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Prevention of Transmission of the Human Immuno Deficiency Virus from MOTHER to her FETUS & INFANT

Prevention of Transmission of the Human Immuno Deficiency Virus from MOTHER to her FETUS & INFANT. Th.Nabachandra. Global Estimates (Dec. 2004). 40 million HIV-I infected. 95% infections in developing countries 47% occur in women of child bearing age. 15000 new infections a day.

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Prevention of Transmission of the Human Immuno Deficiency Virus from MOTHER to her FETUS & INFANT

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  1. Prevention of Transmission of theHuman Immuno Deficiency VirusfromMOTHER to her FETUS & INFANT Th.Nabachandra

  2. Global Estimates (Dec. 2004) • 40 million HIV-I infected. • 95% infections in developing countries • 47% occur in women of child bearing age. • 15000 new infections a day. • One HIV-I infected infant born every minute of the day. • Number of deaths to HIV/AIDS in 2004 – 3.1 million.

  3. GLOBAL ESTIMATES(Children below 15 yrs) 2.2 million children are infected Number of deaths due to HIV/AIDS in 2004 – 5,10, 000 children.

  4. INDIAN SCENARIO • 5.1 million are Sero-Positive • 10% of the global HIV/AIDS prevalence • Prevalence in General Population below 1 percent • 30,000 children are born each year with HIV.

  5. MANIPURSeptember - 2005 Age-Sex Proportion of HIV Positive Cases (Sero-surveillance). Age Group Male Female Total % of total positives (n=20,980) 0-10 Yrs 450 356 806 5.04 11-20 Yrs 820 238 1058 6.62

  6. HIV-I PREVALENCE RATE IN ANTENATAL MOTHER • Sub Saharan Africa 6 % - 30% • United States 0.17 % • India i) Mumbai ii) Pune 2 % - 2.5 % iii) Chennai iv) Manipur 0.64 % - 3.34 %

  7. FREQUENCY OF TRANSMISSION UNITED STATES & WESTERN EUROPE 16 - 20 % THAILAND 19 – 24% AFRICA 25 - 40 %

  8. FREQUENCY OF TRANSMISSION (Contd.) INDIA : • Rshid H. Merchant et al 24 %. • John TJ et al 35 %. • Kumar RM et al 48 %. • Manipur (Sero-Surveillance) 33.05% Estimated frequency of transmission 30%

  9. ROUTES OF TRANSMISSIONChildren • Vertical Transmission 87%. • Contaminated blood (7%) & blood products (4%) • Sexual abuse of children • Multiple injections with inadequately sterilised equipments (IDU).

  10. TIMING OF VERTICAL TRANSMISSION • During gestation (in utero). • During delivery (Intrapartum). • Post partum through breast milk.

  11. VERTICAL TRANSMISSIONDURING GESTATION • 25 - 30% transmission through this route. • Proportion of infants infected each trimester & routes or mechanism – unknown. • Potential Routes - Admixture of maternal – Fetal blood. - Infection across placenta. EVIDENCES: • HIV virus/ Provirus in aborted fetal tissue (8-12wks) amniotic fluid/ blood of infected infants. • P24 antigens 1 fetal blood (16.24 wks) (Cordocentasis). • Positive PCR in first 24-48 hours of life.

  12. Vertical Transmission : (During Delivery) • 70 – 75% of transmission. • Routes or mechanism – Unknown • Potential mechanism - Admixture of maternal & fetal blood - Extensive mucocutaneous (Occular & GIT) exposure of the newborn to maternal blood & vaginal secretion. Evidences : - Higher in first born twin. - Newborn with negative diagnostic studies in 1st and 2 days of life followed by detection of infection at 1 to 3 months of age (PCR).

  13. HIV & BREAST FEEDING • HIV-I detected in cellular & acellular components of breast milk. • Colostral Viral Load High • Proportion of transmission : - Antibody positive before pregnancy 14% - Mother infected during early post natal period 29% • Maximum transmission takes place in the first few months of life. • Infection persists as long as breast feeding continues. • Exclusive breast feeding carries a lower risk of transmission than mixed feeding. - Increased risk in case of breast abscesses, mastitis, nipple cracks.

  14. SUGGESTION: • Breast feeding may be avoided in HIV infected mother if it is economically feasible & safe Other Options: • Exclusive breast feeding for 3-4months followed by early weaning • Issue must be discussed with the family in the ante- natal period & decision about feeding individualized.

  15. FACTORS AFFECTING MOTHER TO CHILD TRANSMISSION OF HIV. MATERNAL FACTORS: Higher Transmission Immunological status: - Low CD4 Count. Clinical Status: - Advanced HIV disease - Seroconverting during pregnancy - Presence of ulcerative STDs at delivery Nutritional Status : - Low Vit. A concentration ?? - Anaemia.

  16. FACTORS AFFECTING MOTHER TO CHILD TRANSMISSION OF HIV. Maternal Factors (Contd.) Behavioral Factors: - Cigarette Smoking - Hard drug use - Unprotected sexual intercourse during pregnancy. Obstetrical Factors: - Prolonged rupture of membrane (>4hrs) - Intrapartum haemorrhage - Obstetrical procedures - Mode of delivery - Invasive fetal monitoring

  17. HOST FACTORS: • PREMATURITY • MULTIPLE PREGNANCY 1st Twin (26%) : 2nd Twin (13%) • GASTRO-INTESTINAL TRACT FACTORS: - Low gastric acidity - Thin mucosa and microvilli. - Deficiency of IgA secreting cells.

  18. HOST FACTORS(Contd). • Ability of Neonatal cell to support viral replication. • Reduced ability to generate virus specific immune responses. - Deficient cell mediated immune responses - Inability for lymphocyte to proliferate & produce ‘’ interferon. - Diminished capability of neonatal natural killer cells to mediate ADCC of HIV 1 infected target cells. - Inability to generate virus specific CTL.

  19. VIRAL FACTORS: • Viral Genotype and Phenotype M-Tropic > T - Tropic High Maternal Viral Load Frequency of Transmission > 50,000 RNA copies/ml - 50 % > 10,000 RNA copies/ml - 29 % < 1000 RNA copies/ml - 12 % • Presence and amount of virus in genital tract.

  20. Strategies To Prevent The VerticalTransmission of HIV Ultimate goal : Effective retroviral Drugs or Vaccine. Three complementary strategies : 1) The protection of girls and women from HIV infection (Primary Prevention) 2) The provision of efficient, acceptable & accessible family planning services. 3) Anti-retroviral drug strategy. Others : 1) Maternal nutritional intervention 2) Bypassing the route of exposure.

  21. PREVENTION OF MTCT A. Protection of girls & women (Primary prevention) - Providing knowledge of HIV/ AIDS - Safe & responsible sexual behavior in couples. - Ensuring necessary personal skills & access to condoms. - Providing good quality, user friendly prevention & treatment program of STDs.

  22. PREVENTION OF MTCT (contd). B. Provision of efficient, acceptable & accessible family planning services. • Aim is to ensure informed reproductive choice. • Abortion where this is legal. - To enable women to avoid unwanted pregnancies and births.

  23. PREVENTION OF MTCT (contd). C.Anti-retroviral drug strategy : • VCT • ARD for HIV+Ve pregnant women (and sometimes for their babies) • Counseling on infant feeding. • Support for the feeding methods chosen by the mother.

  24. REDUCTION OF VIRAL LOAD IN MATERNAL (BLOOD &VAGINAL SECRETIONS) • AZT (ACTG 076) TRIAL 1993 - 402 Mother- Infant pair - 14 – 34 wks of pregnancy - CD4 count >200 cells/ml. • 194 women: - Oral AZT during pregnancy - I/V AZT during labour. - Infants on AZT for 6 wks. No breast feeding: - HIV transmission rate =7.6% • 204 women on placebo. - HIV transmission rate =22.6%.

  25. THAILAND AZT DOUBLE BLIND PLACEBO TRIAL 1996 • 414 Pregnant women • AZT on the last three wks of pregnancy (300 mg BD). 300 mg 3 hourly during labour. • No AZT to infant. • No breast feeding • Study group : 7% transmission rate • Placebo group : 25% transmission rate.

  26. HIV INFECTED WOMEN IN LABOUR NO PRIOR THERAPY REGIMEN: • MOTHER - Nevirapine 200 mg single dose at onset of labour. • NEONATE - 2 mg/kg. NVP oral dose at 48 - 72 hrs. - Breast feeding allowed. • 47% reduction in transmission rate. ADVANTAGES: - Inexpensive - Oral regimen - Simple, easy to administer. - Can give directly observed treatment.

  27. VARIABLE RISK OF MTCT OF HIV 1. No ARD and baby breastfed 30.35% 2. No ARD and baby not breastfed 20% 3. AZT for 1 month & Baby not breastfed 10% 4. AZT for 1 month and baby not breastfed upto 6 months 18%.

  28. VARIABLE RISK OF MTCT OF HIV (Contd.) 5. 2 ARD (AZT & 3TC) at labour with breast feeding at 6 weeks 11%. 6. 2 ARD for 1 month & 1wks after delivery and breast feeding 9% 7. Nevirapine in labour & to baby within 3 days of birth and breast feeding at 3 months of life. 13%.

  29. Thank You

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