Pediatric Infectious disease2015

Bandith S.Department of Pediatric

Mahosot hospital

A 4 month-old boy with fever and seizure

Chief complaint: Uncontrolled seizure, referred from a provincial hospital.Present illness:• Previously has been healthy• 7 days PTA had high grade fever• Brought to District hospital and treated as a bacterial

pharyngitis (unknown ATB)without improvement• A day later , developed right ptosis and generalized

tonic seizure

Present illness:

• Then was referred to provincial hospital on 23/9/2015 and diagnosed Menigo-encephalitis, treated with Ceftriaxone and diazepam.

• 2 day after admission still has fever, generalized non pitting edema and not able to control seizure, watery stool, no vomiting ,no rash or petechia

• Therefore, was referred to MSH on Sep 28 2015

Past history of illness

• 5th child of family• Normal delivery • No vaccination• Only breast feeding• Grandmother had PTB in 2009 with complete

treatment• The others are healthy

Physical examination

• T 38.50c , RR 45, SpO2 99%, BW 10kg, • AVPU (on Diazepam) • generalize tonic seizure and generalize none pitting edema• No bulging fontanel, right ptosis• Abdomen: no HSM ,lower abdominal mass 10x 8 cm • Lung : clear, no adventitious sound• Heart : Normal S1,S2, no murmur• Skin: Normal, no rash, no petechia• Ext: warm, CRT<2s,no cyanosis• No BCG scar

• What is your initial diagnosis?• What are you going to do next?

Initial management

• Control seizure with Midazolam and phenobarbital

• Continue Ceftriaxone• Fundus examination but not success• Fontanel U/S not found ICP• Laboratory investigations

InvestigationBiochemical test

Creatinine 37.551 mmol/l

BUN 19.2mg/dl

ElectrolyteK 4.39

Na 134.2

Cl 99.3

Ca 10.3

CBCWBC 28.17Lym 33.9%MON 7.3%Gran 58.8%RBC 3.79HGB 9.6 g/dlHct 27.15%MCV 72MCH 35.3RDWc 14.1%PLT 783

CRP Positive

ESR 21

Morphoogy of RBC

Microcytic 1+

Hypochromic 1+

Target cell Few

Reticulocyte count 0.4%

InvestigationCSF

Gram stain NegativeCulture NegativePCR Positive for N. meningitidis

CSF

Opened pressure 25

Color Turbid

WBC 670

Polymorphs 88.81

Lymphocytes 11.19

Eosinophil 0

Other 0

Red cells tube 1 0

Red cells tube 3 0

CFS Albumin 55

CSF glucose 65

Blood glucose 77

Final diagnosis

• Meningococcal meningitis with iron deficiency

Meningococcemia• Highest rate of colonization(up to 40%) in

adolescents and young adults; colonization rare in children < 10 years

• Respiratory route of transmission• Peak of disease in children under 2 year of age and

smaller peak in adolescence• Risk of disease increased by smoking ;

overcrowding; prior viral RTI; • Serogroup distribution varies over time and with

geographical ocation: serogroup A in Africa and Asia

Clinical features

• Four presentations:1. Bacteremia without sepsis2. Meningococcemia without meningitis3. Meningitis with or without meningococcemia4. Meningo-encephalitis• Other clinical manifestations: Myocardial

dysfunction , arthritis ,pericarditis ,pneumonia conjunctivitis ,cranial nerve dysfunction

Diagnosis

• Microbiology diagnosis usually is made by Gram stain of CSF and/or culture of blood or CSF

• PCR of blood or CSF can yield higher rate of identification(especially with receipt oa ATB prior sampling)

Treatment

• Early and appropriate antibiotic treatment markedly improves the outcomes.

• Ceftriaxone as empiric therapy for suspected cases

• If the organism is proven to be penicillin susceptible, can be switched to penicillin,

• Also reasonable to continue Ceftriaxone given the excellent efficacy, convenient dosing, and affordability of these agents.

Duration of therapy

• Should be 5-7 days• Some studies suggest one dose of an

appropriate antibiotic may be sufficient• Response to therapy usually is rapid

Chemoprophylaxis Regimens for contacts of patients of Meningococcal disease

Antibiotic DoseRifampin 10 mg/kg/dose(Max. dose 600 mg) PO

every 12 hours for 4 doses ( for infants< 1 month of age,5mg/kg/dose)

Ceftriaxone Single injection of 125 mg IM for children < 15 years; 250 mg IM for children > 15 years and adults

Ciprofloxacin Single dose 20 mg/kg PO(max.500mg)Azithromycin Single dose 10 mg/kg/dose(Max. 500mg)

Case progression

• Seizure stopped • Fully conscious a day later• Stopped anticonvulsive drugs• Continued Ceftriaxone for 14 day• Discharged without sequelae• No prophylaxis needed for staffs

Vaccine prevention

• Monovalent serogroup C meningococcal conjugate vaccine

• Quadrivalent meningococcal A,C,Y,W135 conjugate vaccine

References

• Michael A.Neisseria meningitidis.In Mendell, Douglas, and Benett,s Principles and practice of infectious disease 7th ed.

• Allan R Tunkel et al.IDSA practical guideline for the management of bacterial meningitis CID 2004

• American Academiy of Pediatrics. Meningicoccal infection,In Redbook 2012

Neonatal sepsis Early-onset Late-onset Late-onset (< 7 days (> 7 -89days) (3 – 6 months)

ໄລຍະເວລາທີ່ເກີດ 24 ຊມທີ່�າອິ�ດ(0-6ວ�ນ) 3-4 ອິາທີ່�ດ(7-89 ວ�ນ) 3-6 ເດ ອິນ

ອິ!ບັ�ດກີານ ເດ�ກີເກີດກີອິນກີ�ານ#ດ ເດ�ກີເກີດຖ້%ວນເດ ອິນ ເດ�ກີເກີດກີອິນກີ�ານ#ດ< 32 ອິາທີ່�ດ ຫຼື( ພູ*ມຄຸ້!%ມກີ�ນບັ#ກີຜ່ອິງມາແຕ່ເກີດ

ພູາວະແຊກີຊ%ອິນ ໃນໄລຍະຖ້ ພູາ,ເກີດ

ພູ#ບັເລ %ອິຍ(70%) ບັ�ຄຸ້ອິຍພູ#ບັ/ບັ�ພູ#ບັ ບັ�ຄຸ້ອິຍພູ#ບັ/ບັ�ພູ#ບັ

ແຫຼື(ງຂອິງເຊ %ອິ ຊອິງຄຸ້ອິດ ຊອິງຄຸ້ອິດ ຫຼື( ສຳ�າພູ�ດກີ�ບັສຳ�ງແວດລ%ອິມທີ່ປົ#ນເປົ %ອິນເຊ %ອິ

ສຳ�າພູ�ດກີ�ບັສຳ�ງແວດລ%ອິມທີ່ປົ#ນເປົ %ອິນເຊ %ອິ

ເຊ %ອິທີ່ເປົ�ນສຳາເຫຼືດ

GBS(40%) ສຳວນໃຫຼືຍເປົ�ນtype III(80% meningitis),E.coli(70%)Enteric gram negative bacilli, S.viridans,Enterococci, L.monocytogens

MRCoNS(4%),S.aureus(8%),Candida spp.(6%),E.coli(5%) Enteric gram negative bacilli,(2%),GBS(2% ສຳວນໃຫຼືຍເປົ�ນ type III 75-80%)

MRCoNS, S.aureus,Candida spp.,E.coli,Enteric gram negative bacilli GBS

Neonatal sepsis Early-onset Late-onset Late-onset (< 7 days (> 7 -89days) (3 – 6 months)

Clinical manifestation

Pneumonia 35-55%,septicemia 25-55%,hypotension 25%,meningitis 5-10%

Meningitis 30-40%,septicemia 45-55%,arthritis 5-10%,skin infection or lymphadenitis 1-2 %

Common: Septicemia without source infectionUncommon: Septicemia with source infection

Antibiotics First choice: Ampicilline+GentamycinAlternative:Ampicilline +Cefotaxim

Ampicilline +Gentamycine or Cefotaxime

Cefotaxime+ Amikacin or Gentamycine

Duration of treatment

Septicemia 10-14 daysArthritis or osteomyelitis 3-4 weeks

Meningitis 14 days( E. coli, Enteric gram-negative bacilli 21 days)

Mortality rate

Preterm 5-25%Term 1-3%

2% <5%

References• American Academy of Pediatrics. Group B Streptococcal

infections. In: Pickering LK, Baker CJ, Kimberlin DW, Long SS, editors. 2015 Red Book: Report of the Committee on Infectious Diseases. 30th ed. Elk Grove Village, IL: American Academy of Pediatrics 2015;745-50.

• Morven SE. Postnatal bacterial infections. In: Richard JM, Avroy AF, Michele CW, editors. Fanaroff and Martin’s Neonatal-Perinatal Medicine: Disease of the Fetus and Infant. 10th ed. Saunders Elsevier 2015:793-806.

• Pia SP and Carol JB. Group B Streptococcal infection. In: Ralph DF, James DC, Gail JD, editors. Feigin and Cherry’s Textbook of Pediatric Infectious Diseases, 7th ed. Saunders Elsevier 2014:1239-58.

J Trop Pediatr. 2014 Feb;60(1):10-6. doi: 10.1093/tropej/fmt064. Epub 2013 Jul 31.Epidemiology of bacteremia in young hospitalized infants in Vientiane, Laos, 2000-2011.Anderson M1, Luangxay K, Sisouk K, Vorlasan L, Soumphonphakdy B, Sengmouang V, Chansamouth V, Phommasone K, Van Dyke R, Chong E, Dance DA, Phetsouvanh R, Newton PN.

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Diphtheria outbreak in Laos

What is diphtheria?

Diphtheria is an acute, toxin-mediated disease

Toxin production occurs when a patient is infected with a toxin-producing strain of Corynebacterium diphtheriae (aerobic gram + bacillus)

There are 4 biotypes (gravis, intermedius, mitis, and belfanti), all of which may produce the toxin

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Total 222 casesClinical 188(2 deaths)Confirm 34( 144 specimens , 4 deaths) Total 122 cases

Clinical 113( no deaths)Confirm 09( 30 specimens ,2 deaths)

Total 10 casesClinical 08 no deaths)Confirm 02( 10 specimens ,( 01 deaths)

Total 14 caseClinical 12Death :1Confirm 01Lab. : pending

Total 01 caseClinical 01Lab. : negative

Total 192 casesClinical 162Confirm 21( 82 specimens, 2deaths)

Total: 561 Confirmed:

67 (273 specimen)

Pending: 15 Total death: 9

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Seroprevalence of diphtheria and tetanus antibodies according to the number of DTP vaccine

doses (data from children who providedvaccination records).

Vaccines listed

Children with yellow cards N = 66 (%)

Children with antidiphtheria antibodiesN(%)

Children with anti-tetanus antibodiesN(%)

DTP-HepB (1)

9 (13.6) 3 (33.3) 3 (33.3)

DTP-HepB (1+2)

2 (3.0) 2 (100) 2 (100)

DTP- HepB (1+2+3)

55 (83.3) 46 (83.6) 51 (92.7)

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2007 2008 2009 2010 2011 2012 20130%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Coverage of Penta3 and MR < 1, 2007-2013

Penta3MR

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Transmission

• Usually spread person-to-person via droplets • Prolonged, close contact is usually required for

infection– Close contacts: sleeping in the same house,

kissing/sexual contacts, health-care workers who have given mouth-to-mouth resuscitation

Pathogenesis

The diphtheria toxin inhibits cellular protein synthesis and causes local tissue destruction/ pseudomembrane formation in the pharynx

The toxin is also absorbed into the blood stream where it may cause systemic effects:• myocarditis• neuritis • thrombocytopenia• proteinuria Patient's infected with non-toxin producing strains

may have mild-moderate pharyngitis but do not develop a pseudomembrane or have systemic effects

Clinical Presentation

Incubation: range 1-10 days (avg 2-5)

Classified based on site affected

May involve many sites (anterior nasal,

pharyngeal, tonsillar, laryngeal,

cutaneous, ocular, genital)

ComplicationsMost complications are secondary to the toxin

(including death)

Most frequent complications: myocarditis and neuritis

Myocarditis: may present as cardiac arrhythmias (either early or weeks after initial presentation)-->may lead to heart failure. If myocarditis occurs early, it is often fatal.

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Complications

Demyelinating peripheral neuritis: usually effects the motor nerves. Typically resolves completely.

• Paralysis of soft palate: usually during 3rd week of illness

• Paralysis of eye muscles, limbs, and diaphragm: may occur after the 5th week

• Secondary pneumonia/respiratory failure may result from diaphragmatic paralysis

Death

• Fatality rate: 5-10%• Higher fatal rates among children under 5 yrs

and adults greater than 40 yrs old

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Diagnosis

Clinical manifestations

Swab and culture pharyngeal areas.

Toxin detection

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Differential diagnosis

• Infectious mononucleosis• Group A streptococcal tonsillopharyngitis• Epiglottitis• Viral pharyngitis• Vincent’s angina• Oral candidiasis

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Treatment

• Should begin immediately based on clinical presentation– Antitoxin– Antibiotics – Supportive care

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Antibiotics

• Three major benefits: –Kills the organism –Prevents further toxin from being formed,

slows the spread of local infection, –Reduces transmission.

• The disease is usually not contagious after 48 hours of antibiotics. Two consecutive negative cultures should be obtained after completion of therapy.

Antibiotics

• Erythromycin (500 mg four times daily for 14 days) or

• Roxithromycine 150 mg every 12 hours for adult and 2-2.5 mg /kg divided every 12 hours for 14 days

Anti- toxin

• Patients should be first tested for sensitivity (the anti-toxin is made from horse serum and may cause severe anaphylaxis).

• The anti-toxin will neutralize unbound toxin and prevent disease progression.

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Anti- toxin

• The dose of antitoxin depends upon the site and severity of infection:

• Pharyngeal/laryngeal disease:20,000-400.000 units

• Nasopharyngeal disease: 400,000-600,000 units

• > 3 days of illness or bull neck:80,000-120,000 units

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Prevention

For close contacts (household contacts):• Diphtheria booster• 7-10 days of antibiotics (erythromycin or

penicillin)

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Thank you !