Viral Infections Comprehensive Review

HERPES SIMPLEX VIRUS Viral infections comprehensive review DR. MA. ANNA BANEZ PEDIATRIC INFECTIOUS DISEASES

2 SEROTYPES HSV 1 – mouth and skin above the waist HSV 2 – genital organs

2 TYPES of INFECTION 1. Primary Infection • mostly subclinical • otherwise,local superficial lesions w/                      varying degrees of systemic reaction • w/ serious systemic reaction w/o lesions in  NB and severely malnourished • circulating antibodies and CMI response in  non‐fatal cases                                         

2 TYPES of INFECTION 2. RECURRENT INFECTION • reactivation of latent infection in an immune  host w/ circulating antibodies • follows non‐specific stimuli: cold, uv light,  menstruation, fever, emotional stress • asymptomatic or localized lesions w/o  systemic reactions

3 Distinct Times of Acquisition

Epidemiology • risk of transmission from pregnant women to  fetus/newborn 44% after primary infection 3% after recurrence • neonatal disease more commonly acquired from  maternal GUT during parturition • HSV2 account >/ 75% neonatal infections • majority of women w/ HSV infection are  asymptomatic • genital lesions present at parturition /=12y : 1000‐1200mg/day q8 x3‐5 days

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PREVENTION Stat CS delivery for a woman with ruptured membranes and  active genital lesions at term For exposed asymptomatic infants who were born vaginally  to mothers with active genital lesions (10, recurrent or  unknown status)

• •

– – –

•

CYTOMEGALOVIRUS

Obtain cultures:eyes,mouth,urine,stool Empiric acyclovir therapy after cultures are done Acyclovir therapy after culture is POSITIVE

Since infection rate for infants whose mothers have active  recurrent genital herpes infection is /1 yr old

•

Alternative drugs: – Foscarnet – Cidofovir – Fomivirsen

• 90% with congenital infection demonstrate CNS & hearing defects in later years 30% - death rate of symptomatic congenital cytomegalovirus infection • infants with subclinical infection 5-10% - sensorineural hearing loss 3-5% - chorioretinitis less frequent:developmental abnormalities, microcephaly,neurologic defects

Epstein Barr Virus

Care of exposed persons • Hand hygiene, especially after changing diapers • Pregnant personnel must be educated about the risk of acquisition and practice standard precautions.

• Causes 80 to 95% of mononucleosis syndrome • Epidemiology: Source: Man – sole source Mode of transmission: 1. oral- salivary spread 2. close intimate contact - kissing 3. blood transfusion

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Epstein Barr Virus

Clinical Manifestations

• Incidence: predominantly in children and young adults • Period of communicability: Indeterminate; may be months after infection • Incubation Period: 30 to 50 day • Majority of primary infections in infants and young children are silent

Clinical Manifestations

Infectious Mononucleosis: – Prodromal period: 2‐5  days malaise, fatigue  with or without fever – Triad:  lymphadenopathy splenomegaly exudative pharyngitis

Occasional Signs and Symptoms  Erythematous and maculopapular rash; 80% w/   

– Signs and symptoms: Fever – usually rises to 39?C Adenopathy‐90%;usually in the anterior ,  posterior cervical , & submandibular nodes;suggestive if epitrochlear Splenomegaly – 50%  Hepatomegaly – 10% Tonsillopharyngitis‐ Palatal petechiae

‘ampicillin rash’ if treated w/ ampicillin or  amoxicillin  Enanthem  Edema of eyelids  Jaundice  Guillain‐ Barre syndrome  Myelitis  Bell’s palsy  Acute cerebellar ataxia

Diagnosis • Other distinct disorders associated to EBV: – Lymphoproliferative disorders  – Burkitt’s lymphoma – Nasopharyngeal carcinoma – Undifferentiated B‐cell lymphoma of the CNS

Absolute lymphocytosis : total leukocytes  > 5,000/mm3  ‐ atypical lymphocytes >10% of  total leukocytes Serologic Tests: 1. Paul‐Bunnel heterophil test and slide agglutination  reaction (Monospot test) ‐ negative in children 90% of cases 2. Respiratory – common colds, pharyngitis,  herpangina, stomatitis, pneumonia,      pleurodynia 3. GIT – vomiting, diarrhea, abdominal pain, hepatitis 4. Skin – macular, maculopapular, vesicular,  petechial rashes 5. CNS – encephalitis and paralysis

Hand, foot and mouth disease Acute hemorrhagic conjunctivitis Encephalitis and poliolike paralysis Aseptic meningitis with petechial exanthem Myopericarditis

Coxsackievirus A16 Enterovirus 71 Coxsackievirus A24 Enterovirus 70 Enterovirus 71 Echovirus 9 Coxsackievirus B1- B5

Clinical Syndromes

Clinical Syndromes

– Noteworthy virus/ disease associations Non specific febrile illness with rash Herpangina Pleurodynia or Bornholm’s disease

Echovirus 9

Coxsackieviruses B3 and B5

Orchitis and epidydimitis

Coxsackievirus B5, B2 and B4

Myositis Polymyositis

Coxsackievirus A2 Coxsackievirus A & Echovirus 18

Neonatal infections

Coxsackievirus B1- B5

Herpangina ‐ anorexia, dysphagia,  salivation, sore throat, vesicles and ulcers on anterior  pillars (most    common site),  soft palate, uvula, tonsils,  pharyngeal wall, posterior  buccal surfaces

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Clinical Syndromes

Hand, Foot and Mouth Syndrome

– Pleurodynia or Bornholm’s Disease ‐ sudden onset of fever and muscular pain  (chest or abdomen), spasmodic and  excruciatingly severe with profuse  sweating ‐ usually lasts 1‐2 days ‐ may be biphasic

Clinical Syndromes

Clinical Syndromes

Non‐specific febrile illness with rash  Echovirus 9  rubelliform or petechial rash  rash & fever usually at the same time  mimics meningoccocemia

Neonatal infections • asymptomatic to sepsis‐like illness,fatal encephalitis & myocarditis w/in 2 wks of         life • transplacental transmission immediately  prior to delivery 

Diagnosis

Treatment

– Viral isolation:  stool,throat,csf,blood,biopsy; less specific in stool alone since viral  shedding x6‐ 12 wks in asypmtomatic patients – PCR – for enterovirus RNA in CSF – Rise in neutralizing antibody titer from an  acute and convalescent specimen

– No specific therapy – Immune Globulin Intravenous (IgIV) ‐ may be beneficial for chronic  enteroviral meningoencephalitis

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Poliovirus Infections

Poliovirus Infections (Poliomyelitis)

• Epidemiology WHO Polio Global Eradication Program  ‐ launched in 1988 with the following  strategies: 1. Routine immunization 2. National Immunization Days (NID) 3. Active Acute Flaccid Paralysis (AFP)  Surveillance 4. “Mopping Up”: extra immunization  rounds when a wild virus is found

Poliovirus Infections

Poliovirus Infections • Epidemiology Based on active WHO AFP Surveillance ‐ last case of wild poliovirus in America: in Peru (1991), and by 1994‐ declared polio‐ free ‐ In Philippines‐ last case of wild poliovirus: in Cebu (1993);last case in WPR 1997 ‐ Philippines and the rest of the Western Pacific     Region  were certified polio‐ free by 2000

• Epidemiology Remaining Polio‐ endemic countries : 1. India 2. Pakistan 3. Afghanistan 4. Nigeria

Poliovirus Infections • Epidemiology 2001 – type 1 circulating vaccine‐ derived  poliovirus ( c VDPV) was isolated from 3  children in 3 places:  Cagayan de Oro Cavite Laguna

Poliovirus Infections • Circulating vaccine‐ derived poliovirus ( c VDPV)

‐ dependent of sabin virus ‐ accumulation of small spot mutations over a  period of >/= 6 months resulting in  virologically different strain ‐ recovers properties of wild virus like  neurovirulence, recombination and  transmissibility ‐ ocurs only where there is no wild virus ‐ with accumulation of susceptibles

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Poliovirus Infections

Poliovirus Infections

• Source ‐ feces and possibly, oropharyngeal secretions  of man • Mode of Transmission: ‐ fecal to oral ‐ possibly oral to oral (respiratory) routes

• Period of Communicability ‐ Patients are potentially contagious for as  long as fecal excretion persists ‐ OPV recipient: virus persists in throat for 1‐2  weeks and excreted in feces for several weeks • Incubation period: 3‐6 days – abortive poliomyelitis 7‐21 days – paralysis in paralytic poliomyelitis

Clinical Forms

Clinical Forms

Inapparent illness – account for 90- 95% of cases Abortive Cases (4‐8%) Non specific febrile  illness Malaise Nausea/ vomiting Headache Sorethroat Constipation Diffuse abdominal pain

Non paralytic or aseptic  Paralytic (0.1‐ 2%) meningitis (1‐5%) Signs & symptoms of  Signs & symptoms of  minor illness non‐ paralytic illness + + Nuchal/ spinal skeletal   Weakness of >1 muscle rigidity Or cranial (spinal,  + bulbar, bulbospinal or  encephalitic) Increase/ decrease in  superficial/ or deep  tendon reflexes Flacid paralysis w/o  sensory loss (hallmark) +  Absent DTRs

Post‐polio syndrome • Occurs 30‐40 years later as muscle pain, & exacerbation of weakness or new weakness  or paralysis among 30‐40% of • Patients w/ childhood poliomyelitis

Difference between virus in VAPP & VDPV

Clinical Forms Vaccine‐Associated Paralytic Poliomyelitis • VAPP • a paralytic disease in OPV recipient /close  contact • incidence: 1 case in >/3 million doses  distributed

Features Structure

Virus circulation in a  community Occurrence

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Virus in VAPP

VDPV

Identical to sabin vaccine virus

>3% different from  sabin vaccine virus  (mutant)

None

Circulates or is  transmissible

Wherever OPV is  used

Occurs only where  there is no wild  virus and there is an  accumulation of  susceptibles

Complications

Diagnosis

• GIT: gastric dilatation, hemorrhage, melena,  paralytic ileus • Hypertension, occ pulmonary edema • Skeletal decalcification 2º to immobilization  leading to hypercalcemia, hypercalciuria,  nephrocalcinosis

Treatment: • No specific treatment;symptomatic &  supportive Control Measures: • OPV:vaccine of choice for global eradication in  areas w/ VDPV,developing countries where  inadequate sanitation necessitates optimal  mucosal barrier • IPV:areas not at risk to wild type, immunodeficient patients

• Clinical • Laboratory 1. viral isolation from 2 stool specimen taken 24‐ 48 hours  apart within 14 days of onset of paralysis 2. serology: acute & convalescent sera 3. with CNS involvement: CSF examination ‐ pleocytosis with early PMN predominance followed by  shift to mononuclears ‐ protein: normal or slightly elevated ‐ normal glucose 4. DNA sequence analysis – distinguish wild virus from vaccine  virus 

Influenza ‐Types A,B and C ‐Epidemic disease: Type A and B ‐ Influenza A subclassified by 2 surface antigens: Hemagglutinin (HA) & Neuraminidase (NA) ; examples: H1N1, H1N2, & H3N2 ‐Antigenic drift: minor variations in influenza B or A;  seasonal epidemics ‐Antigenic shift: major variations in HA or NA; only w/  influenza A; pandemics

Influenza

Influenza Diagnosis:

‐predominantly respiratory ‐abrupt onset of coryza,conjunctivitis.pharyngitis, dry cough ‐localize as URI, croup, bronchiolitis or pneumonia ‐commonly associated w/ high fever(2‐4 days), myalgia,  malaise & headache

viral culture, immunofluorescent, or rapid diagnostic tests for antigens, direct fluorescent antibody(DFA) and   indirect  immunofluorescent antibody(IFA) staining for  Influenza A and B antigens in NP specimens

‐close contacts often have similar illness ‐indistinguishable from RSV, parainfluenza viruses &  adenovirus

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Antiviral Drugs for Influenza Drug

Virus

Administration

Treatment Indications

Prophylaxis Indications

Prophylaxis Adverse Effects Central nervous system, anxiety, gastrointestinal

Amantadine

A

Oral

=1 y of age

=1 y of age

Rimantadine

A

Oral

=13 y of age

=1 y of age

Central nervous system, anxiety, gastrointestinal

A&B

Inhalation

=7 y of age

=5 y of age

Bronchospasm

A&B

Oral

=1 y of age

=1 y of age

Nausea, vomiting

Zanamivir Oseltamivir

Influenza Vaccine

* Influenza Vaccine Recommended in: • Children 6mos‐5 yo • High‐risk children:chronic heart  /lung/metabolic diseases,renal disorders  &hemoglobinopathies • Children on long  term aspirin tx

* 2009 Flu pandemic

Children 6mos‐8yo: 2 doses, 4 weeks apart then  yearly Preferably  given Feb to June Healthy children>5 yo who want to be protected  against influenza can be given the  vaccine

• Global outbreak of a novel influenza AH1N1 identified  April 2009 • Infects and transmissible between humans • A re‐assortment of 4 known strains of influenzae A virus  subtype H1N1: 1 endemin in humans, 1 endemic in birds  and 2 endemic in pigs • WHO data as of July 6,2009 : 94,512 cases, 429 deaths • Symptoms similar to other forms of influenzae: fever,  cough, sorethroat, headache, myalgia, chills diarrhea ,  vomiting

Flu vaccine for 2009, Southern strain

Avian influenza (H5N1) ‐mainly in birds; deadly ‐doesn’t usually infect people but human infections have resulted from direct or close contact with      H5N1 infected poultry

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Parainfluenza viruses ‐members of paramyxoviridae family ‐types 1‐4 ‐account for 50% of hospitalizations for croup, 15% of  bronchiolitis and pneumonia ‐not associated with fever; systemic complaints rare ‐diagnosis is based only clinical and epidemiologic criteria ‐”Steeple sign” or progressive narrowing of the subglottic region  on xray : characteristic of parainfluenza virus respiratory tract infection

Respiratory Syncitial Virus ‐association of RSV bronchiolitis early in life and  reactive airway disease remains poorly understoood;  underlying predisposition to reactive airway disease  rather than a direct consequence of RSV infection ‐almost all children infected once by 2 yrs old ;  reinfection common 

Respiratory Syncitial Virus ‐major cause of bronchiolitis and pneumonia in children  half of patients;with diarrhea. pharyngitis pneumonia: types 3,7,& 21 cause severe type w/ 10%    mortality; residual airway damage: bronchiectasis;  bronchiolitis obliterans, rarely pulmonary fibrosis pertussis‐like syndrome

Pharyngoconjunctival fever‐type 3; high fever x  4‐5 days, pharyngitis, non‐purulent  conjunctivitis, preauricular & cervical  lymphadenopathies & rhinitis + headache,  malaise & weakness

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Adenovirus

Adenovirus

Other manifestations:

Infections in the Immunocompromised:

Follicular conjunctivitis Myocarditis GIT Infections‐ diarrhea, intussuception Hemorrhagic cystitis‐ suden onset bacteriologically sterile hematuria,dysuria, frequency & urgency x 1‐2  weeks; types 11 & 21 Reye Syndrome and Reye‐like Syndrome

Chronic meningoencephailtis in B‐cell deficiency Prolonged diarrhea in T‐cell deficiency

Diagnosis: immunohistology in biopsy ,viral culture  or PCR, serology Treatment: posssible role of Cidofivir

Viral Gastroenteritis

DIARLEX ROTA-ADENO

Rotavirus ‐single most important cause of severe  dehydration diarrhea in early childhood Astrovirus ‐2nd most important agent of viral diarrhea in  young children Enteric adenovirus Caliciviruses ‐ most common cause of gastroenteritis outbreaks  on older children & adults

• The latex reagent is composed of either anti‐ rotavirus antibodies(rabbit) or anti‐adenovirus  antibodies (rabbit) bound to red latex particle • When a fecal extract containing rotavirus or  adenovirus particles(antigen) is mixed with  the test latex reagent, an antigen‐antibody  reaction occurs resulting in visible  agglutination (red color)of the latex particles.

Rotavirus Vaccine Monovalent human RV: 2‐dose series 1st dose: 6 wks old, 4 weeks apart  2nd dose: not later than 24 weeks Pentavalent human‐bovine reassortant RV:  1st dose:6‐12 weeks old, 4‐10 wk intervals final dose :not later than 32 weeks  May be given with OPV or 2 weeks apart With a potentially higher risk of intussuception if 1st dose given beyond recommended age

THE END • "Lord, thank you for everything, I can’t name them all but it all comes from You, everyday I am very grateful for everything!"

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RABIES • Primarily a disease of animals • Dogs account for >90% of reported human  cases • 6‐10% ‐ cats, cattle, horse, sheep, bats,  exotic  pets • Small rodents, birds & reptiles are NOT  KNOWN to serve as reservoir of infections

RABIES & HIV

Rabies

• Variation: 

• Transmission: bites of rabid animals or by  licking of the mucosa or open wounds • Period of communicability:  – Dogs & cats‐ 3‐5days before the onset of  symptoms until the entire course of illness – Person to person‐ NOT DOCUMENTED

Rabies

– Severity of the bite – Site of bite in relation to nerve supply  – Size of inoculum, protection offered by clothing & other  factors – Age and immune status of host

• Incidence: WHO:  11th major killer diseases 60,000 deaths worldwide

• Incubation period: 1day to 5 years (8 WEEKS – average)

>30,000 die yearly in Asia about 10M exposed annually

DOH: 2006(219 cases) 2007(281 cases)

Rabies • Infected patients go through 4 stages – Incubation period • • • •

Usually 20‐90 days >95% will present with s/sx within 6 months Virus remains at the site of the bite The only time when vaccination is effective

– Prodrome • 2‐10 days • Virus reaches the spinal cord • 1st rabies specific sx‐pain or itching or paresthesia at  bite site

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Rabies

Rabies

Acute neurologic phase‐2‐7days

• Diagnosis

2 TYPES: 1. Encephalitic or furious rabies ‐80% – – –

2.

Hyperactive episodes(combative,bizarre behavior,apprehensive) Hydrophobia( agitation,cringing,due to painful contractions of  laryngeal muscles upon drinking)  aerophobia

Paralytic or dumb rabies‐20% – – –

Paralysis of bitten area  respiratory paralysis Often missed;hydrophobia & aerophobia absent Rabies suspected if with paralysis or encephalitis

– CBC‐ wbc 20,000‐30,000/mm3 with  polymorphonucleosis – CSF‐ mononuclear cells may increase 100/mm3,  protein is slightly elevated – PREMORTEM DIAGNOSIS • Fluorescent microscopy of skin biopsies from nape • Isolation of virus • Detection of antibody‐serum & CSF in unvaccinated  persons • Detection of viral nucleic acid (PCR) in infected tissues

Coma ‐ 4‐10 days ‐complications: myocarditis, diabetes insipidus,SIADH ‐outcome: death due to respiratory paralysis

Rabies

Rabies

• Diagnosis:

• PROGNOSIS: fatal • TREATMENT: intensive symptomatic or  supportive care • ISOLATION: strict throughout the illness;  caution against contamination of open wound  or mucous membrane with patient’s saliva

– POSTMORTEM DIAGNOSIS‐ fluorescent  microscopy of brain and salivary glands – ANIMAL BRAIN  • Fluorescent antibody stain of brain tissue • Positive for negri bodies

Therapeutic Management of Patients Exposed to Rabies • General principles of post‐exposure treament ‐minimize amount of virus at the site of inoculation ‐develop a high titer of neutralizing antibody early

Local wound care • Immediate vigorous washing & flushing w/ soap & water • Apply alcohol or Povidone Iodine • Suturing avoided  or delayed as it may inoculate virus deeper. If  unavoidable, suturing done loosely. RIG must be instilled deep into  the wound before suturing • Do not apply ointment, cream or occlusive dressing to the bite site • Anti‐tetanus prophylaxis should be initiated or boosted as indicated • Antibiotics for all category III cat bites, category III dog bites that  are on the hand or  deep,multiple & extensive ‐amoxycillin as propjylaxis ‐cloxacillin or amoxyclav if infected • Antibiotics for category I & II only if wound is infected

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Vaccination

Vaccination

CARE OF EXPOSED PERSONS: • ACTIVE IMMUNIZATION 

• STANDARD INTRAMUSCULAR SCHEDULE

– Purified vero cell rabies vaccine 0.5ml/vial – Purified chick embryo cell vaccine 1ml/vial • PASSIVE IMMUNIZATION ‐ for all Category III exposures + anti‐rabies vaccine ‐RIG should be inflitrated around and into the wound as   anatomicaly feasible even if lesion has begun to heal, the       rest IM ‐may be given until 7days after the 1st dose – Human  rabies immune globulin (PREFERRED) 20IU/K   – Hyper immune equine rabies immune globulin(Fab2):

Day of immunization

PVRV

Day 0 Day 3 Day 7 Day 14 Day 28

0.5ml 0.5ml 0.5ml 0.5ml 0.5ml

PDEV/ PCECV 1ml 1ml 1ml 1ml 1ml

Site of injection One deltoid One deltoid One deltoid One deltoid One deltoid

40IU/K IM, needs skin testing

SUMMARY SCHEDULE OF ACTIVE IMMUNIZATION AGAINST RABIES

Postexposure Rabies Prophylaxis

Category I

Category I

• Feeding/touching an animal • Licking of intact skin (with reliable history and  thorough physical examination) • Exposure to patient with S/Sx of rabies by  sharing of eating or drinking utensils • Casual contact to patient with signs and  symptoms of rabies

• Wash exposed skin immediately with soap  and water • No vaccine or RIG needed • May opt to give pre‐exposure prophylaxis

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Category II

Category II

• Nibbling of uncovered skin • Minor scratches/abrasions without bleeding* • Licks on broken skin

• Start vaccine immediately • Complete vaccination regimen until day 28/30 if: – Animal is rabid, killed, had died or unavailable for 14‐day  observation or examination – Animal under observation died within 14 days and was  FAT‐positive or no FAT testing was done or had signs of  rabies

* Includes wounds that are induced to bleed OLD: Complete vaccination regimen until day 90

Category II

Category III

• Complete vaccination regimen until day 7 if: – Animal is alive and remains healthy after 14‐day  observation period – Animal under observation died within 14 days, was FAT‐ negative and without any signs of rabies

• Single or multiple transdermal bites or scratches – Puncture wounds, lacerations, avulsions, deep abrasions

• Contamination of mucous membrane with saliva (i.e.  licks) • Handling of infected carcass or ingestion of raw  infected meat • All Category II exposures on head and neck area

OLD: Complete vaccination regimen until day 30

Category III

Category III

• Exposure to a rabies patient* through bites,  contamination of mucous membranes with  saliva/fluids through splattering, through  mouth‐to mouth resuscitation, licks of eyes,  lips, vulva, sexual activity, exchanging kisses  on the mouth or other direct mucous  membrane contact with saliva * does not include sharing of food/ drink/ utensils and casual contact with rabid patient

• Start vaccine and RIG immediately • Complete vaccination regimen until day 28/30 if: – Animal is rabid, killed, had died or unavailable for 14‐day  observation or examination – Animal under observation died within 14 days and was  FAT‐positive or no FAT testing was done or had signs of  rabies

OLD: Complete vaccination regimen until day 90

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Category III

Passive Immunization

• Complete vaccination regimen until day 7 if: – Animal is alive and remains healthy after 14‐day  observation period – Animal under observation died within 14 days,  was FAT‐negative and without any signs of rabies

• Give anti‐tetanus prophylaxis

• to neutralize rapidly the virus locally in the wound  before it reaches the local nerve endings • To provide the immediate availability of neutralizing  Ab at the site of the exposure before it is  physiologically possible for the patient to begin  producing his or her own Ab after vaccination  (usually 7 to 14 days later) • 3 kinds: HRIG, ERIG, Fab2

OLD: Complete vaccination regimen until day 30

Anti-Rabies Act of 2007 • Republic Act No. 9482 • An Act providing for the control and elimination of human  and animal rabies • Signed into law on May 25,2007; IRR signed in March 2008 • Provisions: – – – – – –

National Rabies Prevention and Control Program, Philippines GOAL:  To eliminate human rabies and declare the  Philippines RABIES FREE by 2020

Mass dog registration/vaccination Dog population control Provision of PEP to bite victims Information‐education Responsible pet ownership Provision of free PreP to high risk individuals and children 5 – 14 yrs in  high incidence areas (IR>2.5/M pop)

Pre-exposure Prophylaxis Day 0

Day 7

Regions with IR > 2.5/M pop

Day 21/28

IM dose = 0.5 ml PVRV or 1.0 ml PCECV ID dose = 0.1 ml PVRV, PCECV Into the deltoid muscle or anterolateral thigh in infants

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2007 N=281 5 (7.76/M) 2 (7.37/M) 8 (4.61/M) 3 (4.55/M) 9 (4.42/M) 7 (3.38/M) 12 (3.9/M) 4A (3.2/M) 1 (2.67/M)

2006 N=216 2 (8.65/M) 12 (5.2/M) 5 (4.16/M) 8 (4.16/M) 1 (3.11/M) 3 (2.36/M) 7 (2.92/M) 4A (1.01/M)

Guidelines for subsequent exposure following primary immunization(PreXP :D0,7,28 0r PEP:D0,3,7) ‐no RIG needed ‐any exposure,regardless of severity,after completion of the  primary immunization should be given as follows: 6mos‐3 yrs                   2 boosters on D0 & D3  > 3 years                        repeat full course  of vaccine without  RIG 

Reported modes of Transmission HIV/AIDS registry Jan 1984-Aug 2008

Reported modes of transmission

N=3358

Heterosexual contact Homosexual contact Bisexual contact Blood/blood product Injecting drug use Needle prick injuries Perinatal No exposure reported

1,934 727 303 19 8 3 46 318

HIV • • • •

Broad spectrum of disease Varied clinical course AIDS‐most severe end of the clinical spectrum Target cells – T‐helper CD 4+ lymphocyte – Monocytes – Macrophages – CNS cells with CD4 + receptors

Mother to infant transmission (vertical) • Primary route of transmission • Rate: 12‐30% in US & Europe • Time of transmission – Before delivery • 30‐40%, (+) PCR within 1st week

– Intra‐partum transmission • 60‐70%, no detectable virus before 1 week of age

– Via breast feeding • WHO recommend breastfeeding in developing countries • 14% risk of transmission in women with HIV before pregnancy • 29% risk in women with HIV postnatally

• Mother‐to‐Child Transmission(n=46) ‐25 M,21 F ‐1‐11 yo ‐30 asymptomatic ‐16 AIDS cases,7 deaths ‐last MTCT wasin FEB 2008 In 2007, 8 cases reported 4 –Region IV 3 –Region III 1 – Region I 

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Clinical manifestations • • • •

Vary widely PE at birth may be normal Initial symptoms may be subtle/ non‐specific Symptoms more common in children than adults – – – –

Recurrent bacterial infections Chronic parotid swelling Lymphoproliferative interstitial pneumonitis Early onset of progressive neurologic disorder

Infections       

20%  of  AIDS‐defining  illnesses  recurrent  bacterial  infections  caused by encapsulated organisms(pneumococcus, salmonella) Most  common  serious  infections:  bacteremia,  sepsis,  pneumonia Opportunistic infections with severe depression of CD4 count PCP  pneumonia:  most  common  opportunistic  infection  children; peak: 3‐6 months;44‐47%  mortality Tuberculosis‐higher  prevalence  of  TB  &  HIV  co‐infection  in  developing countries Oral candidiasis‐most common fungal infection in HIV infected  patients Viral infections with Herpes viruses pose a significant problem

• GI • CNS – occurs in 50‐90 % of perinatally infected children in developing  countries as progressive encephalopathy, loss of developmental  milestone cognitive deterioration and impaired brain growth.

• RESPIRATORY TRACT – Recurrent otitis media and sinusitis are common – LIP – the most common chronic lower respiratory tract  abnormality; affects 30‐40% of HIV infected children; maybe an  exaggerated response to EBV & HIV, non‐productive cough,  insidious hypoxia, bronchiectasis, pulmonary decompensation,  clubbing

• CARDIOVASCULAR SYSTEM

– Oral candidiasis, gingivitis, parotitis – Most common symptoms: chronic or recurrent  diarrhea with malabsorption, abdominal pain,  dysphagia, failure to thrive, chronic hepatitis – Pathogens: salmonella, campylobacter,MAC, giardia,  cryptosporidium, CMV, HSV, rotavirus, candida

• Renal – uncommon

• Skin – Severe & unresponsive seborrheic dermatitis or  eczema

• Hematologic

– Rhythm disturbances; dilated cardiomyopathy & LVH

– Anemia, leukopenia, thrombocytopenia – Malignant diseases infrequent in children – Common reported neoplasms: NHL, primary CNS  lymphoma, leiomyosarcoma

Diagnosis of HIV Infection

Steps to HIV Testing

• Initial clues to consider possibility of HIV infection: 1. Having multiple sex partners(MSP) 2. Unprotected sex w/a person who has MSP 3. Hx of STI 4. Hx of  IV drug use 5. Unprotected sex w/ an HIV infected person 6. (+) clinical conditions suggestive of HIV infection  not  explaned by other causes 7. Children below 13 years born to HIV infected  mothers

A.Pre‐test Counseling ‐important because of the profound psychosocial  impact of an HIV(+) antibody test ‐assess person’s risk for HIV infection ‐provide adequate & correct info  about HIV  antibody test and HIV/AIDS ‐assess how the person would cope with a (+) test ‐promote behaviors that will prevent transmission

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Steps to HIV Testing

Steps to HIV Testing

B.Request for HIV Ab Test ‐informed CONSENT prior to test ‐request for HIV Ab testing must be  written on the  chart using a code name for the test ‐all hospital personnel with whom the patient may  interact for the conduct of HIV testing should act  professionally and responsibly to ensure  CONFIDENTIALITY of the test

Diagnosis of HIV infection

C.Post‐test Counseling ‐provide intitial emotional support in case of a (+)  HIV antibody test ‐provide adequate medical info about HIV/AIDS ‐identify other medical and social support system ‐re‐emphasize behaviors that will prevent HIV  transmission to other people ‐if (‐), explain the meaning of a (‐) test and re‐ emphasize  prevention

Case definition for HIV infection age 18months (CDC, 1999) • HIV antibody positive by repeatedly reactive  EIA and confirmatory test (western blot or  IFA) • Positive result on any HIV virologic test, HIV  culture, HIV PCR, HIV p24 antigen • Any condition that meets criteria for AIDS

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Clinical Categories for Children with Human Immunodeficiency Virus (HIV) Infection CATEGORY N: NOT SYMPTOMATIC • Children who have no signs or symptoms considered to be the result of  HIV infection or who h we only one of the conditions listed in Category A. CATEGORY A: MILDLY SYMPTOMATIC • Children with two or more of the conditions listed bel )W but none of the  conditions listed in Categories B and C. • Lymphadenopathy (>0.5 cm at more than two sites; bilateral= one site) • Hepatomegaly • Splenomegaly • Dermatitis • Parotitis • Recurrent or persistent upper respiratory infections, sinusitis, or otitis media

CATEGORY B: MODERATELY SYMPTOMATIC

• Children who have symptomatic conditions other than those listed for  Category A or C that are attributed to HIV infection. Examples of conditions  in clinical Category B include but are not limited to: • Anemia (6  months of age • Cardiomyopathy • Cytomegalovirus infection, with onset before 1 month of age • Diarrhea, recurrent or chronic • Hepatitis

CATEGORY B: MODERATELY SYMPTOMATIC • Herpes simplex virus (HSV) stomatitis, recurrent (more than two episodes  within 1 year) • HSV bronchitis, pneumonitis, or esophagitis with onset before 1 month of age • Herpes zoster (shingles) involving at least two distinct episodes or more than  one dermatome • Leiomyosarcoma • Lymphoid interstitial pneumonia (LIP) or pulmonary lymphoid hyperplasia  complex • Nephropathy • Nocardiosis • Persistent fever (lasting >1 month) • Toxoplasmosis, onset before 1 month of age • Varicella, disseminated (complicated chickenpox)

CATEGORY C: SEVERELY SYMPTOMATIC

CATEGORY C: SEVERELY SYMPTOMATIC

Serious bacterial infections, multiple or recurrent (i.e., any combination of at least two cul‐ture‐ confirmed infections within a 2‐year period), of the following types: septicemia, pneumonia,  meningitis, bone or joint infection, or abscess of an internal organ or body cavity (excluding otitis media, superficial skin or mucosal abscesses, and indwelling cathe‐ ter‐related infections) Candidiasis, esophageal or pulmonary (bronchi, trachea, lungs) Coccidioidomycosis, disseminated (at site other than or in addition to lungs or cervical or hilar lymph nodes) Cryptococcosis, extrapulmonary Cryptosporidiosis or isosporiasis with diarrhea persisting >1 month Cytomegalovirus disease with onset of symptoms at age >1 month (at a site other than liver,  spleen, or lymph nodes) Encephalopathy (at least one of the following progressive findings present for at least 2 months in  the absence of a concurrent illness other than HIV infection that could explain the findings): a)  failure to attain or loss of developmental milestones or loss of intellectual ability, verified by  standard developmental scale or neuropsychological tests; b) impaired brain growth or acquired  microcephaly demonstrated by head circumference measure‐ments or brain atrophy  demonstrated by computerized tomography or magnetic resonance imaging (serial imaging is  required for children 1 month; or  bronchitis, pneumonitis, or esophagitis for any duration affecting a child >1 month of age

Histoplasmosis, disseminated (at a site other than or in addition to lungs or cervical or hilar lymph  nodes) Kaposi's sarcoma Lymphoma, primary, in brain Lymphoma, small, noncleaved cell (Burkitt’s), or immunobiastic or large cell lymphoma of B‐ceii or  unknown immunologic phenotype Mycobacterium tuberculosis, disseminated or extrapulmonary Mycobacterium, other species or unidentified species, disseminated (at a site other than or in  addition to lungs, skin, or cervical or hilar lymph nodes) Mycobacterium avium complex or Mycobacterium kansasii, disseminated (at site other than or in  addition to lungs, skin, or cervical or hilar lymph nodes) Pneumocystis carinii pneumonia Progressive multifocal leukoencephalopathy Salmonella (nontyphoid) septicemia, recurrent Toxoplasmosis of the brain with onset at >1 month of age Wasting syndrome in the absence of a concurrent illness other than HIV infection that could  explain the following findings: a) persistent weight loss >10% of baseline OR b) downward crossing  of at least two of the following percentile lines on the weight‐for‐age chart (e.g., 95th, 75th, 50th,  25th, 5th) in a child 21 year of age OR c)