Pediatric Infections in Iowa A potpourri of midwestern pathogens
Amaran Moodley MD Pediatric Infectious Diseases Blank Childrens Hospital
Objectives
• Discuss the epidemiology, presentation and management of pediatric infections that are not well recognized but known to occur in Iowa. This will include tick-borne, mosquito-borne and travel related infections
Case #1
23 month old boy presents with fever and limp
HPI: • Fever 3 weeks ago for 3-4 days followed by limp and refusal to straighten left leg or bear weight • Seen on multiple occasions by PCP and diagnosed with viral illness and "muscle sprain“ • No trauma to left leg, no penetrating injury • No antibiotics received
1 Case #1
PMH: • No previous hospitalizations • No history of severe, invasive infections like meningitis, pneumonia or musculoskeletal infections • No previous surgeries except for ear tubes in December 2016
Immunizations: UTD Exposures: no previous MRSA infections
Case #1
Exam: • General: awake, sitting up in bed, no distress, no pallor, non toxic • HEENT: conjunctiva normal, normal oropharynx • Chest: no respiratory distress • CVS: normal rate and rythym, no murmur • Abdomen: soft, non tender, no organomegaly • CNS: grossly non-focal exam • Skin: no rashes • Msk: left thigh and calf non tender. Left knee with swelling and decreased ROM. No other joint or extremity swelling or redness • Lymph: no significant cervical, axillary or inguinal nodes
Case #1
Labs: CRP: 1.2 -> 2.3 ESR: 23 WBC: 16, 000 hgb: 12.0 plts: 354,000 (N:60, L: 26, M13)
Blood culture: no growth
Imaging: contrast MRI
2 Case #1 - Contrast MRI of left extremity
Case #1
Joint fluid: • WBC: 23,000 (N:75%) • Culture negative (aerobic, anaerobic, fungal, AFB) • PCR sent to Arkansas Children’s Hospital
POSITIVE FOR Kingella kingae
Course: • Treated with IV Cefazolin for 2 weeks then switched to oral Cephalexin for 4 weeks with complete recovery
Case #1 – Kingella kingae
Pathogens causing acute bacterial osteomyelitis and septic arthritis in children • Staph Aureus (MSSA and MRSA) • Streptococcus pyogenes (GAS) • Streptococcus pneumoniae • Kingella kingae • Gram negatives like Salmonella species
3 Case #1 – Kingella kingae
Kingella kingae • Colonizes posterior pharynx of children • Invasive infection may follow URI or stomatitis • Children between 6-48 months of age affected • Joints: knee, hip, ankle. Bones: femur, tibia • Subacute presentation more common • Does not readily grow in culture, molecular studies helpful • Susceptible to most beta lactam antibiotics
Case #2
A female infant is born at 32 weeks gestation and is noticed to be small for age
Birth and maternal history • Born by C-section to a 21 year old woman • IUGR diagnosed prenatally by serial US • 1st trimester screens negative (HIV, Hep B, syphilis) • Mother had URI ~8 weeks prior to delivery, otherwise healthy • No travel history during pregnancy
Case #2
Physical exam findings: • Microcephaly (<1%) • Hepatosplenomegaly with mild jaundice • No petechial rash, hypotonia, cataract or heart murmur
Labs • WBC: 14,000 Hgb: 14.0 Plts: 67,000 • AST: 330 U/L ALT: 290 U/L Bilirubin: 5.7 m/dL
• Urine PCR: CMV positive
• Beta Herpes Virus that establishes latency • Asymptomatic shedding of virus in saliva, urine, genital secretions, breast milk, blood • Three clinical syndromes: – Immune compromised hosts (multi-organ) – Congenital CMV infection ~ 1% of US newborns – Mononucleosis syndrome ~ 10% healthy children & adults
Epidemiology of CMV infection
• Common infection – 50.4% of 6-49y infected* – 56% females – 45% males
– 6-11 yrs (37.5%) – 12-19 yrs (42.7%) – 20-29 yrs (49.5%) – 30-39 yrs (56.7%) – 40-49 yrs (58%) – > 80 yrs (90%)
Fig. CMV seroprevalence among US women of reproductive age Bate et al. 2010 CID
Congenital CMV infection
• Most frequent congenital infection (~0.7%) • Trans-placental transmission of CMV from mother to fetus
• Distinct from intrapartum or postnatal infection acquired through infected cervical secretions or breast milk
• Leading cause of non-genetic sensorineural hearing loss
5 Congenital CMV infection
• ~60% of women of reproductive age are seropositive • 1% transmission risk with maternal non-primary CMV
• ~40% of women of reproductive age are seronegative • 1-4% of seronegative women acquire CMV during pregnancy • 30-40% transmission risk with maternal primary CMV
• Risk of symptomatic disease and sequelae highest in 1st trimester infections
Epidemiology of congenital CMV infection
Live born infants CMV seronegative Live born infants Live Live births with congenital women with with congenital Race births per among CMV from primary infection CMV from mothers year CMV + mothers with non- during pregnancy with primary (1988- women primary infection (1-2% risk) infection 1994) (1.4%) (30-40% risk) 1,108,775 White 2,409,000 15523 16150 5218 (46%)
452,360 Black 582,000 6333 6652 2149 (78%)
575,923 Mexican 701,000 8062 4184 1355 (82%)
Total 3,692,000 29,918 (77%) 8,722 (23%)
Wang et al. 2011 CID
Congenital CMV infection
• 30,000-40,000 infants born each year in the US with congenital CMV infection
• 10-15% of CMV infected newborns are symptomatic 50-60% develop sequelae
• 85-90% of CMV infected newborns have subclinical or asymptomatic infection 10-15% develop sequelae
6 Public health impact of congenital CMV in Iowa
USA (2014) Iowa (2015) Number of live births 3,988,076 39,375 Rate of congenital CMV 7/1000 Rate of Down syndrome 1.4/1000 Number of infected infants 27,916 275 Symptomatic at birth (10%) 2,792 27 Fatal disease (5%) 139 1 Permanent sequelae (60%) 1,675 16 Asymptomatic at birth (90%) 25,124 247 Permanent sequelae (10-15%) 2,512-3,769 25-37 Total number with sequelae 4,187-5,444 41-53
Source: IDPH and CDC
Sequelae of congenital CMV infection
• Sensorineural hearing loss 15% • Bilateral Hearing loss 9% • IQ < 70 10% • Retinitis 6% • Cerebral palsy 5% • Seizures 5%
Fig. Estimated annual number of US children with long term sequelae caused by various diseases
Canon M.J. 2009 J Clin Virol
Symptomatic congenital infection
• Small for gestational age 50% • Hepatosplenomegaly 60% • Petechial or purpuric rash 76% • Neurologic: 68% – Hypotonia 27% – Poor suck 19% – Seizures 7% – Microcephaly 53% • Jaundice 67% • Hepatitis (ALT >80 units/L) 83% • Thrombocytopenia – <100 x 103 77% – <50 x 103 53%
Boppana et al. 1992 PIDJ
7 Congenital CMV infection
Fig. CMV infected infant with hepatosplenomegaly and petechial rash. Source: AAP
Congenital CMV: CNS disease
Figures: Periventricular calcifications in infants with early, late 2nd trimester and late perinatal CMV infection
Fink et al. 2010 Radiographics
Hearing Sequelae of Congenital CMV infection
• Leading cause of non-genetic hearing loss in childhood • CMV-related sensorineural hearing loss (SNHL) may be present at birth but is frequently delayed in onset • Severity of hearing loss is variable – Unilateral high frequency loss to profound bilateral loss
• Progression and fluctuation of hearing loss may occur in children with CMV-related SNHL
8 Diagnosis of congenital CMV infection
• Prenatal diagnosis: + maternal serology and amniocentesis • Urine CMV shell vial culture or PCR (gold standard)
• Saliva CMV PCR: sensitivity (97-100%), specificity (100%)* • Dried blood spot: sensitivity (95-100%), specificity (98-99%)** • Serology not recommended: CMV IgM and IgG
• Other evaluations: – LFTs, bilirubin, CBCd, serum creatinine – Neuroimaging (US or MRI) – Hearing assessment (BAER/ABR) – Eye exam
*Leruez-Ville et al. 2011 CID ** Boppana et al. 2011 NEJM
Treatment of Congenital CMV: CASG 112
Randomized Placebo Controlled Blinded Investigation of 6 weeks versus 6 months of Oral Valganciclovir in Infants with Symptomatic Congenital CMV 6 weeks Valganciclovir 6 months treatment
Worse or remained 27% 43% abnormal 57% Improved or remained 73% normal
Figs. Change in hearing between birth and 12 months
Treatment of Congenital CMV: CASG 112
6 weeks versus 6 months of Oral Valganciclovir in Symptomatic Congenital CMV
Toxicity: • No significant difference in degree of neutropenia between 2 treatment groups • Less neutropenia with Valganciclovir than Ganciclovir • Blood CMV viral load did not correlate with outcomes
9 Treatment of Congenital CMV: CASG 112
Conclusions
• Antiviral therapy in neonates with symptomatic congenital CMV disease modestly improves audiologic and developmental outcomes
• Duration of treatment is 6 months
• No controlled data exist to support treatment of babies with asymptomatic congenital CMV
Follow up of Congenital CMV after NICU discharge
• Monthly ID clinic follow up • Monthly CBCd, CMP • Periodic Hearing and developmental assessments • Ophthalmology follow up • Congenital CMV family support groups
Iowa Congenital CMV Bill
10 Prevention of congenital CMV infection
Case #3
PC: 15 year old boy with fever for 8 days
HPC: Illness began with fever, vomiting, nausea and mild cough. Then developed central abdominal pain
Fever for 3-4 days, followed by no fever for 2 days, then fever again for 3 days. Well in between fever episodes
No headache, red eyes, rhinorrhea, rash, joint pain or swelling
Case #3
PMH: Healthy, no previous hospitalizations, fully immunized Meds: Used to take Minocycline for acne for 1 year but stopped 1 month ago
Exposure history: No sick contacts at home or school No travel outside USA or mid-western US No unpasteurized dairy ingestion No TB contacts Positive for recent mosquito bites. No known tick bites No farm animal exposure, no ingestion of well water
11 Case #3
Rocky Mountain National Park
Case #3
Case #3
Physical exam: • BP:101/70, HR:63 RR: 20, Temp: 103.3 F • Gen: No distress, non toxic. No pallor, cyanosis or jaundice • Normal oropharynx • Heart: RRR, normal S1 and S2 without murmurs • Neck: supple, no masses or adenopathy • Abdomen: soft, non-tender, no organo-megaly • CNS: Alert, oriented, grossly non focal exam • Skin: no rash
12 Case #3
Labs: WBC – 3.7, Hgb – 14.4, Plts – 66 (N60%, L23%) CRP: 18.7, ESR: 55 Peripheral smear – no blasts, normocytic anemia Resp multiplex PCR filmarray – negative
ALT: 25, AST 22, ALP: 104, Cr: 0.98, Tbil: 1.5 EBV VCA IgG neg, EBV VCA IgM positive, Anti EBNA negative CMV IgG, IgM neg
CXR normal
Case #3
Labs: Blood sent to CDC Arbovirus lab, vector-borne diseases in Fort Collins, Colorado for testing for Colorado tick fever virus
Diagnosis: Tick borne Relapsing Fever
Source: CDC
Case #3 Borrelia hermsii
Tick prefers coniferous forests at altitudes of 1500 to 8000 feet where it feeds on tree squirrels and chipmunks
Most TBRF cases occur in the summer months when people are vacationing and sleeping in rodent-infested cabins
Fires started to warm a cabin are sufficient to activate ticks resting in the walls and woodwork
The two other U.S. tick species that transmit TBRF, O. parkeri and O. turicata, are generally found at lower altitudes in the Southwest, where they inhabit caves and the burrows of ground squirrels, prairie dogs, and burrowing owls
13 Case #3
Course: Treated with Doxycycline for 10 days with full recovery Observed in ER for Jarisch Herxheimer reaction Colorado Public health department investigation
EBV VCA IgM can be falsely positive Empiric treatment with Doxycycline in a sick child with risk factors for a tick borne infection may be reasonable
Case #4
PC: 16 yr male with painful rash on scalp and forehead for 5 days
HPC: No fever or systemic symptoms Treated for impetigo with oral Bactrim without improvement
PMH: No history of eczema, psoriasis or tinea capitis, no trauma Milks cows with his hands without gloves
Case #4
14 Case #4
Case #4
Skin culture: normal skin flora
Skin HSV PCR: positive for herpes simplex virus 1
Case #4 Herpes gladiatorum
• Cutaneous HSV infection through direct physical contact • Treated with oral Valacyclovir 20 mg/kg/dose (max 1 gram) TID for 7 days
• Cover lesions to prevent further spread • Limit wrestling during outbreaks unless lesions can be covered
15 Case #4
Differential diagnosis: • Impetigo (Staph, Strep) • Varicella zoster • Tinea capitis with kerion • Trichophyton verrucosum (barn itch)
Case #5
16 month ld boy with a non-healing wound on his shoulder for 6 weeks
HPC: • No fever or systemic symptoms • Normal appetite and energy levels • Has not responded to several courses of antibiotics
PMH: • Moved to US 2 months ago from Mexico
Case #5
16 Case #5 BCG vaccine abscess
BCG vaccine adverse effects Local reactions: • formation of a bluish-red pustule accompanied by pain, swelling and erythema within 2-3 weeks after vaccination • pustule ulcerates after 6 weeks and forms a 5mm lesion that typically heals by 3 months with a permanent scar • abscess and regional lymphadenitis with draining sinus tracts and fistulae may occur in 1-2% Other complications: • Osteomyelitis and disseminated disease
Case #6
16 y old girl with chronic cough with positive TST at 28 mm within 24 hours of placement
HPC: No fever, no weight or appetite loss or systemic symptoms No exercise intolerance or shortness of breath No response to several courses of antibiotics and steroids
PMH: History of latent TB treated 2 years ago with 9 months of INH
Case #5
17 Case #5 – TST hypersensitivity reaction
TST allergic reactions: • Systemic allergic reactions (including urticaria, angioedema, dyspnea, and anaphylaxis) are rarely reported (1 to 3 per million) • Early local reactions within 24 hours with absence of induration at 48 to 72 hours is considered an allergic reaction
TB testing in children
• Tuberculin skin test (<4y) • Interferon gamma release assays (IGRA) – Quantiferon Gold – Results in 24-48 hours – Single visit – Not affected by placement error – Not affected by subjective interpretation – Not affected by BCG or most NTM infection
Iowa Refugee Arrivals by Year 900
801 800
692 700
598 600
500 Refugees 431
400 359 331
Number Number of 300
200
100
0 FY10 FY11 FY12 FY13 FY14 FY15 Year
Source: Office of Refugee Resettlement, U.S. Department of Health & Human Services
18 Iowa Refugee Arrivals by Country of Birth, 2015
Afghanistan 2% Burundi Sudan 2% Eritrea 3% Other 3% 7% Ethiopia 3% Iraq Burma/Myanmar 4% 38% Nepal 6%
Malaysia 6% Bhutan Dem. Rep. Congo 7% Thailand 10% 9%
*Countries with >1% shown *Country of birth does not always equal nationality
Iowa Refugee Arrivals by Initial County of Resettlement, 2015
Iowa Refugee Arrivals by Age, 2015 250 231
200
167 160 160
150 Refugees
100 Number Number of 65
50 29 14 6 0 0-10 11-20 21-30 31-40 41-50 51-60 61-70 70+ Age in Years
19 Infectious Diseases in Child Refugees
• Bacteria – Tuberculosis – Salmonella typhi (typhoid fever) – Congenital syphilis • Viruses – HIV – Hepatitis B – Hepatitis C • Parasites – Giardia – Cryptosporidium – Malaria – Hookworm – Schistosomiasis
Role of the Refugee Clinic Health Screen
• General health assessment including complete physical exam
• Diagnose transmissible and non-transmissible infections
• Pre-emptive treatment of malaria and parasites
• Screen for anemia, lead toxicity, thyroid dysfunction
• Initiate catch up immunizations
• Screen for mental health problems
Health Screening Labs
• CBCd • CMP • TB (Quantiferon or TST) • Syphilis antibody • Lead level • TSH • HIV, GC, Chlamydia • Hepatitis A, B, C • Stool O+P
20 Blank Childrens Hospital Refugee Clinic
324 child refugees as of April 13 2017 • HIV positive – 0 • Congenital syphilis – 0 • Hepatitis C – 1 • Hepatitis B – 4 • Latent TB 32 (10%) • Active TB – 0 • Other: Giardia, Schistosomiasis, tinea corporis, dental caries
Case #7
Case #7
21 Case #7
Case #7
Case #7
22