New Approaches to Prevent Mother-to-Child Transmission of HIV in Kenya

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New Approaches to Prevent Mother-to-Child
Transmission of HIV in Kenya
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RESEARCH TEAM

• Chandice Covington,PhD,RN
• Mohamed Abdullah, MD
• Richard Zangar PhD
• Lynne McEnroe,MA,MSN,RN

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Estimated risk timing of mother-to-child
transmission of HIV
Transmission rate () Transmission rate () Transmission rate () Transmission rate ()
Timing No Breastfeeding Breastfeeding through 6 months Breastfeeding through 18-24 months
During pregnancy 5 to 10 5 to 10 5 to 10
During labour 10 to 20 10 to 20 10 to 20
Through breastfeeding
Early (first 2 months) 2 to 10 2 to 10
Late (after 2 months) 1 to 5 5 to 10
Overall 15 to 30 25 to 35 30 to 45
(source DeCock, KM, et al., 2000)
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OTHER MTCT CONCERNS

• Risk increased /w mixed feeding (Coutsoudis et
  al., 2001)
• Risk decreased with perinatal antivirals

• Formula-feeding reduced postnatal transmission by
  40, yet no ? in mortality between breast and
  formula (Nduati et al., 2000)
• About 50 infants who acquire HIV succumb in
  the first 18 months of life

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LONG TERM CONSEQUENCES

• Life expectancy for Japan 77 years for women,
  sub-Saharan Africa it is 32 years
• Over 1-million children orphaned in Kenya by
  AIDS, in Africa gt than 12,000,000

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LONGER TERM CONSEQUENCES

• Youth are our future
• Along with parents, loss of teachers and
  nursessocial carriers.
• Novel approaches needed to reduce this loss of
  life and our future

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WHO RECOMENDS EXCLUSIVE BREASTFEEDING
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DEFENSIVE CELLS IN BREASTMILK
COMPONENT ACTION
B Lymphocytes Give rise to antibodies targeted against specific microbes.
Macrophages Kill microbes outright in the baby's gut, produce lysozyme and activate other components of the immune system.
Neutrophils May act as phagocytes, injecting bacteria in baby's digestive system.
T lymphocytes Kill infected cells directly or send out chemical messages to mobilize other defenses. Proliferate in the presence of organisms that cause serious infant illness. Also manufacture compounds that can strengthen child's immune response.
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Molecules in Breastmilk
Secretory IgA class Bind to microbes in infant digestive tract, prevent from passing through gut walls into body's tissues.
B12 binding protein Reduces amount of vitamin B-2, which bacteria need in order to grow.
Bifidus factor Promotes growth of Lactobacillus bifidus bacterium in gut., helps to crowd out dangerous varieties.
Fatty acids Disrupt membranes surrounding some viruses and destroy them.
Fibronectin Increases antimicrobial activity of macrophages helps to repair tissues that have been damaged by immune reactions in baby's gut.
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PURPOSE

• Surrogate nursing is a tradition across cultures
• Grandmother/elder relatives appreciate low rates
  of HIV infection function as extended family
  caregivers
• Examine the feasibility of grandmother-aged
  womens nipple aspirate fluid (NAF) as a
  replacement or supplemental feeding for
  HIV-influenced neonates

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SURROGATE DEFINED

• Non-puerperal not so novel 200,000 years old
  Margaret Mead 1950s, Slome1 described GM in 1956.
  
• Slome, Cecil (1956). Nonpuerperal lactation in
  grandmothers. Journal of Pediatrics, 49(5),
  550-552.
• The process of re-lactation or induced for the
  purpose of feeding a related or non-related
  child.

Grandmother age 50. Natal, South Africa
1956.
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SETTING AND SAMPLE

• Clinics attended by 60 women (N48)
• Villages coastal Kenya (Vipingo Rabai)
• Weaned women 35 -70 years () of age
• Not pregnant or hypertensive, no wasting
  disease symptoms (n12)
• Youthful multiparity extensive lactation
  histories, some previous surrogate nursing

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PROCEDURES

• Clinic notices 10 miles
• Informed consent, pregnancy test, interview,
  venipuncture, anthropometrics, breast
  examination, non-invasive, patented aspirator
  system
• Incentives Dry milk, maize, Beads for Life,
  cloth

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ASSAYS (Proteomics)

• Mass spectrometric analysis of peptides
  (Thermofinnigan LCQ Deca) with pooled NAF
• Identification parent proteins (Sequest analysis
  software)
• Minimum 3 separate peptide matches (Sequest Xcorr
  values gt 1.5 (1/3 e gt 2.0) to confirm the
  presence of the parent protein in NAF

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RESULTS

• Quantity of NAF range lt10 µl to gt250 µl.
• Proteomic analysis Most abundant proteins
• Immunoglobins, accounting for 40 of the total
  protein content
• Immune complements C3, C4
• Several forms of casein and lactotransferrin

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Summary of NAF Proteomic Analysis Milk or Immune
Proteins

• Albumin
• a-1-Antichymotrypsin
• a-1-Antitrypsin
• a-, b-, k-Casein
• Coagulation factor II

• Complement C3
• Complement C4
• Complement C7
• Complement factor B
• Complement factor D
• Ferroxidase (ceruloplasmin)

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Summary of NAF Proteomic Analysis Milk or Immune
Proteins

• Fibrinogen gamma-B chain
• Haptoglobin
• Ig alpha chain (heavy)
• Ig gamma chain (heavy)
• Ig kappa chain (light)
• Ig lambda chain (light)
• a-Lactalbumin

• Lactoferrin
• b-2-microglobulin, pI 5.3
• Polymeric-immunoglobulin receptor
• Prolactin-induced protein
• Transferrin

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Grandmother Hypothesis Re-visited

• The data support that grandmothers may serve a
  "evolutionary loophole" function to circumvent
  disasters
• Maternal-child morbidity mortality
  in AIDS-impacted populations is a disaster 

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OBSTACLES/CONCERNS

• Availability of female relative caretaker (GM
  currently feeding grandchildren)
• Competing infections e.g. malaria, tuberculosis,
  hookworm, parasites, hepatitis
• Health problems of elder women e.g. nutrition,
  anemia, osteoporosis, hypertension

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OBSTACLES/CONCERNS

• New HIV infection in surrogate
• Risk of reverse transmission HIV infection to
  women low but potentially possible
• Stigma

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Next Step Test Feasibilty in Community

• Community Acceptability
• Potential for elder women to re-lactate
  functionality of immune proteins
• Risk/Cost-benefit model for infant, mother,
  surrogate, family, community