during the compromise of the immune system with immunosuppression
• Transmission of CMV


  • Blood products (transfusions, organ transplantation, intra-uterine)
  • Breastfeeding
  • Viral shedding in close-contact settings
  • Perinatally
  • Sexual transmission
• Primary Infection


  Infection in seronegative patients; may be asymptomatic
• Recurrent Infection


  Reinfection or reactivation of CMV in seropositive patients
• CMV Infection


  Presence of CMV in body fluids (urine, blood) or tissue
• CMV Disease


  CMV infection with associated non-specific signs and symptoms and/or end-organ involvement
• Perinatal infections can be acquired during birth or following ingestion of CMV-containing breast milk
• Almost all cases perinatal infections have not been associated with any clinical manifestations of infection and long-term sequalae
• Congenital Infection


  Can present with symptomatic infections in about 10% of infected newborns, whereas 90% of infected infants will have no clinical manifestations of infection in the newborn period and can be identified only by newborn screening programs
• Congenital CMV (cCMV) may be diagnosed by urine or saliva PCR in the first 21 days of life. After that time it becomes difficult to distinguish congenital infection from postnatal infection
• When based on clinical suspicion alone, 90%of symptomatic cases go undiagnosed at birth
• Preference to the use of urine rather than saliva for CMV PCR because of possible false positives in saliva from CMV shed in breastmilk
• False positives can be reduced by collecting the sample 60 minutes or more after breastmilk consumption
• A positive saliva PCR (cheek swab) result should be confirmed with urine PCR
• Clinical suspicion for cCMV may be raised by a delayed onset or recognition of symptoms, particularly SNHL
• CMV PCR can be performed on a stored residual dried blood spot left over from newborn screening. The sensitivity of this approach is low (30-85%); a negative result cannot definitively rule out cCMV
• A definitive diagnosis of cCMV in an otherwise asymptomatic infant allows for close monitoring of hearing and development, and early intervention should concerns arise
• Differential diagnosis for congenital CMV

  • Congenital rubella
  • Congenital toxoplasmosis
  • Herpes simplex virus
  • Inborn errors of metabolism
  • Connexin 26 mutation
  • Congenital ZIka infection
  • Biliary atresia/obstruction
  • Intrauterine alcohol / substance use
  • Sepsis
• Symptomatic Patients


  • Oral valganciclovir 16 mg/kg PO BID for 6 months
  • Ganciclovir and valacyclovir are also used for HCMV prophylaxis
  • Initiate <1 month of age if possible
  • Check baseline CBC weekly for 6 months, then every other week for a month, then monthly
  • Check baseline LFTs monthly
  • Refer to consult with a paediatric infectious disease
• Asymptomatic Patients


  • HCMV infection in immunocompetent hosts is usually asymptomatic or self-limited, not requiring treatment with antiviral drugs
  • Continue close follow-up and monitoring
• Approximately 15–25% of asymptomatic patients may have neurological sequelae, e.g., SNHL
• A study found that 57% of congenital CMV infants were identified by testing newborns who failed their newborn hearing screen
• Tetanus


  An acute, spastic paralytic illness caused by a neurotoxin produced by Clostridium tetani
• Clostridium tetani


  A motile, gram-positive, spore-forming obligate anaerobe
• Tetanus occurs worldwide and is endemic in many developing countries
• Approximately 57,000 deaths were caused by tetanus globally in 2015. Of these, approximately 20,000 deaths occurred in neonates and 37,000 in older children and adults
• Most non-neonatal cases of tetanus are associated with a traumatic injury, often a penetrating wound inflicted by a dirty object such as a nail, splinter, fragment of glass, or unsterile injection
• Tetanus may also occur in the setting of illicit drug injection, animal bites, abscesses (including dental abscesses), ear and other body piercing, chronic skin ulceration, burns, compound fractures, frostbite, gangrene, etc
• • Jaw cramping
  • Sudden, involuntary muscle spasms — often in the stomach
  • Painful muscle stiffness all over the body
  • Trouble swallowing
  • Seizures (jerking or staring)
  • Headache
  • Fever and sweating
  • Changes in blood pressure and heart rate
• Generalized tetanus


  Occurring in approximately 80% of cases. Patients present with a descending pattern of muscle spasms, first presenting with lockjaw, and risus sardonicus (rigid smile because of sustained contraction of facial musculature)
• Neonatal tetanus


  Generalized form of tetanus that occurs in newborns. Those who are infected, exhibit irritability, poor feeding, facial grimacing, rigidity, and severe spastic contractions triggered by touch
• Localized tetanus


  Limited to the muscles and nerves of the head. Most commonly occurred after head trauma (e.g., skull fracture, head laceration, eye injury, dental procedures, otitis media, etc.). It presents with neck stiffness, dysphagia, trismus, retracted eyelids, deviated gaze, and risus sardonicus
• Cerebral tetanus


  Persistent contraction of muscles at the site of injury that can persist for weeks. This type is uncommonly fatal; however, it can progress to the generalized form of tetanus, which is more life-threatening
• Differential diagnosis for tetanus

  • Localized infections
  • Malignant hyperthermia
  • Stimulant drugs
  • Stiff person syndrome
  • Acute abdomen
  • Serotonin syndrome
  • Dystonic drug effects
  • Black widow spider envenomation
  • Hysteria
• • Laryngospasm (uncontrolled/involuntary tightening of the vocal cords)
  • Fractures (broken bones)
  • Pulmonary