PEDIATRIC RETROVIRAL INFECTION DR SREE DEVI PROF .C.K.SASIDHARAN
A 14 year old girl brought with c/o P/C: cough – 2 weeks fever – 2weeks white patches in the mouth – 2 weeksHOPI: Cough : insidious onset productive - yellow colored sputum, blood stained + more in recumbent posture Fever : intermittent high grade no chills or rigorsOral lesions : white in color not associated with pain gradually increasing in nature
PAST HISTORY : Scaly skin lesions over both legs : 3 years Recurrent respiratory infections : 1 ½ years. Similar oral lesions : 1 year. Loose mucoid stools , on & off : 1 year P/H/O febrile seizures was on regular AED`S till 3 years of age.
BIRTH HISTORY : uneventful DIET HISTORY :Loss of appetite - 1 year IMMUNISATION HISTORY : Immunised . FAMILY HISTORY :
O/E : Afebrile, cachexic, Wt: 35 kg Grade III PEM Pallor + Ht : 142cm GradeII stunting Generalised lymphadenopathy + Grade III clubbing + Oral thrush Dystrophic nail changes, Hypopigmented macules over forehead Scaly plaques over both legs S/E: CVS : s1 s2 normal, No murmur RS : B/L coarse crepitations, bronchial breathing right infrascapular region P/A : soft, no hepatosplenomegaly CNS: No focal neurological deficits
Stage 3 Unexplained moderate malnutrition not adequately responding to standard therapy Unexplained persistent diarrhoea (14 days or more ) Unexplained persistent fever (> 37.5oC intermittent or constant, > one month) Persistent oral candidiasis (after first 6-8 weeks of life) Oral hairy leukoplakia Pulmonary TB Severe recurrent bacterial pneumonia Symptomatic lymphoid interstitial pneumonitis Chronic HIV-associated lung disease including bronchiectasis Unexplained anemia (<8g/dl ) Neutropenia (<0.5X 109/L3) or Chronic thrombocytopenia (<50 x 109/L3)
Stage 4 Unexplained severe wasting, stunting or severe malnutrition not responding to standard therapy Pneumocystis pneumonia Recurrent severe bacterial infections (e.g. empyema, pyomyositis, bone or joint infection, meningitis, but excluding pneumonia) Chronic herpes simplex infection; (orolabial or cutaneous of more than one month’s duration or visceral at any site) Extrapulmonary TB Kaposi sarcoma Oesophageal candidiasis (or candidiasis of trachea, bronchi or lungs) Central nervous system toxoplasmosis (after one month of life)
Contd.. HIV encephalopathy Cytomegalovirus infection: meningitis) Disseminated endemic mycosis (extrapulmonary histoplasmosis renitis or CMV infection affecting another organ, with onset at age over 1 month. Extrapulmonary cryptococcosis (including, coccidiomycosis) cryptosporidiosis Chronic isosporiasis Disseminated non-tuberculous mycobacteria infection Cerebral or B cell non-Hodgkin lymphoma Progressive multifocal leukoencephalopathy Symptomatic HIV-associated nephropathy or HIV- associated cardiomyopathy
HIV is difficult to diagnose in infants Routine HIV antibody tests cannot be used Specialised virological tests are necessary Clinical diagnosis requires clinical and close follow up of infant
Common diagnostic testsAntibody tests:HIV rapid testELISAWestern blot These tests detect antibodies that are produced during immune response to HIV. False negative tests may occur when infected individuals do not produce detectable antibodies, such as during early acute phase of infection (window period) Very late stages of infection ( immune suppression)
All infants born to HIV+ mothers will test HIV antibody positive in the first several months of life Maternal HIV antibody (IgG) is transferred across the placenta during pregnancy A positive HIV antibody test in infants <18 months of age will not distinguish whether or not the infant is HIV-infected; rather it shows that: Mother is HIV-infected Infant is at risk for HIV infection (exposed to HIV) If the child is not infected the HIV antibody fades during first 6 - 18 months of life Most uninfected infants test negative by 12 months of age All uninfected infants test negative by 18 months of age
Virological tests: Specialized virologic tests must be used HIV DNA PCR HIV RNA PCR p24 Antigen Viral Culture Two positive virologic tests = HIV infection One positive virologic test = Presumed HIV infection
HIV DNA PCR HIV DNA PCR is a special laboratory test that detects pieces of the viral gene that are incorporated in the human blood cell By comparison, HIV Antibody testing detects the antibody that the body makes in response to the HIV virus Sensitivity of HIV DNA PCR increases with time during the first month of life The infant may have HIV infection but there may not be enough virus in the blood to detect it at birth. It becomes easier to find/detect as the infant gets a little older
MANAGEMENT OF<6 MONTHS OLD INFANTS BORN TO HIV POSITIVE MOTHER ADVISORY 1: Start cotrimoxazole if not already started. Asses and encourage breast feeding if replacement feeding not started. Collect and send dried blood spot sample(DBS) of babies b/w 6wk to 6 months for DNA PCR
HIV DNA DETECTED collect and send whole blood for DNA PCR HIV DNA DETECTED IF NOT DETECTED HIV INFECTED Repeat with another sample ADVISORY 2 Continue cotrimoxazole IF DNA DETECTED Manage OI if any Start ARV as per protocol Continue breast feeeding Avoid mixed feeding
If DNA DETECTED WITH INITIAL DBS SAMPLE BUT NOT WITH 2 REPEAT WHOLE BLOOD SAMPLES:ADVISORY 3: Infant probably not infected but at risk. Repeat DNA PCR by DBS test at 6mon , or 6wk at last breast feeding or child develops symptoms of HIV infection. Continue cotrimoxazole until definitely negative. Discourage weaning too early - use local guidelines and AFASS criteria met before weaning . 6months is often good time to discuss possibility of weaning
IF DBS SAMPLE AT 6 WKS HIV DNA NOT DETECTED If child develops signs or symptoms of infection at <6mon age repeat DNA PCR by DBS If asymptomatic repeat DNA PCR at 6months HIV DNA DETECTED HIV DNA NOT DETECTED Follow advisory 1 Confirm by rpt DNA PCR by BREAST FED NOT FED whole blood IN 6wk IN 6Wk BEFORE TEST before FOLLOW ADVISORY3HIV DNA DETECTED HIV NOT DETECTED NOT INFECTEDINFANT INFECTED WITH STOP HIV COTRIMOXAZOLEFOLLOW ADVISORY2 AVOID BREASTFEEDING
HIV EXPOSED CHILD > 18MONTHS OF AGEChild > 18 months ofage* HIV Antibody NEGATIVERapid HIV AntibodyTest Breast feeding child Non-breast feeding child remains at risk of infection UNINFECTED HIV Antibody POSITIVE Repeat HIV Rapid Antibody HIV-INFECTED >6-12 weeks after weaning HIV Antibody POSITIVE (after 6months of EBF) HIV-INFECTEDRefer for HIV care& HIV Antibody Refer for HIV NEGATIVEtreatment care & UNINFECTED treatment
HIV DIAGNOSIS IN CHILDREN <18 MONTHS WITH DNA -PCR Delivery HIV + PREGNANT HIV exposed infant Symptomatic HIV- WOMEN (breastfed and non- exposed breastfed infant <18 months 6 – 8 weeks age age (not previously 1st HIV DNA 1st HIV DNA PCR + PCR _ diagnosed Repeat HIV NEGATIVE DNA PCR PCR test To confirm Breastfed Not breast fed +REPORT _ 2nd PCR after 6–8 2nd PCR at 6 monthsHIV Positive weeks of stopping to confirm status breast-feeding +Repeat test and + _ _ Repeat testrefer for REPORT & refer forfollow-up HIV negative follow -up
What if the Initial DNA PCR is Negative but the child is ILL? If the HIV DNA result is negative, but the child develops HIV symptoms Oral thrush Pneumonia Poor growth Developmental delay Chronic diarrhea Repeat HIV DNA PCR testing
Post exposure prophylaxis Health care personnel are at risk of blood borne infection Percutaneous injury( needle stick, sharps) Contact - mucous membrane of eye & mouth of an infected person -non intact skin or blood -potentially infected body fluids . What is infectious and what is not ? Infectious : blood semen vaginal secretions, peritoneal pericardial, amniotic fluid contaminated with visible blood can lead to infection. Non infectious: sweat saliva urine feces unless these contain blood .
First Aid in management of exposure Immediately wash the wound and surrounding skin with soap and water.Don’ts Don’t squeeze the wound to bleed Don’t put pricked finger in mouth Don’t use bleach or antiseptic or alcohol
Establish eligibility for PEP Risk of transmission proportional to amount of HIV transmitted. A baseline rapid HIV test of exposed and source person must be done before PEP. Informed consent must be obtained. A designated person or trained doctor must asses the risk of transmission following an AEB. Assessment must be quick to start treatment without delay ideally within 2 hrs but certainly within 72 hrs after exposure.
Assessing risk of transmission: Mild Moderate Severe Counsel for PEP Psychological support Document exposure
Deciding on PEP regimenExposure Status of source HIV+ and HIV + and HIV status unknown asymptomatic clinically symptomaticMild Consider 2 Start 2 drug PEP Usually no pep or consider 2 drug PEP drug PEPModerate Start 2 drug Start 3drug PEP -DO -Severe Start 3 drug Start 3drug PEP -DO-
Drug regimen for PEP There are 2 types of regimens: Basic regimen : 2 drug combination Zidovudine(AZT)+ Lamivudine (3TC) or Stavudine(d4T) + Lamivudine Expanded regimen: 3 drug combinationabove either combo’s of 2 drugs with protease inhibitors ( Lopinavir or Indinavir or Nelfinavir)_
MANAGEMENT OF CHILDREN WITH HIV INFECTION Attention to growth, nutrition and immunization of child. Treatment and prevention of opportunistic infections. Antiretroviral therapy.
Prophylactic therapy Cotrimoxazole prophylactic therapy: For prevention of pneumocystis jiroveci , toxoplasma , malaria and other bacterial infections. When to start?1 – 5 yrs : WHO clinical stage 2,3 or 4 regardless CD4 counts. If CD4 count <25% irrespective of stage.>5 yrs : WHO stage 2,3, or 4 if CD4 counts not available WHO stage 3 or 4 irrespective of CD4 counts. CD4 count <350 cells/mm3 irrespective of stage.
Dose : 5mg/kg/day Duration : To be continued till 5 years of age. After 5 yrs, consider stopping, if CD4 count >350 cells/mm3 on 2 occasions at least 3 months apart.
ISONIAZID PROPHYLACTIC THERAPY (IPT) Screening for TB strongly recommended for all Children living with HIV OR AIDS(CLHA) > 1 YR : 6 Months IPT who have no contact with a TB case and are unlikely to have active symptoms. <1 YR : IPT recommended for only those who have contact with TB case and who are unlikely to have active TB. Dose : 10 mg/kg/day.
ANTIRETROVIRAL THERAPY ART decreases mortality in CLHA. However ART is not a cure for infection. Pre ART workup: CLINICAL: Weight, height, head circumference, and other measures of growth. Nutritional status, assessment of dietary intake Developmental assessment. Concomitant medical conditions. WHO clinical staging. Details of drugs child receiving including CPT
LABORATORY: Hemoglobin , complete blood counts. Biochemical tests: LFT, RFT, Blood glucose, serum electrolytes, serum lipids, amylase, lipase levels. Pregnancy test in adolescent girls. CD4 counts and percentage. Viral load if available.
PRE ART COUNSELING Identification of primary care giver who understands implications of ART. Identify secondary care giver in absence of primary care giver. Adequate counseling of care giver regarding dose ,duration, timing and side effects of drug is mandatory before initiating ART.
Time of initiation of ART All infected children <24 months of age. All children < 18 months of age with presumptive clinical diagnosis of HIV. In 24 – 59 months of age: WHO stage 3 and 4 CD4 < 25% or CD4 count <750 cells/mm3 For >60 months age: WHO clinical stage 3 or 4 disease. CD4 count < 350 mm3
When to start ART in children, guided by CD4< 11 month infants : if CD4 < 1500 cells/mm3 (< 25%)12–35 months : if CD4 < 750 cells/mm3 (<20%)36–59 months : if CD4 <350 cells/mm3 (15%)> 5 years old : follow adult guidelines ie start ART if < 350 cells/mm3 especially if symptomatic.Initiate ART before CD4 drops below 200 cells/mm
CURRENT ART REGIMENS FOR USEIN CHILDREN Standard first line regimen : 2NRTI + 1 NNRTIcommonly used NRTI are AZT, d4T, 3TC, ABC.commonly used NNRTI are EFV, NVP.
Choice of first line ART CHILDREN NOT EXPOSED TO NNRTI: AZT+ 3TC+ NVP CHILDREN EXPOSED INFANT OR MATERNAL NVP OR OTHER NNRTI`S USED FOR MATERNAL TREATMENT: AZT+3TC+LPV IF EXPOSURE TO ARV IS UNKNOWN: 2NRTI+ 1NNRTI.
FOLLOW –UP Followed up once every month for initial 6 months Evaluation at every visit should include evaluation for efficacy of treatment which include clinical improvement and weight gain. Monitoring for adverse drug reactions.
Role of the Parent/caregiver Parent needs to understand: That infant diagnosis is an ongoing process The importance of early testing, frequent monitoring, and adherence to care Often the first to notice signs and symptoms. Often has multiple complex roles and needs, including self-care, caretaker role for other family members, feelings about transmission of HIV to the infant. Parent needs understanding and support. 51